Migraine and risk of stroke: a national population-based twin study.

PubMed

Lantz, Maria; Sieurin, Johanna; Sjölander, Arvid; Waldenlind, Elisabet; Sjöstrand, Christina; Wirdefeldt, Karin

2017-10-01

Numerous studies have indicated an increased risk for stroke in patients with migraine, especially migraine with aura; however, many studies used self-reported migraine and only a few controlled for familial factors. We aimed to investigate migraine as a risk factor for stroke in a Swedish population-based twin cohort, and whether familial factors contribute to an increased risk. The study population included twins without prior cerebrovascular disease who answered a headache questionnaire during 1998 and 2002 for twins born 1935-58 and during 2005-06 for twins born between 1959 and 1985. Migraine with and without aura and probable migraine was defined by an algorithm mapping on to clinical diagnostic criteria according to the International Classification of Headache Disorders. Stroke diagnoses were obtained from the national patient and cause of death registers. Twins were followed longitudinally, by linkage of national registers, from date of interview until date of first stroke, death, or end of study on 31 Dec 2014. In total, 8635 twins had any migraineous headache, whereof 3553 had migraine with aura and 5082 had non-aura migraineous headache (including migraine without aura and probable migraine), and 44 769 twins had no migraine. During a mean follow-up time of 11.9 years we observed 1297 incident cases of stroke. The Cox proportional hazards model with attained age as underlying time scale was used to estimate hazard ratios with 95% confidence intervals for stroke including ischaemic and haemorrhagic subtypes related to migraine with aura, non-aura migraineous headache, and any migraineous headache. Analyses were adjusted for gender and cardiovascular risk factors. Where appropriate; within-pair analyses were performed to control for confounding by familial factors. The age- and gender-adjusted hazard ratio for stroke related to migraine with aura was 1.27 (95% confidence interval 1.00-1.62), P = 0.05, and 1.07 (95% confidence interval 0.91-1.26), P = 0.39 related to any migraineous headache. Multivariable adjusted analyses showed similar results. When stratified by gender and attained age of ≤50 or >50 years, the estimated hazard ratio for stroke was higher in twins younger than 50 years and in females; however, non-significant. In the within-pair analysis, the hazard ratio for stroke related to migraine with aura was attenuated [hazard ratio 1.09 (95% confidence interval 0.81-1.46), P = 0.59]. In conclusion, we observed no increased stroke risk related to migraine overall but there was a modestly increased risk for stroke related to migraine with aura, and within-pair analyses suggested that familial factors might contribute to this association. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension.

PubMed

MacIsaac, Rachael L; Salatzki, Janek; Higgins, Peter; Walters, Matthew R; Padmanabhan, Sandosh; Dominiczak, Anna F; Touyz, Rhian M; Dawson, Jesse

2016-03-01

Allopurinol lowers blood pressure in adolescents and has other vasoprotective effects. Whether similar benefits occur in older individuals remains unclear. We hypothesized that allopurinol is associated with improved cardiovascular outcomes in older adults with hypertension. Data from the United Kingdom Clinical Research Practice Datalink were used. Multivariate Cox-proportional hazard models were applied to estimate hazard ratios for stroke and cardiac events (defined as myocardial infarction or acute coronary syndrome) associated with allopurinol use over a 10-year period in adults aged >65 years with hypertension. A propensity-matched design was used to reduce potential for confounding. Allopurinol exposure was a time-dependent variable and was defined as any exposure and then as high (≥300 mg daily) or low-dose exposure. A total of 2032 allopurinol-exposed patients and 2032 matched nonexposed patients were studied. Allopurinol use was associated with a significantly lower risk of both stroke (hazard ratio, 0.50; 95% confidence interval, 0.32-0.80) and cardiac events (hazard ratio, 0.61; 95% confidence interval, 0.43-0.87) than nonexposed control patients. In exposed patients, high-dose treatment with allopurinol (n=1052) was associated with a significantly lower risk of both stroke (hazard ratio, 0.58; 95% confidence interval, 0.36-0.94) and cardiac events (hazard ratio, 0.65; 95% confidence interval, 0.46-0.93) than low-dose treatment (n=980). Allopurinol use is associated with lower rates of stroke and cardiac events in older adults with hypertension, particularly at higher doses. Prospective clinical trials are needed to evaluate whether allopurinol improves cardiovascular outcomes in adults with hypertension. © 2016 American Heart Association, Inc.

Periodontal Disease, Regular Dental Care Use, and Incident Ischemic Stroke.

PubMed

Sen, Souvik; Giamberardino, Lauren D; Moss, Kevin; Morelli, Thiago; Rosamond, Wayne D; Gottesman, Rebecca F; Beck, James; Offenbacher, Steven

2018-02-01

Periodontal disease is independently associated with cardiovascular disease. Identification of periodontal disease as a risk factor for incident ischemic stroke raises the possibility that regular dental care utilization may reduce the stroke risk. In the ARIC (Atherosclerosis Risk in Communities) study, pattern of dental visits were classified as regular or episodic dental care users. In the ancillary dental ARIC study, selected subjects from ARIC underwent fullmouth periodontal measurements collected at 6 sites per tooth and classified into 7 periodontal profile classes (PPCs). In the ARIC study 10 362 stroke-free participants, 584 participants had incident ischemic strokes over a 15-year period. In the dental ARIC study, 6736 dentate subjects were assessed for periodontal disease status using PPC with a total of 299 incident ischemic strokes over the 15-year period. The 7 levels of PPC showed a trend toward an increased stroke risk (χ 2 trend P <0.0001); the incidence rate for ischemic stroke/1000-person years was 1.29 for PPC-A (health), 2.82 for PPC-B, 4.80 for PPC-C, 3.81 for PPC-D, 3.50 for PPC-E, 4.78 for PPC-F, and 5.03 for PPC-G (severe periodontal disease). Periodontal disease was significantly associated with cardioembolic (hazard ratio, 2.6; 95% confidence interval, 1.2-5.6) and thrombotic (hazard ratio, 2.2; 95% confidence interval, 1.3-3.8) stroke subtypes. Regular dental care utilization was associated with lower adjusted stroke risk (hazard ratio, 0.77; 95% confidence interval, 0.63-0.94). We confirm an independent association between periodontal disease and incident stroke risk, particularly cardioembolic and thrombotic stroke subtype. Further, we report that regular dental care utilization may lower this risk for stroke. © 2018 American Heart Association, Inc.

The Association Between Kidney Disease and Cardiovascular Risk in a Multiethnic Cohort

PubMed Central

Nickolas, Thomas L.; Khatri, Minesh; Boden-Albala, Bernadette; Kiryluk, Krzysztof; Luo, Xiaodong; Gervasi-Franklin, Palma; Paik, Myunghee; Sacco, Ralph L.

2011-01-01

Background and Purpose The objective of this study was to determine the relationship between chronic kidney disease (CKD), race–ethnicity, and vascular outcomes. Methods A prospective, multiracial cohort of 3298 stroke-free subjects with 6.5 years of mean follow-up time for vascular outcomes (stroke, myocardial infarction, vascular death) was used. Kidney function was estimated using serum creatinine and Cockcroft-Gault formula. Cox proportional hazards models were fitted to evaluate the relationship between kidney function and vascular outcomes. Results In multivariate analysis, Cockcroft-Gault formula between 15 and 59 mL/min was associated with a significant 43% increased stroke risk in the overall cohort. Blacks with Cockcroft-Gault formula between 15 and 59 mL/min had significantly increased risk of both stroke (hazard ratio, 2.65; 95% CI, 1.47 to 4.77) and combined vascular outcomes (hazard ratio, 1.59; 95% CI, 1.10–2.92). Conclusion Chronic kidney disease is a significant risk factor for stroke and combined vascular events, especially in blacks. PMID:18617655

Soluble CD40L Is a Useful Marker to Predict Future Strokes in Patients With Minor Stroke and Transient Ischemic Attack.

PubMed

Li, Jiejie; Wang, Yilong; Lin, Jinxi; Wang, David; Wang, Anxin; Zhao, Xingquan; Liu, Liping; Wang, Chunxue; Wang, Yongjun

2015-07-01

Elevated soluble CD40 ligand (sCD40L) was shown to be related to cardiovascular events, but the role of sCD40L in predicting recurrent stroke remains unclear. Baseline sCD40L levels were measured in 3044 consecutive patients with acute minor stroke and transient ischemic attack, who had previously been enrolled in the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Cox proportional-hazards model was used to assess the association of sCD40L with recurrent stroke. Patients in the top tertile of sCD40L levels had increased risk of recurrent stroke comparing with those in the bottom tertile, after adjusted for conventional confounding factors (hazard ratio, 1.49; 95% confidence interval, 1.11-2.00; P=0.008). The patients with elevated levels of both sCD40L and high-sensitive C-reactive protein also had increased risk of recurrent stroke (hazard ratio, 1.81; 95% confidence interval, 1.23-2.68; P=0.003). Elevated sCD40L levels independently predict recurrent stroke in patients with minor stroke and transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2015 American Heart Association, Inc.

Patent foramen ovale and the risk of ischemic stroke in a multiethnic population.

PubMed

Di Tullio, Marco R; Sacco, Ralph L; Sciacca, Robert R; Jin, Zhezhen; Homma, Shunichi

2007-02-20

We sought to assess the risk of ischemic stroke from a patent foramen ovale (PFO) in the multiethnic prospective cohort of northern Manhattan. Patent foramen ovale has been associated with increased risk of ischemic stroke, mainly in case-control studies. The actual PFO-related stroke risk in the general population is unclear. The presence of PFO was assessed at baseline by using transthoracic 2-dimensional echocardiography with contrast injection in 1,100 stroke-free subjects older than 39 years of age (mean age 68.7 +/- 10.0 years) from the Northern Manhattan Study (NOMAS). The presence of atrial septal aneurysm (ASA) also was recorded. Subjects were followed annually for outcomes. We assessed PFO/ASA-related stroke risk after adjusting for established stroke risk factors. We detected PFO in 164 subjects (14.9%); ASA was present in 27 subjects (2.5%) and associated with PFO in 19 subjects. During a mean follow-up of 79.7 +/- 28.0 months, an ischemic stroke occurred in 68 subjects (6.2%). After adjustment for demographics and risk factors, PFO was not found to be significantly associated with stroke (hazard ratio 1.64, 95% confidence interval [CI] 0.87 to 3.09). The same trend was observed in all age, gender, and race-ethnic subgroups. The coexistence of PFO and ASA did not increase the stroke risk (adjusted hazard ratio 1.25, 95% CI 0.17 to 9.24). Isolated ASA was associated with elevated stroke incidence (2 of 8, or 25%; adjusted hazard ratio 3.66, 95% CI 0.88 to 15.30). Patent foramen ovale, alone or together with ASA, was not associated with an increased stroke risk in this multiethnic cohort. The independent role of ASA needs further assessment in appositely designed and powered studies.

Socioeconomic status inconsistency and risk of stroke among Japanese middle-aged women.

PubMed

Honjo, Kaori; Iso, Hiroyasu; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

2014-09-01

Little research has been conducted to examine the effect of inconsistencies in socioeconomic status on cardiovascular health. In particular, no studies have been reported in Asian countries, including Japan, which is thought to have high socioeconomic status inconsistency among women. We examined the effect of status inconsistency between education level and occupation on stroke risk in a prospective 20-year study of 14 742 middle-aged Japanese women included in the prospective Japan Public Health Center-based (JPHC) Study Cohort I in 1990. Status inconsistency between education level and occupation was determined (qualified, overqualified, and underqualified), and the association with risk of stroke was examined. Cox proportional regression analysis was used to determine hazard ratios, which were adjusted for age, marital status, and geographical area. Adjusted hazard ratio for stroke in overqualified compared with qualified women was 2.06 (95% confidence interval, 1.13-3.78). Adjusted hazard ratios for stroke among highly educated manual workers and workers in service industry were 3.47 (95% confidence interval, 1.54-7.84) and 3.21 (95% confidence interval, 1.49-6.90), respectively, when compared with highly educated professionals/managers. High academic qualifications without an appropriate job could be a risk factor for stroke among Japanese women. Our result suggests that status inconsistency could be a potential explanation for the increased stroke risk among highly educated women. © 2014 American Heart Association, Inc.

Stroke is predicted by low visuospatial in relation to other intellectual abilities and coronary heart disease by low general intelligence.

PubMed

Kajantie, Eero; Räikkönen, Katri; Henriksson, Markus; Leskinen, Jukka T; Forsén, Tom; Heinonen, Kati; Pesonen, Anu-Katriina; Osmond, Clive; Barker, David J P; Eriksson, Johan G

2012-01-01

Low intellectual ability is associated with an increased risk of coronary heart disease and stroke. Most studies have used a general intelligence score. We studied whether three different subscores of intellectual ability predict these disorders. We studied 2,786 men, born between 1934 and 1944 in Helsinki, Finland, who as conscripts at age 20 underwent an intellectual ability test comprising verbal, visuospatial (analogous to Raven's progressive matrices) and arithmetic reasoning subtests. We ascertained the later occurrence of coronary heart disease and stroke from validated national hospital discharge and death registers. 281 men (10.1%) had experienced a coronary heart disease event and 131 (4.7%) a stroke event. Coronary heart disease was predicted by low scores in all subtests, hazard ratios for each standard deviation (SD) lower score ranging from 1.21 to 1.30 (confidence intervals 1.08 to 1.46). Stroke was predicted by a low visuospatial reasoning score, the corresponding hazard ratio being 1.23 (95% confidence interval 1.04 to 1.46), adjusted for year and age at testing. Adjusted in addition for the two other scores, the hazard ratio was 1.40 (1.10 to 1.79). This hazard ratio was little affected by adjustment for socioeconomic status in childhood and adult life, whereas the same adjustments attenuated the associations between intellectual ability and coronary heart disease. The associations with stroke were also unchanged when adjusted for systolic blood pressure at 20 years and reimbursement for adult antihypertensive medication. Stroke is predicted by low visuospatial reasoning scores in relation to scores in the two other subtests. This association may be mediated by common underlying causes such as impaired brain development, rather than by mechanisms associated with risk factors shared by stroke and coronary heart disease, such as socio-economic status, hypertension and atherosclerosis.

Influenza vaccination and cardiovascular risk in patients with recent TIA and stroke.

PubMed

Lavallée, Philippa C; Labreuche, Julien; Fox, Kim M; Lavados, Pablo; Mattle, Heinrich; Steg, Philippe Gabriel; Amarenco, Pierre

2014-05-27

To determine whether current influenza vaccination is associated with reduced risk of major vascular events in patients with recent ischemic stroke or TIA of mainly atherothrombotic origin. Data were pooled from 2 prospective cohort studies, the OPTIC Registry (n = 3,635) and the AMISTAD Study (n = 618), and from the randomized PERFORM Trial (n = 19,120), all of which included patients with recent ischemic stroke or TIA. Influenza vaccination status was determined in 23,110 patients. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or vascular death up to 2 years. Secondary outcomes were myocardial infarction and stroke separately. Influenza vaccination had no association with the primary outcome in the propensity score-matched cohort (hazard ratio 0.97, 95% confidence interval [CI] 0.85-1.11; p = 0.67) or in the propensity score-adjusted cohort (hazard ratio 1.00, 95% CI 0.89-1.12; p = 0.99). Similarly, the risk of stroke and myocardial infarction did not differ between the vaccinated group and the unvaccinated group; in the matched cohort, the hazard ratio was 1.01 (95% CI 0.88-1.17; p = 0.89) for stroke and 0.84 (95% CI 0.59-1.18; p = 0.30) for myocardial infarction. Influenza vaccination was not associated with reduced outcome events in patients with recent atherothrombotic ischemic stroke after considering all baseline characteristics (including concomitant medications) associated with influenza vaccination. © 2014 American Academy of Neurology.

Liver Cirrhosis in Patients With Atrial Fibrillation: Would Oral Anticoagulation Have a Net Clinical Benefit for Stroke Prevention?

PubMed

Kuo, Ling; Chao, Tze-Fan; Liu, Chia-Jen; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Lip, Gregory Y H; Chen, Shih-Ann

2017-06-23

Patients with liver cirrhosis have been excluded from randomized clinical trials of oral anticoagulation therapy for stroke prevention in atrial fibrillation. We hypothesized that patients with liver cirrhosis would have a positive net clinical benefit for oral anticoagulation when used for stroke prevention in atrial fibrillation. This study used the National Health Insurance Research Database in Taiwan. Among 289 559 atrial fibrillation patients aged ≥20 years, there were 10 336 with liver cirrhosis, and 9056 of them having a CHA 2 DS 2 -VASc score ≥2 were divided into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Patients with liver cirrhosis had a higher risk of ischemic stroke (hazard ratio=1.10, P =0.046) and intracranial hemorrhage (hazard ratio=1.20, P =0.043) compared with those without. Among patients with liver cirrhosis, patients taking antiplatelet therapy had a similar risk of ischemic stroke (hazard ratio=1.02, 95%CI=0.88-1.18) compared to those without antithrombotic therapies, but the risk was significantly lowered among warfarin users (hazard ratio=0.76, 95%CI=0.58-0.99). For intracranial hemorrhage, there were no significant differences between those untreated and those taking antiplatelet therapy or warfarin. The use of warfarin was associated with a positive net clinical benefit compared with being untreated or receiving only antiplatelet therapy. For atrial fibrillation patients with liver cirrhosis in the current analysis of an observational study, warfarin use was associated with a lower risk of ischemic stroke and a positive net clinical benefit compared with nontreatment, and thus, thromboprophylaxis should be considered for such patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Burden of Intracranial Atherosclerosis Is Associated With Long-Term Vascular Outcome in Patients With Ischemic Stroke.

PubMed

Kim, Byung-Su; Chung, Pil-Wook; Park, Kwang-Yeol; Won, Hong-Hee; Bang, Oh Young; Chung, Chin-Sang; Lee, Kwang Ho; Kim, Gyeong-Moon

2017-10-01

Ischemic stroke patients often have intracranial atherosclerosis (ICAS), despite heterogeneity in the cause of stroke. We tested the hypothesis that ICAS burden can independently reflect the risk of long-term vascular outcome. This was a retrospective cohort study analyzing data from a prospective stroke registry enrolling consecutive patients with acute ischemic stroke or transient ischemic attack. A total of 1081 patients were categorized into no ICAS, single ICAS, and advanced ICAS (ICAS ≥2 different intracranial arteries) groups. Primary and secondary end points were time to occurrence of recurrent ischemic stroke and composite vascular outcome, respectively. Study end points by ICAS burden were compared using Cox proportional hazards models in overall and propensity-matched patients. ICAS was present in 405 patients (37.3%). During a median 5-year follow-up, recurrent stroke and composite vascular outcome occurred in 6.8% and 16.8% of patients, respectively. As the number of ICAS increased, the risk for study end points increased after adjustment of potential covariates (hazard ratio per 1 increase in ICAS, 1.19; 95% confidence interval, 1.01-1.42 for recurrent ischemic stroke and hazard ratio, 1.18; 95% confidence interval, 1.05-1.33 for composite vascular outcome). The hazard ratios (95% confidence interval) for recurrent stroke and composite vascular outcome in patients with advanced ICAS compared with those without ICAS were 1.56 (0.88-2.74) and 1.72 (1.17-2.53), respectively, in the overall patients. The corresponding values in the propensity-matched patients were 1.28 (0.71-2.30) and 1.95 (1.27-2.99), respectively. ICAS burden was independently associated with the risk of subsequent composite vascular outcome in patients with ischemic stroke. These findings suggest that ICAS burden can reflect the risk of long-term vascular outcome. © 2017 American Heart Association, Inc.

Apixaban versus warfarin in patients with atrial fibrillation.

PubMed

Granger, Christopher B; Alexander, John H; McMurray, John J V; Lopes, Renato D; Hylek, Elaine M; Hanna, Michael; Al-Khalidi, Hussein R; Ansell, Jack; Atar, Dan; Avezum, Alvaro; Bahit, M Cecilia; Diaz, Rafael; Easton, J Donald; Ezekowitz, Justin A; Flaker, Greg; Garcia, David; Geraldes, Margarida; Gersh, Bernard J; Golitsyn, Sergey; Goto, Shinya; Hermosillo, Antonio G; Hohnloser, Stefan H; Horowitz, John; Mohan, Puneet; Jansky, Petr; Lewis, Basil S; Lopez-Sendon, Jose Luis; Pais, Prem; Parkhomenko, Alexander; Verheugt, Freek W A; Zhu, Jun; Wallentin, Lars

2011-09-15

Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).

Postural changes in blood pressure and incidence of ischemic stroke subtypes: the ARIC study.

PubMed

Yatsuya, Hiroshi; Folsom, Aaron R; Alonso, Alvaro; Gottesman, Rebecca F; Rose, Kathryn M

2011-02-01

The relation of orthostatic blood pressure decrease, or increase, with occurrence of ischemic stroke subtypes has not been examined. We investigated the association of orthostatic blood pressure change (within 2 minutes after supine to standing) obtained at baseline (1987 to 1989) in the Atherosclerosis Risk in Communities Study with incidence of ischemic stroke subtypes through 2007. Among 12 817 black and white individuals without a history of stroke at baseline, 680 ischemic strokes (153 lacunar, 383 nonlacunar thrombotic, and 144 cardioembolic strokes) occurred during a median follow-up of 18.7 years. There was a U-shaped association between orthostatic systolic blood pressure change and lacunar stroke incidence (quadratic P=0.004). In contrast, orthostatic systolic blood pressure decrease of 20 mm Hg or more was associated with increased occurrence of nonlacunar thrombotic and cardioembolic strokes independent of sitting systolic blood pressure, antihypertensive medication use, diabetes, and other lifestyle, physiological, biochemical, and medical conditions at baseline (for nonlacunar thrombotic: hazard ratio, 2.02; 95% CI, 1.43 to 2.84; for cardioembolic: hazard ratio, 1.85, 95% CI, 1.01 to 3.39). Orthostatic diastolic blood pressure decrease was associated with increased risk of nonlacunar thrombotic and cardioembolic strokes; the hazard ratios (95% CI) associated with 10 mm Hg lower orthostatic diastolic blood pressure (continuous) were 1.26 (1.06 to 1.50) and 1.41 (1.06 to 1.88), respectively, in fully adjusted models. In conclusion, the present study found that nonlacunar ischemic stroke incidence was positively associated with an orthostatic decrease of systolic and diastolic blood pressure, whereas greater lacunar stroke incidence was associated with both orthostatic increases and decreases in systolic blood pressure.

Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).

PubMed

Halperin, Jonathan L; Hankey, Graeme J; Wojdyla, Daniel M; Piccini, Jonathan P; Lokhnygina, Yuliya; Patel, Manesh R; Breithardt, Günter; Singer, Daniel E; Becker, Richard C; Hacke, Werner; Paolini, John F; Nessel, Christopher C; Mahaffey, Kenneth W; Califf, Robert M; Fox, Keith A A

2014-07-08

Nonvalvular atrial fibrillation is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). This prespecified secondary analysis compares outcomes in older and younger patients. There were 6229 patients (44%) aged ≥75 years with atrial fibrillation and ≥2 stroke risk factors randomized to warfarin (target international normalized ratio=2.0-3.0) or rivaroxaban (20 mg daily; 15 mg if creatinine clearance <50 mL/min), double blind. The primary end point was stroke and systemic embolism by intention to treat. Over 10 866 patient-years, older participants had more primary events (2.57% versus 2.05%/100 patient-years; P=0.0068) and major bleeding (4.63% versus 2.74%/100 patient-years; P<0.0001). Stroke/systemic embolism rates were consistent among older (2.29% rivaroxaban versus 2.85% warfarin per 100 patient-years; hazard ratio=0.80; 95% confidence interval, 0.63-1.02) and younger patients (2.00% versus 2.10%/100 patient-years; hazard ratio=0.95; 95% confidence interval, 0.76-1.19; interaction P=0.313), as were major bleeding rates (≥75 years: 4.86% rivaroxaban versus 4.40% warfarin per 100 patient-years; hazard ratio=1.11; 95% confidence interval, 0.92-1.34; <75 years: 2.69% versus 2.79%/100 patient-years; hazard ratio=0.96; 95% confidence interval, 0.78-1.19; interaction P=0.336). Hemorrhagic stroke rates were similar in both age groups; there was no interaction between age and rivaroxaban response. Elderly patients had higher stroke and major bleeding rates than younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly. © 2014 American Heart Association, Inc.

Adherence to a Healthy Nordic Diet and Risk of Stroke: A Danish Cohort Study.

PubMed

Hansen, Camilla Plambeck; Overvad, Kim; Kyrø, Cecilie; Olsen, Anja; Tjønneland, Anne; Johnsen, Søren Paaske; Jakobsen, Marianne Uhre; Dahm, Christina Catherine

2017-02-01

Specific dietary patterns, including the Mediterranean diet, have been associated with stroke prevention. Our aim was to investigate whether adherence to a healthy Nordic diet, including fish, apples and pears, cabbages, root vegetables, rye bread, and oatmeal, was associated with risk of stroke. Incident cases of stroke among 55 338 men and women from the Danish Diet, Cancer and Health cohort were identified from the Danish National Patient Register and verified by review of records. Cases of ischemic stroke were further subclassified based on etiology according to the TOAST classification system (Trial of Org 10172 in Acute Stroke Treatment). Information on diet was collected at baseline (1993-1997) using a semiquantitative food-frequency questionnaire. Cox proportional hazards models were used to estimate hazards ratios of total stroke and subtypes of ischemic and hemorrhagic stroke. During a median follow-up of 13.5 years, 2283 cases of incident stroke were verified, including 1879 ischemic strokes. Adherence to a healthy Nordic diet, as reflected by a higher Healthy Nordic Food Index score, was associated with a lower risk of stroke. The hazards ratio comparing an index score of 4 to 6 (high adherence) with an index score of 0 to 1 (low adherence) was 0.86 (95% confidence interval 0.76-0.98) for total stroke. Inverse associations were observed for ischemic stroke, including large-artery atherosclerosis. No trend was observed for hemorrhagic stroke; however, a statistically insignificant trend was observed for intracerebral hemorrhage. Our findings suggest that a healthy Nordic diet may be recommended for the prevention of stroke. © 2017 American Heart Association, Inc.

Dietary patterns are associated with incident stroke and contribute to excess risk of stroke in black Americans.

PubMed

Judd, Suzanne E; Gutiérrez, Orlando M; Newby, P K; Howard, George; Howard, Virginia J; Locher, Julie L; Kissela, Brett M; Shikany, James M

2013-12-01

Black Americans and residents of the Southeastern United States are at increased risk of stroke. Diet is one of many potential factors proposed that might explain these racial and regional disparities. Between 2003 and 2007, the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study enrolled 30 239 black and white Americans aged≥45 years. Dietary patterns were derived using factor analysis and foods from food frequency data. Incident strokes were adjudicated using medical records by a team of physicians. Cox-proportional hazards models were used to examine risk of stroke. During 5.7 years, 490 incident strokes were observed. In a multivariable-adjusted analysis, greater adherence to the plant-based pattern was associated with lower stroke risk (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; Ptrend=0.005). This association was attenuated after addition of income, education, total energy intake, smoking, and sedentary behavior. Participants with a higher adherence to the Southern pattern experienced a 39% increased risk of stroke (hazard ratio, 1.39; 95% confidence interval, 1.05, 1.84), with a significant (P=0.009) trend across quartiles. Including Southern pattern in the model mediated the black-white risk of stroke by 63%. These data suggest that adherence to a Southern style diet may increase the risk of stroke, whereas adherence to a more plant-based diet may reduce stroke risk. Given the consistency of finding a dietary effect on stroke risk across studies, discussing nutrition patterns during risk screening may be an important step in reducing stroke.

Pharmacogenetic Associations of β1-Adrenergic Receptor Polymorphisms With Cardiovascular Outcomes in the SPS3 Trial (Secondary Prevention of Small Subcortical Strokes).

PubMed

Magvanjav, Oyunbileg; McDonough, Caitrin W; Gong, Yan; McClure, Leslie A; Talbert, Robert L; Horenstein, Richard B; Shuldiner, Alan R; Benavente, Oscar R; Mitchell, Braxton D; Johnson, Julie A

2017-05-01

Functional polymorphisms (Ser49Gly and Arg389Gly) in ADRB1 have been associated with cardiovascular and β-blocker response outcomes. Herein we examined associations of these polymorphisms with major adverse cardiovascular events (MACE), with and without stratification by β-blocker treatment in patients with a history of stroke. Nine hundred and twenty-six participants of the SPS3 trial's (Secondary Prevention of Small Subcortical Strokes) genetic substudy with hypertension were included. MACE included stroke, myocardial infarction, and all-cause death. Kaplan-Meier and multivariable Cox regression analyses were used. Because the primary component of MACE was ischemic stroke, we tested the association of Ser49Gly with ischemic stroke among 41 475 individuals of European and African ancestry in the NINDS (National Institute of Neurological Disorders and Stroke) SiGN (Stroke Genetics Network). MACE was higher in carriers of the Gly49 allele than in those with the Ser49Ser genotype (10.5% versus 5.4%, log-rank P =0.005). Gly49 carrier status was associated with MACE (hazard ratio, 1.62; 95% confidence interval, 1.00-2.68) and ischemic stroke (hazard ratio, 1.81; 95% confidence interval, 1.01-3.23) in SPS3 and with small artery ischemic stroke (odds ratio, 1.14; 95% confidence interval, 1.03-1.26) in SiGN. In SPS3, β-blocker-treated Gly49 carriers had increased MACE versus non-β-blocker-treated individuals and noncarriers (hazard ratio, 2.03; 95% confidence interval, 1.20-3.45). No associations were observed with the Arg389Gly polymorphism. Among individuals with previous small artery ischemic stroke, the ADRB1 Gly49 polymorphism was associated with MACE, particularly small artery ischemic stroke, a risk that may be increased among β-blocker-treated individuals. Further research is needed to define β-blocker benefit among ischemic stroke patients by ADRB1 genotype. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306. © 2017 American Heart Association, Inc.

Antiplatelet Regimen for Patients With Breakthrough Strokes While on Aspirin: A Systematic Review and Meta-Analysis.

PubMed

Lee, Meng; Saver, Jeffrey L; Hong, Keun-Sik; Rao, Neal M; Wu, Yi-Ling; Ovbiagele, Bruce

2017-09-01

Optimal antiplatelet therapy after an ischemic stroke or transient ischemic attack while on aspirin is uncertain. We, therefore, conducted a systematic review and meta-analysis. We searched PubMed (1966 to August 2016) and bibliographies of relevant published original studies to identify randomized trials and cohort studies reporting patients who were on aspirin at the time of an index ischemic stroke or transient ischemic attack and reported hazard ratio for major adverse cardiovascular events or recurrent stroke associated with a switch to or addition of another antiplatelet agent versus maintaining aspirin monotherapy. Estimates were combined using a random effects model. Five studies with 8723 patients with ischemic stroke or transient ischemic attack were identified. Clopidogrel was used in 4 cohorts, and ticagrelor was used in 1 cohort. Pooling results showed that addition of or a switch to another antiplatelet agent, versus aspirin monotherapy, was associated with reduced risks of major adverse cardiovascular events (hazard ratio, 0.68; 95% confidence interval, 0.54-0.85) and recurrent stroke (hazard ratio, 0.70; 95% confidence interval, 0.54-0.92). Each of the strategies of addition of and switching another antiplatelet agent showed benefit versus continued aspirin monotherapy, and studies with regimen initiation in the first days after index event showed more homogenous evidence of benefit. Among patients who experience an ischemic stroke or transient ischemic attack while on aspirin monotherapy, the addition of or a switch to another antiplatelet agent, especially in the first days after index event, is associated with fewer future vascular events, including stroke. © 2017 American Heart Association, Inc.

Telmisartan to prevent recurrent stroke and cardiovascular events.

PubMed

Yusuf, Salim; Diener, Hans-Christoph; Sacco, Ralph L; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-09-18

Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10). Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.) 2008 Massachusetts Medical Society

Quality of Acute Care and Long-Term Quality of Life and Survival: The Australian Stroke Clinical Registry.

PubMed

Cadilhac, Dominique A; Andrew, Nadine E; Lannin, Natasha A; Middleton, Sandy; Levi, Christopher R; Dewey, Helen M; Grabsch, Brenda; Faux, Steve; Hill, Kelvin; Grimley, Rohan; Wong, Andrew; Sabet, Arman; Butler, Ernest; Bladin, Christopher F; Bates, Timothy R; Groot, Patrick; Castley, Helen; Donnan, Geoffrey A; Anderson, Craig S

2017-04-01

Uncertainty exists over whether quality improvement strategies translate into better health-related quality of life (HRQoL) and survival after acute stroke. We aimed to determine the association of best practice recommended interventions and outcomes after stroke. Data are from the Australian Stroke Clinical Registry during 2010 to 2014. Multivariable regression was used to determine associations between 3 interventions: received acute stroke unit (ASU) care and in various combinations with prescribed antihypertensive medication at discharge, provision of a discharge care plan, and outcomes of survival and HRQoL (EuroQoL 5-dimensional questionnaire visual analogue scale) at 180 days, by stroke type. An assessment was also made of outcomes related to the number of processes patients received. There were 17 585 stroke admissions (median age 77 years, 47% female; 81% managed in ASUs; 80% ischemic stroke) from 42 hospitals (77% metropolitan) assessed. Cumulative benefits on outcomes related to the number of care processes received by patients. ASU care was associated with a reduced likelihood of death (hazard ratio, 0.49; 95% confidence interval, 0.43-0.56) and better HRQoL (coefficient, 21.34; 95% confidence interval, 15.50-27.18) within 180 days. For those discharged from hospital, receiving ASU+antihypertensive medication provided greater 180-day survival (hazard ratio, 0.45; 95% confidence interval, 0.38-0.52) compared with ASU care alone (hazard ratio, 0.64; 95% confidence interval, 0.54-0.76). HRQoL gains were greatest for patients with intracerebral hemorrhage who received care bundles involving discharge processes (range of increase, 11%-19%). Patients with stroke who receive best practice recommended hospital care have improved long-term survival and HRQoL. © 2017 American Heart Association, Inc.

Aspirin for Stroke Prevention in Elderly Patients With Vascular Risk Factors: Japanese Primary Prevention Project.

PubMed

Uchiyama, Shinichiro; Ishizuka, Naoki; Shimada, Kazuyuki; Teramoto, Tamio; Yamazaki, Tsutomu; Oikawa, Shinichi; Sugawara, Masahiro; Ando, Katsuyuki; Murata, Mitsuru; Yokoyama, Kenji; Minematsu, Kazuo; Matsumoto, Masayasu; Ikeda, Yasuo

2016-06-01

The effect of aspirin in primary prevention of stroke is controversial among clinical trials conducted in Western countries, and no data are available for Asian populations with a high risk of intracranial hemorrhage. The objective of this study was to evaluate the effect of aspirin on the risk of stroke and intracranial hemorrhage in the Japanese Primary Prevention Project (JPPP). A total of 14 464 patients (age, 60-85 years) with hypertension, dyslipidemia, and diabetes mellitus participated and were randomized into 2 treatment groups: 100 mg of aspirin or no aspirin. The median follow-up period was 5.02 years. The cumulative rate of fatal or nonfatal stroke was similar for the aspirin (2.068%; 95% confidence interval [CI], 1.750-2.443) and no aspirin (2.299%; 95% CI, 1.963-2.692) groups at 5 years; the estimated hazard ratio was 0.927 (95% CI, 0.741-1.160; P=0.509). Aspirin nonsignificantly reduced the risk of ischemic stroke or transient ischemic attack (hazard ratio, 0.783; 95% CI, 0.606-1.012; P=0.061) and nonsignificantly increased the risk of intracranial hemorrhage (hazard ratio, 1.463; 95% CI; 0.956-2.237; P=0.078). A Cox regression adjusted by the risk factors for all stroke, which were age >70 years, smoking, and diabetes mellitus, supported the above result. Aspirin did not show any net benefit for the primary prevention of stroke in elderly Japanese patients with risk factors for stroke, whereas age >70 years, smoking, and diabetes mellitus were risk factors for stroke regardless of aspirin treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00225849. © 2016 American Heart Association, Inc.

Vitamin D deficiency and incident stroke risk in community-living black and white adults.

PubMed

Judd, Suzanne E; Morgan, Charity J; Panwar, Bhupesh; Howard, Virginia J; Wadley, Virginia G; Jenny, Nancy S; Kissela, Brett M; Gutiérrez, Orlando M

2016-01-01

Black individuals are at greater risk of stroke and vitamin D deficiency than white individuals. Epidemiologic studies have shown that low 25-hydroxyvitamin D concentrations are associated with increased risk of stroke, but these studies had limited representation of black individuals. We examined the association of 25-hydroxyvitamin D with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults ≥45 years of age. Using a case-cohort study design, plasma 25-hydroxyvitamin D was measured in 610 participants who developed incident stroke (cases) and in 937 stroke-free individuals from a stratified cohort random sample of REGARDS participants (comparison cohort). In multivariable models adjusted for socio-demographic factors, co-morbidities and laboratory values including parathyroid hormone, lower 25-hydroxyvitamin D concentrations were associated with higher risk of stroke (25-hydroxyvitamin D >30 ng/mL reference; 25-hydroxyvitamin D concentrations 20-30 ng/mL, hazard ratio 1.33, 95% confidence interval (95% CI) 0.89,1.96; 25-hydroxyvitamin D <20 ng/mL, hazard ratio 1.85, 95% CI 1.17, 2.93). There were no statistically significant differences in the association of lower 25-hydroxyvitamin D with higher risk of stroke in black vs. white participants in fully adjusted models (hazard ratio comparing lowest vs. highest 25-hydroxyvitamin D category 2.62, 95% CI 1.18, 5.83 in blacks vs. 1.64, 95% CI 0.83, 3.24 in whites, P(interaction) = 0.82). The associations were qualitatively unchanged when restricted to ischemic or hemorrhagic stroke subtypes or when using race-specific cut-offs for 25-hydroxyvitamin D categories. Vitamin D deficiency is a risk factor for incident stroke and the strength of this association does not appear to differ by race. © 2016 World Stroke Organization.

Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK.

PubMed

Breuer, Judith; Pacou, Maud; Gautier, Aline; Brown, Martin M

2014-07-08

Stroke and TIA are recognized complications of acute herpes zoster (HZ). Herein, we evaluate HZ as a risk factor for cerebrovascular disease (stroke and TIA) and myocardial infarction (MI) in a UK population cohort. A retrospective cohort of 106,601 HZ cases and 213,202 controls, matched for age, sex, and general practice, was identified from the THIN (The Health Improvement Network) general practice database. Cox proportional hazard models were used to examine the risks of stroke, TIA, and MI in cases and controls, adjusted for vascular risk factors, including body mass index >30 kg/m(2), smoking, cholesterol >6.2 mmol/L, hypertension, diabetes, ischemic heart disease, atrial fibrillation, intermittent arterial claudication, carotid stenosis, and valvular heart disease, over 24 (median 6.3) years after HZ infection. Risk factors for vascular disease were significantly increased in cases of HZ compared with controls. Adjusted hazard ratios for TIA and MI but not stroke were increased in all patients with HZ (adjusted hazard ratios [95% confidence intervals]: 1.15 [1.09-1.21] and 1.10 [1.05-1.16], respectively). However, stroke, TIA, and MI were increased in cases whose HZ occurred when they were younger than 40 years (adjusted hazard ratios [95% confidence intervals]: 1.74 [1.13-2.66], 2.42 [1.34-4.36], and 1.49 [1.04-2.15], respectively). Subjects younger than 40 years were significantly less likely to be asked about vascular risk factors compared with older patients (p < 0.001). HZ is an independent risk factor for vascular disease in the UK population, particularly for stroke, TIA, and MI in subjects affected before the age of 40 years. In older subjects, better ascertainment of vascular risk factors and earlier intervention may explain the reduction in risk of stroke after HZ infection. © 2014 American Academy of Neurology.

Ticagrelor in Acute Stroke or Transient Ischemic Attack in Asian Patients: From the SOCRATES Trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

PubMed

Wang, Yongjun; Minematsu, Kazuo; Wong, Ka Sing Lawrence; Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Jonasson, Jenny; Molina, Carlos A; Johnston, S Claiborne

2017-01-01

In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), ticagrelor was not superior to aspirin. Because of differences in patient demographics and stroke disease pattern in Asia, outcomes of ticagrelor versus aspirin were assessed among Asian patients in a prespecified exploratory analysis. Baseline demographics, treatment effects, and safety of ticagrelor and aspirin were assessed among Asian patients. Differences in outcomes between groups were assessed using Cox proportional hazard model. A total of 3858 (29.2%) SOCRATES participants were recruited in Asia. Among the Asian patients, the primary end point event occurred in 186 (9.6%) of the 1933 patients treated with ticagrelor, versus 224 (11.6%) of the 1925 patients treated with aspirin (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99). The exploratory P value for treatment-by-region interaction was 0.27. The primary end point event rate in the Asian subgroup was numerically higher than that in the non-Asian group (10.6% versus 5.7%; nominal P<0.01). Among the Asian patients, the rate of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeding was similar in the ticagrelor group and the aspirin group (0.6% versus 0.8%; hazard ratio, 0.76; 95% confidence interval, 0.36-1.61). The event rates were numerically higher in the Asian patients. Among the Asian patients with acute stroke or transient ischemic attacks, there was a trend toward a lower hazard ratio in reducing risk of the primary end point of stroke, myocardial infarction, or death in the ticagrelor group. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720. © 2016 American Heart Association, Inc.

Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study

PubMed Central

Markus, Hugh S; King, Alice; Shipley, Martin; Topakian, Raffi; Cullinane, Marisa; Reihill, Sheila; Bornstein, Natan M; Schaafsma, Arjen

2010-01-01

Summary Background Whether surgery is beneficial for patients with asymptomatic carotid stenosis is controversial. Better methods of identifying patients who are likely to develop stroke would improve the risk–benefit ratio for carotid endarterectomy. We aimed to investigate whether detection of asymptomatic embolic signals by use of transcranial doppler (TCD) could predict stroke risk in patients with asymptomatic carotid stenosis. Methods The Asymptomatic Carotid Emboli Study (ACES) was a prospective observational study in patients with asymptomatic carotid stenosis of at least 70% from 26 centres worldwide. To detect the presence of embolic signals, patients had two 1 h TCD recordings from the ipsilateral middle cerebral artery at baseline and one 1 h recording at 6, 12, and 18 months. Patients were followed up for 2 years. The primary endpoint was ipsilateral stroke and transient ischaemic attack. All recordings were analysed centrally by investigators masked to patient identity. Findings 482 patients were recruited, of whom 467 had evaluable recordings. Embolic signals were present in 77 of 467 patients at baseline. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack from baseline to 2 years in patients with embolic signals compared with those without was 2·54 (95% CI 1·20–5·36; p=0·015). For ipsilateral stroke alone, the hazard ratio was 5·57 (1·61–19·32; p=0·007). The absolute annual risk of ipsilateral stroke or transient ischaemic attack between baseline and 2 years was 7·13% in patients with embolic signals and 3·04% in those without, and for ipsilateral stroke was 3·62% in patients with embolic signals and 0·70% in those without. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack for patients who had embolic signals on the recording preceding the next 6-month follow-up compared with those who did not was 2·63 (95% CI 1·01–6·88; p=0·049), and for ipsilateral stroke alone the hazard ratio was 6·37 (1·59–25·57; p=0·009). Controlling for antiplatelet therapy, degree of stenosis, and other risk factors did not alter the results. Interpretation Detection of asymptomatic embolisation on TCD can be used to identify patients with asymptomatic carotid stenosis who are at a higher risk of stroke and transient ischaemic attack, and also those with a low absolute stroke risk. Assessment of the presence of embolic signals on TCD might be useful in the selection of patients with asymptomatic carotid stenosis who are likely to benefit from endarterectomy. Funding British Heart Foundation. PMID:20554250

Demographic and cardiovascular risk factors modify association of fasting insulin with incident coronary heart disease and ischemic stroke (from the Atherosclerosis Risk In Communities Study).

PubMed

Rasmussen-Torvik, Laura J; Yatsuya, Hiroshi; Selvin, Elizabeth; Alonso, Alvaro; Folsom, Aaron R

2010-05-15

Previous studies have reported an association between circulating insulin and incident cardiovascular disease, but limited knowledge is available on the association across subgroups. We examined the associations of fasting insulin with incident coronary heart disease (CHD) and ischemic stroke in multiple subgroups of a biracial, middle-age cohort. A total of 12,323 subjects were included in the analysis. The incidence of CHD (n = 960) and ischemic stroke (n = 445) through 2005 was determined through annual interviews, repeat examinations, and community surveillance. Serum insulin was measured at baseline. Cox regression analysis was used to estimate the hazard ratios by quintile of fasting insulin at baseline and to determine the significance of effect modification. In the minimally adjusted models (age, gender, race, and field center), the baseline fasting insulin quintile was positively associated with both incident CHD (hazard ratio per quintile insulin = 1.12, p-trend <0.0001) and ischemic stroke (hazard ratio per quintile insulin = 1.11, p = 0.0018). The adjustment for high-density lipoprotein completely attenuated the association of insulin with CHD but not with stroke. The associations of insulin with CHD were stronger in nonsmokers (p-interaction = 0.018) and in those without hypertension (p-interaction = 0.0087). The associations of insulin with stroke were stronger in women (p-interaction = 0.037), whites (compared to blacks; p-interaction = 0.036), and those without hypertension (p-interaction = 0.0027). Copyright 2010 Elsevier Inc. All rights reserved.

Combined effect of blood pressure and total cholesterol levels on long-term risks of subtypes of cardiovascular death: Evidence for Cardiovascular Prevention from Observational Cohorts in Japan.

PubMed

Satoh, Michihiro; Ohkubo, Takayoshi; Asayama, Kei; Murakami, Yoshitaka; Sakurai, Masaru; Nakagawa, Hideaki; Iso, Hiroyasu; Okayama, Akira; Miura, Katsuyuki; Imai, Yutaka; Ueshima, Hirotsugu; Okamura, Tomonori

2015-03-01

No large-scale, longitudinal studies have examined the combined effects of blood pressure (BP) and total cholesterol levels on long-term risks for subtypes of cardiovascular death in an Asian population. To investigate these relationships, a meta-analysis of individual participant data, which included 73 916 Japanese subjects (age, 57.7 years; men, 41.1%) from 11 cohorts, was conducted. During a mean follow-up of 15.0 years, deaths from coronary heart disease, ischemic stroke, and intraparenchymal hemorrhage occurred in 770, 724, and 345 cases, respectively. Cohort-stratified Cox proportional hazard models were used. After stratifying the participants by 4 systolic BP ×4 total cholesterol categories, the group with systolic BP ≥160 mm Hg with total cholesterol ≥5.7 mmol/L had the greatest risk for coronary heart disease death (adjusted hazard ratio, 4.39; P<0.0001 versus group with systolic BP <120 mm Hg and total cholesterol <4.7 mmol/L). The adjusted hazard ratios of systolic BP (per 20 mm Hg) increased with increases in total cholesterol categories (hazard ratio, 1.52; P<0.0001 in group with total cholesterol ≥5.7 mmol/L). Similarly, the adjusted hazard ratios of total cholesterol increased with increases in systolic BP categories (P for interaction ≤0.04). Systolic BP was positively associated with ischemic stroke and intraparenchymal hemorrhage death, and total cholesterol was inversely associated with intraparenchymal hemorrhage, but no significant interactions between BP and total cholesterol were observed for stroke. High BP and high total cholesterol can synergistically increase the risk for coronary heart disease death but not for stroke in the Asian population. © 2015 American Heart Association, Inc.

Rivaroxaban Versus Dabigatran or Warfarin in Real-World Studies of Stroke Prevention in Atrial Fibrillation: Systematic Review and Meta-Analysis.

PubMed

Bai, Ying; Deng, Hai; Shantsila, Alena; Lip, Gregory Y H

2017-04-01

This study was designed to evaluate the effectiveness and safety of rivaroxaban in real-world practice compared with effectiveness and safety of dabigatran or warfarin for stroke prevention in atrial fibrillation through meta-analyzing observational studies. Seventeen studies were included after searching in PubMed for studies reporting the comparative effectiveness and safety of rivaroxaban versus dabigatran (n=3), rivaroxaban versus Warfarin (n=11), or both (n=3) for stroke prevention in atrial fibrillation. Overall, the risks of stroke/systematic thromboembolism with rivaroxaban were similar when compared with those with dabigatran (stroke/thromboembolism: hazard ratio, 1.02; 95% confidence interval, 0.91-1.13; I 2 =70.2%, N=5), but were significantly reduced when compared with those with warfarin (hazard ratio, 0.75; 95% confidence interval, 0.64-0.85; I 2 =45.1%, N=9). Major bleeding risk was significantly higher with rivaroxaban than with dabigatran (hazard ratio, 1.38; 95% confidence interval, 1.27-1.49; I 2 =26.1%, N=5), but similar to that with warfarin (hazard ratio, 0.99; 95% confidence interval, 0.91-1.07; I 2 =0.0%, N=6). Rivaroxaban was associated with increased all-cause mortality and gastrointestinal bleeding, but similar risk of acute myocardial infarction and intracranial hemorrhage when compared with dabigatran. When compared with warfarin, rivaroxaban was associated with similar risk of any bleeding, mortality, and acute myocardial infarction, but a higher risk of gastrointestinal bleeding and lower risk of intracranial hemorrhage. In this systematic review and meta-analysis, rivaroxaban was as effective as dabigatran, but was more effective than warfarin for the prevention of stroke/thromboembolism in atrial fibrillation patients. Major bleeding risk was significantly higher with rivaroxaban than with dabigatran, as was all-cause mortality and gastrointestinal bleeding. Rivaroxaban was comparable to warfarin for major bleeding, with an increased risk in gastrointestinal bleeding and decreased risk of intracranial hemorrhage. © 2017 American Heart Association, Inc.

Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Caso, Valeria; Tsivgoulis, Georgios; Furie, Karen L; Tadi, Prasanna; Becattini, Cecilia; Falocci, Nicola; Zedde, Marialuisa; Abdul-Rahim, Azmil H; Lees, Kennedy R; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Procopio, Antonio; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Cappellari, Manuel; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Bandini, Fabio; Marcheselli, Simona; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Masotti, Luca; Vannucchi, Vieri; Sohn, Sung-Il; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Ntaios, George; Karagkiozi, Efstathia; Athanasakis, George; Makaritsis, Kostantinos; Vadikolias, Kostantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Mumoli, Nicola; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Colombo, Giovanna; Silvestrelli, Giorgio; Ciccone, Alfonso; Scoditti, Umberto; Denti, Licia; Mancuso, Michelangelo; Maccarrone, Miriam; Orlandi, Giovanni; Giannini, Nicola; Gialdini, Gino; Tassinari, Tiziana; De Lodovici, Maria Luisa; Bono, Giorgio; Rueckert, Christina; Baldi, Antonio; D'Anna, Sebastiano; Toni, Danilo; Letteri, Federica; Giuntini, Martina; Lotti, Enrico Maria; Flomin, Yuriy; Pieroni, Alessio; Kargiotis, Odysseas; Karapanayiotides, Theodore; Monaco, Serena; Baronello, Mario Maimone; Csiba, Laszló; Szabó, Lilla; Chiti, Alberto; Giorli, Elisa; Del Sette, Massimo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Michel, Patrik; Vanacker, Peter; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Gourbali, Vanessa; Yaghi, Shadi

2017-03-01

This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P =0.10) for major bleedings. The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P =0.009) for ischemic outcome events and 0.407 (0.275-0.540; P =0.14) for hemorrhagic outcome events. In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

Impact of Neighborhood Socioeconomic Conditions on the Risk of Stroke in Japan

PubMed Central

Honjo, Kaori; Iso, Hiroyasu; Nakaya, Tomoki; Hanibuchi, Tomoya; Ikeda, Ai; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

2015-01-01

Background Neighborhood deprivation has been shown in many studies to be an influential factor in cardiovascular disease risk. However, no previous studies have examined the effect of neighborhood socioeconomic conditions on the risk of stroke in Asian countries. Methods This study investigated whether neighborhood deprivation was associated with the risk of stroke and stroke death using data from the Japan Public Health Center-based Prospective Study. We calculated the adjusted hazard ratios of stroke mortality (mean follow-up, 16.4 years) and stroke incidence (mean follow-up, 15.4 years) according to the area deprivation index (ADI) among 90 843 Japanese men and women aged 40–69 years. A Cox proportional-hazard regression model using a shared frailty model was applied. Results The adjusted hazard ratios of stroke incidence, in order of increasing deprivation with reference to the least deprived area, were 1.16 (95% CI, 1.04–1.29), 1.12 (95% CI, 1.00–1.26), 1.18 (95% CI, 1.02–1.35), and 1.19 (95% CI, 1.01–1.41), after adjustment for individual socioeconomic conditions. Behavioral and psychosocial factors attenuated the association, but the association remained significant. The associations were explained by adjusting for biological cardiovascular risk factors. No significant association with stroke mortality was identified. Conclusions Our results indicate that the neighborhood deprivation level influences stroke incidence in Japan, suggesting that area socioeconomic conditions could be a potential target for public health intervention to reduce the risk of stroke. PMID:25757802

Combined effects of family history of CVD and heart rate on ischemic stroke incidence among Inner Mongolians in China.

PubMed

Zhou, Yipeng; Tian, Yunfan; Zhong, Chongke; Batu, Buren; Xu, Tian; Li, Hongmei; Zhang, Mingzhi; Wang, Aili; Zhang, Yonghong

2016-05-01

This study aimed to evaluate the combined effects of family history of cardiovascular diseases (FHCVD) and heart rate on ischemic stroke incidence among Inner Mongolians in China. A prospective cohort study was conducted among 2589 participants aged 20 years and older from Inner Mongolia, China. The participants were divided into four groups according to status of FHCVD and heart rate and followed up from June 2002 to July 2012. Cox proportional hazards models were used to evaluate the combined effects of FHCVD and heart rate on the incidence of ischemic stroke. A total of 76 ischemic stroke occurred during the follow-up period. The observed ischemic stroke cases tended to be older and male, and had higher prevalence of smoking, drinking, hypertension and FHCVD as well as higher systolic and diastolic blood pressures at baseline compared with those who did not experience ischemic stroke. Age- and gender-adjusted hazard ratio (95% confidence interval) of ischemic stroke in the participants with both FHCVD and heart rate ≥ 80 were 2.89 (1.51-5.53), compared with those without FHCVD and heart rate < 80. After multiple adjustment, the association between ischemic stroke risk and both FHCVD and heart rate ≥ 80 remained statistically significant (hazard ratio, 2.47; 95% confidence interval: 1.22-5.01). Our main finding that participants with both FHCVD and faster heart rate have the highest risk of ischemic stroke suggests that faster heart rate may increase the risk of ischemic stroke among people with FHCVD.

Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

PubMed

Tsinovoi, Cari L; Xun, Pengcheng; McClure, Leslie A; Carioni, Vivian M O; Brockman, John D; Cai, Jianwen; Guallar, Eliseo; Cushman, Mary; Unverzagt, Frederick W; Howard, Virginia J; He, Ka

2018-01-01

The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States. We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species. The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident. A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research. © 2017 American Heart Association, Inc.

Plasma FGF23 and the risk of stroke

PubMed Central

Dong, Chuanhui; Stark, Matthew; Silverberg, Shonni; Rundek, Tatjana; Elkind, Mitchell S.V.; Sacco, Ralph L.; Mendez, Armando; Wolf, Myles

2014-01-01

Objective: To examine fibroblast growth factor 23 (FGF23) as a risk factor for incident stroke in a racially/ethnically diverse population-based urban cohort. Methods: Stroke-free Northern Manhattan Study participants with FGF23 measurements (n = 2,525) were followed for a mean of 12 (±5) years to detect incident strokes. We used Cox proportional hazards models to estimate the association of baseline FGF23 with incident total, ischemic, and hemorrhagic stroke. Results: Median FGF23 was 57 relative units (RU)/mL (interquartile range = 44–81 RU/mL). Each unit increase of natural log-transformed FGF23 conferred a 40% greater overall stroke risk after adjusting for estimated glomerular filtration rate and sociodemographic and vascular risk factors (hazard ratio = 1.4, 95% confidence interval 1.1–1.6, p = 0.004). Penalized spline analysis revealed a linear association with overall stroke risk at ≥90 RU/mL FGF23, compared with <90 RU/mL (hazard ratio = 1.5, 95% confidence interval = 1.2–2.1, p = 0.004). Greater FGF23 conferred a doubling of intracerebral hemorrhage (ICH) risk but no significant increased risk of ischemic stroke. The associations of elevated FGF23 levels with greater risks of overall stroke and ICH events were independent of phosphate and parathyroid hormone levels and were similar among participants without chronic kidney disease. Conclusions: Elevated FGF23 was a risk factor for overall stroke and ICH events, in particular in a racially and ethnically diverse urban community, independent of chronic kidney disease. PMID:24706015

Potassium intake and risk of stroke in hypertensive and non-hypertensive women in the Women’s Health Initiative

PubMed Central

Seth, Arjun; Mossavar-Rahmani, Yasmin; Kamensky, Victor; Silver, Brian; Lakshminarayan, Kamakshi; Prentice, Ross; Van Horn, Linda; Wassertheil-Smoller, Sylvia

2014-01-01

Background and Purpose Dietary potassium has been associated with lower risk of stroke but there is little data on dietary potassium effects on different stroke subtypes or in older hypertensive and non-hypertensive women. Methods The study population consisted of 90,137 postmenopausal women aged 50–79 at enrollment, free of stroke history at baseline, followed prospectively for an average of 11 years. Outcome variables were total, ischemic, and hemorrhagic stroke, and all-cause mortality. Incidence was compared across quartiles of dietary potassium intake and hazard ratios were obtained from Cox proportional hazards models after adjusting for potential confounding variables, and in hypertensive and non-hypertensive women separately. Results Mean dietary potassium intake was 2611 mg/day. Highest quartile of potassium intake was associated with lower incidence of ischemic and hemorrhagic stroke, and total mortality. Multivariate analyses comparing highest to lowest quartile of potassium intake, indicated a hazard ratio (HR) for all-cause mortality of 0.90 (95% CI: 0.85 – 0.95), for all stroke of HR=0.88 (95% CI: 0.79 – 0.98), and for ischemic stroke of 0.84 (95% CI: 0.74 – 0.96). The effect on ischemic stroke was more apparent in non-hypertensive women among whom there was a 27% lower risk with HR of 0.73 (95% CI: 0.60 – 0.88), interaction p-value <.10. There was no association with hemorrhagic stroke. Conclusions High potassium intake is associated with a lower risk of all stroke and ischemic stroke as well as all-cause mortality in older women, particularly those who are not hypertensive. PMID:25190445

Predictors of stroke associated with coronary artery bypass grafting in patients with diabetes mellitus and multivessel coronary artery disease.

PubMed

Domanski, Michael J; Farkouh, Michael E; Zak, Victor; Feske, Steven; Easton, Donald; Weinberger, Jesse; Hamon, Martial; Escobedo, Jorge; Shrader, Peter; Siami, Flora S; Fuster, Valentin

2015-05-15

This study assesses demographic and clinical variables associated with perioperative and late stroke in diabetes mellitus patients after multivessel coronary artery bypass grafting (CABG). Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) is the largest randomized trial of diabetic patients undergoing multivessel CABG. FREEDOM patients had improved survival free of death, myocardial infarction, or stroke and increased overall survival after CABG compared to percutaneous intervention. However, the stroke rate was greater following CABG than percutaneous intervention. We studied predictors of stroke in CABG-treated patients analyzing separately overall, perioperative (≤30 days after surgery), and late (>30 days after surgery) stroke. For long-term outcomes (overall stroke and late stroke), Cox proportional hazards regression was used, accounting for time to event, and logistic regression was used for perioperative stroke. Independent perioperative stroke predictors were previous stroke (odds ratio [OR] 6.96, 95% confidence interval [CI] 1.43 to 33.96; p = 0.02), warfarin use (OR 10.26, 95% CI 1.10 to 96.03; p = 0.02), and surgery outside the United States or Canada (OR 9.81, 95% CI 1.28 to 75.40; p = 0.03). Independent late stroke predictors: renal insufficiency (hazard ratio [HR] 3.57, 95% CI 1.01 to 12.64; p = 0.048), baseline low-density lipoprotein ≥105 mg/dl (HR 3.28, 95% CI 1.19 to 9.02; p = 0.02), and baseline diastolic blood pressure (each 1 mm Hg increase reduces stroke hazard by 5%; HR 0.95, 95% CI 0.91 to 0.99; p = 0.03). There was no overlap between predictors of perioperative versus late stroke. In conclusion, late post-CABG strokes were associated with well-described risk factors. Nearly half of the strokes were perioperative. Independent risk factors for perioperative stroke: previous stroke, previous warfarin use, and CABG performed outside the United States or Canada. Copyright © 2015 Elsevier Inc. All rights reserved.

Residential Proximity to Major Roadways and Risk of Incident Ischemic Stroke in NOMAS (The Northern Manhattan Study).

PubMed

Kulick, Erin R; Wellenius, Gregory A; Boehme, Amelia K; Sacco, Ralph L; Elkind, Mitchell S

2018-04-01

The evidence supporting the deleterious cardiovascular health effects of living near a major roadway is growing, although this association is not universal. In primary analyses, we hypothesized that residential proximity to a major roadway would be associated with incident ischemic stroke and that cardiovascular risk factors would modify that association. NOMAS (The Northern Manhattan Study) is an ongoing, population-based cohort study designed to measure cardiovascular risk factors, stroke incidence, and other outcomes in a multiethnic urban population. Recruitment occurred from 1993 to 2001 and participants are followed-up annually by telephone. Residential addresses at baseline were geocoded and Euclidean distance to nearest major roadway was estimated and categorized as in prior studies. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals for the association of this distance to incidence of stroke and other outcomes, adjusting for sociodemographic and cardiovascular risk factors, year at baseline, and neighborhood socioeconomic status. We assessed whether these associations varied by age, sex, smoking status, diabetes mellitus, and hypertension. During a median follow-up period of 15 years (n=3287), 11% of participants were diagnosed with ischemic stroke. Participants living <100 m from a roadway had a 42% (95% confidence interval, 1.01-2.02) higher rate of ischemic stroke versus those living >400 m away. This association was more pronounced among noncurrent smokers (hazard ratio, 1.54; 95% confidence interval, 1.05-2.26) and not evident among smokers (hazard ratio, 0.69; 95% confidence interval, 0.23-2.06). There was no clear pattern of association between proximity to major roadways and other cardiovascular events including myocardial infarction, all-cause death, or vascular death. In this urban multiethnic cohort, we found evidence supporting that within-city variation in residential proximity to major roadway is associated with higher risk of ischemic stroke. An individual's smoking history modified this association, with the association remaining only among participants not currently smokers. © 2018 American Heart Association, Inc.

Stroke or transient ischemic attack in patients with transvenous pacemaker or defibrillator and echocardiographically detected patent foramen ovale.

PubMed

DeSimone, Christopher V; Friedman, Paul A; Noheria, Amit; Patel, Nikhil A; DeSimone, Daniel C; Bdeir, Sami; Aakre, Christopher A; Vaidya, Vaibhav R; Slusser, Joshua P; Hodge, David O; Ackerman, Michael J; Rabinstein, Alejandro A; Asirvatham, Samuel J

2013-09-24

A patent foramen ovale (PFO) may permit arterial embolization of thrombi that accumulate on the leads of cardiac implantable electronic devices in the right-sided cardiac chambers. We sought to determine whether a PFO increases the risk of stroke/transient ischemic attack (TIA) in patients with endocardial leads. We retrospectively evaluated all patients who had endocardial leads implanted between January 1, 2000, and October 25, 2010, at Mayo Clinic Rochester. Echocardiography was used to establish definite PFO and non-PFO cohorts. The primary end point of stroke/TIA consistent with a cardioembolic etiology and the secondary end point of mortality during postimplantation follow-up were compared in PFO versus non-PFO patients with the use of Cox proportional hazards models. We analyzed 6075 patients (364 with PFO) followed for a mean 4.7 ± 3.1 years. The primary end point of stroke/TIA was met in 30/364 (8.2%) PFO versus 117/5711 (2.0%) non-PFO patients (hazard ratio, 3.49; 95% confidence interval, 2.33-5.25; P<0.0001). The association of PFO with stroke/TIA remained significant after multivariable adjustment for age, sex, history of stroke/TIA, atrial fibrillation, and baseline aspirin/warfarin use (hazard ratio, 3.30; 95% confidence interval, 2.19-4.96; P<0.0001). There was no significant difference in all-cause mortality between PFO and non-PFO patients (hazard ratio, 0.91; 95% confidence interval, 0.77-1.07; P=0.25). In patients with endocardial leads, the presence of a PFO on routine echocardiography is associated with a substantially increased risk of embolic stroke/TIA. This finding suggests a role of screening for PFOs in patients who require cardiac implantable electronic devices; if a PFO is detected, PFO closure, anticoagulation, or nonvascular lead placement may be considered.

Changes in the Employment Status and Risk of Stroke and Stroke Types.

PubMed

Eshak, Ehab S; Honjo, Kaori; Iso, Hiroyasu; Ikeda, Ai; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

2017-05-01

Because of limited evidence, we investigated a long-term impact of changes in employment status on risk of stroke. This was a prospective study of 21 902 Japanese men and 19 826 women aged 40 to 59 years from 9 public health centers across Japan. Participants were followed up from 1990 to 1993 to the end of 2009 to 2014. Cox proportional hazard ratio of stroke (incidence and mortality) and its types (hemorrhagic and ischemic) was calculated according to changes in the employment status within 5 years interval between 1990 to 1993 and 1995 to 1998 (continuously employed, job loss, reemployed, and continuously unemployed). During the follow-up period, 973 incident cases and 275 deaths from stroke in men and 460 cases and 131 deaths in women were documented. Experiencing 1 spell of unemployment was associated with higher risks of morbidity and mortality from total, hemorrhagic, and ischemic stroke in both men and women, even after propensity score matching. Compared with continuously employed subjects, the multivariable hazard ratio (95% confidence interval) for total stroke incidence in job lost men was 1.58 (1.18-2.13) and in job lost women was 1.51 (1.08-2.29), and those for total stroke mortality were 2.22 (1.34-3.68) in men and 2.48 (1.26-4.77) in women. The respective hazard ratio (95% confidence interval) in reemployed men was 2.96 (1.89-4.62) for total stroke incidence and 4.21 (1.97-8.97) for mortality, whereas those in reemployed women were 1.30 (0.98-1.69) for incidence and 1.28 (0.76-2.17) for mortality. Job lost men and women and reemployed men had increased risks for both hemorrhagic and ischemic stroke incidence and mortality. © 2017 American Heart Association, Inc.

Increased stroke risk in Bell's palsy patients without steroid treatment.

PubMed

Lee, C-C; Su, Y-C; Chien, S-H; Ho, H-C; Hung, S-K; Lee, M-S; Chou, P; Chiu, B C-H; Huang, Y-S

2013-04-01

To investigate the risk of stroke development following a diagnosis of Bell's palsy in a nationwide follow-up study. Information on Bell's palsy and other factors relevant for stroke was obtained for 433218 eligible subjects without previous stroke who had ambulatory visit in 2004. Of those, 897 patients with Bell's palsy were identified. Over a median 2.9 years of follow-up, 4581 incident strokes were identified. We estimated hazard ratios (HR) and 95% confidence intervals [CI] with Cox proportional hazard models adjusting for age, sex, co-morbidities, and important risk factors. Standardized incidence ratio of stroke amongst patients with Bell's palsy was analyzed. Compared with non-Bell's palsy patients, patients with Bell's palsy had a 2.02-times (95% CI, 1.42-2.86) higher risk of stroke. The adjusted HR of developing stroke for patients with Bell's palsy treated with and without systemic steroid were 1.67 (95% CI, 0.69-4) and 2.10 (95%, 1.40-3.07), respectively. Patients with Bell's palsy carry a higher risk of stroke than the general population. Our data suggest that these patients might benefit from a more intensive stroke prevention therapy and regular follow-up after initial diagnosis. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Long-Term Survival After Intravenous Thrombolysis for Ischemic Stroke: A Propensity Score-Matched Cohort With up to 10-Year Follow-Up.

PubMed

Muruet, Walter; Rudd, Anthony; Wolfe, Charles D A; Douiri, Abdel

2018-03-01

Intravenous thrombolysis with alteplase is one of the few approved treatments for acute ischemic stroke; nevertheless, little is known about its long-term effects on survival and recovery because clinical trials follow-up times are limited. Patients registered between January 2005 and December 2015, to the population-based South London Stroke Register of first-ever strokes. Propensity score was used to match thrombolyzed and control cases to a 1:2 ratio by demographical and clinical covariates. The primary outcome was survival up to 10 years using Kaplan-Meier estimates, Cox proportional hazards, and restricted mean survival time. Secondary outcomes included stroke recurrence and functional status (Barthel Index and Frenchay Activities Index scores) at 5 years. From 2052 ischemic strokes, 246 treated patients were matched to 492 controls. Median follow-up time 5.45 years (interquartile range, 4.56). Survival was higher in the treatment group (median, 5.72 years) compared with control group (4.98 years, stratified log-rank test <0.001). The number needed to treat to prevent 1 death at 5 years was 12 and 20 at 10 years. After Cox regression analysis, thrombolysis reduced risk of mortality by 37% (hazard ratio, 0.63; 95% confidence interval [CI], 0.48-0.82) at 10 years; however, after introducing a multiplicative interaction term into the model, mortality risk reduction was 42% (hazard ratio, 0.58; 95% CI, 0.40-0.82) at 10 years for those arriving within 3 hours to the hospital. On average, in a 10-year period, treated patients lived 1 year longer than controls. At 5 years, thrombolysis was associated with independence (Barthel Index≥90; odds ratio, 3.76; 95% CI, 1.22-13.34) and increased odds of a higher Frenchay Activities Index (proportional odds ratio, 2.37; 95% CI, 1.16-4.91). There was no difference in stroke recurrence. Thrombolysis with intravenous alteplase is associated with improved long-term survival and functional status after ischemic stroke. © 2018 The Authors.

Warfarin Use in Patients With Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Population-Based Study.

PubMed

Yoon, Chang-Yun; Noh, Juhwan; Jhee, Jong Hyun; Chang, Tae Ik; Kang, Ea Wha; Kee, Youn Kyung; Kim, Hyoungnae; Park, Seohyun; Yun, Hae-Ryong; Jung, Su-Young; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Kang, Shin-Wook; Kim, Changsoo; Yoo, Tae-Hyun

2017-09-01

The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry. Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models. Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09-1.91; P =0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P =0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78-1.15; P =0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90-1.26; P =0.470). Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications. © 2017 American Heart Association, Inc.

Neutrophil counts, neutrophil ratio, and new stroke in minor ischemic stroke or TIA.

PubMed

Zhu, Bihong; Pan, Yuesong; Jing, Jing; Meng, Xia; Zhao, Xingquan; Liu, Liping; Wang, David; Johnston, S Claiborne; Li, Hao; Wang, Yilong; Wang, Zhimin; Wang, Yongjun

2018-05-22

Evidence about whether neutrophil counts or neutrophil ratio is associated with new stroke is scant. The aim of this study is to assess the association of neutrophil counts or neutrophil ratio with a new stroke in patients with minor stroke or TIA. We derived data from the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events trial. Patients with a minor stroke or TIA were categorized into 4 groups according to the quartile of neutrophil counts or neutrophil ratio. The primary outcome was a new stroke (ischemic or hemorrhagic), and secondary outcomes included a new composite vascular event (stroke, myocardial infarction, or death resulting from cardiovascular causes) and ischemic stroke during the 90-day follow-up. We assessed the association between neutrophil counts, neutrophil ratio, and risk of new stroke. A total of 4,854 participants were enrolled, among whom 495 had new strokes at 90 days. Compared with the first quartile, the second, third, and fourth quartiles of neutrophil counts were associated with increased risk of new stroke (adjusted hazard ratio 1.40 [95% confidence interval (CI) 1.05-1.87], 1.55 [95% CI 1.17-2.05], and 1.69 [95% CI 1.28-2.23], respectively, p for trend <0.001). Similar results were observed for the endpoint of composite events and ischemic stroke. Parallel results were found for neutrophil ratio. High levels of both neutrophil counts and neutrophil ratio were associated with an increased risk of new stroke, composite events, and ischemic stroke in patients with a minor ischemic stroke or TIA. © 2018 American Academy of Neurology.

Sleep duration and risk of stroke mortality among Chinese adults: Singapore Chinese health study.

PubMed

Pan, An; De Silva, Deidre Anne; Yuan, Jian-Min; Koh, Woon-Puay

2014-06-01

Prospective relation between sleep duration and stroke risk is less studied, particularly in Asians. We examined the association between sleep duration and stroke mortality among Chinese adults. The Singapore Chinese Health Study is a population-based cohort of 63 257 Chinese adults aged 45 to 74 years enrolled during 1993 through 1998. Sleep duration at baseline was assessed via in-person interview, and death information during follow-up was ascertained via record linkage with the death registry up to December 31, 2011. Cox proportional hazard models were used to calculate hazard ratios with adjustment for other comorbidities and lifestyle risk factors of stroke mortality. During 926 752 person-years of follow-up, we documented 1381 stroke deaths (322 from hemorrhagic and 1059 from ischemic or nonspecified strokes). Compared with individuals with 7 hours per day of sleep, the multivariate-adjusted hazard ratio (95% confidence interval) of total stroke mortality was 1.25 (1.05-1.50) for ≤5 hours per day (short duration), 1.01 (0.87-1.18) for 6 hours per day, 1.09 (0.95-1.26) for 8 hours per day, and 1.54 (1.28-1.85) for ≥9 hours per day (long duration). The increased risk of stroke death with short (1.54; 1.16-2.03) and long durations of sleep (1.95; 1.48-2.57) was seen among subjects with a history of hypertension, but not in those without hypertension. These findings were limited to risk of death from ischemic or nonspecified stroke, but not observed for hemorrhagic stroke. Both short and long sleep durations are associated with increased risk of stroke mortality in a Chinese population, particularly among those with a history of hypertension. © 2014 American Heart Association, Inc.

Sickle cell trait and incident ischemic stroke in the Atherosclerosis Risk in Communities study.

PubMed

Caughey, Melissa C; Loehr, Laura R; Key, Nigel S; Derebail, Vimal K; Gottesman, Rebecca F; Kshirsagar, Abhijit V; Grove, Megan L; Heiss, Gerardo

2014-10-01

Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. A population-based sample of blacks (n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. SCT was identified in 223 (6.4%) participants. During a median follow-up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than those with homozygous hemoglobin A (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0-2.0) and an incidence rate difference amounting to 1.9 (0.4-3.8) extra strokes per 1000 person-years. We observed an increased risk of ischemic stroke in blacks with SCT. Further investigation of the incidence and pathophysiology of stroke in patients with SCT is warranted. © 2014 American Heart Association, Inc.

Impact of age on the importance of systolic and diastolic blood pressures for stroke risk: the MOnica, Risk, Genetics, Archiving, and Monograph (MORGAM) Project.

PubMed

Vishram, Julie K K; Borglykke, Anders; Andreasen, Anne H; Jeppesen, Jørgen; Ibsen, Hans; Jørgensen, Torben; Broda, Grazyna; Palmieri, Luigi; Giampaoli, Simona; Donfrancesco, Chiara; Kee, Frank; Mancia, Giuseppe; Cesana, Giancarlo; Kuulasmaa, Kari; Sans, Susana; Olsen, Michael H

2012-11-01

This study investigates age-related shifts in the relative importance of systolic (SBP) and diastolic (DBP) blood pressures as predictors of stroke and whether these relations are influenced by other cardiovascular risk factors. Using 34 European cohorts from the MOnica, Risk, Genetics, Archiving, and Monograph (MORGAM) Project with baseline between 1982 and 1997, 68 551 subjects aged 19 to 78 years, without cardiovascular disease and not receiving antihypertensive treatment, were included. During a mean of 13.2 years of follow-up, stroke incidence was 2.8%. Stroke risk was analyzed using hazard ratios per 10-mm Hg/5-mm Hg increase in SBP/DBP by multivariate-adjusted Cox regressions, including SBP and DBP simultaneously. Because of nonlinearity, DBP was analyzed separately for DBP ≥ 71 mm Hg and DBP <71 mm Hg. Stroke risk was associated positively with SBP and DBP ≥ 71 mm Hg (SBP/DBP ≥ 71 mm Hg; hazard ratios: 1.15/1.06 [95% CI: 1.12-1.18/1.03-1.09]) and negatively with DBP <71 mm Hg (0.88[0.79-0.98]). The hazard ratio for DBP decreased with age (P<0.001) and was not influenced by other cardiovascular risk factors. Taking into account the age × DBP interaction, both SBP and DBP ≥ 71 mm Hg were significantly associated with stroke risk until age 62 years, but in subjects older than 46 years the superiority of SBP for stroke risk exceeded that of DBP ≥ 71 mm Hg and remained significant until age 78 years. DBP <71 mm Hg became significant at age 50 years with an inverse relation to stroke risk. In Europeans, stroke risk should be assessed by both SBP and DBP until age 62 years with increased focus on SBP from age 47 years. From age 62 years, emphasis should be on SBP without neglecting the potential harm of very low DBP.

Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke: The Framingham Study.

PubMed

Saber, Hamidreza; Himali, Jayandra J; Beiser, Alexa S; Shoamanesh, Ashkan; Pikula, Aleksandra; Roubenoff, Ronenn; Romero, Jose R; Kase, Carlos S; Vasan, Ramachandran S; Seshadri, Sudha

2017-07-01

Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09-5.06; P =0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist-hip ratio for the association between IGF-1 and ischemic stroke ( P <0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist-hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P =0.007) and 41% (hazard ratio, 0.59; 95% confidence interval, 0.37-0.95; P =0.031) lower risk of incident ischemic stroke, respectively. IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance. © 2017 American Heart Association, Inc.

Long-term heart disease and stroke mortality among former American prisoners of war of World War II and the Korean Conflict: results of a 50-year follow-up.

PubMed

Page, W F; Brass, L M

2001-09-01

For the first 30 years after repatriation, former American prisoners of war (POWs) of World War II and the Korean Conflict had lower death rates for heart disease and stroke than non-POW veteran controls and the U.S. population, but subsequent morbidity data suggested that this survival advantage may have disappeared. We used U.S. federal records to obtain death data through 1996 and used proportional hazards analysis to compare the mortality experience of POWs and controls. POWs aged 75 years and older showed a significantly higher risk of heart disease deaths than controls (hazard ratio = 1.25; 95% confidence interval, 1.01-1.56), and their stroke mortality was also increased, although not significantly (hazard ratio = 1.13; 95% confidence interval, 0.66-1.91). These results suggest that circulatory disease sequelae of serious, acute malnutrition and the stresses associated with imprisonment may not appear until after many decades.

Prevention of Stroke with Ticagrelor in Patients with Prior Myocardial Infarction: Insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54).

PubMed

Bonaca, Marc P; Goto, Shinya; Bhatt, Deepak L; Steg, P Gabriel; Storey, Robert F; Cohen, Marc; Goodrich, Erica; Mauri, Laura; Ophuis, Ton Oude; Ruda, Mikhail; Špinar, Jindřich; Seung, Ki-Bae; Hu, Dayi; Dalby, Anthony J; Jensen, Eva; Held, Peter; Morrow, David A; Braunwald, Eugene; Sabatine, Marc S

2016-09-20

In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population. Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis. Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001). High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562. © 2016 American Heart Association, Inc.

Copeptin and Long-Term Risk of Recurrent Vascular Events After Transient Ischemic Attack and Ischemic Stroke: Population-Based Study.

PubMed

Greisenegger, Stefan; Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Rothwell, Peter M

2015-11-01

Copeptin, the c-terminal portion of provasopressin, is a useful prognostic marker in patients after myocardial infarction and heart failure. More recently, high levels of copeptin have also been associated with worse functional outcome and increased mortality within the first year after ischemic stroke and transient ischemic attack (TIA). However, to date, there are no published data on whether copeptin predicts long-term risk of vascular events after TIA and stroke. We measured copeptin levels in consecutive patients with TIA or ischemic stroke in a population-based study (Oxford Vascular Study) recruited from 2002 to 2007 and followed up to 2014. Associations with risk of recurrent vascular events were determined by Cox-regression. During ≈6000 patient-years in 1076 patients, there were 357 recurrent vascular events, including 174 ischemic strokes. After adjustment for age, sex, and risk factors, copeptin was predictive of recurrent vascular events (adjusted hazard ratio per SD, 1.47; 95% confidence interval, 1.31-1.64; P=0.0001), vascular death (1.85; 1.60-2.14; P<0.0001), all-cause death (1.75; 1.58-1.93; P<0.0001), and recurrent ischemic stroke (1.22; 1.04-1.44; P=0.017); and improved model-discrimination significantly: net reclassification improvement for recurrent vascular events (32%; P<0.0001), vascular death (55%; P<0.0001), death (66%; P<0.0001), and recurrent stroke (16%; P=0.044). The predictive value of copeptin was largest in patients with cardioembolic index events (adjusted hazard ratio, 1.84; 95% confidence interval, 1.53-2.20 versus 1.31, 1.14-1.50 in noncardioembolic stroke; P=0.0025). In patients with cardioembolic stroke, high copeptin levels were associated with a 4-fold increased risk of vascular events within the first year of follow-up (adjusted hazard ratio, 4.02; 95% confidence interval, 2.13-7.70). In patients with TIA and ischemic stroke, copeptin predicted recurrent vascular events and death, particularly after cardioembolic TIA/stroke. Further validation is required, in particular, in studies using more extensive cardiac evaluation. © 2015 American Heart Association, Inc.

Atrial fibrillation and risk of stroke in dialysis patients.

PubMed

Wetmore, James B; Ellerbeck, Edward F; Mahnken, Jonathan D; Phadnis, Milind; Rigler, Sally K; Mukhopadhyay, Purna; Spertus, John A; Zhou, Xinhua; Hou, Qingjiang; Shireman, Theresa I

2013-03-01

Both stroke and chronic atrial fibrillation (AF) are common in dialysis patients, but uncertainty exists in the incidence of new strokes and the risk conferred by chronic AF. A cohort of dually eligible (Medicare and Medicaid) incident dialysis patients was constructed. Medicare claims were used to determine the onset of chronic AF, which was specifically treated as a time-dependent covariate. Cox proportional hazards models were used to model time to stroke. Of 56,734 patients studied, 5629 (9.9%) developed chronic AF. There were 22.8 ischemic and 5.0 hemorrhagic strokes per 1000 patient-years, a ratio of approximately 4.5:1. Chronic AF was independently associated with time to ischemic (hazard ratio [HR], 1.26; 99% confidence interval [CI], 1.06-1.49; P = .0005), but not hemorrhagic, stroke. Race was strongly associated with hemorrhagic stroke: African Americans (HR, 1.46; 99% CI, 1.08-1.96), Hispanics (HR, 1.64; 99% CI, 1.16-2.31), and others (HR, 1.76; 99% CI, 1.16-2.78) had higher rates than did Caucasians (all P < .001). Chronic AF has a significant, but modest, association with ischemic stroke. Race/ethnicity is strongly associated with hemorrhagic strokes. The proportion of strokes owing to hemorrhage is much higher than in the general population. Copyright © 2013 Elsevier Inc. All rights reserved.

Over-the-counter and prescription sleep medication and incident stroke: the REasons for Geographic and Racial Differences in Stroke study.

PubMed

Petrov, Megan E; Howard, Virginia J; Kleindorfer, Dawn; Grandner, Michael A; Molano, Jennifer R; Howard, George

2014-09-01

Preliminary evidence suggests sleep medications are associated with risk of vascular events; however, the long-term vascular consequences are understudied. This study investigated the relation between sleep medication use and incident stroke. Within the REasons for Geographic And Racial Differences in Stroke study, 21,678 black participants and white participants (≥45 years) with no history of stroke were studied. Participants were recruited from 2003 to 2007. From 2008 to 2010, participants self reported their prescription and over-the-counter sleep medication use over the past month. Suspected stroke events were identified by telephone contact at 6-month intervals and associated medical records were retrieved and physician-adjudicated. Proportional hazards analysis was used to estimate hazard ratios for incident stroke associated with sleep medication use (0, 1-14, and 15+ days per month) controlling for sociodemographics, stroke risk factors, mental health symptoms, and sleep apnea risk. At the sleep assessment, 9.6% of the sample used prescription sleep medication and 11.1% used over-the-counter sleep aids. Over an average follow-up of 3.3 ± 1.0 years, 297 stroke events occurred. Over-the-counter sleep medication use was associated with increased risk of incident stroke in a frequency-response relationship (P = .014), with a 46% increased risk for 1-14 days of use per month (hazards ratio [HR] = 1.46; 95% confidence interval [CI], .99-2.15) and a 65% increased risk for 15+ days (HR = 1.65; 95% CI, .96-2.85). There was no significant association with prescription sleep medications (P = .80). Over-the-counter sleep medication use may independently increase the risk of stroke beyond other risk factors in middle-aged to older individuals with no history of stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Highly Prevalent Hyperuricaemia is Associated with Adverse Clinical Outcomes Among Ghanaian Stroke Patients: An Observational Prospective Study.

PubMed

Sarfo, F S; Akassi, J; Antwi, N K B; Obese, V; Adamu, S; Akpalu, A; Bedu-Addo, G

2015-09-01

Although a direct causal relationship between hyperuricaemia and stroke continues to be debated, strong associations between serum uric acid (SUA) and cerebrovascular disease exist. Very few studies have been conducted to evaluate the frequency and association between this potentially modifiable biomarker of vascular risk and stroke in sub-Saharan Africa. Therefore the aim of this study was to examine the association between hyperuricaemia and the traditional risk factors and the outcomes of stroke in Ghanaian patients. In this prospective observational study, 147 patients presenting with stroke at a tertiary referral centre in Ghana were consecutively recruited. Patients were screened for vascular risk factors and SUA concentrations measured after an overnight fast. Associations between hyperuricaemia and stroke outcomes were analysed using Kaplan-Meier and Cox proportional hazards regression analysis. The frequency of hyperuricaemia among Ghanaian stroke patients was 46.3%. Non-significant associations were observed between hyperuricaemia and the traditional risk factors of stroke. SUA concentration was positively correlated with stroke severity and associated with early mortality after an acute stroke with unadjusted hazards ratio of 2.3 (1.4 - 4.2, p=0.001). A potent and independent dose-response association between increasing SUA concentration and hazard of mortality was found on Cox proportional hazards regression, aHR (95% CI) of 1.65 (1.14-2.39), p=0.009 for each 100µmol/l increase in SUA. Hyperuricaemia is highly frequent and associated with adverse functional outcomes among Ghanaian stroke patients. Further studies are warranted to determine whether reducing SUA levels after a stroke would be beneficial within our setting.

P-wave morphology and the risk of incident ischemic stroke in the Multi-Ethnic Study of Atherosclerosis.

PubMed

Kamel, Hooman; Soliman, Elsayed Z; Heckbert, Susan R; Kronmal, Richard A; Longstreth, W T; Nazarian, Saman; Okin, Peter M

2014-09-01

Emerging data suggest that left atrial disease may cause ischemic stroke in the absence of atrial fibrillation or flutter (AF). If true, this condition may provide a cause for many strokes currently classified as cryptogenic. Among 6741 participants in the Multi-Ethnic Study of Atherosclerosis who were free of clinically apparent cerebrovascular or cardiovascular disease (including AF) at baseline, we examined the association between markers of left atrial abnormality on a standard 12-lead ECG-specifically P-wave area, duration, and terminal force in lead V1-and the subsequent risk of ischemic stroke while accounting for incident AF. During a median follow-up of 8.5 years, 121 participants (1.8%) had a stroke and 541 participants (8.0%) were diagnosed with AF. In Cox proportional hazards models adjusting for potential baseline confounders, P-wave terminal force in lead V1 was more strongly associated with incident stroke (hazard ratio per 1 SD increase, 1.21; 95% confidence interval, 1.02-1.44) than with incident AF (hazard ratio per 1 SD, 1.11; 95% confidence interval, 1.03-1.21). The association between P-wave terminal force in lead V1 and stroke was robust in numerous sensitivity analyses accounting for AF, including analyses that excluded those with any incident AF or modeled any incident AF as having been present from baseline. We found an association between baseline P-wave morphology and incident stroke even after accounting for AF. This association may reflect an atrial cardiopathy that leads to stroke in the absence of AF. © 2014 American Heart Association, Inc.

Alcohol consumption and risk of cardiovascular disease among hypertensive women.

PubMed

Bos, Sarah; Grobbee, Diederick E; Boer, Jolanda M A; Verschuren, W Monique; Beulens, Joline W J

2010-02-01

This study investigated the relation between alcohol consumption and the risk of cardiovascular disease (CVD) among 10 530-hypertensive women from the EPIC-NL cohort. Alcohol consumption was assessed using a validated food-frequency questionnaire and participants were followed for occurrence of CVD. During 9.4 years follow-up, we documented 580 coronary heart disease (CHD) events and 254 strokes, 165 of which were ischemic. An inverse association (Ptrend=0.009) between alcohol consumption and risk of CHD was observed with a multivariate-adjusted hazard ratio of 0.72 (95% confidence interval: 0.52-1.01) for those consuming 70-139.9 g alcohol/week compared to lifetime abstainers. Of different beverages, only red wine consumption was associated with a reduced risk of CHD. A U-shaped relation (P=0.08) was observed for total stroke with a hazard ratio of 0.65 (0.44-0.95) for consuming 5-69.9 g alcohol/week compared with lifetime abstainers. Similar results were observed for ischemic stroke with a hazard ratio of 0.56 (0.35-0.89) for consuming of 5-69.9 g alcohol/week. We conclude that moderate alcohol consumption is associated with a reduced risk of CHD among hypertensive women. Light alcohol consumption tended to be related to a lower risk of stroke. Current guidelines for alcohol consumption in the general population also apply to hypertensive women.

The Impacts of Peptic Ulcer on Stroke Recurrence.

PubMed

Xu, Zongliang; Wang, Ling; Lin, Ying; Wang, Zhaojun; Zhang, Yun; Li, Junrong; Li, Shenghua; Ye, Zusen; Yuan, Kunxiong; Shan, Wanying; Liu, Xinfeng; Fan, Xinying; Xu, Gelin

2018-04-10

Peptic ulcer has been associated with an increased risk of stroke. This study aimed to evaluate the impacts of peptic ulcer on stroke recurrence and mortality. Patients with first-ever ischemic stroke were retrospectively confirmed with or without a history of peptic ulcer. The primary end point was defined as fatal and nonfatal stroke recurrence. Risks of 1-year fatal and nonfatal stroke recurrence were analyzed with the Kaplan-Meier method. Predictors of fatal and nonfatal stroke recurrence were evaluated with the Cox proportional hazards model. Among the 2577 enrolled patients with ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The fatal and nonfatal stroke recurrence within 1 year of the index stroke was higher in patients with peptic ulcer than in patients without peptic ulcer (12.4% versus 7.2%, P = .030). Cox proportional hazards model detected that age (hazard ratio [HR] = 1.018, 95% confidence interval [CI] 1.005-1.031, P = .008), hypertension (HR = 1.397, 95% CI 1.017-1.918, P = .039), and history of peptic ulcer (HR = 1.853, 95% CI 1.111-3.091, P = .018) were associated with stroke recurrence. Ischemic stroke patients with peptic ulcer may have an increased risk of stroke recurrence. The results emphasize the importance of appropriate prevention and management of peptic ulcer for secondary stroke prevention. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Whole Grain Consumption and Risk of Ischemic Stroke: Results From 2 Prospective Cohort Studies.

PubMed

Juan, Juan; Liu, Gang; Willett, Walter C; Hu, Frank B; Rexrode, Kathryn M; Sun, Qi

2017-12-01

Higher intake of whole grains may exert cardiometabolic benefits, although findings on stroke risk are inconclusive. The potentially differential effects of individual whole grain foods on ischemic stroke have not been examined. We analyzed whole grain consumption in relation to ischemic stroke among 71 750 women from the Nurses' Health Study and 42 823 men from the Health Professionals Follow-up Study who were free of cardiovascular disease, diabetes mellitus, and cancer at baseline (1984 and 1986, respectively) through 2010 using a Cox proportional hazards model. Validated semiquantitative food frequency questionnaires were used to assess consumption of whole grain intake, including whole grain cold breakfast cereal, dark bread, oatmeal, brown rice, popcorn, bran, and germ. Self-reported incident cases of ischemic stroke were confirmed through medical record review. During 2 820 128 person-years of follow-up in the 2 cohorts, 2458 cases of ischemic stroke were identified and confirmed. Intake of total whole grains was not associated with risk of ischemic stroke after adjustment for covariates: the pooled hazard ratio (95% confidence interval) comparing extreme intake levels was 1.04 (0.91-1.19). However, intake of whole grain cold breakfast cereal and total bran was inversely associated with ischemic stroke after multivariate adjustment: the pooled hazard ratios (95% confidence intervals) were 0.88 (0.80-0.96; P trend =0.008) and 0.89 (0.79-1.00; P trend =0.004), respectively. Other whole grain foods were not associated with a lower risk of ischemic stroke. Although overall consumption of whole grains was not associated with lower risk of ischemic stroke, greater consumption of whole grain cold breakfast cereal and bran was significantly associated with a lower risk of ischemic stroke. More studies are needed to replicate these associations between individual whole grain foods and risk of ischemic stroke among other populations. © 2017 American Heart Association, Inc.

Lipid Profile Components and Risk of Ischemic Stroke

PubMed Central

Willey, Joshua Z.; Xu, Qiang; Boden-Albala, Bernadette; Paik, Myunghee C.; Moon, Yeseon Park; Sacco, Ralph L.; Elkind, Mitchell S. V.

2010-01-01

Objective To explore the relationship between lipid profile components and incident ischemic stroke in a stroke-free prospective cohort. Design Population-based prospective cohort study. Setting Northern Manhattan, New York. Patients Stroke-free community residents. Intervention As part of the Northern Manhattan Study, baseline fasting blood samples were collected on stroke-free community residents followed up for a mean of 7.5 years. Main Outcome Measures Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for lipid profile components and ischemic stroke after adjusting for demographic and risk factors. In secondary analyses, we used repeated lipid measures over 5 years from a 10% sample of the population to calculate the change per year of each of the lipid parameters and to impute time-dependent lipid parameters for the full cohort. Results After excluding those with a history of myocardial infarction, 2940 participants were available for analysis. Baseline high-density lipoprotein cholesterol, triglyceride, and total cholesterol levels were not associated with risk of ischemic stroke. Low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol levels were associated with a paradoxical reduction in risk of stroke. There was an interaction with use of cholesterol-lowering medication on follow-up, such that LDL-C level was only associated with a reduction in stroke risk among those taking medications. An LDL-C level greater than 130 mg/dL as a time-dependent covariate showed an increased risk of ischemic stroke (adjusted hazard ratio, 3.81; 95% confidence interval, 1.53–9.51). Conclusions Baseline lipid panel components were not associated with an increased stroke risk in this cohort. Treatment with cholesterol-lowering medications and changes in LDL-C level over time may have attenuated the risk in this population, and lipid measurements at several points may be a better marker of stroke risk. PMID:19901173

Physical activity and risk of ischemic stroke in the Northern Manhattan Study

PubMed Central

Willey, J Z.; Moon, Y P.; Paik, M C.; Boden-Albala, B; Sacco, R L.; Elkind, M S.V.

2009-01-01

Background: It is controversial whether physical activity is protective against first stroke among older persons. We sought to examine whether physical activity, as measured by intensity of exercise and energy expended, is protective against ischemic stroke. Methods: The Northern Manhattan Study is a prospective cohort study in older, urban-dwelling, multiethnic, stroke-free individuals. Baseline measures of leisure-time physical activity were collected via in-person questionnaires. Cox proportional hazards models were constructed to examine whether energy expended and intensity of physical activity were associated with the risk of incident ischemic stroke. Results: Physical inactivity was present in 40.5% of the cohort. Over a median follow-up of 9.1 years, there were 238 incident ischemic strokes. Moderate- to heavy-intensity physical activity was associated with a lower risk of ischemic stroke (adjusted hazard ratio [HR] 0.65, 95% confidence interval [0.44–0.98]). Engaging in any physical activity vs none (adjusted HR 1.16, 95% CI 0.88–1.51) and energy expended in kcal/wk (adjusted HR per 500-unit increase 1.01, 95% CI 0.99–1.03) were not associated with ischemic stroke risk. There was an interaction of sex with intensity of physical activity (p = 0.04), such that moderate to heavy activity was protective against ischemic stroke in men (adjusted HR 0.37, 95% CI 0.18–0.78), but not in women (adjusted HR 0.92, 95% CI 0.57–1.50). Conclusions: Moderate- to heavy-intensity physical activity, but not energy expended, is protective against risk of ischemic stroke independent of other stroke risk factors in men in our cohort. Engaging in moderate to heavy physical activities may be an important component of primary prevention strategies aimed at reducing stroke risk. GLOSSARY CI = confidence interval; HR = hazard ratio; MET = metabolic equivalents. PMID:19933979

Associations of Lipoprotein(a) Levels With Incident Atrial Fibrillation and Ischemic Stroke: The ARIC (Atherosclerosis Risk in Communities) Study.

PubMed

Aronis, Konstantinos N; Zhao, Di; Hoogeveen, Ron C; Alonso, Alvaro; Ballantyne, Christie M; Guallar, Eliseo; Jones, Steven R; Martin, Seth S; Nazarian, Saman; Steffen, Brian T; Virani, Salim S; Michos, Erin D

2017-12-15

Lipoprotein(a) (Lp[a]) is proatherosclerotic and prothrombotic, causally related to coronary disease, and associated with other cardiovascular diseases. The association of Lp(a) with incident atrial fibrillation (AF) and with ischemic stroke among individuals with AF remains to be elucidated. In the community-based ARIC (Atherosclerosis Risk in Communities) study cohort, Lp(a) levels were measured by a Denka Seiken assay at visit 4 (1996-1998). We used multivariable-adjusted Cox models to compare AF and ischemic stroke risk across Lp(a) levels. First, we evaluated incident AF in 9908 participants free of AF at baseline. AF was ascertained by electrocardiography at study visits, hospital International Statistical Classification of Diseases, 9th Revision ( ICD-9 ) codes, and death certificates. We then evaluated incident ischemic stroke in 10 127 participants free of stroke at baseline. Stroke was identified by annual phone calls, hospital ICD-9 Revision codes, and death certificates. The baseline age was 62.7±5.6 years. Median Lp(a) levels were 13.3 mg/dL (interquartile range, 5.2-39.7 mg/dL). Median follow-up was 13.9 and 15.8 years for AF and stroke, respectively. Lp(a) was not associated with incident AF (hazard ratio, 0.98; 95% confidence interval, 0.82-1.17), comparing those with Lp(a) ≥50 with those with Lp(a) <10 mg/dL. High Lp(a) was associated with a 42% relative increase in stroke risk among participants without AF (hazard ratio, 1.42; 95% confidence interval, 1.07-1.90) but not in those with AF (hazard ratio, 1.06; 95% confidence interval, 0.70-1.61 [ P interaction for AF=0.25]). There were no interactions by race or sex. No association was found for cardioembolic stroke subtype. High Lp(a) levels were not associated with incident AF. Lp(a) levels were associated with increased ischemic stroke risk, primarily among individuals without AF but not in those with AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Can Survival Bias Explain the Age Attenuation of Racial Inequalities in Stroke Incidence?: A Simulation Study.

PubMed

Mayeda, Elizabeth Rose; Banack, Hailey R; Bibbins-Domingo, Kirsten; Zeki Al Hazzouri, Adina; Marden, Jessica R; Whitmer, Rachel A; Glymour, M Maria

2018-07-01

In middle age, stroke incidence is higher among black than white Americans. For unknown reasons, this inequality decreases and reverses with age. We conducted simulations to evaluate whether selective survival could account for observed age patterning of black-white stroke inequalities. We simulated birth cohorts of 20,000 blacks and 20,000 whites with survival distributions based on US life tables for the 1919-1921 birth cohort. We generated stroke incidence rates for ages 45-94 years using Reasons for Geographic and Racial Disparities in Stroke (REGARDS) study rates for whites and setting the effect of black race on stroke to incidence rate difference (IRD) = 20/10,000 person-years at all ages, the inequality observed at younger ages in REGARDS. We compared observed age-specific stroke incidence across scenarios, varying effects of U, representing unobserved factors influencing mortality and stroke risk. Despite a constant adverse effect of black race on stroke risk, the observed black-white inequality in stroke incidence attenuated at older age. When the hazard ratio for U on stroke was 1.5 for both blacks and whites, but U only directly influenced mortality for blacks (hazard ratio for U on mortality =1.5 for blacks; 1.0 for whites), stroke incidence rates in late life were lower among blacks (average observed IRD = -43/10,000 person-years at ages 85-94 years versus causal IRD = 20/10,000 person-years) and mirrored patterns observed in REGARDS. A relatively moderate unmeasured common cause of stroke and survival could fully account for observed age attenuation of racial inequalities in stroke.

Edoxaban versus warfarin in patients with atrial fibrillation.

PubMed

Giugliano, Robert P; Ruff, Christian T; Braunwald, Eugene; Murphy, Sabina A; Wiviott, Stephen D; Halperin, Jonathan L; Waldo, Albert L; Ezekowitz, Michael D; Weitz, Jeffrey I; Špinar, Jindřich; Ruzyllo, Witold; Ruda, Mikhail; Koretsune, Yukihiro; Betcher, Joshua; Shi, Minggao; Grip, Laura T; Patel, Shirali P; Patel, Indravadan; Hanyok, James J; Mercuri, Michele; Antman, Elliott M

2013-11-28

Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.).

Home blood pressure predicts stroke incidence among older adults with impaired physical function: the Ohasama study.

PubMed

Murakami, Keiko; Asayama, Kei; Satoh, Michihiro; Hosaka, Miki; Matsuda, Ayako; Inoue, Ryusuke; Tsubota-Utsugi, Megumi; Murakami, Takahisa; Nomura, Kyoko; Kikuya, Masahiro; Metoki, Hirohito; Imai, Yutaka; Ohkubo, Takayoshi

2017-12-01

Several observational studies have found modifying effects of functional status on the association between conventional office blood pressure (BP) and adverse outcomes. We aimed to examine whether the association between higher BP and stroke was attenuated or inverted among older adults with impaired function using self-measured home BP measurements. We followed 501 Japanese community-dwelling adults aged at least 60 years (mean age, 68.6 years) with no history of stroke. Multivariate-adjusted hazard ratios for 1-SD increase in home BP and office BP measurements were calculated by the Cox proportional hazards model. Functional status was assessed by self-reported physical function. During a median follow-up of 11.5 years, first strokes were observed in 47 participants. Higher home SBP, but not office SBP, was significantly associated with increased risk of stroke among both 349 participants with normal physical function and 152 participants with impaired physical function [hazard ratio (95% confidence interval) per 14.4-mmHg increase: 1.74 (1.12-2.69) and 1.77 (1.06-2.94), respectively], with no significant interaction for physical function (P = 0.56). Higher home DBP, but not office DBP, was also significantly associated with increased risk of stroke (P ≤ 0.029) irrespective of physical function (all P > 0.05 for interaction). Neither home BP nor office BP was significantly associated with all-cause mortality irrespective of physical function. Higher home BP was associated with increased risk of stroke even among those with impaired physical function. Measurements of home BP would be useful for stroke prevention, even after physical function decline.

Gene variants associated with ischemic stroke: the cardiovascular health study.

PubMed

Luke, May M; O'Meara, Ellen S; Rowland, Charles M; Shiffman, Dov; Bare, Lance A; Arellano, Andre R; Longstreth, W T; Lumley, Thomas; Rice, Kenneth; Tracy, Russell P; Devlin, James J; Psaty, Bruce M

2009-02-01

The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke. Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS). In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1, and BAT2) were nominally associated with increased risk of stroke (one-sided P<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in KRT4, LY6G5B, EDG1, DMXL2, and ABCG2) were nominally associated with stroke (one-sided P<0.05, false discovery rate=0.55). The Val12Met SNP in ABCG2 was associated with stroke in both white (hazard ratio, 1.46; 90% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10% versus 6%) and black (12% versus 3%) participants of CHS. The Val12Met SNP in ABCG2 (encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS.

Non-traditional Serum Lipid Variables and Recurrent Stroke Risk

PubMed Central

Park, Jong-Ho; Lee, Juneyoung; Ovbiagele, Bruce

2014-01-01

Background and Purpose Expert consensus guidelines recommend low-density lipoprotein cholesterol (LDL-C) as the primary serum lipid target for recurrent stroke risk reduction. However, mounting evidence suggests that other lipid parameters might be additional therapeutic targets or at least also predict cardiovascular risk. Little is known about the effects of non-traditional lipid variables on recurrent stroke risk. Methods We analyzed the Vitamin Intervention for Stroke Prevention study database comprising 3680 recent (<120 days) ischemic stroke patients followed up for 2 years. Independent associations of baseline serum lipid variables with recurrent ischemic stroke (primary outcome) and the composite endpoint of ischemic stroke/coronary heart disease (CHD)/vascular death (secondary outcomes) were assessed. Results Of all variables evaluated, only triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio was consistently and independently related to both outcomes: compared with the lowest quintile, the highest TG/HDL-C ratio quintile was associated with stroke (adjusted hazard ratio, 1.56; 95% CI, 1.05−2.32) and stroke/CHD/vascular death (1.39; 1.05−1.83), including adjustment for lipid modifier use. Compared with the lowest quintile, the highest total cholesterol/HDL-C ratio quintile was associated with stroke/CHD/vascular death (1.45; 1.03−2.03). LDL-C/HDL-C ratio, non-HDL-C, elevated TG alone, and low HDL-C alone were not independently linked to either outcome. Conclusions Of various non-traditional lipid variables, elevated baseline TG/HDL-C and TC/HDL-C ratios predict future vascular risk after a stroke, but only elevated TG/HDL-C ratio is related to risk of recurrent stroke. Future studies should assess the role of TG/HDL as a potential therapeutic target for global vascular risk reduction after stroke. PMID:25236873

Optimal Systolic Blood Pressure Levels for Primary Prevention of Stroke in General Hypertensive Adults: Findings From the CSPPT (China Stroke Primary Prevention Trial).

PubMed

Fan, Fangfang; Yuan, Ziwen; Qin, Xianhui; Li, Jianping; Zhang, Yan; Li, Youbao; Yu, Tao; Ji, Meng; Ge, Junbo; Zheng, Meili; Yang, Xinchun; Bao, Huihui; Cheng, Xiaoshu; Gu, Dongfeng; Zhao, Dong; Wang, Jiguang; Sun, Ningling; Chen, Yundai; Wang, Hong; Wang, Xiaobin; Parati, Gianfranco; Hou, Fanfan; Xu, Xiping; Wang, Xian; Zhao, Gang; Huo, Yong

2017-04-01

We aimed to investigate the relationship of time-averaged on-treatment systolic blood pressure (SBP) with the risk of first stroke in the CSPPT (China Stroke Primary Prevention Trial). A post hoc analysis was conducted using data from 17 720 hypertensive adults without cardiovascular disease, diabetes mellitus, and renal function decline from the CSPPT, a randomized double-blind controlled trial. The primary outcome was first stroke. Over a median follow-up duration of 4.5 years, the association between averaged on-treatment SBP and risk for first stoke followed a U-shape curve, with increased risk above and below the reference range of 120 to 130 mm Hg. Compared with participants with time-averaged on-treatment SBP at 120 to 130 mm Hg (mean, 126.2 mm Hg), the risk of first stroke was not only increased in participants with SBP at 130 to 135 mm Hg (mean, 132.6 mm Hg; 1.5% versus 0.8%; hazard ratio, 1.63; 95% confidence interval, 1.01-2.63) or 135 to 140 mm Hg (mean, 137.5 mm Hg; 1.9% versus 0.8%; hazard ratio, 1.85; 95% confidence interval, 1.17-2.93), but also increased in participants with SBP <120 mm Hg (mean, 116.7 mm Hg; 3.1% versus 0.8%; hazard ratio, 4.37; 95% confidence interval, 2.10-9.07). Similar results were found in various subgroups stratified by age, sex, and treatment group. Furthermore, lower diastolic blood pressure was associated with lower risk of stroke, with a plateau at a time-average on-treatment diastolic blood pressure <80 mm Hg. In conclusion, among adults with hypertension and without a history of stroke or myocardial infarction, diabetes mellitus, or renal function decline, a lower SBP goal of 120 to 130 mm Hg, as compared with a target SBP of 130 to 140 mm Hg or <120 mm Hg, resulted in the lowest risk of first stroke. © 2017 American Heart Association, Inc.

Total antioxidant capacity of diet and risk of stroke: a population-based prospective cohort of women.

PubMed

Rautiainen, Susanne; Larsson, Susanna; Virtamo, Jarmo; Wolk, Alicja

2012-02-01

Consumption of antioxidant-rich foods may reduce the risk of stroke by inhibition of oxidative stress and inflammation. Total antioxidant capacity (TAC) takes into account all antioxidants and the synergistic effects between them. We examined the association between dietary TAC and stroke incidence in cardiovascular disease (CVD)-free women and in women with CVD history at baseline. The study included women (31,035 CVD-free and 5680 with CVD history at baseline), aged 49 to 83 years, from the Swedish Mammography Cohort. Diet was assessed with a food frequency questionnaire. Dietary TAC was calculated using oxygen radical absorbance capacity values. Stroke cases were ascertained by linkage with the Swedish Hospital Discharge Registry. During follow-up (September 1997 to December 2009), we identified 1322 stroke cases (988 cerebral infarctions, 226 hemorrhagic strokes, and 108 unspecified strokes) among CVD-free women and 1007 stroke cases (796 cerebral infarctions, 100 hemorrhagic strokes, and 111 unspecified strokes) among women with a CVD history. The multivariable hazard ratio of total stroke comparing the highest with the lowest quintile of dietary TAC was 0.83 (95% CI, 0.70-0.99; P for trend=0.04) in CVD-free women. Among women with a CVD history, the hazard ratios for the highest versus lowest quartile of TAC were 0.90 (95% CI, 0.75-1.07; P for trend=0.30) for total stroke and 0.55 (95% CI, 0.32-0.95; P for trend=0.03) for hemorrhagic stroke. These findings suggest that dietary TAC is inversely associated with total stroke among CVD-free women and hemorrhagic stroke among women with CVD history.

Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke: The ACROSS-China Study (Abnormal Glucose Regulation in Patients With Acute Stroke Across China).

PubMed

Jing, Jing; Pan, Yuesong; Zhao, Xingquan; Zheng, Huaguang; Jia, Qian; Mi, Donghua; Chen, Weiqi; Li, Hao; Liu, Liping; Wang, Chunxue; He, Yan; Wang, David; Wang, Yilong; Wang, Yongjun

2017-04-01

Insulin resistance was common in patients with stroke. This study investigated the association between insulin resistance and outcomes in nondiabetic patients with first-ever acute ischemic stroke. Patients with ischemic stroke without history of diabetes mellitus in the ACROSS-China registry (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) were included. Insulin resistance was defined as a homeostatis model assessment-insulin resistance (HOMA-IR) index in the top quartile (Q4). HOMA-IR was calculated as fasting insulin (μU/mL)×fasting glucose (mmol/L)/22.5. Multivariable logistic regression or Cox regression was performed to estimate the association between HOMA-IR and 1-year prognosis (mortality, stroke recurrence, poor functional outcome [modified Rankin scale score 3-6], and dependence [modified Rankin scale score 3-5]). Among the 1245 patients with acute ischemic stroke enrolled in this study, the median HOMA-IR was 1.9 (interquartile range, 1.1-3.1). Patients with insulin resistance were associated with a higher mortality risk than those without (adjusted hazard ratio, 1.68; 95% confidence interval, 1.12-2.53; P =0.01), stroke recurrence (adjusted hazard ratio, 1.57, 95% confidence interval, 1.12-2.19; P =0.008), and poor outcome (adjusted odds ratio, 1.42; 95% confidence interval, 1.03-1.95; P =0.03) but not dependence after adjustment for potential confounders. Higher HOMA-IR quartile categories were associated with a higher risk of 1-year death, stroke recurrence, and poor outcome ( P for trend =0.005, 0.005, and 0.001, respectively). Insulin resistance was associated with an increased risk of death, stroke recurrence, and poor outcome but not dependence in nondiabetic patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack.

PubMed

Brookes, Rebecca L; Crichton, Siobhan; Wolfe, Charles D A; Yi, Qilong; Li, Linxin; Hankey, Graeme J; Rothwell, Peter M; Markus, Hugh S

2018-01-01

A variant in the histone deacetylase 9 ( HDAC9 ) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate. Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study. Patients receiving SVA were compared with patients who received antiepileptic drugs other than SVA using survival analysis and Cox Regression. A total of 11 949 patients with confirmed ischemic event were included. Recurrent stroke rate was lower in patient taking SVA (17 of 168) than other antiepileptic drugs (105 of 530; log-rank survival analysis P =0.002). On Cox regression, controlling for potential cofounders, SVA remained associated with reduced stroke (hazard ratio=0.44; 95% confidence interval: 0.3-0.7; P =0.002). A similar result was obtained when patients taking SVA were compared with all cases not taking SVA (Cox regression, hazard ratio=0.47; 95% confidence interval: 0.29-0.77; P =0.003). These results suggest that exposure to SVA, an inhibitor of HDAC, may be associated with a lower recurrent stroke risk although we cannot exclude residual confounding in this study design. This supports the hypothesis that HDAC9 is important in the ischemic stroke pathogenesis and that its inhibition, by SVA or a more specific HDAC9 inhibitor, is worthy of evaluation as a treatment to prevent recurrent ischemic stroke. © 2017 The Authors.

APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults.

PubMed

Gutiérrez, Orlando M; Irvin, Marguerite R; Chaudhary, Ninad S; Cushman, Mary; Zakai, Neil A; David, Victor A; Limou, Sophie; Pamir, Nathalie; Reiner, Alex P; Naik, Rakhi P; Sale, Michele M; Safford, Monika M; Hyacinth, Hyacinth I; Judd, Suzanne E; Kopp, Jeffrey B; Winkler, Cheryl A

2018-06-01

APOL1 renal risk variants are strongly associated with chronic kidney disease in Black adults, but reported associations with cardiovascular disease (CVD) have been conflicting. We examined associations of APOL1 with incident coronary heart disease (n=323), ischemic stroke (n=331), and the composite CVD outcome (n=500) in 10 605 Black participants of the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Primary analyses compared individuals with APOL1 high-risk genotypes to APOL1 low-risk genotypes in Cox proportional hazards models adjusted for CVD risk factors and African ancestry. APOL1 high-risk participants were younger and more likely to have albuminuria at baseline than APOL1 low-risk participants. The risk of incident stroke, coronary heart disease, or composite CVD end point did not significantly differ by APOL1 genotype status in multivariable models. The association of APOL1 genotype with incident composite CVD differed by diabetes mellitus status ( P interaction =0.004). In those without diabetes mellitus, APOL1 high-risk genotypes associated with greater risk of incident composite CVD (hazard ratio, 1.67; 95% confidence interval, 1.12-2.47) compared with those with APOL1 low-risk genotypes in multivariable adjusted models. This latter association was driven by ischemic strokes (hazard ratio, 2.32; 95% confidence interval, 1.33-4.07), in particular, those related to small vessel disease (hazard ratio, 5.10; 95% confidence interval, 1.55-16.56). There was no statistically significant association of APOL1 genotypes with incident CVD in subjects with diabetes mellitus. The APOL1 high-risk genotype was associated with higher stroke risk in individuals without but not those with chronic kidney disease in fully adjusted models. APOL1 high-risk status is associated with CVD events in community-dwelling Black adults without diabetes mellitus. © 2018 American Heart Association, Inc.

Association between atherogenic dyslipidemia and recurrent stroke risk in patients with different subtypes of ischemic stroke.

PubMed

Zhao, Lu; Wang, Ruihao; Song, Bo; Tan, Song; Gao, Yuan; Fang, Hui; Lu, Jie; Xu, Yuming

2015-07-01

The association between atherogenic dyslipidemia and stroke recurrence remains unclear, and may be influenced by different subtypes of ischemic stroke. We aimed to investigate whether atherogenic dyslipidemia contributed to stroke recurrence in ischemic stroke patients and in those with certain subtypes of ischemic stroke. We conducted a prospective hospital-based study enrolling patients with acute ischemic stroke. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol <40 mg/dl and triglycerides ≥200 mg/dl. Ischemic stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The patients were followed up at 3, 6, 12 and 24 months after stroke onset. The association between atherogenic dyslipidemia and stroke recurrence was analyzed by using multivariable Cox regression model. In the 510 ischemic stroke patients, 64 patients (12·5%) had atherogenic dyslipidemia, and 66 patients (12·9%) experienced stroke recurrence events within 24 months. Kaplan-Meier analysis revealed that stroke recurrence rate was significantly higher in patients with atherogenic dyslipidemia than those without in all the stroke patients (20·3% vs. 11·9%; P = 0·048), and more evident in those of large-artery atherosclerosis subtype (31·0% vs. 14·1%; P = 0·014), but not in the other subtypes. Multivariable Cox regression analysis revealed that atherogenic dyslipidemia was associated with higher stroke recurrence risk among stroke patients of large-artery atherosclerosis subtype (hazard ratio, 2·79; 95% confidence interval, 1·24-6·28), but not significant in all the stroke patients (hazard ratio, 1·69; 95% confidence interval, 0·85-3·37). Atherogenic dyslipidemia is associated with higher risk of stroke recurrence in ischemic stroke patients. Such association might be more pronounced in large-artery atherosclerosis subtype and needs further investigation to establish such relationship. © 2015 World Stroke Organization.

Statin use increases the risk of depressive disorder in stroke patients: a population-based study.

PubMed

Kang, Jiunn-Horng; Kao, Li-Ting; Lin, Herng-Ching; Tsai, Ming-Chieh; Chung, Shiu-Dong

2015-01-15

This study aimed to explore the risk for depressive disorder (DD) among stroke patients with statin use. Totally, 11,218 patients who had a first-time acute hospitalization for stroke were identified from Taiwan's Longitudinal Health Insurance Database 2000. We individually followed each study subject for a 1-year period to identify those patients who were subsequently diagnosed with DD during the follow-up period. We found that the incidence rate of DD during the 1-year follow-up period was 5.52 (95% CI: 4.70-6.43) and 3.46 (95% CI: 3.08-3.88) per 100 person-years for stroke patients who were statin users and nonusers, respectively. Cox proportional hazards regressions revealed that the adjusted hazard ratio (HR) for DD during the 1-year follow-up period was 1.59 for stroke patients who were statin users compared to those who were non-statin users. We further found that the adjusted HR for DD for stroke patients who were regular statin users was 1.65 compared to stroke patients who had never been prescribed statin. However, there was no increased hazard of DD for stroke patients who were irregular statin users compared to stroke patients who had never been prescribed statin (HR: 1.22, 95% CI: 0.70-2.11). Copyright © 2014. Published by Elsevier B.V.

Stroke Risk and Mortality in Patients with Ventricular Assist Devices

PubMed Central

Parikh, Neal S.; Cool, Joséphine; Karas, Maria G.; Boehme, Amelia K.; Kamel, Hooman

2016-01-01

Background and Purpose Ventricular assist devices (VADs) have advanced the management of end-stage heart failure. However, these devices are associated with hemorrhagic and thrombotic complications, including stroke. We assessed the incidence, risk factors, and outcomes of ischemic and hemorrhagic stroke after VAD placement. Methods Using administrative claims data from acute care hospitals in California, Florida, and New York from 2005–2013, we identified patients who underwent VAD placement, defined by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 37.66. Ischemic and hemorrhagic strokes were identified by previously validated coding algorithms. We used survival statistics to determine incidence rates and Cox proportional hazard analyses to examine associations. Results Among 1,813 patients, we identified 201 ischemic strokes and 116 hemorrhagic strokes during 3.4 (±2.0) years of follow-up after implantation of a VAD. The incidence of stroke was 8.7% per year (95% confidence interval [CI], 7.7–9.7%). The annual incidence of ischemic stroke (5.5%; 95% CI, 4.8–6.4%) was nearly double that of hemorrhagic stroke (3.1%; 95% CI, 2.6–3.8%). Women faced a higher hazard of stroke than men (hazard ratio [HR], 1.6; 95% CI, 1.2–2.1), particularly hemorrhagic stroke (HR, 2.2; 95% CI, 1.4–3.4). Stroke was strongly associated with subsequent in-hospital mortality (HR, 6.1; 95% CI, 4.6–7.9). Conclusions The incidence of stroke after VAD implantation was 8.7% per year, and incident stroke was strongly associated with subsequent in-hospital mortality. Notably, ischemic stroke occurred at nearly twice the rate of hemorrhagic stroke. Women appeared to face a higher risk for hemorrhagic stroke than men. PMID:27650070

Cardiac Calcifications on Echocardiography Are Associated with Mortality and Stroke.

PubMed

Lu, Marvin Louis Roy; Gupta, Shuchita; Romero-Corral, Abel; Matejková, Magdaléna; De Venecia, Toni; Obasare, Edinrin; Bhalla, Vikas; Pressman, Gregg S

2016-12-01

Calcium deposits in the aortic valve and mitral annulus have been associated with cardiovascular events and mortality. However, there is no accepted standard method for scoring such cardiac calcifications, and most existing methods are simplistic. The aim of this study was to test the hypothesis that a semiquantitative score, one that accounts for all visible calcium on echocardiography, could predict all-cause mortality and stroke in a graded fashion. This was a retrospective study of 443 unselected subjects derived from a general echocardiography database. A global cardiac calcium score (GCCS) was applied that assigned points for calcification in the aortic root and valve, mitral annulus and valve, and submitral apparatus, and points for restricted leaflet mobility. The primary outcome was all-cause mortality, and the secondary outcome was stroke. Over a mean 3.8 ± 1.7 years of follow-up, there were 116 deaths and 34 strokes. Crude mortality increased in a graded fashion with increasing GCCS. In unadjusted proportional hazard analysis, the GCCS was significantly associated with total mortality (hazard ratio, 1.26; 95% CI, 1.17-1.35; P < .0001) and stroke (hazard ratio, 1.23; 95% CI, 1.07-1.40; P = .003). After adjusting for demographic and clinical factors (age, gender, body mass index, diabetes, hypertension, dyslipidemia, smoking, family history of coronary disease, chronic kidney disease, history of atrial fibrillation, and history of stroke), these associations remained significant. The GCCS is easily applied to routinely acquired echocardiograms and has clinically significant associations with total mortality and stroke. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Comparison of Ischemic Stroke Incidence in HIV-Infected and Non-HIV-Infected Patients in a U.S. Health Care System

PubMed Central

Chow, Felicia C.; Regan, Susan; Feske, Steven; Meigs, James B.; Grinspoon, Steven K.; Triant, Virginia A.

2013-01-01

Background Cardiovascular disease is increased among HIV-infected patients, but little is known regarding ischemic stroke rates. We sought to compare stroke rates and determine stroke risk factors in HIV versus non-HIV patients. Methods An HIV cohort and matched non-HIV comparator cohort seen between 1996 and 2009 were identified from a Boston health care system. The primary endpoint was ischemic stroke, defined using International Classification of Diseases (ICD) codes. Unadjusted stroke incidence rates were calculated. Cox proportional hazards modeling was used to determine adjusted hazard ratios (HR). Results The incidence rate of ischemic stroke was 5.27 per 1000 person years (PY) in HIV compared with 3.75 in non-HIV patients, with an unadjusted HR of 1.40 (95% confidence interval [CI] 1.17-1.69, P<0.001). HIV remained an independent predictor of stroke after controlling for demographics and stroke risk factors (1.21, 1.01-1.46, P=0.043). The relative increase in stroke rates (HIV vs. non-HIV) was significantly higher in younger HIV patients (incidence rate ratio 4.42, 95% CI 1.56-11.09 age 18-29; 2.96, 1.69-4.96 age 30-39; 1.53, 1.06-2.17 age 40-49), and in women (HR 2.16 [1.53-3.04] for women vs. 1.18 [0.95-1.47] for men). Among HIV patients, increased HIV RNA (HR 1.10, 95% CI 1.04-1.17, P=0.001) was associated with an increased risk of stroke. Conclusions Stroke rates were increased among HIV-infected patients, independent of common stroke risk factors, particularly among young patients and women. PMID:22580566

Dronedarone in high-risk permanent atrial fibrillation.

PubMed

Connolly, Stuart J; Camm, A John; Halperin, Jonathan L; Joyner, Campbell; Alings, Marco; Amerena, John; Atar, Dan; Avezum, Álvaro; Blomström, Per; Borggrefe, Martin; Budaj, Andrzej; Chen, Shih-Ann; Ching, Chi Keong; Commerford, Patrick; Dans, Antonio; Davy, Jean-Marc; Delacrétaz, Etienne; Di Pasquale, Giuseppe; Diaz, Rafael; Dorian, Paul; Flaker, Greg; Golitsyn, Sergey; Gonzalez-Hermosillo, Antonio; Granger, Christopher B; Heidbüchel, Hein; Kautzner, Josef; Kim, June Soo; Lanas, Fernando; Lewis, Basil S; Merino, Jose L; Morillo, Carlos; Murin, Jan; Narasimhan, Calambur; Paolasso, Ernesto; Parkhomenko, Alexander; Peters, Nicholas S; Sim, Kui-Hian; Stiles, Martin K; Tanomsup, Supachai; Toivonen, Lauri; Tomcsányi, János; Torp-Pedersen, Christian; Tse, Hung-Fat; Vardas, Panos; Vinereanu, Dragos; Xavier, Denis; Zhu, Jun; Zhu, Jun-Ren; Baret-Cormel, Lydie; Weinling, Estelle; Staiger, Christoph; Yusuf, Salim; Chrolavicius, Susan; Afzal, Rizwan; Hohnloser, Stefan H

2011-12-15

Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).

Subclinical atrial fibrillation and the risk of stroke.

PubMed

Healey, Jeff S; Connolly, Stuart J; Gold, Michael R; Israel, Carsten W; Van Gelder, Isabelle C; Capucci, Alessandro; Lau, C P; Fain, Eric; Yang, Sean; Bailleul, Christophe; Morillo, Carlos A; Carlson, Mark; Themeles, Ellison; Kaufman, Elizabeth S; Hohnloser, Stefan H

2012-01-12

One quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation. We enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted. We monitored the patients for 3 months to detect subclinical atrial tachyarrhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing. By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P=0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P=0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation. Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism. (Funded by St. Jude Medical; ASSERT ClinicalTrials.gov number, NCT00256152.).

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

PubMed

Kernan, Walter N; Viscoli, Catherine M; Furie, Karen L; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Guarino, Peter D; Lovejoy, Anne M; Peduzzi, Peter N; Conwit, Robin; Brass, Lawrence M; Schwartz, Gregory G; Adams, Harold P; Berger, Leo; Carolei, Antonio; Clark, Wayne; Coull, Bruce; Ford, Gary A; Kleindorfer, Dawn; O'Leary, John R; Parsons, Mark W; Ringleb, Peter; Sen, Souvik; Spence, J David; Tanne, David; Wang, David; Winder, Toni R

2016-04-07

Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003). In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

Baseline Quality of Life and Risk of Stroke in the ALLHAT Study (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

PubMed

Shams, Tanzila; Auchus, Alexander P; Oparil, Suzanne; Wright, Clinton B; Wright, Jackson; Furlan, Anthony J; Sila, Cathy A; Davis, Barry R; Pressel, Sara; Yamal, Jose-Miguel; Einhorn, Paula T; Lerner, Alan J

2017-11-01

The visual analogue scale is a self-reported, validated tool to measure quality of life (QoL). Our purpose was to determine whether baseline QoL predicted strokes in the ALLHAT study (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) and evaluate determinants of poststroke change in QoL. In the ALLHAT study, among the 33 357 patients randomized to treatment arms, 1525 experienced strokes; 1202 (79%) strokes were nonfatal. This study cohort includes 32 318 (97%) subjects who completed the baseline visual analogue scale QoL estimate. QoL was measured on a visual analogue scale and adjusted using a Torrance transformation (transformed QoL [TQoL]). Kaplan-Meier curves and adjusted proportional hazards analyses were used to estimate the effect of TQoL on the risk of stroke, on a continuous scale (0-1) and by quartiles (≤0.81, >0.81≤0.89, >0.89≤0.95, >0.95). We analyzed the change from baseline to first poststroke TQoL using adjusted linear regression. After adjusting for multiple stroke risk factors, the hazard ratio for stroke events for baseline TQoL was 0.93 (95% confidence interval, 0.89-0.98) per 0.1 U increase. The lowest baseline TQoL quartile had a 20% increased stroke risk (hazard ratio=1.20 [95% confidence interval, 1.00-1.44]) compared with the reference highest quartile TQoL. Poststroke TQoL change was significant within all treatment groups ( P ≤0.001). Multivariate regression analysis revealed that baseline TQoL was the strongest predictor of poststroke TQoL with similar results for the untransformed QoL. The lowest baseline TQoL quartile had a 20% higher stroke risk than the highest quartile. Baseline TQoL was the only factor that predicted poststroke change in TQoL. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542. © 2017 American Heart Association, Inc.

Associations between Stroke Mortality and Weekend Working by Stroke Specialist Physicians and Registered Nurses: Prospective Multicentre Cohort Study

PubMed Central

Bray, Benjamin D.; Ayis, Salma; Campbell, James; Cloud, Geoffrey C.; James, Martin; Hoffman, Alex; Tyrrell, Pippa J.; Wolfe, Charles D. A.; Rudd, Anthony G.

2014-01-01

Background Observational studies have reported higher mortality for patients admitted on weekends. It is not known whether this “weekend effect” is modified by clinical staffing levels on weekends. We aimed to test the hypotheses that rounds by stroke specialist physicians 7 d per week and the ratio of registered nurses to beds on weekends are associated with mortality after stroke. Methods and Findings We conducted a prospective cohort study of 103 stroke units (SUs) in England. Data of 56,666 patients with stroke admitted between 1 June 2011 and 1 December 2012 were extracted from a national register of stroke care in England. SU characteristics and staffing levels were derived from cross-sectional survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) of 30-d post-admission mortality, adjusting for case mix, organisational, staffing, and care quality variables. After adjusting for confounders, there was no significant difference in mortality risk for patients admitted to a stroke service with stroke specialist physician rounds fewer than 7 d per week (adjusted HR [aHR] 1.04, 95% CI 0.91–1.18) compared to patients admitted to a service with rounds 7 d per week. There was a dose–response relationship between weekend nurse/bed ratios and mortality risk, with the highest risk of death observed in stroke services with the lowest nurse/bed ratios. In multivariable analysis, patients admitted on a weekend to a SU with 1.5 nurses/ten beds had an estimated adjusted 30-d mortality risk of 15.2% (aHR 1.18, 95% CI 1.07–1.29) compared to 11.2% for patients admitted to a unit with 3.0 nurses/ten beds (aHR 0.85, 95% CI 0.77–0.93), equivalent to one excess death per 25 admissions. The main limitation is the risk of confounding from unmeasured characteristics of stroke services. Conclusions Mortality outcomes after stroke are associated with the intensity of weekend staffing by registered nurses but not 7-d/wk ward rounds by stroke specialist physicians. The findings have implications for quality improvement and resource allocation in stroke care. Please see later in the article for the Editors' Summary PMID:25137386

Cerebral Microbleeds and the Risk of Incident Ischemic Stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy).

PubMed

Puy, Laurent; De Guio, François; Godin, Ophélia; Duering, Marco; Dichgans, Martin; Chabriat, Hugues; Jouvent, Eric

2017-10-01

Cerebral microbleeds are associated with an increased risk of intracerebral hemorrhage. Recent data suggest that microbleeds may also predict the risk of incident ischemic stroke. However, these results were observed in elderly individuals undertaking various medications and for whom causes of microbleeds and ischemic stroke may differ. We aimed to test the relationship between the presence of microbleeds and incident stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy)-a severe monogenic small vessel disease known to be responsible for both highly prevalent microbleeds and a high incidence of ischemic stroke in young patients. We assessed microbleeds on baseline MRI in all 378 patients from the Paris-Munich cohort study. Incident ischemic strokes were recorded during 54 months. Survival analyses were used to test the relationship between microbleeds and incident ischemic stroke. Three hundred sixty-nine patients (mean age, 51.4±11.4 years) were followed-up during a median time of 39 months (interquartile range, 19 months). The risk of incident ischemic stroke was higher in patients with microbleeds than in patients without (35.8% versus 19.6%, hazard ratio, 1.87; 95% confidence interval, 1.16-3.01; P =0.009). These results persisted after adjustment for history of ischemic stroke, age, sex, vascular risk factors, and antiplatelet agents use (hazard ratio, 1.89; 95% confidence interval, 1.10-3.26; P =0.02). The presence of microbleeds is an independent risk marker of incident ischemic stroke in CADASIL, emphasizing the need to carefully interpret MRI data. © 2017 American Heart Association, Inc.

Noninvasive Assessment of Preload Reserve Enhances Risk Stratification of Patients With Heart Failure With Reduced Ejection Fraction.

PubMed

Matsumoto, Kensuke; Onishi, Akira; Yamada, Hirotsugu; Kusunose, Kenya; Suto, Makiko; Hatani, Yutaka; Matsuzoe, Hiroki; Tatsumi, Kazuhiro; Tanaka, Hidekazu; Hirata, Ken-Ichi

2018-05-01

The leg-positive pressure maneuver can safely and noninvasively apply preload stress without increase in total body fluid volume. The purpose of this study was to determine whether preload stress could be useful for risk stratification of patients with heart failure with reduced ejection fraction. For this study, 120 consecutive patients with heart failure with reduced ejection fraction were prospectively recruited. The stroke work index was estimated as product of stroke volume index and mean blood pressure, and the E/e' ratio was calculated to estimate ventricular filling pressure. The echocardiographic parameters were obtained both at rest and during leg-positive pressure stress. During the median follow-up period of 20 months, 30 patients developed adverse cardiovascular events. During preload stress, stroke work index increased significantly (from 3280±1371 to 3857±1581 mm Hg·mL/m 2 ; P <0.001) along with minimal changes in ventricular filling pressure (E/e', from 16±10 to 17±9; P <0.05) in patients without cardiovascular events. However, patients with cardiovascular events showed impairment of Frank-Starling mechanism (stroke work index, from 2863±969 to 2903±1084 mm Hg·mL/m 2 ; P =0.70) and a serious increase in E/e' ratio (from 19±11 to 25±14; P <0.001). Both the patients without contractile reserve and those without diastolic reserve exhibited worse event-free survival than the others ( P <0.001). In a Cox proportional-hazards analysis, the changes in stroke work index (hazard ratio: 0.44 per 500 mm Hg·mL/m 2 increase; P =0.001) and in E/e' (hazard ratio: 2.58 per 5-U increase; P <0.001) were predictors of cardiovascular events. Contractile reserve and diastolic reserve during leg-positive pressure stress are important determinants of cardiovascular outcomes for patients with heart failure with reduced ejection fraction. © 2018 American Heart Association, Inc.

Association between implementation of a code stroke system and poststroke epilepsy.

PubMed

Chen, Ziyi; Churilov, Leonid; Chen, Ziyuan; Naylor, Jillian; Koome, Miriam; Yan, Bernard; Kwan, Patrick

2018-03-27

We aimed to investigate the effect of a code stroke system on the development of poststroke epilepsy. We retrospectively analyzed consecutive patients treated with IV thrombolysis under or outside the code stroke system between 2003 and 2012. Patients were followed up for at least 2 years or until death. Factors with p < 0.1 in univariate comparisons were selected for multivariable logistic and Cox regression. A total of 409 patients met the eligibility criteria. Their median age at stroke onset was 75 years (interquartile range 64-83 years); 220 (53.8%) were male. The median follow-up duration was 1,074 days (interquartile range 119-1,671 days). Thirty-two patients (7.8%) had poststroke seizures during follow-up, comprising 7 (1.7%) with acute symptomatic seizures and 25 (6.1%) with late-onset seizures. Twenty-six patients (6.4%) fulfilled the definition of poststroke epilepsy. Three hundred eighteen patients (77.8%) were treated with the code stroke system while 91 (22.2%) were not. After adjustment for age and stroke etiology, use of the code stroke system was associated with decreased odds of poststroke epilepsy (odds ratio = 0.36, 95% confidence interval 0.14-0.87, p = 0.024). Cox regression showed lower adjusted hazard rates for poststroke epilepsy within 5 years for patients managed under the code stroke system (hazard ratio = 0.60, 95% confidence interval 0.47-0.79, p < 0.001). The code stroke system was associated with reduced odds and instantaneous risk of poststroke epilepsy. Further studies are required to identify the contribution of the individual components and mechanisms against epileptogenesis after stroke. This study provides Class III evidence that for people with acute ischemic stroke, implementation of a code stroke system reduces the risk of poststroke epilepsy. © 2018 American Academy of Neurology.

Associations of obesity measures with subtypes of ischemic stroke in the ARIC Study.

PubMed

Yatsuya, Hiroshi; Yamagishi, Kazumasa; North, Kari E; Brancati, Frederick L; Stevens, June; Folsom, Aaron R

2010-01-01

Associations between obesity and lacunar, nonlacunar thrombotic, and cardioembolic stroke are not firmly established. Body mass index (BMI), waist circumference, and waist-to-hip ratio (WHR) were recorded at baseline between 1987 and 1989 in the Atherosclerosis Risk in Communities (ARIC) Study for 13 549 black and white adults who were aged from 45 to 64 years and had no history of cardiovascular disease or cancer. The incidence of ischemic stroke subtypes was ascertained from surveillance of hospital records over a median follow-up of 16.9 years. Cox proportional hazards regression analyses adjusted for age, sex, race, education, smoking status and cigarette years, usual ethanol intake, and leisure time sports index were used to estimate hazard ratios (HRs). The ARIC sample at baseline was 43.8% men and 27.3% blacks; mean age was 53.9 years. Mean BMI, waist circumference, and WHR were 27.7 kg/m(2), 96.8 cm, and 0.92, respectively. The associations of lacunar (n = 138), nonlacunar (n = 338), and cardioembolic (n = 122) ischemic stroke incidence with obesity measures were all generally positive and linear. The HRs for the highest versus lowest quintile of the 3 obesity measures ranged from 1.43-2.21 for lacunar stroke, 1.90-2.16 for nonlacunar stroke, and 2.37-2.91 for cardioembolic stroke. Although different pathophysiological mechanisms may exist, the incidences of lacunar, nonlacunar, and cardioembolic stroke were all significantly positively associated with the degree of obesity, regardless of the measure used.

Aortic Valve Calcification and Risk of Stroke: The Rotterdam Study.

PubMed

Bos, Daniel; Bozorgpourniazi, Atefeh; Mutlu, Unal; Kavousi, Maryam; Vernooij, Meike W; Moelker, Adriaan; Franco, Oscar H; Koudstaal, Peter J; Ikram, M Arfan; van der Lugt, Aad

2016-11-01

It remains uncertain whether aortic valve calcification (AVC) is a risk factor for stroke. From the population-based Rotterdam Study, 2471 participants (mean age: 69.6 years; 51.8% women) underwent computed tomography to quantify AVC. We assessed prevalent stroke and continuously monitored the remaining participants for the incidence of stroke. Logistic and Cox regression models were used to investigate associations of AVC with prevalent stroke and risk of incident stroke. AVC was present in 33.1% of people. At baseline, 97 participants had ever suffered a stroke. During 18 665 person-years of follow-up (mean: 7.9 years), 135 people experienced a first-ever stroke. The presence of AVC was not associated with prevalent stroke (fully adjusted odds ratio: 0.97 (95% confidence interval, 0.61-1.53]) or with an increased risk of stroke (fully adjusted hazard ratio: 0.99 (95% confidence interval, 0.69-1.44]). Although AVC is a common finding in middle-aged and elderly community-dwelling people, our results suggest that AVC is not associated with an increased risk of stroke. © 2016 American Heart Association, Inc.

Stress Hyperglycemia and Prognosis of Minor Ischemic Stroke and Transient Ischemic Attack: The CHANCE Study (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events).

PubMed

Pan, Yuesong; Cai, Xueli; Jing, Jing; Meng, Xia; Li, Hao; Wang, Yongjun; Zhao, Xingquan; Liu, Liping; Wang, David; Johnston, S Claiborne; Wei, Tiemin; Wang, Yilong

2017-11-01

We aimed to determine the association between stress hyperglycemia and risk of new stroke in patients with a minor ischemic stroke or transient ischemic attack. A subgroup of 3026 consecutive patients from 73 prespecified sites of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) were analyzed. Stress hyperglycemia was measured by glucose/glycated albumin (GA) ratio. Glucose/GA ratio was calculated by fasting plasma glucose divided by GA and categorized into 4 even groups according to the quartiles. The primary outcome was a new stroke (ischemic or hemorrhagic) at 90 days. We assessed the association between glucose/GA ratio and risk of stroke by multivariable Cox regression models adjusted for potential covariates. Among 3026 patients included, a total of 299 (9.9%) new stroke occurred at 3 months. Compared with patients with the lowest quartile, patients with the highest quartile of glucose/GA ratio was associated with an increased risk of stroke at 3 months after adjusted for potential covariates (12.0% versus 9.2%; adjusted hazard ratio, 1.46; 95% confidence interval, 1.06-2.01). Similar results were observed after further adjusted for fasting plasma glucose. We also observed that higher level of glucose/GA ratio was associated with an increased risk of stroke with a threshold of 0.29 using a Cox regression model with restricted cubic spline. Stress hyperglycemia, measured by glucose/GA ratio, was associated with an increased risk of stroke in patients with a minor ischemic stroke or transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2017 American Heart Association, Inc.

Recurrent Stroke in Minor Ischemic Stroke or Transient Ischemic Attack With Metabolic Syndrome and/or Diabetes Mellitus.

PubMed

Chen, Weiqi; Pan, Yuesong; Jing, Jing; Zhao, Xingquan; Liu, Liping; Meng, Xia; Wang, Yilong; Wang, Yongjun

2017-06-01

We aimed to determine the risk conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent stroke in patients with minor ischemic stroke or transient ischemic attack from the CHANCE (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events) trial. In total, 3044 patients were included. Patients were stratified into 4 groups: neither, METS only, DM only, or both. METS was defined using the Chinese Diabetes Society (CDS) and International Diabetes Foundation (IDF) definitions. The primary outcome was new stroke (including ischemic and hemorrhagic) at 90 days. A multivariable Cox regression model was used to assess the relationship of METS and DM status to the risk of recurrent stroke adjusted for potential covariates. Using the CDS criteria of METS, 53.2%, 17.2%, 19.8%, and 9.8% of patients were diagnosed as neither, METS only, DM only, and both, respectively. After 90 days of follow-up, there were 299 new strokes (293 ischemic, 6 hemorrhagic). Patients with DM only (16.1% versus 6.8%; adjusted hazard ratio 2.50, 95% CI 1.89-3.39) and both (17.1% versus 6.8%; adjusted hazard ratio 2.76, 95% CI 1.98-3.86) had significantly increased rates of recurrent stroke. No interaction effect of antiplatelet therapy by different METS or DM status for the risk of recurrent stroke ( P =0.82 for interaction in the fully adjusted model of CDS) was observed. Using the METS (IDF) criteria demonstrated similar results. Concurrent METS and DM was associated with an increased risk of recurrent stroke in patients with minor stroke and transient ischemic attack. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Chagas disease predicts 10-year stroke mortality in community-dwelling elderly: the Bambui cohort study of aging.

PubMed

Lima-Costa, Maria Fernanda; Matos, Divane L; Ribeiro, Antônio Luiz P

2010-11-01

Previous case-control studies have suggested a causal link between Chagas disease, which is caused by the protozoan Trypanosoma cruzi, and stroke. We investigated the relationship between Chagas disease and long-term stroke mortality in a large community-based cohort of older adults. Participants were 1398 (80.3% from total) residents aged ≥ 60 years in Bambuí City, Brazil. The end point was death from stroke. Potential confounding variables included age, sex, conventional stroke risk factors, and high sensitive C-reactive protein. Participants of this study were followed from 1997 to 2007 leading to 9740 person-years of observation. The baseline prevalence of T. cruzi infection was 37.5% and the overall mortality rate from stroke was 4.62 per 1000 person-years. The risk of death from stroke among T. cruzi-infected participants was twice that of those noninfected (adjusted hazard ratio, 2.36; 95% CI, 1.25 to 4.44). A B-type natriuretic peptide level in the top quartile was a strong and independent predictor of stroke mortality among those infected (adjusted hazard ratio, 2.72; 95% CI, 1.25 to 5.91). The presence of both a high B-type natriuretic peptide level and electrocardiographic atrial fibrillation increased the risk of stroke mortality by 11.49 (95% CI, 3.19 to 41.38) in these individuals. This study provides new evidence supporting a causal link between Chagas disease and stroke. The results also showed that B-type natriuretic peptide alone or in association with atrial fibrillation has prognostic value for stroke mortality in T. cruzi chronically infected older adults.

How Does Cardiovascular Disease First Present in Women and Men? Incidence of 12 Cardiovascular Diseases in a Contemporary Cohort of 1,937,360 People.

PubMed

George, Julie; Rapsomaniki, Eleni; Pujades-Rodriguez, Mar; Shah, Anoop Dinesh; Denaxas, Spiros; Herrett, Emily; Smeeth, Liam; Timmis, Adam; Hemingway, Harry

2015-10-06

Given the recent declines in heart attack and stroke incidence, it is unclear how women and men differ in first lifetime presentations of cardiovascular diseases (CVDs). We compared the incidence of 12 cardiac, cerebrovascular, and peripheral vascular diseases in women and men at different ages. We studied 1 937 360 people, aged ≥ 30 years and free from diagnosed CVD at baseline (51% women), using linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry, and mortality (Cardiovascular Research Using LInked Bespoke Studies and Electronic Records [CALIBER] research platform). During 6 years median follow-up between 1997 and 2010, 114 859 people experienced an incident cardiovascular diagnosis, the majority (66%) of which were neither myocardial infarction nor ischemic stroke. Associations of male sex with initial diagnoses of CVD, however, varied from strong (age-adjusted hazard ratios, 3.6-5.0) for abdominal aortic aneurysm, myocardial infarction, and unheralded coronary death (particularly >60 years), through modest (hazard ratio, 1.5-2.0) for stable angina, ischemic stroke, peripheral arterial disease, heart failure, and cardiac arrest, to weak (hazard ratio <1.5) for transient ischemic attack, intracerebral hemorrhage, and unstable angina, and inverse (0.69) for subarachnoid hemorrhage (all P<0.001). The majority of initial presentations of CVD are neither myocardial infarction nor ischemic stroke, yet most primary prevention studies focus on these presentations. Sex has differing associations with different CVDs, with implications for risk prediction and management strategies. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01164371. © 2015 The Authors.

Rates of Atrial Fibrillation in Black Versus White Patients With Pacemakers.

PubMed

Kamel, Hooman; Kleindorfer, Dawn O; Bhave, Prashant D; Cushman, Mary; Levitan, Emily B; Howard, George; Soliman, Elsayed Z

2016-02-12

Black US residents experience higher rates of ischemic stroke than white residents but have lower rates of clinically apparent atrial fibrillation (AF), a strong risk factor for stroke. It is unclear whether black persons truly have less AF or simply more undiagnosed AF. We obtained administrative claims data from state health agencies regarding all emergency department visits and hospitalizations in California, Florida, and New York. We identified a cohort of patients with pacemakers, the regular interrogation of which reduces the likelihood of undiagnosed AF. We compared rates of documented AF or atrial flutter at follow-up visits using Kaplan-Meier survival statistics and Cox proportional hazards models adjusted for demographic characteristics and vascular risk factors. We identified 10 393 black and 91 380 white patients without documented AF or atrial flutter before or at the index visit for pacemaker implantation. During 3.7 (±1.8) years of follow-up, black patients had a significantly lower rate of AF (21.4%; 95% CI 19.8-23.2) than white patients (25.5%; 95% CI 24.9-26.0). After adjustment for demographic characteristics and comorbidities, black patients had a lower hazard of AF (hazard ratio 0.91; 95% CI 0.86-0.96), a higher hazard of atrial flutter (hazard ratio 1.29; 95% CI 1.11-1.49), and a lower hazard of the composite of AF or atrial flutter (hazard ratio 0.94; 95% CI 0.88-99). In a population-based sample of patients with pacemakers, black patients had a lower rate of AF compared with white patients. These findings indicate that the persistent racial disparities in rates of ischemic stroke are likely to be related to factors other than undiagnosed AF. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Effects of Statin Intensity and Adherence on the Long-Term Prognosis After Acute Ischemic Stroke.

PubMed

Kim, Jinkwon; Lee, Hye Sun; Nam, Chung Mo; Heo, Ji Hoe

2017-10-01

Statin is an established treatment for secondary prevention after ischemic stroke. However, the effects of statin intensity and adherence on the long-term prognosis after acute stroke are not well known. This retrospective cohort study using a nationwide health insurance claim data in South Korea included patients admitted with acute ischemic stroke between 2002 and 2012. Statin adherence and intensity were determined from the prescription data for a period of 1 year after the index stroke. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. We performed multivariate Cox proportional regression analyses. We included 8001 patients with acute ischemic stroke. During the mean follow-up period of 4.69±2.72 years, 2284 patients developed a primary outcome. Compared with patients with no statin, adjusted hazard ratios (95% confidence interval) were 0.74 (0.64-0.84) for good adherence, 0.93 (0.79-1.09) for intermediate adherence, and 1.07 (0.95-1.20) for poor adherence to statin. Among the 1712 patients with good adherence, risk of adverse events was lower in patients with high-intensity statin (adjusted hazard ratio [95% confidence interval], 0.48 [0.24-0.96]) compared with those with low-intensity statin. Neither good adherence nor high intensity of statin was associated with an increased risk of hemorrhagic stroke. After acute ischemic stroke, high-intensity statin therapy with good adherence was significantly associated with a lower risk of adverse events. © 2017 American Heart Association, Inc.

Longitudinal Change of Perceived Salt Intake and Stroke Risk in a Chinese Population.

PubMed

Li, Yun; Huang, Zhe; Jin, Cheng; Xing, Aijun; Liu, Yesong; Huangfu, Chunmei; Lichtenstein, Alice H; Tucker, Katherine L; Wu, Shouling; Gao, Xiang

2018-06-01

Data for a relationship between salt intake and stroke have been inconsistent. This inconstancy could be because of the majority of studies evaluated salt intake at a single time point, which may be insufficient to accurately characterize salt intake throughout the observation period. Included were 77 605 participants from the Kailuan study. We assessed perceived salt intake via questionnaire in 2006, 2008, and 2010. Salt intake trajectories from 2006 to 2010 were identified using latent mixture models. Incident stroke cases were identified from 2010 to 2015 and confirmed by review of medical records. Cox proportional hazards model was used to examine the association between salt intake trajectories and stroke risk after adjusting for possible confounders, including age, sex, lifestyle, social economic status, body mass index, use of medicines, blood pressure, and lipoprotein profiles. Identified were 5 distinct salt intake trajectories: moderate-stable (n=59 241), moderate-decreasing (n=9268), moderate-increasing (n=2975), low-increasing (n=2879), and high-decreasing (n=3242). During the 5-year follow-up period, there were 1564 incident strokes cases. Compared with individuals with the moderate-stable salt intake trajectory, individuals with moderate-decreasing salt intake trajectory had significantly lower cerebral infarction stroke risk (adjusted hazard ratio, 0.76; 95% confidence interval, 0.63-0.92) but not intracerebral hemorrhage risk (adjusted hazard ratio, 0.84; 95% confidence interval, 0.55-1.29). Further adjustment for 2006 or 2010 perceived salt intakes generated similar results. When baseline perceived salt intake only was used as the exposure, a significant dose-response relationship between higher perceived salt intake and higher stroke risk was observed ( P trend=0.006). Change in salt intake was associated with the stroke risk. These data support the dietary recommendation to the reduction of salt intake. © 2018 American Heart Association, Inc.

Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study.

PubMed

Ricci, Cristian; Wood, Angela; Muller, David; Gunter, Marc J; Agudo, Antonio; Boeing, Heiner; van der Schouw, Yvonne T; Warnakula, Samantha; Saieva, Calogero; Spijkerman, Annemieke; Sluijs, Ivonne; Tjønneland, Anne; Kyrø, Cecilie; Weiderpass, Elisabete; Kühn, Tilman; Kaaks, Rudolf; Sánchez, Maria-Jose; Panico, Salvatore; Agnoli, Claudia; Palli, Domenico; Tumino, Rosario; Engström, Gunnar; Melander, Olle; Bonnet, Fabrice; Boer, Jolanda M A; Key, Timothy J; Travis, Ruth C; Overvad, Kim; Verschuren, W M Monique; Quirós, J Ramón; Trichopoulou, Antonia; Papatesta, Eleni-Maria; Peppa, Eleni; Iribas, Conchi Moreno; Gavrila, Diana; Forslund, Ann-Sofie; Jansson, Jan-Håkan; Matullo, Giuseppe; Arriola, Larraitz; Freisling, Heinz; Lassale, Camille; Tzoulaki, Ioanna; Sharp, Stephen J; Forouhi, Nita G; Langenberg, Claudia; Saracci, Rodolfo; Sweeting, Michael; Brennan, Paul; Butterworth, Adam S; Riboli, Elio; Wareham, Nick J; Danesh, John; Ferrari, Pietro

2018-05-29

To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. Multicentre case-cohort study. A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Relationship Between Dietary Vitamin D and Deaths From Stroke and Coronary Heart Disease: The Japan Collaborative Cohort Study.

PubMed

Sheerah, Haytham A; Eshak, Ehab S; Cui, Renzhe; Imano, Hironori; Iso, Hiroyasu; Tamakoshi, Akiko

2018-02-01

There is growing evidence about the importance of vitamin D for cardiovascular health. Therefore, we examined the relationship between dietary vitamin D intake and risk of mortality from stroke and coronary heart disease in Japanese population. A prospective study encompassing 58 646 healthy Japanese adults (23 099 men and 35  547 women) aged of 40 to 79 years in whom dietary vitamin D intake was determined via a self-administered food frequency questionnaire. The median follow-up period was 19.3 years (1989-2009). The hazard ratios and 95% confidence intervals of mortality were calculated using categories of vitamin D intake. During 965 970 person-years of follow-up, 1514 stroke and 702 coronary heart disease deaths were documented. Vitamin D intake was inversely associated with risk of mortality from total stroke especially intraparenchymal hemorrhage but not from coronary heart disease; the multivariable hazard ratios (95% confidence intervals) for the highest (≥440 IU/d) versus lowest (<110 IU/D) categories of vitamin D intake were 0.70 (0.54-0.91; P for trend=0.04) for total stroke and 0.66 (0.46-0.96; P for trend=0.04) for intraparenchymal hemorrhage. Dietary vitamin D intake seems to be inversely associated with mortality from stroke. © 2018 American Heart Association, Inc.

The Brazilian Family Health Program and Secondary Stroke and Myocardial Infarction Prevention: A 6-Year Cohort Study

PubMed Central

Franco, Selma; Longo, Alexandre; Moro, Carla; Buss, Talita A.; Collares, Daniel; Werlich, Roberta; Dadan, Danieli D.; Fissmer, Cristiane S.; Aragão, Ana; Ferst, Priscilla; Palharini, Felipe G.; Eluf-Neto, Jose; Fonseca, Luiz A. M.; Whiteley, William N.; Gonçalves, Anderson R. R.

2012-01-01

Objectives. We compared the incidence of recurrent or fatal cardiovascular disease in patients using Brazil’s government-run Family Health Program (FHP) with those using non-FHP models of care. Methods. From 2005 to 2010, we followed outpatients discharged from city public hospitals after a first ever stroke for stroke recurrence and myocardial infarction, using data from all city hospitals, death certificates, and outpatient monitoring in state-run and private units. Results. In the follow-up period, 103 patients in the FHP units and 138 in the non-FHP units had exclusively state-run care. Stroke or myocardial infarction occurred in 30.1% of patients in the FHP group and 36.2% of patients in non-FHP care (rate ratio [RR] = 0.85; 95% confidence interval [CI] = 0.61, 1.18; P = .39); 37.9% of patients in FHP care and 54.3% in non-FHP care (RR = 0.68; 95% CI = 0.50, 0.92; P = .01) died. FHP use was associated with lower hazard of death from all causes (hazard ratio [HR] = 0.58; P = .005) after adjusting for age and stroke severity. The absolute risk reduction for death by all causes was 16.4%. Conclusions. FHP care is more effective than is non-FHP care at preventing death from secondary stroke and myocardial infarction. PMID:23078478

Lifecourse social conditions and racial disparities in incidence of first stroke.

PubMed

Glymour, M Maria; Avendaño, Mauricio; Haas, Steven; Berkman, Lisa F

2008-12-01

Some previous studies found excess stroke rates among black subjects persisted after adjustment for socioeconomic status (SES), fueling speculation regarding racially patterned genetic predispositions to stroke. Previous research was hampered by incomplete SES assessments, without measures of childhood conditions or adult wealth. We assess the role of lifecourse SES in explaining stroke risk and stroke disparities. Health and Retirement Study participants age 50+ (n = 20,661) were followed on average 9.9 years for self- or proxy-reported first stroke (2175 events). Childhood social conditions (southern state of birth, parental SES, self-reported fair/poor childhood health, and attained height), adult SES (education, income, wealth, and occupational status) and traditional cardiovascular risk factors were used to predict first stroke onset using Cox proportional hazards models. Black subjects had a 48% greater risk of first stroke incidence than whites (95% confidence interval, 1.33-1.65). Childhood conditions predicted stroke risk in both blacks and whites, independently of adult SES. Adjustment for both childhood social conditions and adult SES measures attenuated racial differences to marginal significance (hazard ratio, 1.13; 95% CI, 1.00-1.28). Childhood social conditions predict stroke risk in black and White American adults. Additional adjustment for adult SES, in particular wealth, nearly eliminated the disparity in stroke risk between black and white subjects.

Predictors and Outcomes of Dysphagia Screening After Acute Ischemic Stroke.

PubMed

Joundi, Raed A; Martino, Rosemary; Saposnik, Gustavo; Giannakeas, Vasily; Fang, Jiming; Kapral, Moira K

2017-04-01

Guidelines advocate screening all acute stroke patients for dysphagia. However, limited data are available regarding how many and which patients are screened and how failing a swallowing screen affects patient outcomes. We sought to evaluate predictors of receiving dysphagia screening after acute ischemic stroke and outcomes after failing a screening test. We used the Ontario Stroke Registry from April 1, 2010, to March 31, 2013, to identify patients hospitalized with acute ischemic stroke and determine predictors of documented dysphagia screening and outcomes after failing the screening test, including pneumonia, disability, and death. Among 7171 patients, 6677 patients were eligible to receive dysphagia screening within 72 hours, yet 1280 (19.2%) patients did not undergo documented screening. Patients with mild strokes were significantly less likely than those with more severe strokes to have documented screening (adjusted odds ratio, 0.51; 95% confidence interval [CI], 0.41-0.64). Failing dysphagia screening was associated with poor outcomes, including pneumonia (adjusted odds ratio, 4.71; 95% CI, 3.43-6.47), severe disability (adjusted odds ratio, 5.19; 95% CI, 4.48-6.02), discharge to long-term care (adjusted odds ratio, 2.79; 95% CI, 2.11-3.79), and 1-year mortality (adjusted hazard ratio, 2.42; 95% CI, 2.09-2.80). Associations were maintained in patients with mild strokes. One in 5 patients with acute ischemic stroke did not have documented dysphagia screening, and patients with mild strokes were substantially less likely to have documented screening. Failing dysphagia screening was associated with poor outcomes, including in patients with mild strokes, highlighting the importance of dysphagia screening for all patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.

PubMed

Woodward, M; Zhang, X; Barzi, F; Pan, W; Ueshima, H; Rodgers, A; MacMahon, S

2003-02-01

To provide reliable age- and region-specific estimates of the associations between diabetes and major cardiovascular diseases and death in populations from the Asia-Pacific region. Twenty-four cohort studies from Asia, Australia, and New Zealand (median follow-up, 5.4 years) provided individual participant data from 161,214 people (58% from Asia) of whom 4,873 had a history of diabetes at baseline. The associations of diabetes with the risks of coronary heart disease, stroke, and cause-specific mortality during follow-up were estimated using time-dependent Cox models, stratified by study cohort and sex and adjusted for age at risk. In all, 9,277 deaths occurred (3,635 from cardiovascular disease). The hazard ratio (95% CI) associated with diabetes was 1.97 (1.72-2.25) for fatal cardiovascular disease; there were similar hazard ratios for fatal coronary heart disease, fatal stroke, and composites of fatal and nonfatal outcomes. For all cardiovascular outcomes, hazard ratios were similar in Asian and non-Asian populations and in men and women, but were greater in younger than older individuals. For noncardiovascular death, the hazard ratio was 1.56 (1.38-1.77), with separately significant increases in the risks of death from renal disease, cancer, respiratory infections, and other infective causes. The hazard ratio for all-causes mortality was 1.68 (1.55-1.84), with similar ratios in Asian and non-Asian populations, but with significantly higher ratios in younger than older individuals. The relative effect of diabetes on the risks of cardiovascular disease and death in Asian populations is much the same as that in the largely Caucasian populations of Australia and New Zealand. Hazard ratios were severalfold greater in younger people than older people. The rapidly growing prevalence of diabetes in Asia heralds a large increase in the incidence of diabetes-related death in the coming decades.

Socioeconomic deprivation and survival after stroke: findings from the prospective South London Stroke Register of 1995 to 2011.

PubMed

Chen, Ruoling; McKevitt, Christopher; Rudd, Anthony G; Wolfe, Charles D A

2014-01-01

Previous findings of the association between socioeconomic deprivation (SED) and survival after stroke are inconsistent. There is less investigation on long-term survival. We assessed the associations in a multi-ethnic population in England. We examined data from 4398 patients (3103 whites, 932 blacks, and 253 Asians/others) with first-ever stroke, collected by a population-based stroke register in South London from 1995 to 2011. SED was measured using the Carstairs index score-the higher score, the more deprived. It was analyzed in multivariate Cox regression models in relation to survival after stroke. During 17-year follow-up 2754 patients died. The quartile data of Carstairs score showed no significant association of SED with survival in patients, except for black Caribbeans and Africans. Black patients with the fourth quartile SED had a multivariate adjusted hazard ratio of 1.76 (95% confidence interval, 1.06-2.94) for 3-month mortality and 1.54 (1.00-2.37) for 1-year mortality. After adjustment for acute stroke care provisions, these were no longer significant. However, the sextile data of Carstairs score showed a consistent association of SED with survival after stroke; all patients with the sixth sextile had a fully adjusted hazard ratio of 1.23 (1.05-1.44) for 3-month mortality and 1.13 (1.01-1.25) for 17-year mortality. There is a weak but significant association of SED with reduced survival after stroke in England. SED in blacks may have a stronger impact on short-term survival when compared with white patients. Further efforts are required to achieve equality in survival among patients with stroke of different socioeconomic groups.

Racial differences in vascular risk factors and outcomes of patients with intracranial atherosclerotic arterial stenosis.

PubMed

Waddy, Salina P; Cotsonis, George; Lynn, Michael J; Frankel, Michael R; Chaturvedi, Seemant; Williams, Janice E; Chimowitz, Marc

2009-03-01

Atherosclerotic intracranial stenosis is an important cause of stroke in blacks, yet there are limited data on vascular risk factors and outcome. We analyzed the vascular risk factors and outcomes of blacks and whites in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. Baseline characteristics and outcomes (ischemic stroke, brain hemorrhage, or vascular death combined and ischemic stroke alone) were compared between blacks (n=174) and whites (n=331) using univariate and multivariate analyses. Blacks were significantly (P<0.05) more likely than whites to be/have: female, hypertension history, diabetes history, higher LDL, higher total cholesterol, lower triglycerides, unmarried, unemployed, nonprivate insurance, no insurance, stroke as qualifying event, <70% stenosis, symptomatic anterior circulation vessel, no antithrombotic medication before qualifying event, and no family history of myocardial infarction. Blacks more frequently reached an end point of ischemic stroke, brain hemorrhage or vascular death (28% versus 20%; hazard ratio of 1.49, 95% CI 1.03 to 2.17, P=0.03), had a higher 2-year event rate (0.28 versus 0.19), and reached the end point of ischemic stroke alone (25% versus 16% at 2 years; hazard ratio of 1.62, P=0.017). In multivariate analysis, race was associated with ischemic stroke (P=0.0488) but not with the end point ischemic stroke, brain hemorrhage or vascular death (P=0.188). Blacks with intracranial stenosis are at higher risk of stroke recurrence than whites. This risk warrants additional study of factors contributing to stroke in blacks and highlights the need for aggressive risk factor management in blacks to prevent recurrence.

Prospective observational study of isoflavone and the risk of stroke recurrence: potential clinical implications beyond vascular function.

PubMed

Chan, Y-H; Lau, K-K; Yiu, K-H; Siu, C-W; Chan, H-T; Li, S-W; Tam, S; Lam, T-H; Lau, C-P; Tse, H-F

2012-04-01

Whether isoflavone has any effect on recurrent cardiovascular events is unknown. To investigate the relations between isoflavone intake and the risk of stroke recurrence. We recruited 127 consecutive patients with prior history of atherothrombotic/ hemorrhagic stroke (mean age: 67 ± 11 years, 69% male) and prospectively followed up for a mean duration of 30 months. Stroke recurrence and major adverse cardiovascular events (MACE) were documented. Brachial flow-mediated dilatation (FMD) was measured using high-resolution ultrasound. Isoflavone intake was estimated using a validated food frequency questionnaire. Median isoflavone intake was 6.9 (range: 2.1 - 14.5) mg/day. Isoflavone intake was independently associated with increased FMD (Pearson R=0.23, p=0.012). At 30 months, there were 10 stroke recurrence and 12 MACE. Kaplan-Meier analysis showed that patients with isoflavone intake higher than median value had significantly longer median stroke recurrence-free survival time (19.0 [range: 10.4 - 27.6] mth versus 5.0 [range: 4.1 - 5.9] mth, p=0.021) and MACE-free survival time (19.0 [range: 10.4 - 27.6] mth versus 4.0 [range: 2.4 - 5.6] mth, p=0.013). Using multivariate cox regression, higher isoflavone intake was an independent predictor for lower risk of stroke recurrence (hazards ratio 0.18 [95%CI: 0.03 - 0.95], risk reduction 82%, p=0.043) and MACE (hazards ratio 0.16 [95%CI: 0.03 - 0.84], risk reduction 84%, p=0.030). Higher isoflavone intake in stroke patients was associated with prolonged recurrence-free survival, and reduced risk of stroke recurrence and MACE independent of baseline vascular function. Whether isoflavone may confer clinically significant secondary protection in stroke patients should be further investigated in a randomized controlled trial.

Prognostic Significance of Blood Pressure Variability on Beat-to-Beat Monitoring After Transient Ischemic Attack and Stroke.

PubMed

Webb, Alastair J S; Mazzucco, Sara; Li, Linxin; Rothwell, Peter M

2018-01-01

Visit-to-visit and day-to-day blood pressure (BP) variability (BPV) predict an increased risk of cardiovascular events but only reflect 1 form of BPV. Beat-to-beat BPV can be rapidly assessed and might also be predictive. In consecutive patients within 6 weeks of transient ischemic attack or nondisabling stroke (Oxford Vascular Study), BPV (coefficient of variation) was measured beat-to-beat for 5 minutes (Finometer), day-to-day for 1 week on home monitoring (3 readings, 3× daily), and on awake ambulatory BP monitoring. BPV after 1-month standard treatment was related (Cox proportional hazards) to recurrent stroke and cardiovascular events for 2 to 5 years, adjusted for mean systolic BP. Among 520 patients, 26 had inadequate beat-to-beat recordings, and 22 patients were in atrial fibrillation. Four hundred five patients had all forms of monitoring. Beat-to-beat BPV predicted recurrent stroke and cardiovascular events independently of mean systolic BP (hazard ratio per group SD, stroke: 1.47 [1.12-1.91]; P =0.005; cardiovascular events: 1.41 [1.08-1.83]; P =0.01), including after adjustment for age and sex (stroke: 1.47 [1.12-1.92]; P =0.005) and all risk factors (1.40 [1.00-1.94]; P =0.047). Day-to-day BPV was less strongly associated with stroke (adjusted hazard ratio, 1.29 [0.97-1.71]; P =0.08) but similarly with cardiovascular events (1.41 [1.09-1.83]; P =0.009). BPV on awake ambulatory BP monitoring was nonpredictive (stroke: 0.89 [0.59-1.35]; P =0.59; cardiovascular events: 1.08 [0.77-1.52]; P =0.65). Despite a weak correlation ( r =0.119; P =0.02), beat-to-beat BPV was associated with risk of recurrent stroke independently of day-to-day BPV (1.41 [1.05-1.90]; P =0.02). Beat-to-beat BPV predicted recurrent stroke and cardiovascular events, independently of mean systolic BP and risk factors but short-term BPV on ambulatory BP monitoring did not. Beat-to-beat BPV may be a useful additional marker of cardiovascular risk. © 2017 The Authors.

Clinical Effectiveness of Statin Therapy After Ischemic Stroke: Primary Results From the Statin Therapeutic Area of the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study.

PubMed

O'Brien, Emily C; Greiner, Melissa A; Xian, Ying; Fonarow, Gregg C; Olson, DaiWai M; Schwamm, Lee H; Bhatt, Deepak L; Smith, Eric E; Maisch, Lesley; Hannah, Deidre; Lindholm, Brianna; Peterson, Eric D; Pencina, Michael J; Hernandez, Adrian F

2015-10-13

In patients with ischemic stroke, data on the real-world effectiveness of statin therapy for clinical and patient-centered outcomes are needed to better inform shared decision making. Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) is a Patient-Centered Outcomes Research Institute-funded research program designed with stroke survivors to evaluate the effectiveness of poststroke therapies. We linked data on patients ≥65 years of age enrolled in the Get With The Guidelines-Stroke Registry to Medicare claims. Two-year to postdischarge outcomes of those discharged on a statin versus not on a statin were adjusted through inverse probability weighting. Our coprimary outcomes were major adverse cardiovascular events and home time (days alive and out of a hospital or skilled nursing facility). Secondary outcomes included all-cause mortality, all-cause readmission, cardiovascular readmission, and hemorrhagic stroke. From 2007 to 2011, 77 468 patients who were not taking statins at the time of admission were hospitalized with ischemic stroke; of these, 71% were discharged on statin therapy. After adjustment, statin therapy at discharge was associated with a lower hazard of major adverse cardiovascular events (hazard ratio, 0.91; 95% confidence interval, 0.87-0.94), 28 more home-time days after discharge (P<0.001), and lower all-cause mortality and readmission. Statin therapy at discharge was not associated with increased risk of hemorrhagic stroke (hazard ratio, 0.94; 95% confidence interval, 0.72-1.23). Among statin-treated patients, 31% received a high-intensity dose; after risk adjustment, these patients had outcomes similar to those of recipients of moderate-intensity statin. In older ischemic stroke patients who were not taking statins at the time of admission, discharge statin therapy was associated with lower risk of major adverse cardiovascular events and nearly 1 month more home time during the 2-year period after hospitalization. © 2015 American Heart Association, Inc.

Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack

PubMed Central

Brookes, Rebecca L.; Crichton, Siobhan; Wolfe, Charles D.A.; Yi, Qilong; Li, Linxin; Hankey, Graeme J.; Rothwell, Peter M.

2018-01-01

Background and Purpose— A variant in the histone deacetylase 9 (HDAC9) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate. Methods— Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study. Patients receiving SVA were compared with patients who received antiepileptic drugs other than SVA using survival analysis and Cox Regression. Results— A total of 11 949 patients with confirmed ischemic event were included. Recurrent stroke rate was lower in patient taking SVA (17 of 168) than other antiepileptic drugs (105 of 530; log-rank survival analysis P=0.002). On Cox regression, controlling for potential cofounders, SVA remained associated with reduced stroke (hazard ratio=0.44; 95% confidence interval: 0.3–0.7; P=0.002). A similar result was obtained when patients taking SVA were compared with all cases not taking SVA (Cox regression, hazard ratio=0.47; 95% confidence interval: 0.29–0.77; P=0.003). Conclusions— These results suggest that exposure to SVA, an inhibitor of HDAC, may be associated with a lower recurrent stroke risk although we cannot exclude residual confounding in this study design. This supports the hypothesis that HDAC9 is important in the ischemic stroke pathogenesis and that its inhibition, by SVA or a more specific HDAC9 inhibitor, is worthy of evaluation as a treatment to prevent recurrent ischemic stroke. PMID:29247141

Stroke symptoms and risk for incident coronary heart disease in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

PubMed Central

Colantonio, Lisandro D.; Gamboa, Christopher M.; Kleindorfer, Dawn O.; Carson, April P.; Howard, Virginia J.; Muntner, Paul; Cushman, Mary; Howard, George; Safford, Monika M.

2016-01-01

Background Many adults without cerebrovascular disease report a history of stroke symptoms, which is associated with higher risk for stroke. Because stroke and coronary heart disease (CHD) share many risk factors, we examined the association between a history of stroke symptoms and incident CHD. Methods We analyzed data from 8,999 black and 12,499 white REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants without a prior myocardial infarction, stroke or transitory ischemic attack enrolled in 2003-2007 (total participants=21,498, all ≥45 years of age). A history of stroke symptoms (i.e., unilateral weakness, unilateral numbness, full-field vision loss, half-field vision loss, understanding problems and communication problems) was assessed at baseline using the Questionnaire for Verifying Stroke-Free Status. Participants were followed for incident CHD and CHD death through December 2011. Results Overall, 3,432 (16.0%) participants reported a history of stroke symptoms (1,771 [19.7%] blacks and 1,661 [13.3%] whites). There were 701 incident CHD events including 209 CHD deaths over a median follow-up of 5.8 years. After adjustment for CHD risk factors, hazard ratios (95% confidence interval [95%CI]) for incident CHD associated with reporting any versus no stroke symptoms were 1.26 (1.04-1.51) in the overall population, 1.28 (0.99-1.65) among blacks and 1.23 (0.94-1.61) among whites. Multivariable-adjusted hazard ratios (95%CI) for CHD death associated with any versus no stroke symptoms were 1.50 (1.10-2.06) overall, 1.58 (1.07-2.32) among blacks and 1.41 (0.82-2.43) among whites. Conclusion A history of stroke symptoms is associated with a higher incidence of CHD among black and white adults. PMID:27376567

Stroke symptoms and risk for incident coronary heart disease in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

PubMed

Colantonio, Lisandro D; Gamboa, Christopher M; Kleindorfer, Dawn O; Carson, April P; Howard, Virginia J; Muntner, Paul; Cushman, Mary; Howard, George; Safford, Monika M

2016-10-01

Many adults without cerebrovascular disease report a history of stroke symptoms, which is associated with higher risk for stroke. Because stroke and coronary heart disease (CHD) share many risk factors, we examined the association between a history of stroke symptoms and incident CHD. We analyzed data from 8999 black and 12,499 white REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants without a prior myocardial infarction, stroke or transitory ischemic attack enrolled in 2003-2007 (total participants=21,498, all ≥45years of age). A history of stroke symptoms (i.e., unilateral weakness, unilateral numbness, full-field vision loss, half-field vision loss, understanding problems and communication problems) was assessed at baseline using the Questionnaire for Verifying Stroke-Free Status. Participants were followed for incident CHD and CHD death through December 2011. Overall, 3432 (16.0%) participants reported a history of stroke symptoms (1771 [19.7%] blacks and 1661 [13.3%] whites). There were 701 incident CHD events including 209 CHD deaths over a median follow-up of 5.8years. After adjustment for CHD risk factors, hazard ratios (95% confidence interval [95% CI]) for incident CHD associated with reporting any versus no stroke symptoms were 1.26 (1.04-1.51) in the overall population, 1.28 (0.99-1.65) among blacks and 1.23 (0.94-1.61) among whites. Multivariable-adjusted hazard ratios (95% CI) for CHD death associated with any versus no stroke symptoms were 1.50 (1.10-2.06) overall, 1.58 (1.07-2.32) among blacks and 1.41 (0.82-2.43) among whites. A history of stroke symptoms is associated with a higher incidence of CHD among black and white adults. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus.

PubMed

Young, Lawrence H; Viscoli, Catherine M; Curtis, Jeptha P; Inzucchi, Silvio E; Schwartz, Gregory G; Lovejoy, Anne M; Furie, Karen L; Gorman, Mark J; Conwit, Robin; Abbott, J Dawn; Jacoby, Daniel L; Kolansky, Daniel M; Pfau, Steven E; Ling, Frederick S; Kernan, Walter N

2017-05-16

Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54-0.94; P =0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96; log-rank P =0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58-1.91; P =0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87; P =0.02), but not smaller MIs. Among patients with insulin resistance without diabetes mellitus, pioglitazone reduced the risk for acute coronary syndromes after a recent cerebrovascular event. Pioglitazone appeared to have its most prominent effect in preventing spontaneous type 1 MIs. URL: http://clinicaltrials.gov. Unique identifier: NCT00091949. © 2017 American Heart Association, Inc.

Risk of Stroke Among Survivors of the September 11, 2001 World Trade Center Disaster.

PubMed

Yu, Shengchao; Alper, Howard E; Nguyen, Angela-Maithy; Brackbill, Robert M

2018-05-30

The aim of this study was to investigate the association between 9/11-related posttraumatic stress disorder (PTSD), dust cloud exposure, and subsequent development of stroke among 42,527 enrollees in the World Trade Center (WTC) Health Registry. Using four waves of longitudinal data from the WTC Health Registry surveys, we employed Cox proportional hazards regression models to assess the associations. Incidence of stroke was higher among those with PTSD or intense dust cloud exposure than those without, and it was even higher for those who had experienced both. In fully adjusted models, participants with PTSD had an increased risk of developing stroke [adjusted hazards ratio (AHR) 1.69, 95% confidence interval (95% CI) 1.42 to 2.02], as did those with intense dust exposure (AHR 1.29, 95% CI 1.09 to 1.53). We found that individuals with 9/11-related PTSD and/or intense dust exposure may have an increased risk of developing stroke.

Epidemiological evidence of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease in Japan.

PubMed

Saito, Isao

2012-01-01

Although epidemiological studies in the US and Europe have confirmed that type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD) events, evidence is limited in Japan. Earlier studies in Japan showed that hypertension has a major effect on atherosclerosis in relatively lean subjects, with type 2 DM contributing more to CVD events, because of a decline in blood pressure levels in both sexes and an increase in body mass index in men. Recent cohort studies in Japan using baseline assessments carried out during the 1990s have confirmed that type 2 DM is associated with an increased risk of coronary heart disease (CHD) and all types of stroke, except hemorrhagic stroke. In addition, the metabolic syndrome, a constellation of metabolic risk factors, was shown to predict CVD events in Japanese people, independent of the presence or absence of obesity. The strong association of type 2 DM with CHD (hazard ratio: 1.5-4) and ischemic stroke (hazard ratio: 2-4) events was confirmed in Japanese adults. Individuals with impaired glucose tolerance or impaired fasting glucose were also shown to have an increased risk of a CHD event, but not a stroke.

Radiation, Atherosclerotic Risk Factors, and Stroke Risk in Survivors of Pediatric Cancer: A Report From the Childhood Cancer Survivor Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, Sabine, E-mail: muellers@neuropeds.ucsf.edu; Fullerton, Heather J.; Stratton, Kayla

Purpose: To test the hypotheses that (1) the increased risk of stroke conferred by childhood cranial radiation therapy (CRT) persists into adulthood; and (2) atherosclerotic risk factors further increase the stroke risk in cancer survivors. Methods and Materials: The Childhood Cancer Survivor Study is a multi-institutional retrospective cohort study of 14,358 5-year survivors of childhood cancer and 4023 randomly selected sibling controls with longitudinal follow-up. Age-adjusted incidence rates of self-reported late-occurring (≥5 years after diagnosis) first stroke were calculated. Multivariable Cox proportional hazards models were used to identify independent stroke predictors. Results: During a mean follow-up of 23.3 years, 292more » survivors reported a late-occurring stroke. The age-adjusted stroke rate per 100,000 person-years was 77 (95% confidence interval [CI] 62-96), compared with 9.3 (95% CI 4-23) for siblings. Treatment with CRT increased stroke risk in a dose-dependent manner: hazard ratio 5.9 (95% CI 3.5-9.9) for 30-49 Gy CRT and 11.0 (7.4-17.0) for 50+ Gy CRT. The cumulative stroke incidence in survivors treated with 50+ Gy CRT was 1.1% (95% CI 0.4-1.8%) at 10 years after diagnosis and 12% (95% CI 8.9-15.0%) at 30 years. Hypertension increased stroke hazard by 4-fold (95% CI 2.8-5.5) and in black survivors by 16-fold (95% CI 6.9-36.6). Conclusion: Young adult pediatric cancer survivors have an increased stroke risk that is associated with CRT in a dose-dependent manner. Atherosclerotic risk factors enhanced this risk and should be treated aggressively.« less

Comparison of risk scores for the prediction of stroke in African Americans: Findings from the Jackson Heart Study.

PubMed

Foraker, Randi E; Greiner, Melissa; Sims, Mario; Tucker, Katherine L; Towfighi, Amytis; Bidulescu, Aurelian; Shoben, Abigail B; Smith, Sakima; Talegawkar, Sameera; Blackshear, Chad; Wang, Wei; Hardy, Natalie Chantelle; O'Brien, Emily

2016-07-01

Evidence from existing cohort studies supports the prediction of incident coronary heart disease and stroke using 10-year cardiovascular disease (CVD) risk scores and the American Heart Association/American Stroke Association's cardiovascular health (CVH) metric. We included all Jackson Heart Study participants with complete scoring information at the baseline study visit (2000-2004) who had no history of stroke (n = 4,140). We used Kaplan-Meier methods to calculate the cumulative incidence of stroke and used Cox models to estimate hazard ratios and 95% CIs for stroke according to CVD risk and CVH score. We compared the discrimination of the 2 models according to the Harrell c index and plotted predicted vs observed stroke risk calibration plots for each of the 2 models. The median age of the African American participants was 54.5 years, and 65% were female. The cumulative incidence of stroke increased across worsening categories of CVD risk and CVH. A 1-unit increase in CVD risk increased the hazard of stroke (1.07, 1.06-1.08), whereas each 1-unit increase in CVH corresponded to a decreased hazard of stroke (0.76, 0.69-0.83). As evidenced by the c statistics, the CVH model was less discriminating than the CVD risk model (0.59 [0.55-0.64] vs 0.79 [0.76-0.83]). Both scores were associated with incident stroke in a dose-response fashion; however, the CVD risk model was more discriminating than the CVH model. The CVH score may still be preferable for its simplicity in application to broad patient populations and public health efforts. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased pulse wave velocity in patients with acute lacunar infarction doubled the risk of future ischemic stroke.

PubMed

Saji, Naoki; Murotani, Kenta; Shimizu, Hirotaka; Uehara, Toshiyuki; Kita, Yasushi; Toba, Kenji; Sakurai, Takashi

2017-04-01

The aim of this study was to determine whether pulse wave velocity (PWV), a marker of vascular endothelial impairment and arteriosclerosis, predicts future ischemic stroke in patients who developed acute lacunar infarction. Patients with a first-ever ischemic stroke due to acute lacunar infarction were enrolled in this study. An oscillometric device (Form PWV/ABI; Omron Colin, Tokyo, Japan) was used to measure brachial-ankle PWV 1 week after stroke onset. Patients were followed for at least 5 years. The main end point of the study was recurrent ischemic stroke. Event-free survival was analyzed using Kaplan-Meier plots and log-rank tests. The risk of recurrent ischemic stroke was estimated using the Cox proportional-hazards model. Of the 156 patients (61% male, mean age: 69.2±11.3 years) assessed in this study, 29 developed recurrent ischemic stroke. The median brachial-ankle PWV value was 20.4 m s -1 . Patients with high PWV values had a greater risk of recurrent ischemic stroke than patients with low PWV values (28% vs. 15%, P=0.08). Kaplan-Meier curve analysis showed that patients with high PWV values had a less favorable (that is, free of recurrent ischemic stroke) survival time (P=0.015). A multivariate Cox proportional-hazards model identified high PWV as an independent predictor of recurrent ischemic stroke after adjusting for age, sex and blood pressure (hazard ratio 2.35, 95% confidence interval, 1.02-5.70, P=0.044). In patients with acute lacunar infarction, a high PWV predicts a twofold greater risk of future ischemic stroke, independent of patient age, sex and blood pressure levels.

Migraine and risk of cardiovascular diseases: Danish population based matched cohort study

PubMed Central

Szépligeti, Szimonetta Komjáthiné; Holland-Bill, Louise; Ehrenstein, Vera; Horváth-Puhó, Erzsébet; Henderson, Victor W; Sørensen, Henrik Toft

2018-01-01

Abstract Objective To examine the risks of myocardial infarction, stroke (ischaemic and haemorrhagic), peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter, and heart failure in patients with migraine and in a general population comparison cohort. Design Nationwide, population based cohort study. Setting All Danish hospitals and hospital outpatient clinics from 1995 to 2013. Participants 51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year. Main outcome measures Comorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis. Results Higher absolute risks were observed among patients with incident migraine than in the general population across most outcomes and follow-up periods. After 19 years of follow-up, the cumulative incidences per 1000 people for the migraine cohort compared with the general population were 25 v 17 for myocardial infarction, 45 v 25 for ischaemic stroke, 11 v 6 for haemorrhagic stroke, 13 v 11 for peripheral artery disease, 27 v 18 for venous thromboembolism, 47 v 34 for atrial fibrillation or atrial flutter, and 19 v 18 for heart failure. Correspondingly, migraine was positively associated with myocardial infarction (adjusted hazard ratio 1.49, 95% confidence interval 1.36 to 1.64), ischaemic stroke (2.26, 2.11 to 2.41), and haemorrhagic stroke (1.94, 1.68 to 2.23), as well as venous thromboembolism (1.59, 1.45 to 1.74) and atrial fibrillation or atrial flutter (1.25, 1.16 to 1.36). No meaningful association was found with peripheral artery disease (adjusted hazard ratio 1.12, 0.96 to 1.30) or heart failure (1.04, 0.93 to 1.16). The associations, particularly for stroke outcomes, were stronger during the short term (0-1 years) after diagnosis than the long term (up to 19 years), in patients with aura than in those without aura, and in women than in men. In a subcohort of patients, the associations persisted after additional multivariable adjustment for body mass index and smoking. Conclusions Migraine was associated with increased risks of myocardial infarction, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter. Migraine may be an important risk factor for most cardiovascular diseases. PMID:29386181

Migraine and risk of cardiovascular diseases: Danish population based matched cohort study.

PubMed

Adelborg, Kasper; Szépligeti, Szimonetta Komjáthiné; Holland-Bill, Louise; Ehrenstein, Vera; Horváth-Puhó, Erzsébet; Henderson, Victor W; Sørensen, Henrik Toft

2018-01-31

To examine the risks of myocardial infarction, stroke (ischaemic and haemorrhagic), peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter, and heart failure in patients with migraine and in a general population comparison cohort. Nationwide, population based cohort study. All Danish hospitals and hospital outpatient clinics from 1995 to 2013. 51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year. Comorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis. Higher absolute risks were observed among patients with incident migraine than in the general population across most outcomes and follow-up periods. After 19 years of follow-up, the cumulative incidences per 1000 people for the migraine cohort compared with the general population were 25 v 17 for myocardial infarction, 45 v 25 for ischaemic stroke, 11 v 6 for haemorrhagic stroke, 13 v 11 for peripheral artery disease, 27 v 18 for venous thromboembolism, 47 v 34 for atrial fibrillation or atrial flutter, and 19 v 18 for heart failure. Correspondingly, migraine was positively associated with myocardial infarction (adjusted hazard ratio 1.49, 95% confidence interval 1.36 to 1.64), ischaemic stroke (2.26, 2.11 to 2.41), and haemorrhagic stroke (1.94, 1.68 to 2.23), as well as venous thromboembolism (1.59, 1.45 to 1.74) and atrial fibrillation or atrial flutter (1.25, 1.16 to 1.36). No meaningful association was found with peripheral artery disease (adjusted hazard ratio 1.12, 0.96 to 1.30) or heart failure (1.04, 0.93 to 1.16). The associations, particularly for stroke outcomes, were stronger during the short term (0-1 years) after diagnosis than the long term (up to 19 years), in patients with aura than in those without aura, and in women than in men. In a subcohort of patients, the associations persisted after additional multivariable adjustment for body mass index and smoking. Migraine was associated with increased risks of myocardial infarction, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter. Migraine may be an important risk factor for most cardiovascular diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pre-hospital Delay as Determinant of Ischemic Stroke Outcome in an Italian Cohort of Patients Not Receiving Thrombolysis.

PubMed

Denti, Licia; Artoni, Andrea; Scoditti, Umberto; Gatti, Elisa; Bussolati, Chiara; Ceda, Gian Paolo

2016-06-01

Pre-hospital delay in acute stroke is critical to the administration of thrombolysis and affects patients' clinical outcome. In this study, the impact of pre-hospital delay on the outcome of ischemic stroke was investigated in an Italian cohort of patients who did not receive thrombolysis. Data from a cohort of 1847 patients, suffering from first-ever ischemic stroke and referred to an in-hospital clinical pathway were analyzed retrospectively. The relationship between pre-hospital delay and 1-month mortality was assessed with adjustment for demographics, premorbid disability, and stroke severity, which was graded according to the Scandinavian Stroke Scale, with higher scores indicating less severity. Five hundred and twelve patients (27.7%) arrived at hospital within 2 hours of symptom onset. A significant correlation was found between early arrival and a reduced risk of 1-month mortality (hazard ratio .65; 95% confidence interval .48-.89; P = .02). There was a significant interaction (P = .01) between pre-hospital delay and the neurological score on mortality in the multivariate model, and the survival advantage of early admission was significant only for patients with scores on the Scandinavian Stroke Scale less than 18 (hazard ratio .54; 95% confidence interval .34-.85; P = .008). Our study suggests that reducing pre-hospital delay can increase the probability of survival in patients with ischemic stroke, especially those who are most severely affected. Even if the patients cannot benefit from thrombolysis, survival rates can be increased provided that they are managed according to standardized care processes. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Long-term outcome of endovascular treatment versus medical care for carotid artery stenosis in patients not suitable for surgery and randomised in the Carotid and Vertebral Artery Transluminal Angioplasty study (CAVATAS).

PubMed

Ederle, Jörg; Featherstone, Roland L; Brown, Martin M

2009-01-01

Optimal treatment of carotid stenosis in patients not suitable for surgery is unclear. The Carotid and Vertebral Artery Transluminal Angioplasty study contained a trial comparing medical and endovascular treatment in patients not suitable for surgery. Forty patients were randomised to medical or endovascular treatment in equal numbers, and patients were followed up for up to 10 years. The primary outcome measure was defined as stroke or death during follow-up, analysed by intention-to-treat. Secondary analyses included disabling stroke, death, any stroke, any stroke or transient ischemic attack (TIA), all during follow-up. Baseline characteristics were similar. The risk of stroke, retinal infarction or death within 30 days of endovascular treatment was 5% (95% CI: 0.1-24.9%). By the study end, >50% of patients had suffered a recurrent TIA, stroke or died. One third of events were non-stroke deaths. Overall, there was no significant difference between medical and endovascular treatment in the primary outcome rate of stroke or death after randomisation (hazard ratio: 0.98, 95% CI: 0.39-2.48) or the rate of any stroke or TIA (hazard ratio: 1.43, 95% CI: 0.54-3.75). We failed to show superiority of endovascular treatment above medical care alone for carotid stenosis in a very small group of patients not suitable for surgical treatment. However, the trial randomised only 40 patients, and was therefore severely underpowered to detect clinically relevant treatment differences. Ongoing trials of carotid stenting will need to demonstrate improved safety and efficacy before endovascular treatment should enter routine practice. (c) 2009 S. Karger AG, Basel.

Migraine and risk of stroke in older adults

PubMed Central

Gardener, Hannah; Rundek, Tatjana; Elkind, Mitchell S.V.; Sacco, Ralph L.

2015-01-01

Objective: To examine the association between migraine and stroke/vascular outcomes in a racially/ethnically diverse, older cohort. Methods: Participants from the Northern Manhattan Study, a population-based cohort study of stroke incidence, were assessed for migraine symptoms using a self-report questionnaire based on criteria from the International Classification of Headache Disorders, second edition. We estimated the association between migraine and combined vascular events including stroke and stroke only over a mean follow-up of 11 years, using Cox models adjusted for sociodemographic and vascular risk factors. Results: Of 1,292 participants (mean age 68 ± 9 years) with migraine data followed prospectively for vascular events, 262 patients (20%) had migraine and 75 (6%) had migraine with aura. No association was found between migraine (with or without aura) and risk of either stroke or combined cardiovascular events. There was an interaction between migraine and current smoking (p = 0.02 in relation to stroke and p = 0.03 for combined vascular events), such that those with migraine and smoking were at an increased risk. The hazard ratio of stroke for migraine among current smokers was 3.17 (95% confidence interval [CI] 1.13–8.85) and among current nonsmokers was 0.77 (95% CI 0.44–1.35). In relation to combined vascular events, the hazard ratio for migraine vs no migraine among current smokers was 1.83 (95% CI 0.89–3.75) and among current nonsmokers was 0.63 (95% CI 0.43–0.94). Conclusion: In our racially/ethnically diverse population-based cohort, migraine was associated with an increased risk of stroke among active smokers but not among nonsmokers. PMID:26203088

Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.

PubMed

Johnston, S Claiborne; Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Jonasson, Jenny; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence

2016-07-07

Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia. We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days. During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%. In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin.

PubMed

Vinereanu, Dragos; Lopes, Renato D; Mulder, Hillary; Gersh, Bernard J; Hanna, Michael; de Barros E Silva, Pedro G M; Atar, Dan; Wallentin, Lars; Granger, Christopher B; Alexander, John H

2017-12-01

Few data exist on the long-term outcomes of patients with spontaneous echo contrast (SEC), left atrial/left atrial appendage (LA/LAA) thrombus, and complex aortic plaque (CAP), in patients with atrial fibrillation receiving oral anticoagulation. We explored the relationship between these 3 echocardiographic findings and clinical outcomes, and the comparative efficacy and safety of apixaban and warfarin for each finding. Patients from the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) with SEC, LA/LAA thrombus, or CAP diagnosed by either transthoracic or transesophageal echocardiography were compared with patients with none of these findings on transesophageal echocardiography. A total of 1251 patients were included: 217 had SEC, 127 had LA/LAA thrombus, 241 had CAP, and 746 had none. The rates of stroke/systemic embolism were not significantly different among patients with and without these echocardiographic findings (hazard ratio, 0.96; 95% confidence interval, 0.25-3.60 for SEC; hazard ratio, 1.27; 95% confidence interval, 0.23-6.86 for LA/LAA thrombus; hazard ratio, 2.21; 95% confidence interval, 0.71-6.85 for CAP). Rates of ischemic stroke, myocardial infarction, cardiovascular death, and all-cause death were also not different between patients with and without these findings. For patients with either SEC or CAP, there was no evidence of a differential effect of apixaban over warfarin. For patients with LA/LAA thrombus, there was also no significant interaction, with the exception of all-cause death and any bleeding where there was a greater benefit of apixaban compared with warfarin among patients with no LA/LAA thrombus. In anticoagulated patients with atrial fibrillation and risk factors for stroke, echocardiographic findings do not seem to add to the risk of thromboembolic events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2017 American Heart Association, Inc.

Stroke incidence and mortality trends in US communities, 1987 to 2011.

PubMed

Koton, Silvia; Schneider, Andrea L C; Rosamond, Wayne D; Shahar, Eyal; Sang, Yingying; Gottesman, Rebecca F; Coresh, Josef

2014-07-16

Prior studies have shown decreases in stroke mortality over time, but data on validated stroke incidence and long-term trends by race are limited. To study trends in stroke incidence and subsequent mortality among black and white adults in the Atherosclerosis Risk in Communities (ARIC) cohort from 1987 to 2011. Prospective cohort study of 14,357 participants (282,097 person-years) free of stroke at baseline was facilitated in 4 different US communities. Participants were recruited for the purpose of studying all stroke hospitalizations and deaths and for collection of baseline information on cardiovascular risk factors (via interviews and physical examinations) in 1987-1989. Participants were followed up (via examinations, annual phone interviews, active surveillance of discharges from local hospitals, and linkage with the National Death Index) through December 31, 2011. The study physician reviewers adjudicated all possible strokes and classified them as definite or probable ischemic or hemorrhagic events. Trends in rates of first-ever stroke per 10 years of calendar time were estimated using Poisson regression incidence rate ratios (IRRs), with subsequent mortality analyzed using Cox proportional hazards regression models and hazard ratios (HRs) overall and by race, sex, and age divided at 65 years. Among 1051 (7%) participants with incident stroke, there were 929 with incident ischemic stroke and 140 with incident hemorrhagic stroke (18 participants had both during the study period). Crude incidence rates were 3.73 (95% CI, 3.51-3.96) per 1000 person-years for total stroke, 3.29 (95% CI, 3.08-3.50) per 1000 person-years for ischemic stroke, and 0.49 (95% CI, 0.41-0.57) per 1000 person-years for hemorrhagic stroke. Stroke incidence decreased over time in white and black participants (age-adjusted IRRs per 10-year period, 0.76 [95% CI, 0.66-0.87]; absolute decrease of 0.93 per 1000 person-years overall). The decrease in age-adjusted incidence was evident in participants age 65 years and older (age-adjusted IRR per 10-year period, 0.69 [95% CI, 0.59-0.81]; absolute decrease of 1.35 per 1000 person-years) but not evident in participants younger than 65 years (age-adjusted IRR per 10-year period, 0.97 [95% CI, 0.76-1.25]; absolute decrease of 0.09 per 1000 person-years) (P = .02 for interaction). The decrease in incidence was similar by sex. Of participants with incident stroke, 614 (58%) died through 2011. The mortality rate was higher for hemorrhagic stroke (68%) than for ischemic stroke (57%). Overall, mortality after stroke decreased over time (hazard ratio [HR], 0.80 [95% CI, 0.66-0.98]; absolute decrease of 8.09 per 100 strokes after 10 years [per 10-year period]). The decrease in mortality was mostly accounted for by the decrease at younger than age 65 years (HR, 0.65 [95% CI, 0.46-0.93]; absolute decrease of 14.19 per 100 strokes after 10 years [per 10-year period]), but was similar across race and sex. In a multicenter cohort of black and white adults in US communities, stroke incidence and mortality rates decreased from 1987 to 2011. The decreases varied across age groups, but were similar across sex and race, showing that improvements in stroke incidence and outcome continued to 2011.

Acupuncture Therapy and Incidence of Depression After Stroke.

PubMed

Lu, Chung-Yen; Huang, Hsin-Chia; Chang, Hen-Hong; Yang, Tsung-Hsien; Chang, Chee-Jen; Chang, Su-Wei; Chen, Pei-Chun

2017-06-01

We investigated whether use of acupuncture within a 3-month poststroke period after hospital discharge is associated with reduced risk of depression. This cohort study included 16 046 patients aged ≥18 years with an initial hospitalization for stroke during 2000 and 2012 in the claims database of a universal health insurance program. Patients who had received acupuncture therapies within 3 months of discharge were defined as acupuncture users (n=1714). All patients were followed up for incidence of depression until the end of 2013. We assessed the association between use of acupuncture and incidence of depression using Cox proportional hazards models in all subjects and in propensity score-matched samples consisting of 1714 pairs of users and nonusers. During the follow-up period, the incidence of depression per 1000 person-years was 11.1 and 9.7 in users and nonusers, respectively. Neither multivariable-adjusted Cox models (hazard ratio, 1.04; 95% confidence interval, 0.84-1.29) nor the propensity score-matching model (hazard ratio, 1.06; 95% confidence interval, 0.79-1.42) revealed an association between use of acupuncture and incidence of depression. In patients admitted to hospital for stroke, acupuncture therapy within 3 months after discharge was not associated with subsequent incidence of depression. © 2017 American Heart Association, Inc.

Usefulness of the Left Ventricular Myocardial Contraction Fraction in Healthy Men and Women to Predict Cardiovascular Morbidity and Mortality

PubMed Central

Chuang, Michael L.; Gona, Philimon; Salton, Carol J.; Yeon, Susan B.; Kissinger, Kraig V.; Blease, Susan J.; Levy, Daniel; O'Donnell, Christopher J.; Manning, Warren J.

2013-01-01

We sought to determine whether depressed myocardial contraction fraction (MCF, the ratio of left ventricular (LV) stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (N=318, 60±9 yrs, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance (CMR) imaging in 1998–1999. LV ejection fraction (EF), mass and MCF were determined. “Hard” CVD events comprised cardiovascular death, myocardial infarction, stroke or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score (FCRS) was used to estimate hazard ratios for incident hard CVD events for sex-specific quartiles of MCF, LV mass and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referent. Kaplan-Meier survival plots and the log rank test were used to compare event-free survival. MCF was greater in women (0.58±0.13) than men (0.52±0.11), p<0.01. Nearly all (99%) participants had EF ≥ 0.55. Over up to 9-year (median 5.2) follow-up, 31 participants (10%) experienced an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop hard CVD (hazard ratio 7.11, p=0.010) compared to the lowest quartile, and the elevated hazards persisted even after adjustment for LV mass (hazard ratio=6.09, p=0.020). The highest-quartile LV mass/height2.7 had nearly five-fold risk (hazard ratio 4.68, p=0.016). Event-free survival was shorter in lowest-quartile MCF, p = 0.0006, but not in lowest-quartile LVEF. Conclusion: In a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass. PMID:22381161

Usefulness of the left ventricular myocardial contraction fraction in healthy men and women to predict cardiovascular morbidity and mortality.

PubMed

Chuang, Michael L; Gona, Philimon; Salton, Carol J; Yeon, Susan B; Kissinger, Kraig V; Blease, Susan J; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J

2012-05-15

We sought to determine whether depressed myocardial contraction fraction (MCF; ratio of left ventricular [LV] stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (n = 318, 60 ± 9 years old, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance imaging in 1998 through 1999. LV ejection fraction (EF), mass, and MCF were determined. "Hard" CVD events consisted of cardiovascular death, myocardial infarction, stroke, or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score was used to estimate hazard ratios for incident hard CVD events for gender-specific quartiles of MCF, LV mass, and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referents. Kaplan-Meier survival plots and log-rank test were used to compare event-free survival. MCF was greater in women (0.58 ± 0.13) than in men (0.52 ± 0.11, p <0.01). Nearly all participants (99%) had EF ≥0.55. During an up to 9-year follow-up (median 5.2), 31 participants (10%) developed an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop a hard CVD (hazard ratio 7.11, p = 0.010) compared to the remaining quartiles, and increased hazards persisted even after adjustment for LV mass (hazard ratio 6.09, p = 0.020). The highest-quartile LV mass/height 2.7 had a nearly fivefold risk (hazard ratio 4.68, p = 0.016). Event-free survival was shorter in lowest-quartile MCF (p = 0.0006) but not in lowest-quartile LVEF. In conclusion, in a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass. Copyright © 2012 Elsevier Inc. All rights reserved.

The Multidisciplinary Swallowing Team Approach Decreases Pneumonia Onset in Acute Stroke Patients.

PubMed

Aoki, Shiro; Hosomi, Naohisa; Hirayama, Junko; Nakamori, Masahiro; Yoshikawa, Mineka; Nezu, Tomohisa; Kubo, Satoshi; Nagano, Yuka; Nagao, Akiko; Yamane, Naoya; Nishikawa, Yuichi; Takamoto, Megumi; Ueno, Hiroki; Ochi, Kazuhide; Maruyama, Hirofumi; Yamamoto, Hiromi; Matsumoto, Masayasu

2016-01-01

Dysphagia occurs in acute stroke patients at high rates, and many of them develop aspiration pneumonia. Team approaches with the cooperation of various professionals have the power to improve the quality of medical care, utilizing the specialized knowledge and skills of each professional. In our hospital, a multidisciplinary participatory swallowing team was organized. The aim of this study was to clarify the influence of a team approach on dysphagia by comparing the rates of pneumonia in acute stroke patients prior to and post team organization. All consecutive acute stroke patients who were admitted to our hospital between April 2009 and March 2014 were registered. We analyzed the difference in the rate of pneumonia onset between the periods before team organization (prior period) and after team organization (post period). Univariate and multivariate analyses were performed using a Cox proportional hazards model to determine the predictors of pneumonia. We recruited 132 acute stroke patients from the prior period and 173 patients from the post period. Pneumonia onset was less frequent in the post period compared with the prior period (6.9% vs. 15.9%, respectively; p = 0.01). Based on a multivariate analysis using a Cox proportional hazards model, it was determined that a swallowing team approach was related to pneumonia onset independent from the National Institutes of Health Stroke Scale score on admission (adjusted hazard ratio 0.41, 95% confidence interval 0.19-0.84, p = 0.02). The multidisciplinary participatory swallowing team effectively decreased the pneumonia onset in acute stroke patients.

Warfarin use and the risk of mortality, stroke, and bleeding in hemodialysis patients with atrial fibrillation.

PubMed

Kai, Brandon; Bogorad, Yuliya; Nguyen, Leigh-Anh N; Yang, Su-Jau; Chen, Wansu; Spencer, Hillard T; Shen, Albert Y-J; Lee, Ming-Sum

2017-05-01

The optimal management of stroke prophylaxis in hemodialysis patients with atrial fibrillation is controversial. The purpose of this study was to determine the risk of mortality, stroke, and bleeding associated with the use of warfarin in hemodialysis patients with atrial fibrillation. This was a retrospective, population-based study of hemodialysis patients with atrial fibrillation between January 1, 2006, and September 30, 2015. Association of warfarin use with mortality, stroke, and bleeding was determined by propensity score-matched, Cox proportional hazard models. Among the 4286 patients with atrial fibrillation on hemodialysis, 989 (23%) were prescribed warfarin. Propensity score matching was used to identify 888 matched pairs with similar baseline characteristics. Warfarin use was associated with lower risk of all-cause death (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.69-0.84) and lower risk of ischemic stroke (HR 0.68, 95% CI 0.52-0.91). Warfarin use was not associated with a higher risk of hemorrhagic stroke (HR 1.2, 95% CI 0.6-2.2) or gastrointestinal bleeding (HR 0.97, 95% CI 0.77-1.2). The treatment effect was largest in the group with the best international normalized ratio control as measured by time in therapeutic range. Subgroup analyses showed warfarin use was associated with survival benefit in most subgroups. The 2 subgroups that did not benefit were patients with a history of hemorrhagic stroke and patients with concurrent aspirin use. Warfarin use is associated with lower all-cause mortality and ischemic stroke, without significantly increasing the risk of bleeding in hemodialysis patients with atrial fibrillation. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Malnutrition risk predicts recovery of full oral intake among older adult stroke patients undergoing enteral nutrition: Secondary analysis of a multicentre survey (the APPLE study).

PubMed

Nishioka, Shinta; Okamoto, Takatsugu; Takayama, Masako; Urushihara, Maki; Watanabe, Misuzu; Kiriya, Yumiko; Shintani, Keiko; Nakagomi, Hiromi; Kageyama, Noriko

2017-08-01

Whether malnutrition risk correlates with recovery of swallowing function of convalescent stroke patients is unknown. This study was conducted to clarify whether malnutrition risks predict achievement of full oral intake in convalescent stroke patients undergoing enteral nutrition. We conducted a secondary analysis of 466 convalescent stroke patients, aged 65 years or over, who were undergoing enteral nutrition. Patients were extracted from the "Algorithm for Post-stroke Patients to improve oral intake Level; APPLE" study database compiled at the Kaifukuki (convalescent) rehabilitation wards. Malnutrition risk was determined by the Geriatric Nutritional Risk Index as follows: severe (<82), moderate (82 to <92), mild (92 to <98), and no malnutrition risks (≥98). Swallowing function was assessed by Fujishima's swallowing grade (FSG) on admission and discharge. The primary outcome was achievement of full oral intake, indicated by FSG ≥ 7. Binary logistic regression analysis was performed to identify predictive factors, including malnutrition risk, for achieving full oral intake. Estimated hazard risk was computed by Cox's hazard model. Of the 466 individuals, 264 were ultimately included in this study. Participants with severe malnutrition risk showed a significantly lower proportion of achievement of full oral intake than lower severity groups (P = 0.001). After adjusting for potential confounders, binary logistic regression analysis showed that patients with severe malnutrition risk were less likely to achieve full oral intake (adjusted odds ratio: 0.232, 95% confidence interval [95% CI]: 0.047-1.141). Cox's proportional hazard model revealed that severe malnutrition risk was an independent predictor of full oral intake (adjusted hazard ratio: 0.374, 95% CI: 0.166-0.842). Compared to patients who did not achieve full oral intake, patients who achieved full oral intake had significantly higher energy intake, but there was no difference in protein intake and weight change. Severe malnutrition risk independently predicts the achievement of full oral intake in convalescent stroke patients undergoing enteral nutrition. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Associations of Biomarker-Calibrated Sodium and Potassium Intakes With Cardiovascular Disease Risk Among Postmenopausal Women.

PubMed

Prentice, Ross L; Huang, Ying; Neuhouser, Marian L; Manson, JoAnn E; Mossavar-Rahmani, Yasmin; Thomas, Fridtjof; Tinker, Lesley F; Allison, Matthew; Johnson, Karen C; Wassertheil-Smoller, Sylvia; Seth, Arjun; Rossouw, Jacques E; Shikany, James; Carbone, Laura D; Martin, Lisa W; Stefanick, Marcia L; Haring, Bernhard; Van Horn, Linda

2017-11-01

Studies of the associations of sodium and potassium intakes with cardiovascular disease incidence often rely on self-reported dietary data. In the present study, self-reported intakes from postmenopausal women at 40 participating US clinical centers are calibrated using 24-hour urinary excretion measures in cohorts from the Women's Health Initiative, with follow-up from 1993 to 2010. The incidence of hypertension was positively related to (calibrated) sodium intake and to the ratio of sodium to potassium. The sodium-to-potassium ratio was associated with cardiovascular disease incidence during an average follow-up period of 12 years. The estimated hazard ratio for a 20% increase in the sodium-to-potassium ratio was 1.13 (95% confidence interval (CI): 1.04, 1.22) for coronary heart disease, 1.20 (95% CI: 1.01, 1.42) for heart failure, and 1.11 (95% CI: 1.04, 1.19) for a composite cardiovascular disease outcome. The association with total stroke was not significant, but it was positive for ischemic stroke and inverse for hemorrhagic stroke. Aside from hemorrhagic stroke, corresponding associations of cardiovascular disease with sodium and potassium jointly were positive for sodium and inverse for potassium, although some were not statistically significant. Specifically, for coronary heart disease, the hazard ratios for 20% increases were 1.11 (95% CI: 0.95, 1.30) for sodium and 0.85 (95% CI: 0.73, 0.99) for potassium; and corresponding values for heart failure were 1.36 (95% CI: 1.02, 1.82) for sodium and 0.90 (95% CI: 0.69, 1.18) for potassium. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Simultaneously Measured Interarm Blood Pressure Difference and Stroke: An Individual Participants Data Meta-Analysis.

PubMed

Tomiyama, Hirofumi; Ohkuma, Toshiaki; Ninomiya, Toshiharu; Mastumoto, Chisa; Kario, Kazuomi; Hoshide, Satoshi; Kita, Yoshikuni; Inoguchi, Toyoshi; Maeda, Yasutaka; Kohara, Katsuhiko; Tabara, Yasuharu; Nakamura, Motoyuki; Ohkubo, Takayoshi; Watada, Hirotaka; Munakata, Masanori; Ohishi, Mitsuru; Ito, Norihisa; Nakamura, Michinari; Shoji, Tetsuo; Vlachopoulos, Charalambos; Yamashina, Akira

2018-06-01

We conducted individual participant data meta-analysis to examine the validity of interarm blood pressure difference in simultaneous measurement as a marker to identify subjects with ankle-brachial pressure index <0.90 and to predict future cardiovascular events. We collected individual participant data on 13 317 Japanese subjects from 10 cohorts (general population-based cohorts, cohorts of patients with past history of cardiovascular events, and those with cardiovascular risk factors). Binary logistic regression analysis with adjustments identified interarm blood pressure difference >5 mm Hg as being associated with a significant odds ratio for the presence of ankle-brachial pressure index <0.90 (odds ratio, 2.19; 95% confidence interval, 1.60-3.03; P <0.01). Among 11 726 subjects without a past history of cardiovascular disease, 249 developed stroke during the average follow-up period of 7.4 years. Interarm blood pressure difference >15 mm Hg was associated with a significant Cox stratified adjusted hazard ratio for subsequent stroke (hazard ratio, 2.42; 95% confidence interval, 1.27-4.60; P <0.01). Therefore, interarm blood pressure differences, measured simultaneously in both arms, may be associated with vascular damage in the systemic arterial tree. These differences may be useful for identifying subjects with an ankle-brachial pressure index of <0.90 in the overall study population, and also a reliable predictor of future stroke in subjects without a past history of cardiovascular disease. These findings support the recommendation to measure blood pressure in both arms at the first visit. © 2018 American Heart Association, Inc.

Closure of patent foramen ovale versus medical therapy after cryptogenic stroke.

PubMed

Carroll, John D; Saver, Jeffrey L; Thaler, David E; Smalling, Richard W; Berry, Scott; MacDonald, Lee A; Marks, David S; Tirschwell, David L

2013-03-21

Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age. In this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated. We enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased. In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270.).

Dietary sodium-to-potassium ratio as a risk factor for stroke, cardiovascular disease and all-cause mortality in Japan: the NIPPON DATA80 cohort study

PubMed Central

Okayama, Akira; Okuda, Nagako; Miura, Katsuyuki; Okamura, Tomonori; Hayakawa, Takehito; Akasaka, Hiroshi; Ohnishi, Hirofumi; Saitoh, Shigeyuki; Arai, Yusuke; Kiyohara, Yutaka; Takashima, Naoyuki; Yoshita, Katsushi; Fujiyoshi, Akira; Zaid, Maryam; Ohkubo, Takayoshi; Ueshima, Hirotsugu

2016-01-01

Objectives To evaluate the impact of dietary sodium and potassium (Na–K) ratio on mortality from total and subtypes of stroke, cardiovascular disease (CVD) and all causes, using 24-year follow-up data of a representative sample of the Japanese population. Setting Prospective cohort study. Participants In the 1980 National Cardiovascular Survey, participants were followed for 24 years (NIPPON DATA80, National Integrated Project for Prospective Observation of Non-communicable Disease And its Trends in the Aged). Men and women aged 30–79 years without hypertensive treatment, history of stroke or acute myocardial infarction (n=8283) were divided into quintiles according to dietary Na–K ratio assessed by a 3-day weighing dietary record at baseline. Age-adjusted and multivariable-adjusted HRs were calculated using the Mantel-Haenszel method and Cox proportional hazards model. Primary outcome measures Mortality from total and subtypes of stroke, CVD and all causes. Results A total of 1938 deaths from all causes were observed over 176 926 person-years. Na–K ratio was significantly and non-linearly related to mortality from all stroke (p=0.002), CVD (p=0.005) and total mortality (p=0.001). For stroke subtypes, mortality from haemorrhagic stroke was positively related to Na–K ratio (p=0.024). Similar relationships were observed for men and women. The observed relationships remained significant after adjustment for other risk factors. Quadratic non-linear multivariable-adjusted HRs (95% CI) in the highest quintile versus the lowest quintile of Na–K ratio were 1.42 (1.07 to 1.90) for ischaemic stroke, 1.57 (1.05 to 2.34) for haemorrhagic stroke, 1.43 (1.17 to 1.76) for all stroke, 1.39 (1.20 to 1.61) for CVD and 1.16 (1.06 to 1.27) for all-cause mortality. Conclusions Dietary Na–K ratio assessed by a 3-day weighing dietary record was a significant risk factor for mortality from haemorrhagic stroke, all stroke, CVD and all causes among a Japanese population. PMID:27412107

Stroke rehabilitation and risk of mortality: a population-based cohort study stratified by age and gender.

PubMed

Hou, Wen-Hsuan; Ni, Cheng-Hua; Li, Chung-Yi; Tsai, Pei-Shan; Lin, Li-Fong; Shen, Hsiu-Nien

2015-06-01

To determine the survival of patients with stroke for up to 10 years after a first-time stroke and to investigate whether stroke rehabilitation within the first 3 months reduced long-term mortality in these patients. We used the medical claims data for a random sample of 1 million insured Taiwanese registered in the year 2000. A total of 7767 patients admitted for a first-time stroke between 2000 and 2005; 1285 (16.7%) received rehabilitation within the first 3 months after stroke admission. The other 83.3% of patients served as a comparison cohort. A Cox proportional hazards model was used to estimate the relative risk of mortality in relation to the rehabilitation intervention. In all, 181 patients with rehabilitation and 1123 controls died, representing respective mortality rates of 25.0 and 32.7 per 1000 person-years. Rehabilitation was significantly associated with a lower risk of mortality (hazard ratio .68, 95% confidence interval .58-.79). Such a beneficial effect tended to be more obvious as the frequency of rehabilitation increased (P for the trend <.0001) and was more evident in female patients. Stroke rehabilitation initiated in the first 3 months after a stroke admission may significantly reduce the risk of mortality for 10 years after the stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

PubMed

Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Gorst-Rasmussen, Anders; Rasmussen, Lars Hvilsted; Lip, Gregory Y H

2015-08-11

Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively. Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality rates, supporting oral anticoagulant treatment reintroduction after intracranial hemorrhage as feasible. Future trials are encouraged to guide clinical practice in these patients. © 2015 American Heart Association, Inc.

Brain Perivascular Spaces as Biomarkers of Vascular Risk: Results from the Northern Manhattan Study.

PubMed

Gutierrez, J; Elkind, M S V; Dong, C; Di Tullio, M; Rundek, T; Sacco, R L; Wright, C B

2017-05-01

Dilated perivascular spaces in the brain are associated with greater arterial pulsatility. We hypothesized that perivascular spaces identify individuals at higher risk for systemic and cerebral vascular events. Stroke-free participants in the population-based Northern Manhattan Study had brain MR imaging performed and were followed for myocardial infarction, any stroke, and death. Imaging analyses distinguished perivascular spaces from lesions presumably ischemic. Perivascular spaces were further subdivided into lesions with diameters of ≤3 mm (small perivascular spaces) and >3 mm (large perivascular spaces). We calculated relative rates of events with Poisson models and hazard ratios with Cox proportional models. The Northern Manhattan Study participants who had MR imaging data available for review ( n = 1228; 59% women, 65% Hispanic; mean age, 71 ± 9 years) were followed for an average of 9 ± 2 years. Participants in the highest tertile of the small perivascular space score had a higher relative rate of all deaths (relative rate, 1.38; 95% CI, 1.01-1.91), vascular death (relative rate, 1.87; 95% CI, 1.12-3.14), myocardial infarction (relative rate, 2.08; 95% CI, 1.01-4.31), any stroke (relative rate, 1.79; 95% CI, 1.03-3.11), and any vascular event (relative rate, 1.74; 95% CI, 1.18-2.56). After we adjusted for confounders, there was a higher risk of vascular death (hazard ratio, 1.06; 95% CI, 1.01-1.11), myocardial infarction (hazard ratio, 2.22; 95% CI, 1.12-4.42), and any vascular event (hazard ratio, 1.04; 95% CI, 1.01-1.08) with higher small perivascular space scores. In this multiethnic, population-based study, participants with a high burden of small perivascular spaces had increased risk of vascular events. By gaining pathophysiologic insight into the mechanism of perivascular space dilation, we may be able to propose novel therapies to better prevent vascular disorders in the population. © 2017 by American Journal of Neuroradiology.

Randomized trial of primary PCI with or without routine manual thrombectomy.

PubMed

Jolly, Sanjit S; Cairns, John A; Yusuf, Salim; Meeks, Brandi; Pogue, Janice; Rokoss, Michael J; Kedev, Sasko; Thabane, Lehana; Stankovic, Goran; Moreno, Raul; Gershlick, Anthony; Chowdhary, Saqib; Lavi, Shahar; Niemelä, Kari; Steg, Philippe Gabriel; Bernat, Ivo; Xu, Yawei; Cantor, Warren J; Overgaard, Christopher B; Naber, Christoph K; Cheema, Asim N; Welsh, Robert C; Bertrand, Olivier F; Avezum, Alvaro; Bhindi, Ravinay; Pancholy, Samir; Rao, Sunil V; Natarajan, Madhu K; ten Berg, Jurriën M; Shestakovska, Olga; Gao, Peggy; Widimsky, Petr; Džavík, Vladimír

2015-04-09

During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results. We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days. The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).

Association of Race With Mortality and Cardiovascular Events in a Large Cohort of US Veterans.

PubMed

Kovesdy, Csaba P; Norris, Keith C; Boulware, L Ebony; Lu, Jun L; Ma, Jennie Z; Streja, Elani; Molnar, Miklos Z; Kalantar-Zadeh, Kamyar

2015-10-20

In the general population, blacks experience higher mortality than their white peers, attributed in part to their lower socioeconomic status, reduced access to care, and possibly intrinsic biological factors. Patients with kidney disease are a notable exception, among whom blacks experience lower mortality. It is unclear if similar differences affecting outcomes exist in patients with no kidney disease but with equal or similar access to health care. We compared all-cause mortality, incident coronary heart disease, and incident ischemic stroke using multivariable-adjusted Cox models in a nationwide cohort of 547 441 black and 2 525 525 white patients with baseline estimated glomerular filtration rate ≥ 60 mL·min⁻¹·1.73 m⁻² receiving care from the US Veterans Health Administration. In parallel analyses, we compared outcomes in black versus white individuals in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. After multivariable adjustments in veterans, black race was associated with 24% lower all-cause mortality (adjusted hazard ratio, 0.76; 95% confidence interval, 0.75-0.77; P<0.001) and 37% lower incidence of coronary heart disease (adjusted hazard ratio, 0.63; 95% confidence interval, 0.62-0.65; P<0.001) but a similar incidence of ischemic stroke (adjusted hazard ratio, 0.99; 95% confidence interval, 0.97-1.01; P=0.3). Black race was associated with a 42% higher adjusted mortality among individuals with estimated glomerular filtration rate ≥ 60 mL·min⁻¹·1.73 m⁻² in NHANES (adjusted hazard ratio, 1.42; 95% confidence interval, 1.09-1.87). Black veterans with normal estimated glomerular filtration rate and equal access to healthcare have lower all-cause mortality and incidence of coronary heart disease and a similar incidence of ischemic stroke. These associations are in contrast to the higher mortality experienced by black individuals in the general US population. © 2015 American Heart Association, Inc.

Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.

PubMed

Ridker, Paul M; Danielson, Eleanor; Fonseca, Francisco A H; Genest, Jacques; Gotto, Antonio M; Kastelein, John J P; Koenig, Wolfgang; Libby, Peter; Lorenzatti, Alberto J; MacFadyen, Jean G; Nordestgaard, Børge G; Shepherd, James; Willerson, James T; Glynn, Robert J

2008-11-20

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.) 2008 Massachusetts Medical Society

Psychosocial distress and stroke risk in older adults.

PubMed

Henderson, Kimberly M; Clark, Cari J; Lewis, Tené T; Aggarwal, Neelum T; Beck, Todd; Guo, Hongfei; Lunos, Scott; Brearley, Ann; Mendes de Leon, Carlos F; Evans, Denis A; Everson-Rose, Susan A

2013-02-01

To investigate the association of psychosocial distress with risk of stroke mortality and incident stroke in older adults. Data were from the Chicago Health and Aging Project, a longitudinal population-based study conducted in 3 contiguous neighborhoods on the south side of Chicago, IL. Participants were community-dwelling black and non-Hispanic white adults, aged 65 years and older (n=4120 for stroke mortality; n=2649 for incident stroke). Psychosocial distress was an analytically derived composite measure of depressive symptoms, perceived stress, neuroticism, and life dissatisfaction. Cox proportional hazards models examined the association of distress with stroke mortality and incident stroke over 6 years of follow-up. Stroke deaths (151) and 452 incident strokes were identified. Adjusting for age, race, and sex, the hazard ratio (HR) for each 1-SD increase in distress was 1.47 (95% confidence interval [CI]=1.28-1.70) for stroke mortality and 1.18 (95% CI=1.07-1.30) for incident stroke. Associations were reduced after adjustment for stroke risk factors and remained significant for stroke mortality (HR=1.29; 95% CI=1.10-1.52) but not for incident stroke (HR=1.09; 95% CI=0.98-1.21). Secondary analyses of stroke subtypes showed that distress was strongly related to incident hemorrhagic strokes (HR=1.70; 95% CI=1.28-2.25) but not ischemic strokes (HR=1.02; 95% CI=0.91-1.15) in fully adjusted models. Increasing levels of psychosocial distress are related to excess risk of both fatal and nonfatal stroke in older black and white adults. Additional research is needed to examine pathways linking psychosocial distress to cerebrovascular disease risk.

Premature ventricular complexes on screening electrocardiogram and risk of ischemic stroke.

PubMed

Agarwal, Sunil K; Chao, Jennifer; Peace, Frederick; Judd, Suzanne E; Kissela, Brett; Kleindorfer, Dawn; Howard, Virginia J; Howard, George; Soliman, Elsayed Z

2015-05-01

Premature ventricular complexes (PVCs) detected from long-term ECG recordings have been associated with an increased risk of ischemic stroke. Whether PVCs seen on routine ECG, commonly used in clinical practice, are associated with an increased risk of ischemic stroke remains unstudied. This analysis included 24 460 participants (aged, 64.5+9.3 years; 55.1% women; 40.0% blacks) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were free of stroke at the time of enrollment. PVCs were ascertained from baseline ECG (2003-2007), and incident stroke cases through 2011 were confirmed by an adjudication committee. A total of 1415 (5.8%) participants had at least 1 PVC at baseline, and 591 developed incident ischemic stroke during an average (SD) follow-up of 6.0 (2.0) years. In a cox proportional hazards model adjusted for age, sex, race, geographic region, education, previous heart disease, systolic blood pressure, blood pressure-lowering medications, current smoking, diabetes mellitus, left ventricular hypertrophy by ECG, and aspirin use and warfarin use, the presence of PVCs was associated with 38% increased risk of ischemic stroke (hazard ratio [95% confidence interval], 1.38 [1.05-1.81]). PVCs are common on routine screening ECGs and are associated with an increased risk of ischemic stroke. © 2015 American Heart Association, Inc.

Risk of ischemic stroke after atrial fibrillation diagnosis: A national sample cohort

PubMed Central

Son, Mi Kyoung; Lim, Nam-Kyoo; Kim, Hyung Woo

2017-01-01

Atrial fibrillation (AF) is a major risk factor for ischemic stroke and associated with a 5-fold higher risk of stroke. In this retrospective cohort study, the incidence of and risk factors for ischemic stroke in patients with AF were identified. All patients (≥30 years old) without previous stroke who were diagnosed with AF in 2007–2013 were selected from the National Health Insurance Service-National Sample Cohort. To identify factors that influenced ischemic stroke risk, Cox proportional hazard regression analysis was conducted. During a mean follow-up duration of 3.2 years, 1022 (9.6%) patients were diagnosed with ischemic stroke. The overall incidence rate of ischemic stroke was 30.8/1000 person-years. Of all the ischemic stroke that occurred during the follow-up period, 61.0% occurred within 1-year after AF diagnosis. Of the patients with CHA2DS2-VASc score of ≥2, only 13.6% were receiving warfarin therapy within 30 days after AF diagnosis. Relative to no antithrombotic therapy, warfarin treatment for >90 days before the index event (ischemic stroke in stroke patients and death/study end in non-stroke patients) associated with decreased ischemic stroke risk (Hazard Ratio = 0.41, 95%confidence intervals = 0.32–0.53). Heart failure, hypertension, and diabetes mellitus associated with greater ischemic stroke risk. AF patients in Korea had a higher ischemic stroke incidence rate than patients in other countries and ischemic stroke commonly occurred at early phase after AF diagnosis. Long-term (>90 days) continuous warfarin treatment may be beneficial for AF patients. However, warfarin treatment rates were very low. To prevent stroke, programs that actively detect AF and provide anticoagulation therapy are needed. PMID:28636620

Is the long-term prognosis of transient ischemic attack or minor ischemic stroke affected by the occurrence of nonfocal symptoms?

PubMed

Compter, Annette; van der Worp, H Bart; van Gijn, Jan; Kappelle, L Jaap; Koudstaal, Peter J; Algra, Ale

2014-05-01

In patients with a transient ischemic attack or ischemic stroke, nonfocal neurological symptoms, such as confusion and nonrotatory dizziness, may be associated with a higher risk of vascular events. We assessed the relationship between nonfocal symptoms and the long-term risk of vascular events or death in patients with a transient ischemic attack or minor ischemic stroke. We related initial symptoms with outcome events in 2409 patients with a transient ischemic attack (n=723) or minor ischemic stroke (n=1686), included in the Life Long After Cerebral ischemia cohort. All patients underwent a standardized interview on the occurrence of focal and nonfocal neurological symptoms during the qualifying event. The primary outcome was the composite of any stroke, myocardial infarction, or vascular death. Secondary outcomes were all-cause death, vascular death, cardiac death, myocardial infarction, and stroke. Hazard ratios were calculated with Cox regression. Focal symptoms were accompanied by nonfocal symptoms in 739 (31%) patients. During a mean follow-up of 10.1 years, the primary outcome occurred in 1313 (55%) patients. There was no difference in the risk of the primary outcome between patients with both focal and nonfocal symptoms and patients with focal symptoms alone (adjusted hazard ratio, 0.97; 95% confidence interval, 0.86-1.09; P=0.60). The risk of each of the secondary outcomes was also similar in both groups. About one third of the patients with a transient ischemic attack or minor ischemic stroke has both focal and nonfocal neurological symptoms. Nonfocal symptoms are not associated with an increased long-term risk of vascular events or death. This trial was not registered because enrollment began before July 1, 2005.

Risk for myocardial infarction and stroke after community-acquired bacteremia: a 20-year population-based cohort study.

PubMed

Dalager-Pedersen, Michael; Søgaard, Mette; Schønheyder, Henrik Carl; Nielsen, Henrik; Thomsen, Reimar Wernich

2014-04-01

Infections may trigger acute cardiovascular events, but the risk after community-acquired bacteremia is unknown. We assessed the risk for acute myocardial infarction and ischemic stroke within 1 year of community-acquired bacteremia. This population-based cohort study was conducted in Northern Denmark. We included 4389 hospitalized medical patients with positive blood cultures obtained on the day of admission. Patients hospitalized with bacteremia were matched with up to 10 general population controls and up to 5 acutely admitted nonbacteremic controls, matched on age, sex, and calendar time. All incident events of myocardial infarction and stroke during the following 365 days were ascertained from population-based healthcare databases. Multivariable regression analyses were used to assess relative risks with 95% confidence intervals (CIs) for myocardial infarction and stroke among bacteremia patients and their controls. The risk for myocardial infarction or stroke was greatly increased within 30 days of community-acquired bacteremia: 3.6% versus 0.2% among population controls (adjusted relative risk, 20.86; 95% CI, 15.38-28.29) and 1.7% among hospitalized controls (adjusted relative risk, 2.18; 95% CI, 1.80-2.65). The risks for myocardial infarction or stroke remained modestly increased from 31 to 180 days after bacteremia in comparison with population controls (adjusted hazard ratio, 1.64; 95% CI, 1.18-2.27), but not versus hospitalized controls (adjusted hazard ratio, 0.95; 95% CI, 0.69-1.32). No differences in cardiovascular risk were seen after >6 months. Increased 30-day risks were consistently found for a variety of etiologic agents and infectious foci. Community-acquired bacteremia is associated with increased short-term risk of myocardial infarction and stroke.

Executive function, but not memory, associates with incident coronary heart disease and stroke.

PubMed

Rostamian, Somayeh; van Buchem, Mark A; Westendorp, Rudi G J; Jukema, J Wouter; Mooijaart, Simon P; Sabayan, Behnam; de Craen, Anton J M

2015-09-01

To evaluate the association of performance in cognitive domains executive function and memory with incident coronary heart disease and stroke in older participants without dementia. We included 3,926 participants (mean age 75 years, 44% male) at risk for cardiovascular diseases from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) with Mini-Mental State Examination score ≥24 points. Scores on the Stroop Color-Word Test (selective attention) and the Letter Digit Substitution Test (processing speed) were converted to Z scores and averaged into a composite executive function score. Likewise, scores of the Picture Learning Test (immediate and delayed memory) were transformed into a composite memory score. Associations of executive function and memory were longitudinally assessed with risk of coronary heart disease and stroke using multivariable Cox regression models. During 3.2 years of follow-up, incidence rates of coronary heart disease and stroke were 30.5 and 12.4 per 1,000 person-years, respectively. In multivariable models, participants in the lowest third of executive function, as compared to participants in the highest third, had 1.85-fold (95% confidence interval [CI] 1.39-2.45) higher risk of coronary heart disease and 1.51-fold (95% CI 0.99-2.30) higher risk of stroke. Participants in the lowest third of memory had no increased risk of coronary heart disease (hazard ratio 0.99, 95% CI 0.74-1.32) or stroke (hazard ratio 0.87, 95% CI 0.57-1.32). Lower executive function, but not memory, is associated with higher risk of coronary heart disease and stroke. Lower executive function, as an independent risk indicator, might better reflect brain vascular pathologies. © 2015 American Academy of Neurology.

Irregularity and lack of p waves in short tachycardia episodes predict atrial fibrillation and ischemic stroke.

PubMed

Johnson, Linda S B; Persson, Anders P; Wollmer, Per; Juul-Möller, Steen; Juhlin, Tord; Engström, Gunnar

2018-02-13

Atrial fibrillation (AF) is defined as an irregular supraventricular tachycardia (SVT) without p waves, with duration >30 seconds. Whether AF characteristics during short SVT episodes predict AF and stroke is not known. The purpose of this study was to determine whether irregularity and lack of p waves, alone or in combination, during short SVT episodes increase the risk of incident AF and ischemic stroke. The population-based Malmö Diet and Cancer study includes 24-hour ECG screening of 377 AF-free individuals (mean age 64.5 years; 43% men) who were prospectively followed for >13 years. There were 65 AF events and 25 ischemic stroke events during follow-up. Subjects with an SVT episode ≥5 beats were identified, and the longest SVT episode was assessed for irregularity and lack of p waves. The association between SVT classification and AF and stroke was assessed using multivariable adjusted Cox regression. The incidence of AF increased with increasing abnormality of the SVTs. The risk-factor adjusted hazard ratio for AF was 4.95 (95% confidence interval 2.06-11.9; P <.0001) for those with short irregular SVTs (<70 beats) without p waves. The incidence of ischemic stroke was highest in the group with regular SVT episodes without p waves (hazard ratio 14.2; 95% confidence interval 3.76-57.6; P <.0001, adjusted for age and sex). Characteristics of short SVT episodes detected at 24-hour ECG screening are associated with incident AF and ischemic stroke. Short irregular SVTs without p waves likely represent early stages of AF or atrial myopathy. Twenty-four-hour ECG could identify subjects suitable for primary prevention efforts. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

White Matter Hyperintensities Improve Ischemic Stroke Recurrence Prediction.

PubMed

Andersen, Søren Due; Larsen, Torben Bjerregaard; Gorst-Rasmussen, Anders; Yavarian, Yousef; Lip, Gregory Y H; Bach, Flemming W

2017-01-01

Nearly one in 5 patients with ischemic stroke will invariably experience a second stroke within 5 years. Stroke risk stratification schemes based solely on clinical variables perform only modestly in non-atrial fibrillation (AF) patients and improvement of these schemes will enhance their clinical utility. Cerebral white matter hyperintensities are associated with an increased risk of incident ischemic stroke in the general population, whereas their association with the risk of ischemic stroke recurrence is more ambiguous. In a non-AF stroke cohort, we investigated the association between cerebral white matter hyperintensities and the risk of recurrent ischemic stroke, and we evaluated the predictive performance of the CHA2DS2VASc score and the Essen Stroke Risk Score (clinical scores) when augmented with information on white matter hyperintensities. In a registry-based, observational cohort study, we included 832 patients (mean age 59.6 (SD 13.9); 42.0% females) with incident ischemic stroke and no AF. We assessed the severity of white matter hyperintensities using MRI. Hazard ratios stratified by the white matter hyperintensities score and adjusted for the components of the CHA2DS2VASc score were calculated based on the Cox proportional hazards analysis. Recalibrated clinical scores were calculated by adding one point to the score for the presence of moderate to severe white matter hyperintensities. The discriminatory performance of the scores was assessed with the C-statistic. White matter hyperintensities were significantly associated with the risk of recurrent ischemic stroke after adjusting for clinical risk factors. The hazard ratios ranged from 1.65 (95% CI 0.70-3.86) for mild changes to 5.28 (95% CI 1.98-14.07) for the most severe changes. C-statistics for the prediction of recurrent ischemic stroke were 0.59 (95% CI 0.51-0.65) for the CHA2DS2VASc score and 0.60 (95% CI 0.53-0.68) for the Essen Stroke Risk Score. The recalibrated clinical scores showed improved C-statistics: the recalibrated CHA2DS2VASc score 0.62 (95% CI 0.54-0.70; p = 0.024) and the recalibrated Essen Stroke Risk Score 0.63 (95% CI 0.56-0.71; p = 0.031). C-statistics of the white matter hyperintensities score were 0.62 (95% CI 0.52-0.68) to 0.65 (95% CI 0.58-0.73). An increasing burden of white matter hyperintensities was independently associated with recurrent ischemic stroke in a cohort of non-AF ischemic stroke patients. Recalibration of the CHA2DS2VASc score and the Essen Stroke Risk Score with one point for the presence of moderate to severe white matter hyperintensities led to improved discriminatory performance in ischemic stroke recurrence prediction. Risk scores based on white matter hyperintensities alone were at least as accurate as the established clinical risk scores in the prediction of ischemic stroke recurrence. © 2016 S. Karger AG, Basel.

Association between trace elements in the environment and stroke risk: The reasons for geographic and racial differences in stroke (REGARDS) study.

PubMed

Merrill, Peter D; Ampah, Steve B; He, Ka; Rembert, Nicole J; Brockman, John; Kleindorfer, Dawn; McClure, Leslie A

2017-07-01

The disparities in stroke mortality between blacks and whites, as well as the increased stroke mortality in the "stroke belt" have long been noted. The reasons for these disparities have yet to be fully explained. The association between trace element status and cardiovascular diseases, including stroke, has been suggested as a possible contributor to the disparities in stroke mortality but has not been fully explored. The purpose of this study is to investigate distributions of four trace elements (arsenic, mercury, magnesium, and selenium) in the environment in relation to stroke risk. The study population (N=27,770) is drawn from the Reasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort. Environmental distribution of each trace element was determined using data from the United States Geological Survey (USGS) and was categorized in quartiles. A proportional hazards model, adjusted for demographic data and stroke risk factors, was used to examine the association of interest. The results showed that higher selenium levels in the environment were associated with increased stroke risk, and the hazard ratio for the 4th quartile compared to the 1st quartile was 1.33 (95% CI: 1.09, 1.62). However, there was no statistically significant relationship between environmental arsenic, mercury or magnesium and the risk of stroke. Because of dietary and non-dietary exposure as well as bioavailability, further research using biomarkers is warranted to examine the association between these trace elements and the risk of stroke. Copyright © 2017 Elsevier GmbH. All rights reserved.

Heart rate as a predictor of stroke in high-risk, hypertensive patients with previous stroke or transient ischemic attack.

PubMed

Sandset, Else Charlotte; Berge, Eivind; Kjeldsen, Sverre E; Julius, Stevo; Holzhauer, Björn; Krarup, Lars-Henrik; Hua, Tsushung A

2014-01-01

Risk factors for first stroke are well established, but less is known about risk factors for recurrent stroke. In the present analysis, we aimed to assess the effect of heart rate and other possible predictors of stroke in a hypertensive population with previous stroke or transient ischemic attack (TIA). The Valsartan Antihypertensive Long-Term Use Evaluation trial was a multicentre, double-masked, randomized controlled, parallel group trial comparing the effects of an angiotensin receptor blocker (valsartan) and a calcium channel blocker (amlodipine) in patients with hypertension and high cardiovascular risk. We used Cox proportional hazard models to investigate the effect of baseline variables on the risk of stroke. Quadratic terms of the continuous variables were entered in the models to test for linearity. Of 15,245 patients included in the trial, 3014 had a previous stroke or TIA at baseline and were included in the present analysis. Stroke recurrence occurred in 239 patients (7.9%) during a median of 4.5 years of follow-up. Resting heart rate (per 10 beats per minute; hazard ratio [HR], 2.78; 95% confidence interval [CI], 1.18-6.58) and diabetes mellitus at baseline (HR, 1.47; 95% CI, 1.03-2.10) were significantly associated with an increased risk of stroke recurrence in the multivariable analysis. In high-risk, hypertensive patients with previous stroke or TIA, resting heart rate was the strongest predictor of recurrent stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Multivitamin use and risk of stroke mortality: the Japan collaborative cohort study.

PubMed

Dong, Jia-Yi; Iso, Hiroyasu; Kitamura, Akihiko; Tamakoshi, Akiko

2015-05-01

An effect of multivitamin supplement on stroke risk is uncertain. We aimed to examine the association between multivitamin use and risk of death from stroke and its subtypes. A total of 72 180 Japanese men and women free from cardiovascular diseases and cancers at baseline in 1988 to 1990 were followed up until December 31, 2009. Lifestyles including multivitamin use were collected using self-administered questionnaires. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of total stroke and its subtypes in relation to multivitamin use. During a median follow-up of 19.1 years, we identified 2087 deaths from stroke, including 1148 ischemic strokes and 877 hemorrhagic strokes. After adjustment for potential confounders, multivitamin use was associated with lower but borderline significant risk of death from total stroke (HR, 0.87; 95% confidence interval, 0.76-1.01), primarily ischemic stroke (HR, 0.80; 95% confidence interval, 0.63-1.01), but not hemorrhagic stroke (HR, 0.96; 95% confidence interval, 0.78-1.18). In a subgroup analysis, there was a significant association between multivitamin use and lower risk of mortality from total stroke among people with fruit and vegetable intake <3 times/d (HR, 0.80; 95% confidence interval, 0.65-0.98). That association seemed to be more evident among regular users than casual users. Similar results were found for ischemic stroke. Multivitamin use, particularly frequent use, was associated with reduced risk of total and ischemic stroke mortality among Japanese people with lower intake of fruits and vegetables. © 2015 American Heart Association, Inc.

Measures of adiposity and risk of stroke in China: a result from the Kailuan study.

PubMed

Wang, Anxin; Wu, Jianwei; Zhou, Yong; Guo, Xiuhua; Luo, Yanxia; Wu, Shouling; Zhao, Xingquan

2013-01-01

The objective of this study was to explore the association between adiposity and risk of incident stroke among men and women. We studied the relationship between adiposity and stroke among 94,744 participants (18-98 years old) in the Kailuan study. During a follow-up of 4 years, 1,547 ischemic or hemorrhagic strokes were recorded. Measurements of adiposity included body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR). Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated from Cox regression models and each model fit was assessed using -2log-likelihood. Every measurement of adiposity was associated with the risk for total stroke and ischemic stroke, but not for hemorrhagic stroke. After adjusting for confounders and intermediates, the HR (comparing the mean of the highest quintile with that of the lowest quintile) for total stroke was 1.34(1.13-1.60) for BMI, 1.26(1.06-1.52) for WC, 1.29(1.08-1.56) for WHpR, and 1.38(1.15-1.66) for WHtR. The HR for ischemic stroke was 1.52(1.24-1.88) for BMI, 1.46(1.17-1.81) for WC, 1.40(1.12-1.74) for WHpR, and 1.62(1.29-2.04) for WHtR. The model fit for each of the indices was similar. Adiposity increases the total risk of stroke and ischemic stroke, but not of hemorrhagic stroke. No clinically meaningful differences among the associations between BMI, WC, WHpR, and WHtR and stroke incidence were identified in this study.

Increased risk of stroke in contact dermatitis patients

PubMed Central

Chang, Wei-Lun; Hsu, Min-Hsien; Lin, Cheng-Li; Chan, Po-Chi; Chang, Ko-Shih; Lee, Ching-Hsiao; Hsu, Chung-Yi; Tsai, Min-Tein; Yeh, Chung-Hsin; Sung, Fung-Chang

2017-01-01

Abstract Dermatologic diseases are not traditional risk factors of stroke, but recent studies show atopic dermatitis, psoriasis, and bullous skin disease may increase the risk of stroke and other cardiovascular diseases. No previous studies have focused on the association between contact dermatitis and stroke. We established a cohort comprised of 48,169 contact dermatitis patients newly diagnosed in 2000–2003 and 96,338 randomly selected subjects without the disorder, frequency matched by sex, age, and diagnosis year, as the comparison cohort. None of them had a history of stroke. Stroke incidence was assessed by the end of 2011 for both cohorts. The incidence stroke was 1.1-fold higher in the contact dermatitis cohort than in the comparison cohort (5.93 vs 5.37 per 1000 person-years, P < 0.01). The multivariable Cox method analyzed adjusted hazard ratios (aHRs) were 1.12 (95% confidence interval [CI], 1.05–1.19) for all stroke types and 1.12 (95% CI, 1.05–1.20) for ischemic stroke and 1.11 (95% CI, 0.94–1.30) for hemorrhagic stroke. The age-specific aHR of stroke for contact dermatitis cohort increased with age, from 1.14 (95% CI, 1.03–1.27) for 65 to 74 years; to 1.27 (95% CI, 1.15–1.42) for 75 years and older. The aHR of stroke were 1.16 (95% CI, 1.07–1.27) and 1.09 (95% CI, 1.00–1.18) for men and women, respectively. This study suggests that patients with contact dermatitis were at a modestly increased risk of stroke, significant for ischemic stroke but not for hemorrhagic stroke. Comorbidity, particularly hypertension, increased the hazard of stroke further. PMID:28272195

Left Atrial Enlargement and Stroke Recurrence: The Northern Manhattan Stroke Study

PubMed Central

Yaghi, Shadi; Moon, Yeseon P.; Mora-McLaughlin, Consuelo; Willey, Joshua Z.; Cheung, Ken; Tullio, Marco R. Di; Homma, Shunichi; Kamel, Hooman; Sacco, Ralph L.; Elkind, Mitchell S. V.

2015-01-01

Background and purpose While left atrial enlargement (LAE) increases incident stroke risk, the association with recurrent stroke is less clear. Our aim was to determine the association of LAE with recurrent stroke most likely related to embolism (cryptogenic and cardioembolic), and all ischemic stroke recurrences. Methods We followed 655 first ischemic stroke patients in the Northern Manhattan Stroke Study for up to 5 years. LA size from 2-D echocardiography was categorized as normal (52.7%), mild LAE (31.6%), and moderate-severe LAE (15.7%). We used Cox proportional hazard models to calculate the hazard ratios and 95% confidence intervals (HR, 95%CI) for the association of LA size and LAE with recurrent cryptogenic/cardioembolic and total recurrent ischemic stroke. Results LA size was available in 529 (81%) patients. Mean age at enrollment was 69±13 years; 45.8% were male, 54.0% Hispanic, and 18.5% had atrial fibrillation. Over a median of 4 years there were 65 recurrent ischemic strokes (29 were cardioembolic or cryptogenic). In multivariable models adjusted for confounders including atrial fibrillation and heart failure, moderate-severe LAE compared to normal LA size was associated with greater risk of recurrent cardioembolic/cryptogenic stroke (adjusted HR 2.83, 95% CI 1.03-7.81), but not total ischemic stroke (adjusted HR 1.06, 95% CI, 0.48-2.30). Mild LAE was not associated with recurrent stroke. Conclusion Moderate to severe LAE was an independent marker of recurrent cardioembolic or cryptogenic stroke in a multiethnic cohort of ischemic stroke patients. Further research is needed to determine whether anticoagulant use may reduce risk of recurrence in ischemic stroke patients with moderate to severe LAE. PMID:25908460

Efficacy and Safety of Vorapaxar With and Without a Thienopyridine for Secondary Prevention in Patients With Previous Myocardial Infarction and No History of Stroke or Transient Ischemic Attack: Results from TRA 2°P-TIMI 50.

PubMed

Bohula, Erin A; Aylward, Philip E; Bonaca, Marc P; Corbalan, Ramon L; Kiss, Robert G; Murphy, Sabina A; Scirica, Benjamin M; White, Harvey; Braunwald, Eugene; Morrow, David A

2015-11-17

Vorapaxar antagonizes protease-activated receptor 1, the primary receptor for thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a previous myocardial infarction (MI). We wished to determine whether the efficacy and safety of antiplatelet therapy with vorapaxar was modified by concurrent thienopyridine use. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26,449 patients with previous atherothrombosis. This prespecified analysis included 16,897 patients who qualified with a MI in the preceding 2 weeks to 12 months and was restricted to patients without a history of stroke or transient ischemic attack given its contraindication in that population. Randomization was stratified on the basis of planned thienopyridine use. Thienopyridine was planned at randomization in 12,410 (73%). Vorapaxar significantly reduced the composite of cardiovascular death, MI, and stroke in comparison with placebo regardless of planned thienopyridine therapy (planned thienopyridine, hazard ratio, 0.80, 0.70-0.91, P<0.001; no planned thienopyridine, hazard ratio, 0.75; 0.60-0.94, P=0.011; P-interaction=0.67). Findings were similar when patients were stratified by actual thienopyridine use at baseline (P-interaction=0.82) and through 18 months (P-interaction=0.44). Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate or severe bleeding risk was increased with vorapaxar and was not significantly altered by planned thienopyridine (planned, hazard ratio, 1.50; 1.18-1.89, P<0.001; no planned, hazard ratio, 1.90, 1.17-3.07, P=0.009; P-interaction=0.37) or actual thienopyridine use (P-interaction=0.24). Vorapaxar reduced cardiovascular death, MI, or stroke in stable patients with a history of previous MI, whether treated concomitantly with a thienopyridine or not. The relative risk of moderate or severe bleeding was similarly increased irrespective of thienopyridine use. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00526474. © 2015 American Heart Association, Inc.

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

PubMed

Marso, Steven P; Bain, Stephen C; Consoli, Agostino; Eliaschewitz, Freddy G; Jódar, Esteban; Leiter, Lawrence A; Lingvay, Ildiko; Rosenstock, Julio; Seufert, Jochen; Warren, Mark L; Woo, Vincent; Hansen, Oluf; Holst, Anders G; Pettersson, Jonas; Vilsbøll, Tina

2016-11-10

Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown. We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio. At baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.58 to 0.95; P<0.001 for noninferiority). Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74; 95% CI, 0.51 to 1.08; P=0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P=0.04). Rates of death from cardiovascular causes were similar in the two groups. Rates of new or worsening nephropathy were lower in the semaglutide group, but rates of retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation) were significantly higher (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P=0.02). Fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment because of adverse events, mainly gastrointestinal. In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide. (Funded by Novo Nordisk; SUSTAIN-6 ClinicalTrials.gov number, NCT01720446 .).

The risk of stroke after bilateral salpingo-oophorectomy at hysterectomy for benign diseases: A nationwide cohort study.

PubMed

Lai, Jerry Cheng-Yen; Chou, Yiing-Jenq; Huang, Nicole; Chen, Hung-Hui; Wang, Kung-Liahng; Wang, Chien-Wei; Shen, I-Hsuan; Chang, Hung-Chang

2018-08-01

To assess the risk of stroke (and subtypes of stroke) in women after elective bilateral salpingo-oophorectomy at hysterectomy for benign diseases. We conducted a nationwide population-based, retrospective cohort study using claims data from Taiwan's National Health Insurance program between 1997 and 2013. Women aged 20 years or more who underwent bilateral salpingo-oophorectomy at hysterectomy for benign diseases (n = 1083) were compared with women who did not undergo bilateral salpingo-oophorectomy at hysterectomy for benign diseases (n = 3903). The follow-up period ranged from 10 to 16 years. Age-adjusted (or unadjusted) and multivariate Cox proportional hazards regression models were used to estimate the risk of stroke between the two groups. A diagnosis of stroke (and subtypes of stroke). We did not find a significant association between bilateral salpingo-oophorectomy and the risk of incident stroke (or subtypes of stroke) over an average follow-up of 13 years. Among women aged 50 years or more who used estrogen therapy, the risk of developing stroke was 64% lower in those who had undergone bilateral salpingo-oophorectomy (hazard ratio, 0.36; 95% confidence interval, 0.16-0.79) than in those who had undergone hysterectomy only. This study suggests that the use of estrogen after bilateral salpingo-oophorectomy at hysterectomy for benign diseases reduces the risk of stroke in women aged 50 years or more. Copyright © 2018 Elsevier B.V. All rights reserved.

Uric acid predicts mortality and ischaemic stroke in subjects with diastolic dysfunction: the Tromsø Study 1994-2013.

PubMed

Norvik, Jon V; Schirmer, Henrik; Ytrehus, Kirsti; Storhaug, Hilde M; Jenssen, Trond G; Eriksen, Bjørn O; Mathiesen, Ellisiv B; Løchen, Maja-Lisa; Wilsgaard, Tom; Solbu, Marit D

2017-05-01

To investigate whether serum uric acid predicts adverse outcomes in persons with indices of diastolic dysfunction in a general population. We performed a prospective cohort study among 1460 women and 1480 men from 1994 to 2013. Endpoints were all-cause mortality, incident myocardial infarction, and incident ischaemic stroke. We stratified the analyses by echocardiographic markers of diastolic dysfunction, and uric acid was the independent variable of interest. Hazard ratios (HR) were estimated per 59 μmol/L increase in baseline uric acid. Multivariable adjusted Cox proportional hazards models showed that uric acid predicted all-cause mortality in subjects with E/A ratio <0.75 (HR 1.12, 95% confidence interval [CI] 1.00-1.25) or E/A ratio >1.5 (HR 1.51, 95% CI 1.09-2.09, P for interaction between E/A ratio category and uric acid = 0.02). Elevated uric acid increased mortality risk in persons with E-wave deceleration time <140 ms or >220 ms (HR 1.46, 95% CI 1.01-2.12 and HR 1.13, 95% CI 1.02-1.26, respectively; P for interaction = 0.04). Furthermore, in participants with isovolumetric relaxation time ≤60 ms, mortality risk was higher with increasing uric acid (HR 4.98, 95% CI 2.02-12.26, P for interaction = 0.004). Finally, elevated uric acid predicted ischaemic stroke in subjects with severely enlarged left atria (HR 1.62, 95% CI 1.03-2.53, P for interaction = 0.047). Increased uric acid was associated with higher all-cause mortality risk in subjects with echocardiographic indices of diastolic dysfunction, and with higher ischaemic stroke risk in persons with severely enlarged left atria.

Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.

PubMed

Hart, Robert G; Sharma, Mukul; Mundl, Hardi; Kasner, Scott E; Bangdiwala, Shrikant I; Berkowitz, Scott D; Swaminathan, Balakumar; Lavados, Pablo; Wang, Yongjun; Wang, Yilong; Davalos, Antonio; Shamalov, Nikolay; Mikulik, Robert; Cunha, Luis; Lindgren, Arne; Arauz, Antonio; Lang, Wilfried; Czlonkowska, Anna; Eckstein, Jens; Gagliardi, Rubens J; Amarenco, Pierre; Ameriso, Sebastian F; Tatlisumak, Turgut; Veltkamp, Roland; Hankey, Graeme J; Toni, Danilo; Bereczki, Daniel; Uchiyama, Shinichiro; Ntaios, George; Yoon, Byung-Woo; Brouns, Raf; Endres, Matthias; Muir, Keith W; Bornstein, Natan; Ozturk, Serefnur; O'Donnell, Martin J; De Vries Basson, Matthys M; Pare, Guillaume; Pater, Calin; Kirsch, Bodo; Sheridan, Patrick; Peters, Gary; Weitz, Jeffrey I; Peacock, W Frank; Shoamanesh, Ashkan; Benavente, Oscar R; Joyner, Campbell; Themeles, Ellison; Connolly, Stuart J

2018-06-07

Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .).

Stroke Symptoms as a Predictor of Future Hospitalization.

PubMed

Howard, Virginia J; Safford, Monika M; Allen, Shauntice; Judd, Suzanne E; Rhodes, J David; Kleindorfer, Dawn O; Soliman, Elsayed Z; Meschia, James F; Howard, George

2016-03-01

Stroke symptoms in the general adult population are common and associated with stroke risk factors, lower physical and mental functioning, impaired cognitive status, and future stroke. Our objective was to determine the association of stroke symptoms with self-reported hospitalization or emergency department (ED) visit. Lifetime history of stroke symptoms (sudden weakness, numbness, unilateral or general loss of vision, loss of ability to communicate or understand) was assessed at baseline in a national, population-based, longitudinal cohort study of 30,239 blacks and whites younger than 45 years, enrolled from 2003 to 2007. Self-reported hospitalization or ED visit and reason were collected during follow-up through March 2013. The symptom-hospitalization association was assessed by proportional hazards analysis in persons who were stroke/transient ischemic attack-free at baseline (27,126) with adjustment for sociodemographics and further adjustment for risk factors. One or more stroke symptoms were reported by 4758 (17.5%). After adjustment for sociodemographics, stroke symptoms were most strongly associated with greater risk of hospitalization/ED for cardiovascular disease (CVD) (hazard ratio [HR] = 1.87, 95% confidence interval [CI]: 1.78-1.96), stroke (HR = 1.69, 95% CI: 1.55-1.85), and any reason (HR = 1.39, 95% CI: 1.34-1.44). These associations remained significant and only modestly reduced after risk factor adjustment. Stroke symptoms are a marker for future hospitalization and ED visit not only for stroke but also for CVD in general. Findings suggest a role for stroke symptom assessment as a novel and simple approach for identifying individuals at high risk for CVD including stroke in whom preventive strategies could be implemented. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Does non-central nervous system tuberculosis increase the risk of ischemic stroke? A population-based propensity score-matched follow-up study.

PubMed

Wu, Chueh-Hung; Chen, Li-Sheng; Yen, Ming-Fang; Chiu, Yueh-Hsia; Fann, Ching-Yuan; Chen, Hsiu-Hsi; Pan, Shin-Liang

2014-01-01

Previous studies on the association between tuberculosis and the risk of developing ischemic stroke have generated inconsistent results. We therefore performed a population-based, propensity score-matched longitudinal follow-up study to investigate whether contracting non-central nervous system (CNS) tuberculosis leads to an increased risk of ischemic stroke. We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 5804 persons with at least three ambulatory visits in 2001 with the principal diagnosis of non-CNS tuberculosis were enrolled in the tuberculosis group. The non-tuberculosis group consisted of 5804, propensity score-matched subjects without tuberculosis. The three-year ischemic stroke-free survival rates for these 2 groups were estimated using the Kaplan-Meier method. The stratified Cox proportional hazards regression was used to estimate the effect of tuberculosis on the occurrence of ischemic stroke. During three-year follow-up, 176 subjects in the tuberculosis group (3.0%) and 207 in the non-tuberculosis group (3.6%) had ischemic stroke. The hazard ratio for developing ischemic stroke in the tuberculosis group was 0.92 compared to the non-tuberculosis group (95% confidence interval: 0.73-1.14, P = 0.4299). Non-CNS tuberculosis does not increase the risk of subsequent ischemic stroke.

Association of Traditional Chinese Medicine Therapy and the Risk of Vascular Complications in Patients With Type II Diabetes Mellitus

PubMed Central

Lee, Ai-Lin; Chen, Bor-Chyuan; Mou, Chih-Hsin; Sun, Mao-Feng; Yen, Hung-Rong

2016-01-01

Abstract With an increasing use of traditional Chinese medicine (TCM) in type 2 diabetes mellitus (T2DM), evidence of long-term benefit with adjunctive TCM treatment is limited. This study investigated whether the concurrent TCM treatment reduces the risk of vascular complications in T2DM patients by using a large population from National Health Insurance Research Database (NHIRD). We identified 33,457 adult patients with newly diagnosed T2DM using anti-diabetic agents from a random sample of one million beneficiaries in the NHIRD between January 1, 2000 and December 31, 2011. We recruited 1049 TCM users (received TCM over 30 days with a diagnosis of T2DM) and randomly selected 4092 controls as the non-TCM cohort at a ratio of 1:4 frequency-matched by age, sex, hypertension, hyperlipidemia, and index year. We investigated the prescription pattern of TCM and conducted a Cox proportional hazards regression to calculate the hazard ratios (HRs) of stroke, chronic kidney diseases (CKD), and diabetic foot between the 2 cohorts. In the TCM cohort, the prescription pattern of TCM was different between insulin and noninsulin patients. The most common herbs were Dan-Shen (Radix Salviae Miltiorrhizae) in noninsulin group and Da-Huang (Radix et Rhizoma Rhei) in insulin group. The most common formulae were Liu-Wei-Di-Huang-Wan in noninsulin group and Yu-Quan-Wan in insulin group. Although no significant reduction in the hazard ratio of CKD and diabetic foot, the incidence rate of stroke was 7.19 per 1000 person-years in the TCM cohort and 10.66 per 1000 person-years in the control cohort, respectively. After adjustment of age, sex, hypertension, hyperlipidemia, and antidiabetes agent use (including sulfonylureas, α-glucosidase, metformin, meglitinide, thiazolidinediones, and insulin), TCM cohorts were found to have a 33% decreased risk of stroke (95% CI = 0.46–0.97; P < 0.05). This population-based retrospective study showed that the complementary TCM therapy might associate with the decreased risk of stroke in T2DM, suggesting TCM as an adjunctive therapy for T2DM to prevent subsequent stroke. PMID:26817897

Vorapaxar in the secondary prevention of atherothrombotic events.

PubMed

Morrow, David A; Braunwald, Eugene; Bonaca, Marc P; Ameriso, Sebastian F; Dalby, Anthony J; Fish, Mary Polly; Fox, Keith A A; Lipka, Leslie J; Liu, Xuan; Nicolau, José Carlos; Ophuis, A J Oude; Paolasso, Ernesto; Scirica, Benjamin M; Spinar, Jindrich; Theroux, Pierre; Wiviott, Stephen D; Strony, John; Murphy, Sabina A

2012-04-12

Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.).

A post hoc evaluation of a sample size re-estimation in the Secondary Prevention of Small Subcortical Strokes study.

PubMed

McClure, Leslie A; Szychowski, Jeff M; Benavente, Oscar; Hart, Robert G; Coffey, Christopher S

2016-10-01

The use of adaptive designs has been increasing in randomized clinical trials. Sample size re-estimation is a type of adaptation in which nuisance parameters are estimated at an interim point in the trial and the sample size re-computed based on these estimates. The Secondary Prevention of Small Subcortical Strokes study was a randomized clinical trial assessing the impact of single- versus dual-antiplatelet therapy and control of systolic blood pressure to a higher (130-149 mmHg) versus lower (<130 mmHg) target on recurrent stroke risk in a two-by-two factorial design. A sample size re-estimation was performed during the Secondary Prevention of Small Subcortical Strokes study resulting in an increase from the planned sample size of 2500-3020, and we sought to determine the impact of the sample size re-estimation on the study results. We assessed the results of the primary efficacy and safety analyses with the full 3020 patients and compared them to the results that would have been observed had randomization ended with 2500 patients. The primary efficacy outcome considered was recurrent stroke, and the primary safety outcomes were major bleeds and death. We computed incidence rates for the efficacy and safety outcomes and used Cox proportional hazards models to examine the hazard ratios for each of the two treatment interventions (i.e. the antiplatelet and blood pressure interventions). In the antiplatelet intervention, the hazard ratio was not materially modified by increasing the sample size, nor did the conclusions regarding the efficacy of mono versus dual-therapy change: there was no difference in the effect of dual- versus monotherapy on the risk of recurrent stroke hazard ratios (n = 3020 HR (95% confidence interval): 0.92 (0.72, 1.2), p = 0.48; n = 2500 HR (95% confidence interval): 1.0 (0.78, 1.3), p = 0.85). With respect to the blood pressure intervention, increasing the sample size resulted in less certainty in the results, as the hazard ratio for higher versus lower systolic blood pressure target approached, but did not achieve, statistical significance with the larger sample (n = 3020 HR (95% confidence interval): 0.81 (0.63, 1.0), p = 0.089; n = 2500 HR (95% confidence interval): 0.89 (0.68, 1.17), p = 0.40). The results from the safety analyses were similar to 3020 and 2500 patients for both study interventions. Other trial-related factors, such as contracts, finances, and study management, were impacted as well. Adaptive designs can have benefits in randomized clinical trials, but do not always result in significant findings. The impact of adaptive designs should be measured in terms of both trial results, as well as practical issues related to trial management. More post hoc analyses of study adaptations will lead to better understanding of the balance between the benefits and the costs. © The Author(s) 2016.

Socioeconomic disparities in first stroke incidence, quality of care, and survival: a nationwide registry-based cohort study of 44 million adults in England.

PubMed

Bray, Benjamin D; Paley, Lizz; Hoffman, Alex; James, Martin; Gompertz, Patrick; Wolfe, Charles D A; Hemingway, Harry; Rudd, Anthony G

2018-04-01

We aimed to estimate socioeconomic disparities in the incidence of hospitalisation for first-ever stroke, quality of care, and post-stroke survival for the adult population of England. In this cohort study, we obtained data collected by a nationwide register on patients aged 18 years or older hospitalised for first-ever acute ischaemic stroke or primary intracerebral haemorrhage in England from July 1, 2013, to March 31, 2016. We classified socioeconomic status at the level of Lower Super Output Areas using the Index of Multiple Deprivation, a neighbourhood measure of deprivation. Multivariable models were fitted to estimate the incidence of hospitalisation for first stroke (negative binomial), quality of care using 12 quality metrics (multilevel logistic), and all-cause 1 year case fatality (Cox proportional hazards). Of the 43·8 million adults in England, 145 324 were admitted to hospital with their first-ever stroke: 126 640 (87%) with ischaemic stroke, 17 233 (12%) with intracerebral haemorrhage, and 1451 (1%) with undetermined stroke type. We observed a socioeconomic gradient in the incidence of hospitalisation for ischaemic stroke (adjusted incidence rate ratio 2·0, 95% CI 1·7-2·3 for the most vs least deprived deciles) and intracerebral haemorrhage (1·6, 1·3-1·9). Patients from the lowest socioeconomic groups had first stroke a median of 7 years earlier than those from the highest (p<0·0001), and had a higher prevalence of pre-stroke disability and diabetes. Patients from lower socioeconomic groups were less likely to receive five of 12 care processes but were more likely to receive early supported discharge (adjusted odds ratio 1·14, 95% CI 1·07-1·22). Low socioeconomic status was associated with a 26% higher adjusted risk of 1-year mortality (adjusted hazard ratio 1·26, 95% CI 1·20-1·33, for highest vs lowest deprivation decile), but this gradient was largely attenuated after adjustment for the presence of pre-stroke diabetes, hypertension, and atrial fibrillation (1·11, 1·05-1·17). Wide socioeconomic disparities exist in the burden of ischaemic stroke and intracerebral haemorrhage in England, most notably in stroke hospitalisation risk and case fatality and, to a lesser extent, in the quality of health care. Reducing these disparities requires interventions to improve the quality of acute stroke care and address disparities in cardiovascular risk factors present before stroke. NHS England and the Welsh Government. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

PubMed

Hijazi, Ziad; Siegbahn, Agneta; Andersson, Ulrika; Granger, Christopher B; Alexander, John H; Atar, Dan; Gersh, Bernard J; Mohan, Puneet; Harjola, Veli-Pekka; Horowitz, John; Husted, Steen; Hylek, Elaine M; Lopes, Renato D; McMurray, John J V; Wallentin, Lars

2014-02-11

High-sensitivity troponin-I (hs-TnI) measurement improves risk assessment for cardiovascular events in many clinical settings, but the added value in atrial fibrillation patients has not been described. At randomization, hs-TnI was analyzed in 14 821 atrial fibrillation patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial comparing apixaban with warfarin. The associations between hs-TnI concentrations and clinical outcomes were evaluated by using adjusted Cox analysis. The hs-TnI assay detected troponin (≥1.3 ng/L) in 98.5% patients, 50% had levels >5.4, 25% had levels >10.1, and 9.2% had levels ≥23 ng/L (the 99th percentile in healthy individuals). During a median of 1.9 years follow-up, annual rates of stroke or systemic embolism ranged from 0.76% in the lowest hs-TnI quartile to 2.26% in the highest quartile (>10.1 ng/L). In multivariable analysis, hs-TnI was significantly associated with stroke or systemic embolism, adjusted hazard ratio 1.98 (1.42-2.78), P=0.0007. hs-TnI was also significantly associated with cardiac death; annual rates ranged from 0.40% to 4.24%, hazard ratio 4.52 (3.05-6.70), P<0.0001, in the corresponding groups, and for major bleeding hazard ratio 1.44 (1.11-1.86), P=0.0250. Adding hs-TnI levels to the CHA2DS2VASc score improved c-statistics from 0.629 to 0.653 for stroke or systemic embolism, and from 0.591 to 0.731 for cardiac death. There were no significant interactions with study treatment. Troponin-I is detected in 98.5% and elevated in 9.2% of atrial fibrillation patients. The hs-TnI level is independently associated with a raised risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA2DS2VASc score. The benefits of apixaban in comparison with warfarin are consistent regardless of hs-TnI levels. http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Neighborhood socioeconomic index and stroke incidence in a national cohort of blacks and whites

PubMed Central

McClure, Leslie A.; Kleindorfer, Dawn O.; Cunningham, Solveig A.; Thrift, Amanda G.; Diez Roux, Ana V.; Howard, George

2016-01-01

Objective: To assess the relationship between neighborhood socioeconomic characteristics and incident stroke in a national cohort of black and white participants. Methods: The study comprised black (n = 10,274, 41%) and white (n = 14,601) stroke-free participants, aged 45 and older, enrolled in 2003–2007 in Reasons for Geographic and Racial Differences in Stroke (REGARDS), a national population-based cohort. A neighborhood socioeconomic score (nSES) was constructed using 6 neighborhood variables. Incident stroke was defined as first occurrence of stroke over an average 7.5 (SD 3.0) years of follow-up. Proportional hazards models were used to estimate associations between nSES score and incident stroke, adjusted for demographics (age, race, sex, region), individual socioeconomic status (SES) (education, household income), and other risk factors for stroke. Results: After adjustment for demographics, compared to the highest nSES quartile, stroke incidence increased with each decreasing nSES quartile. The hazard ratio (95% confidence interval) ranged from 1.28 (1.05–1.56) in quartile 3 to 1.38 (1.13–1.68) in quartile 2 to 1.56 (1.26–1.92) in quartile 1 (p < 0.0001 for linear trend). After adjustment for individual SES, the trend remained marginally significant (p = 0.085). Although there was no evidence of a differential effect by race or sex, adjustment for stroke risk factors attenuated the association between nSES and stroke in both black and white participants, with greater attenuation in black participants. Conclusions: Risk of incident stroke increased with decreasing nSES but the effect of nSES is attenuated through individual SES and stroke risk factors. The effect of neighborhood socioeconomic characteristics that contribute to increased stroke risk is similar in black and white participants. PMID:27742815

Effect of duration and age at exposure to the Stroke Belt on incident stroke in adulthood

PubMed Central

McClure, Leslie A.; Glymour, M. Maria; Cunningham, Solveig A.; Kleindorfer, Dawn O.; Crowe, Michael; Wadley, Virginia G.; Peace, Fredrick; Howard, George; Lackland, Daniel T.

2013-01-01

Objective: To assess whether there are differences in the strength of association with incident stroke for specific periods of life in the Stroke Belt (SB). Methods: The risk of stroke was studied in 24,544 black and white stroke-free participants, aged 45+, in the Reasons for Geographic and Racial Differences in Stroke study, a national population-based cohort enrolled 2003–2007. Incident stroke was defined as first occurrence of stroke over an average 5.8 years of follow-up. Residential histories (city/state) were obtained by questionnaire. SB exposure was quantified by combinations of SB birthplace and current residence and proportion of years in SB during discrete age categories (0–12, 13–18, 19–30, 31–45, last 20 years) and entire life. Proportional hazards models were used to establish association of incident stroke with indices of exposure to SB, adjusted for demographic, socioeconomic (SES), and stroke risk factors. Results: In the demographic and SES models, risk of stroke was significantly associated with proportion of life in the SB and with all other exposure periods except birth, ages 31–45, and current residence. The strongest association was for the proportion of the entire life in SB. After adjustment for risk factors, the risk of stroke remained significantly associated only with proportion of residence in SB in adolescence (hazard ratio 1.17, 95% confidence interval 1.00–1.37). Conclusions: Childhood emerged as the most important period of vulnerability to SB residence as a predictor of future stroke. Improvement in childhood health circumstances should be considered as part of long-term health improvement strategies in the SB. PMID:23616168

A comparative analysis of risk factors for stroke in blacks and whites: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Huxley, Rachel; Bell, Elizabeth J.; Lutsey, Pamela L.; Bushnell, Cheryl; Shahar, Eyal; Rosamond, Wayne; Gottesman, Rebecca; Folsom, Aaron

2013-01-01

Objective Previous studies have speculated that the higher stroke incidence rate in blacks compared with whites may be due, in part, to stroke risk factors exerting a more adverse effect among blacks than whites. To determine whether such racial differences exist we compared the prospective associations between novel, traditional and emerging stroke risk factors in blacks and whites. Design Baseline characteristics on risk factor levels were obtained on 15,407 participants from the Atherosclerosis Risk in Communities Study. Stroke incidence was ascertained from 1987–2008. Adjusted Cox proportional hazard models were used to compute hazard ratios (HRs) and their 95% confidence intervals (CIs) for stroke in relation to stroke risk factor levels stratified by race. Results During follow-up 988 stroke events occurred: Blacks had higher stroke incident rates compared with whites with the greatest difference in those aged <60 years: 4.34, 3.24, 1.20 and 0.84 per 1,000 person-years, in black men, black women, white men and white women, respectively. Associations between risk factors with incident stroke were similar in blacks and whites excluding diabetes which was more strongly associated with risk of stroke in blacks than in whites: HR 2.54 (95% CI: 2.03–3.18) vs. 1.74 (1.37–2.21), respectively; p for race interaction=0.02. Conclusions At all ages, blacks are at considerably higher risk of incident stroke compared with whites, although the effect is most marked in younger age groups. This is most likely due to blacks having a greater burden of stroke risk factors rather than there being any substantial race differences in the associations between risk factors and stroke outcomes. PMID:24261746

Neighborhood socioeconomic index and stroke incidence in a national cohort of blacks and whites.

PubMed

Howard, Virginia J; McClure, Leslie A; Kleindorfer, Dawn O; Cunningham, Solveig A; Thrift, Amanda G; Diez Roux, Ana V; Howard, George

2016-11-29

To assess the relationship between neighborhood socioeconomic characteristics and incident stroke in a national cohort of black and white participants. The study comprised black (n = 10,274, 41%) and white (n = 14,601) stroke-free participants, aged 45 and older, enrolled in 2003-2007 in Reasons for Geographic and Racial Differences in Stroke (REGARDS), a national population-based cohort. A neighborhood socioeconomic score (nSES) was constructed using 6 neighborhood variables. Incident stroke was defined as first occurrence of stroke over an average 7.5 (SD 3.0) years of follow-up. Proportional hazards models were used to estimate associations between nSES score and incident stroke, adjusted for demographics (age, race, sex, region), individual socioeconomic status (SES) (education, household income), and other risk factors for stroke. After adjustment for demographics, compared to the highest nSES quartile, stroke incidence increased with each decreasing nSES quartile. The hazard ratio (95% confidence interval) ranged from 1.28 (1.05-1.56) in quartile 3 to 1.38 (1.13-1.68) in quartile 2 to 1.56 (1.26-1.92) in quartile 1 (p < 0.0001 for linear trend). After adjustment for individual SES, the trend remained marginally significant (p = 0.085). Although there was no evidence of a differential effect by race or sex, adjustment for stroke risk factors attenuated the association between nSES and stroke in both black and white participants, with greater attenuation in black participants. Risk of incident stroke increased with decreasing nSES but the effect of nSES is attenuated through individual SES and stroke risk factors. The effect of neighborhood socioeconomic characteristics that contribute to increased stroke risk is similar in black and white participants. © 2016 American Academy of Neurology.

Risk of Stroke in Patients With Short-Run Atrial Tachyarrhythmia.

PubMed

Yamada, Shinya; Lin, Chin-Yu; Chang, Shih-Lin; Chao, Tze-Fan; Lin, Yenn-Jiang; Lo, Li-Wei; Chung, Fa-Po; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Te, Abigail Louise D; Chang, Yao-Ting; Chang, Ting-Yung; Wu, Cheng-I; Higa, Satoshi; Chen, Shih-Ann

2017-12-01

The risk of stroke in patients with short-run atrial tachyarrhythmia (AT) remains unclear. This study aimed to investigate the relationship between short-run AT and the stroke and the use of the CHA 2 DS 2 -VASc score for the risk stratification. From the registry of 24-hour Holter monitoring, 5342 subjects without known atrial fibrillation or stroke were enrolled. Short-run AT was defined as episodes of supraventricular ectopic beats <5 seconds. There were 1595 subjects (29.8%) with short-run AT. During the median follow-up period of 9.0 years, 494 subjects developed new-onset stroke. Patients with short-run AT had significantly higher stroke rates compared with patients without short-run AT (11.4% versus 8.3%; P <0.001). In patients with short-run AT, the number of strokes per 100 person-years for patients with CHA 2 DS 2 -VASc score of 0 and 1 were 0.23 and 0.67, respectively. However, the number of them for patients with CHA 2 DS 2 -VASc score of 2, 3, 4, and ≥5 were 1.62, 1.89, 1.30, and 2.91, respectively. In patients with CHA 2 DS 2 -VASc score of 0 or 1, age (>61 years old) and burden of premature atrial contractions (>25 beats/d) independently predicted the risk of stroke. In subgroup analyses, short-run AT patients were divided into 3 groups based on their CHA 2 DS 2 -VASc scores: low score (score of 0 [men] or 1 [women]; n=324), intermediate score (score of 1 [men] or 2 [women]; n=275), and high score (score of ≥2 [men] or ≥3 [women]; n=996). When compared with low score, intermediate and high scores were independent predictors for stroke (hazard ratio, 6.165; P <0.001 and hazard ratio, 8.577; P <0.001, respectively). Short-run AT increases the risk of stroke. Therefore, the CHA 2 DS 2 -VASc score could be used for the risk stratification. Age and burden of premature atrial contractions were independent predictors for stroke in patients with CHA 2 DS 2 -VASc score of 0 or 1. © 2017 American Heart Association, Inc.

High-sensitivity C-reactive protein predicts mortality but not stroke

PubMed Central

Elkind, M S.V.; Luna, J M.; Moon, Y P.; Liu, K M.; Spitalnik, S L.; Paik, M C.; Sacco, R L.

2009-01-01

Objective: To determine whether high-sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) predict stroke, vascular events, and mortality in a prospective cohort study. Background: Markers of inflammation have been associated with risk of myocardial infarction (MI). Their association with stroke is controversial. Methods: The Northern Manhattan Study includes a stroke-free community-based cohort study in participants aged ≥40 years (median follow-up 7.9 years). hsCRP and SAA were measured using nephelometry. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association of markers with risk of ischemic stroke and other outcomes after adjusting for demographics and risk factors. Results: hsCRP measurements were available in 2,240 participants (mean age 68.9 ± 10.1 years; 64.2% women; 18.8% white, 23.5% black, and 55.1% Hispanic). The median hsCRP was 2.5 mg/L. Compared with those with hsCRP <1 mg/L, those with hsCRP >3 mg/L were at increased risk of ischemic stroke in a model adjusted for demographics (HR = 1.60, 95% CI 1.06–2.41), but the effect was attenuated after adjusting for other risk factors (adjusted HR = 1.20, 95% CI 0.78–1.86). hsCRP >3 mg/L was associated with risk of MI (adjusted HR = 1.70, 95% CI 1.04–2.77) and death (adjusted HR = 1.55, 95% CI 1.23–1.96). SAA was not associated with stroke risk. Conclusion: In this multiethnic cohort, high-sensitivity C-reactive protein (hsCRP) was not associated with ischemic stroke, but was modestly associated with myocardial infarction and mortality. The value of hsCRP and serum amyloid A may depend on population characteristics such as age and other risk factors. GLOSSARY AHA = American Heart Association; BP = blood pressure; CDC = Centers for Disease Control and Prevention; CI = confidence interval; CRP = C-reactive protein; CUMC = Columbia University Medical Center; HR = hazard ratio; hsCRP = high-sensitivity C-reactive protein; IQR = interquartile range; JUPITER = Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin; MI = myocardial infarction; NOMAS = Northern Manhattan Study; SAA = serum amyloid A. PMID:19841382

Determinants in Adolescence of Stroke-Related Hospital Stay Duration in Men: A National Cohort Study.

PubMed

Bergh, Cecilia; Udumyan, Ruzan; Appelros, Peter; Fall, Katja; Montgomery, Scott

2016-09-01

Physical and psychological characteristics in adolescence are associated with subsequent stroke risk. Our aim is to investigate their relevance to length of hospital stay and risk of second stroke. Swedish men born between 1952 and 1956 (n=237 879) were followed from 1987 to 2010 using information from population-based national registers. Stress resilience, body mass index, cognitive function, physical fitness, and blood pressure were measured at compulsory military conscription examinations in late adolescence. Joint Cox proportional hazards models estimated the associations of these characteristics with long compared with short duration of stroke-related hospital stay and with second stroke compared with first. Some 3000 men were diagnosed with nonfatal stroke between ages 31 and 58 years. Low stress resilience, underweight, and higher systolic blood pressure (per 1-mm Hg increase) during adolescence were associated with longer hospital stay (compared with shorter) in ischemic stroke, with adjusted relative hazard ratios (and 95% confidence intervals) of 1.46 (1.08-1.89), 1.41 (1.04-1.91), and 1.01 (1.00-1.02), respectively. Elevated systolic and diastolic blood pressures during adolescence were associated with longer hospital stay in men with intracerebral hemorrhage: 1.01 (1.00-1.03) and 1.02 (1.00-1.04), respectively. Among both stroke types, obesity in adolescence conferred an increased risk of second stroke: 2.06 (1.21-3.45). Some characteristics relevant to length of stroke-related hospital stay and risk of second stroke are already present in adolescence. Early lifestyle influences are of importance not only to stroke risk by middle age but also to recurrence and use of healthcare resources among stroke survivors. © 2016 American Heart Association, Inc.

Impact of proteinuria and glomerular filtration rate on risk of ischaemic and intracerebral hemorrhagic stroke: a result from the Kailuan study.

PubMed

Li, Z; Wang, A; Cai, J; Gao, X; Zhou, Y; Luo, Y; Wu, S; Zhao, X

2015-02-01

Persons with chronic kidney disease, defined by a reduced estimated glomerular filtration rate and proteinuria, have an increased risk of cardiovascular disease including stroke. However, data from developing countries are limited. Our aim was to assess the relationship between chronic kidney disease and risk of stroke and its subtypes in a community-based population in China. The study was based on 92,013 participants (18-98 years old; 73,248 men and 18,765 women) of the Kailuan study who at baseline were free from stroke and myocardial infarction and had undergone tests for serum creatinine or proteinuria. Glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration formula and proteinuria by the urine dipstick result in laboratory databases. The primary outcome was the first occurrence of stroke. Data were analyzed using Cox proportional hazards models adjusted for relevant confounders and results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). During a follow-up of 4 years, 1575 stroke events (1128 ischaemic, 406 intracerebral hemorrhagic and 41 subarachnoid hemorrhagic strokes) occurred. After adjustment for variable confounders, patients with proteinuria were found to have increased HRs for the total and subtypes of stroke events (HR 1.61; 95% CI 1.35-1.92 for total stroke; HR 1.53; 95% CI 1.24-1.89 for ischaemic stroke; and HR 1.90; 95% CI 1.35-2.67 for hemorrhagic stroke). However, estimated glomerular filtration rate was not associated with incident stroke after adjustment for established cardiovascular risk factors. Proteinuria increased the risk of stroke in a general Chinese population. © 2014 EAN.

Empagliflozin and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk

PubMed Central

Inzucchi, Silvio E.; Lachin, John M.; Wanner, Christoph; Fitchett, David; Kohler, Sven; Mattheus, Michaela; Woerle, Hans J.; Broedl, Uli C.; Johansen, Odd Erik; Albers, Gregory W.; Diener, Hans Christoph

2017-01-01

Background and Purpose— In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), empagliflozin added to standard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events, driven by a reduction in cardiovascular mortality, with no significant difference between empagliflozin and placebo in risk of myocardial infarction or stroke. In a modified intent-to-treat analysis, the hazard ratio for stroke was 1.18 (95% confidence interval, 0.89–1.56; P=0.26). We further investigated cerebrovascular events. Methods— Patients were randomized to empagliflozin 10 mg, empagliflozin 25 mg, or placebo; 7020 patients were treated. Median observation time was 3.1 years. Results— The numeric difference in stroke between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event >90 days after last intake of study drug (versus 3 on placebo). In a sensitivity analysis based on events during treatment or ≤90 days after last dose of drug, the hazard ratio for stroke with empagliflozin versus placebo was 1.08 (95% confidence interval, 0.81–1.45; P=0.60). There were no differences in risk of recurrent, fatal, or disabling strokes, or transient ischemic attack, with empagliflozin versus placebo. Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke. Conclusions— In patients with type 2 diabetes mellitus and high cardiovascular risk, there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01131676. PMID:28386035

Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Wellons, Melissa; Ouyang, Pamela; Schreiner, Pamela J; Herrington, David M; Vaidya, Dhananjay

2012-10-01

Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if self-reported early menopause (menopause at an age <46 y) identifies women as at risk for future coronary heart disease or stroke. The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46 y) and future coronary heart disease and stroke was assessed in 2,509 women (ages 45-84 y; 987 white, 331 Chinese, 641 black, and 550 Hispanic) from the Multi-ethnic Study Atherosclerosis who were free of cardiovascular disease at baseline. Of 2,509 women, 693 (28%) reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank P = 0.008 and P = 0.0158). In models adjusted for age, race/ethnicity, Multi-ethnic Study Atherosclerosis site, and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (hazard ratio, 2.08; 95% CI, 1.17-3.70; and hazard ratio, 2.19; 95% CI, 1.11-4.32, respectively). Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors.

Empagliflozin and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk.

PubMed

Zinman, Bernard; Inzucchi, Silvio E; Lachin, John M; Wanner, Christoph; Fitchett, David; Kohler, Sven; Mattheus, Michaela; Woerle, Hans J; Broedl, Uli C; Johansen, Odd Erik; Albers, Gregory W; Diener, Hans Christoph

2017-05-01

In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), empagliflozin added to standard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events, driven by a reduction in cardiovascular mortality, with no significant difference between empagliflozin and placebo in risk of myocardial infarction or stroke. In a modified intent-to-treat analysis, the hazard ratio for stroke was 1.18 (95% confidence interval, 0.89-1.56; P =0.26). We further investigated cerebrovascular events. Patients were randomized to empagliflozin 10 mg, empagliflozin 25 mg, or placebo; 7020 patients were treated. Median observation time was 3.1 years. The numeric difference in stroke between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event >90 days after last intake of study drug (versus 3 on placebo). In a sensitivity analysis based on events during treatment or ≤90 days after last dose of drug, the hazard ratio for stroke with empagliflozin versus placebo was 1.08 (95% confidence interval, 0.81-1.45; P =0.60). There were no differences in risk of recurrent, fatal, or disabling strokes, or transient ischemic attack, with empagliflozin versus placebo. Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke. In patients with type 2 diabetes mellitus and high cardiovascular risk, there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01131676. © 2017 The Authors.

Common Carotid Artery Diameter and Risk of Cardiovascular Events and Mortality: Pooled Analyses of Four Cohort Studies.

PubMed

Sedaghat, Sanaz; van Sloten, Thomas T; Laurent, Stéphane; London, Gérard M; Pannier, Bruno; Kavousi, Maryam; Mattace-Raso, Francesco; Franco, Oscar H; Boutouyrie, Pierre; Ikram, M Arfan; Stehouwer, Coen D A

2018-05-21

Carotid arterial diameter enlargement is a manifestation of arterial remodeling and may be a risk factor for cardiovascular disease (CVD). We evaluated the association between carotid artery diameter and risk of stroke, coronary heart disease, CVD, and all-cause mortality and explored whether the associations could be explained by processes involved in arterial remodeling, that is, blood pressure-related media thickening, arterial stiffness, arterial wall stress, and atherosclerosis. We included 4887 participants (mean age 67±9 years; 54% women) from 4 cohort studies: Rotterdam Study, NEPHROTEST, Hoorn Study, and a study by Blacher et al. Common carotid artery properties were measured using echotracking. Incident cases were recorded based on medical records. We used Cox proportional hazard models adjusting for cardiovascular risk factors and estimates of processes underlying arterial remodeling. During follow-up (mean, 11 years), 379 (8%) individuals had a stroke, 516 had a (11%) coronary heart disease, 807 had a (17%) CVD, and 1486 (30%) had died. After adjustment for cardiovascular risk factors, individuals in the highest tertile of carotid diameter (diameter >8 mm) compared with those in the lowest tertile (diameter <7 mm) had a higher incidence of stroke (hazard ratio, 1.5; 95% confidence interval, 1.1-2.0). From all estimates of processes underlying arterial remodeling, adjustment for carotid intima-media thickness attenuated this association (hazard ratio after adjustment for intima-media thickness, 1.2; 95% confidence interval, 0.9-1.6). Larger carotid diameter was associated with risk of CVD and mortality but not clearly with coronary heart disease risk. We showed that a larger carotid diameter is associated with incident stroke, CVD, and mortality. Carotid intima-media thickness, a measure of blood pressure-related media thickening, partially explained the association with stroke incidence. © 2018 American Heart Association, Inc.

Risk of Intracranial Hemorrhage From Statin Use in Asians: A Nationwide Cohort Study.

PubMed

Chang, Chia-Hsuin; Lin, Chin-Hsien; Caffrey, James L; Lee, Yen-Chieh; Liu, Ying-Chun; Lin, Jou-Wei; Lai, Mei-Shu

2015-06-09

Reports of statin usage and increased risk of intracranial hemorrhage (ICH) have been inconsistent. This study examined potential associations between statin usage and the risk of ICH in subjects without a previous history of stroke. Patients initiating statin therapy between 2005 and 2009 without a previous history of ischemic or hemorrhagic stroke were identified from Taiwan's National Health Insurance database. Participants were stratified by advanced age (≥70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH (International Classification of Diseases, Ninth Revision, Clinical Modification codes 430, 431, 432). Cox regression models were applied to estimate the hazard ratio of ICH. The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable using the lowest quartile of cumulative dosage as a reference. There were 1 096 547 statin initiators with an average follow-up of 3.3 years. The adjusted hazard ratio for ICH between the highest and the lowest quartile was nonsignificant at 1.06 with a 95% confidence interval spanning 1.00 (0.94-1.19). Similar nonsignificant results were found in sensitivity analyses using different outcome definitions or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients without diagnosed hypertension (adjusted hazard ratio 1.36 [1.11-1.67]). In general, no association was observed between cumulative statin use and the risk of ICH among subjects without a previous history of stroke. An increased risk was identified among the nonhypertensive cohort, but this finding should be interpreted with caution. © 2015 American Heart Association, Inc.

Effect of Rehabilitation Intensity on Mortality Risk After Stroke.

PubMed

Hsieh, Cheng-Yang; Huang, Hsiu-Chen; Wu, Darren Philbert; Li, Chung-Yi; Chiu, Meng-Jun; Sung, Sheng-Feng

2018-06-01

To determine the relation between rehabilitation intensity and poststroke mortality. Retrospective cohort study. Nationwide claims data. From Taiwan's National Health Insurance claims databases, patients (N=6737; mean age, 66.9y; 40.3% women) hospitalized between 2001 and 2013 for a first-ever stroke who had mild to moderate stroke and survived the first 90 days of stroke were enrolled. The intensity of rehabilitation therapy within 90 days after stroke was categorized into low, medium, or high based on the tertile distribution of the number of rehabilitation sessions. Long-term all-cause mortality. The Cox proportional hazard models with Bonferroni correction were used to assess the association between rehabilitation intensity and mortality, adjusting for age, comorbidities, stroke severity, and other covariates. Patients in the high-intensity group were younger but had a higher burden of comorbidities and greater stroke severity. During follow-up, the high-intensity group was associated with a significantly lower adjusted risk (hazard ratio [HR], .73; 95% confidence interval [CI], .63-.84) of mortality than the low-intensity group, whereas the medium-intensity group carried a similar risk of mortality (HR, 0.94; 95% CI, 0.84-1.06) compared with the low-intensity group. This association was not modified by stroke severity. Among patients with mild to moderate stroke severity, high-intensity rehabilitation therapy within the first 90 days was associated with a lower mortality risk than low-intensity therapy. Efforts to promote high-intensity rehabilitation therapy for this group of patients with stroke should be encouraged. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Post-ischemic stroke rehabilitation is associated with a higher risk of fractures in older women: A population-based cohort study.

PubMed

Huang, Huei Kai; Lin, Shu Man; Yang, Clement Shih Hsien; Liang, Chung Chao; Cheng, Hung Yu

2017-01-01

Rehabilitation can improve physical activity after stroke. However, patients may be more prone to falls and fractures because of balance and gait deficits. Few reports have studied the relationship between rehabilitation and subsequent fractures after ischemic stroke. To investigate whether post-stroke rehabilitation affects fracture risk. We conducted a population-based retrospective cohort study based on the Taiwan National Health Insurance Research Database. Patients with a newly diagnosed ischemic stroke between 2000 and 2012 were included. After propensity score matching, a total of 8,384 patients were enrolled. Half of the patients (4,192) received post-stroke rehabilitation within 1 month; the other half did not receive any post-stroke rehabilitation. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) for fractures among patients with and without rehabilitation within 1 year after ischemic stroke. Patients were further stratified by sex and age (20-64 and ≥65 years). Patients receiving post-stroke rehabilitation had a higher incidence of fracture (6.2 per 100 person-years) than those who did not (4.1 per 100 person-years) after adjustment for sociodemographic and coexisting medical conditions [HR = 1.53, 95% confidence interval (CI) = 1.25-1.87, p < 0.001]. The analyses performed after stratifying for sex and age showed that only older women undergoing rehabilitation had a significantly higher risk of fracture (HR = 1.62, 95% CI = 1.21-2.17, p = 0.001). Rehabilitation after ischemic stroke is associated with an increased fracture risk in older women.

Ten-year risk of stroke in patients with previous cerebral infarction and the impact of carotid surgery in the Asymptomatic Carotid Surgery Trial.

PubMed

Streifler, Jonathan Y; den Hartog, Anne G; Pan, Samuel; Pan, Hongchao; Bulbulia, Richard; Thomas, Dafydd J; Brown, Martin M; Halliday, Alison

2016-12-01

Silent brain infarcts are common in patients at increased risk of stroke and are associated with a poor prognosis. In patients with asymptomatic carotid stenosis, similar adverse associations were claimed, but the impact of previous infarction or symptoms on the beneficial effects of carotid endarterectomy is not clear. Our aim was to evaluate the impact of prior cerebral infarction in patients enrolled in the Asymptomatic Carotid Surgery Trial, a large trial with 10-year follow-up in which participants whose carotid stenosis had not caused symptoms for at least six months were randomly allocated either immediate or deferred carotid endarterectomy. The first Asymptomatic Carotid Surgery Trial included 3120 patients. Of these, 2333 patients with baseline brain imaging were identified and divided into two groups irrespective of treatment assignment, 1331 with evidence of previous cerebral infarction, defined as a history of ischemic stroke or transient ischemic attack > 6 months prior to randomization or radiological evidence of an asymptomatic infarct (group 1) and 1002 with normal imaging and no prior stroke or transient ischemic attack (group 2). Stroke and vascular deaths were compared during follow-up, and the impact of carotid endarterectomy was observed in both groups. Baseline characteristics of patients with and without baseline brain imaging were broadly similar. Of those included in the present report, male gender and hypertension were more common in group 1, while mean ipsilateral stenosis was slightly greater in group 2. At 10 years follow-up, stroke was more common among participants with cerebral infarction before randomization (absolute risk increase 5.8% (1.8-9.8), p = 0.004), and the risk of stroke and vascular death was also higher in this group (absolute risk increase 6.9% (1.9-12.0), p = 0.007). On multivariate analysis, prior cerebral infarction was associated with a greater risk of stroke (hazard ratio = 1.51, 95% confidence interval: 1.17-1.95, p = 0.002) and of stroke or other vascular death (hazard ratio = 1.30, 95% confidence interval: 1.11-1.52, p = 0.001). At 10 years, greater absolute benefits from immediate carotid endarterectomy were seen in those patients with prior cerebral infarction (6.7% strokes immediate carotid endarterectomy vs. 14.7% delayed carotid endarterectomy; hazard ratio 0.47 (0.34-0.65), p = 0.003), compared to those lower risk patients without prior cerebral infarction (6.0% vs. 9.9%, respectively; hazard ratio 0.61 (0.39-0.94), p = 0.005), though it must be emphasized that the first Asymptomatic Carotid Surgery Trial was not designed to test this retrospective and non-randomized comparison. Asymptomatic carotid stenosis patients with prior cerebral infarction have a higher stroke risk during long-term follow-up than those without prior cerebral infarction. Evidence of prior ischemic events might help identify patients in whom carotid intervention is particularly beneficial. © 2016 World Stroke Organization.

Multivitamin use and risk of stroke incidence and mortality amongst women.

PubMed

Adebamowo, S N; Feskanich, D; Stampfer, M; Rexrode, K; Willett, W C

2017-10-01

Few studies have examined the association between multivitamin use and the risk of stroke incidence and mortality, and the results remain inconclusive as to whether multivitamins are beneficial. The associations between multivitamin use and the risk of incident stroke and stroke mortality were prospectively examined in 86 142 women in the Nurses' Health Study, aged 34-59 years and free of diagnosed cardiovascular disease at baseline. Multivitamin use and covariates were updated every 2 years and strokes were documented by review of medical records. Hazard ratios of total, ischaemic and hemorrhagic strokes were calculated across categories of multivitamin use (non-user, past, current user) and duration (years), using Cox proportional hazards models. During 32 years of follow-up from 1980 to 2012, 3615 incident strokes were documented, including 758 deaths from stroke. In multivariate analyses, women who were current multivitamin users did not have a lower risk of incident total stroke compared to non-users [relative risk (RR) 1.02, 95% confidence interval (CI) 0.93-1.11], even those with longer durations of 15 or more years of use (RR 1.08, 95% CI 0.97-1.20) or those with a lower quality diet (RR 0.96, 95% CI 0.80-1.15). There was also no indication of benefit from multivitamin use for incident ischaemic or hemorrhagic strokes or for total stroke mortality. Long-term multivitamin use was not associated with reduced risk of stroke incidence or mortality amongst women in the study population, even amongst those with a lower diet quality. An effect in a less well-nourished population cannot be ruled out. © 2017 EAN.

Symptoms of Insomnia and Sleep Duration and Their Association with Incident Strokes: Findings from the Population-Based MONICA/KORA Augsburg Cohort Study.

PubMed

Helbig, A Katharina; Stöckl, Doris; Heier, Margit; Ladwig, Karl-Heinz; Meisinger, Christa

2015-01-01

To examine the relationship between symptoms of insomnia and sleep duration and incident total (non-fatal plus fatal) strokes, non-fatal strokes, and fatal strokes in a large cohort of men and women from the general population in Germany. In four population-based MONICA (monitoring trends and determinants in cardiovascular disease)/KORA (Cooperative Health Research in the Region of Augsburg) surveys conducted between 1984 and 2001, 17,604 men and women (aged 25 to 74 years) were asked about issues like sleep, health behavior, and medical history. In subsequent surveys and mortality follow-ups, incident stroke cases (cerebral hemorrhage, ischemic stroke, transient ischemic attack, unknown stroke type) were gathered prospectively until 2009. Sex-specific hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using sequential Cox proportional hazards regression models. During a mean follow-up of 14 years, 917 strokes (710 non-fatal strokes and 207 fatal strokes) were observed. Trouble falling asleep and difficulty staying asleep were not significantly related to any incident stroke outcome in either sex in the multivariable models. Among men, the HR for the association between short (≤5 hours) and long (≥10 hours) daily sleep duration and total strokes were 1.44 (95% CI: 1.01-2.06) and 1.63 (95% CI: 1.16-2.29), after adjustment for basic confounding variables. As for non-fatal strokes and fatal strokes, in the analyses adjusted for age, survey, education, physical activity, alcohol consumption, smoking habits, body mass index, hypertension, diabetes, and dyslipidemia, the increased risks persisted, albeit somewhat attenuated, but no longer remained significant. Among women, in the multivariable analyses the quantity of sleep was also not related to any stroke outcome. In the present study, symptoms of insomnia and exceptional sleep duration were not significantly predictive of incident total strokes, non-fatal strokes, and fatal strokes in either sex.

Symptoms of Insomnia and Sleep Duration and Their Association with Incident Strokes: Findings from the Population-Based MONICA/KORA Augsburg Cohort Study

PubMed Central

Helbig, A. Katharina; Stöckl, Doris; Heier, Margit; Ladwig, Karl-Heinz; Meisinger, Christa

2015-01-01

Objective To examine the relationship between symptoms of insomnia and sleep duration and incident total (non-fatal plus fatal) strokes, non-fatal strokes, and fatal strokes in a large cohort of men and women from the general population in Germany. Methods In four population-based MONICA (monitoring trends and determinants in cardiovascular disease)/KORA (Cooperative Health Research in the Region of Augsburg) surveys conducted between 1984 and 2001, 17,604 men and women (aged 25 to 74 years) were asked about issues like sleep, health behavior, and medical history. In subsequent surveys and mortality follow-ups, incident stroke cases (cerebral hemorrhage, ischemic stroke, transient ischemic attack, unknown stroke type) were gathered prospectively until 2009. Sex-specific hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using sequential Cox proportional hazards regression models. Results During a mean follow-up of 14 years, 917 strokes (710 non-fatal strokes and 207 fatal strokes) were observed. Trouble falling asleep and difficulty staying asleep were not significantly related to any incident stroke outcome in either sex in the multivariable models. Among men, the HR for the association between short (≤5 hours) and long (≥10 hours) daily sleep duration and total strokes were 1.44 (95% CI: 1.01–2.06) and 1.63 (95% CI: 1.16–2.29), after adjustment for basic confounding variables. As for non-fatal strokes and fatal strokes, in the analyses adjusted for age, survey, education, physical activity, alcohol consumption, smoking habits, body mass index, hypertension, diabetes, and dyslipidemia, the increased risks persisted, albeit somewhat attenuated, but no longer remained significant. Among women, in the multivariable analyses the quantity of sleep was also not related to any stroke outcome. Conclusion In the present study, symptoms of insomnia and exceptional sleep duration were not significantly predictive of incident total strokes, non-fatal strokes, and fatal strokes in either sex. PMID:26230576

The effects of sleep duration on the incidence of cardiovascular events among middle-aged male workers in Japan.

PubMed

Hamazaki, Yuko; Morikawa, Yuko; Nakamura, Koshi; Sakurai, Masaru; Miura, Katsuyuki; Ishizaki, Masao; Kido, Teruhiko; Naruse, Yuchi; Suwazono, Yasushi; Nakagawa, Hideaki

2011-09-01

Although previous epidemiological studies have investigated the relationship between sleep duration and various cardiovascular events, the results have been inconsistent. Accordingly, we conducted a follow-up survey to investigate the relationship between sleep duration and cardiovascular events among male workers, accounting for occupational factors that might confound the true relationship. A total of 2282 male employees aged 35-54 years based in a factory in Japan were followed for 14 years. The risk of cardiovascular events was compared among 4 groups stratified based on sleep duration at baseline (<6, 6-6.9, 7-7.9, and ≥8 hours). Cardiovascular events included stroke, coronary events and sudden cardiac death. The hazard ratios for events were calculated using a Cox proportional hazards model, with the 7-7.9-hour group serving as a reference. The model was adjusted for potential confounders including traditional cardiovascular risk factors and working characteristics. During 14 years of follow-up, 64 cardiovascular events were recorded including 30 strokes, 27 coronary events and 7 sudden cardiac deaths. After adjustment for possible confounders, the hazard ratios for cardiovascular and coronary events in the <6-hour group were 3.49 [95% confidence interval (95% CI) 1.30-9.40] and 4.95 (95% CI 1.31-18.73), respectively. There was no significant increment in the risk of stroke for any sleep duration groups. Short sleep duration (<6 hours) was a significant risk factor for coronary events in a Japanese male working population.

Serum leptin levels and the risk of stroke: The Framingham Study

PubMed Central

Saber, Hamidreza; Himali, Jayandra J.; Shoamanesh, Ashkan; Beiser, Alexa; Pikula, Alexandra; Harris, Tamara B.; Roubenoff, Ronenn; Romero, Jose Rafael; Kase, Carlos S.; Vasan, Ramachandran S.; Seshadri, Sudha

2015-01-01

Background and Purpose Leptin is a major adipokine that regulates weight balance and energy homeostasis. There is inconsistent evidence linking circulating leptin levels to risk of stroke. We tested the hypothesis that leptin levels are associated with risk of incident stroke in an elderly community-based sample. Methods Serum leptin levels were assayed in 757 stroke-free individuals (mean age 79 years, 62% women) from the Framingham Original cohort at the 22nd examination cycle (1990–1994). Incidence of all-stroke and ischemic stroke were prospectively ascertained. Results During a mean follow-up of 10 years, 119 individuals developed stroke (99 ischemic stroke). In multivariable Cox regression models, log-leptin levels were not associated with incidence of all-stroke or ischemic stroke (hazard ratios[HR] per standard deviation(SD) increment in log-leptin 0.9 [0.73–1.09] and 0.89 [0.72–1.11], respectively). The results were suggestive for potential effect modification by waist-hip ratio(WHR) for the association between leptin and stroke (P=0.03). Adjusting for age, sex and established stroke risk factors, analysis stratified by WHR quartiles revealed a lower incidence of first-ever all-stroke and ischemic stroke associated with higher leptin levels among only subjects in the top WHR quartile (HR, 0.64 [0.43, 0.95] versus 0.98 [0.77, 1.25], for incident all-stroke and 0.61 [0.39, 0.95] versus 0.96 [0.74, 1.26] for ischemic stroke). Conclusions Leptin levels were not directly related to risk of incident stroke overall but there was an inverse association with stroke in the top WHR quartile. Further investigations are required to confirm these findings and explore possible mechanisms for the observed association. PMID:26337973

Relationship Between Blood Pressure Values, Depressive Symptoms, and Cardiovascular Outcomes in Patients With Cardiometabolic Disease.

PubMed

Jani, Bhautesh Dinesh; Cavanagh, Jonathan; Barry, Sarah J E; Der, Geoff; Sattar, Naveed; Mair, Frances S

2016-10-01

The authors studied the joint effect of blood pressure (BP) and depression on the risk of major adverse cardiovascular outcome in patients with existing cardiometabolic disease. A cohort of 35,537 patients with coronary heart disease, diabetes, or stroke underwent depression screening and BP measurement recorded concurrently. The authors used Cox's proportional hazards to calculate risk of major adverse cardiovascular event (MACE; myocardial infarction/heart failure/stroke or cardiovascular death) over 4 years associated with baseline BP and depression. A total of 11% (3939) had experienced a MACE within 4 years. Patients with very high systolic BP (160-240 mm Hg; hazard ratio, 1.28) and depression (hazard ratio, 1.22) at baseline had significantly higher adjusted risk. Depression had a significant interaction with systolic BP in risk prediction (P=.03). Patients with a combination of high systolic BP and depression at baseline had 83% higher adjusted risk of MACE, as compared with patients with reference systolic BP without depression. Patients with cardiometabolic disease and comorbid depression may benefit from closer monitoring of systolic BP. © 2016 The Authors. The Journal of Clinical Hypertension Published by Wiley Periodicals, Inc.

Impact of MCA stenosis on the early outcome in acute ischemic stroke patients

PubMed Central

Jeng, Jiann-Shing; Hsieh, Fang-I; Yeh, Hsu-Ling; Chen, Wei-Hung; Chiu, Hou-Chang; Tang, Sung-Chun; Liu, Chung-Hsiang; Lin, Huey-Juan; Hsu, Shih-Pin; Lo, Yuk-Keung; Chan, Lung; Chen, Chih-Hung; Lin, Ruey-Tay; Chen, Yu-Wei; Lee, Jiunn-Tay; Yeh, Chung-Hsin; Sun, Ming-Hui; Lai, Ta-Chang; Sun, Yu; Sun, Mu-Chien; Chen, Po-Lin; Chiang, Tsuey-Ru; Lin, Shinn-Kuang; Yip, Bak-Sau; Chen, Chin-I; Bai, Chi-Huey; Chen, Sien-Tsong; Chiou, Hung-Yi; Lien, Li-Ming; Hsu, Chung Y.

2017-01-01

Background Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). Methods Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups. Results Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440–3.374; p<0.001) at 3 months after stroke than those without MCA stenosis. Conclusions In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome. PMID:28388675

Four ECG left ventricular hypertrophy criteria and the risk of cardiovascular events and mortality in patients with vascular disease.

PubMed

van Kleef, Monique E A M; Visseren, Frank L J; Vernooij, Joris W P; Nathoe, Hendrik M; Cramer, Maarten-Jan M; Bemelmans, Remy H H; van der Graaf, Yolanda; Spiering, Wilko

2018-06-06

The relation between different electrocardiographic left ventricular hypertrophy (ECG-LVH) criteria and cardiovascular risk in patients with clinical manifest arterial disease is unclear. Therefore, we determined the association between four ECG-LVH criteria: Sokolow-Lyon, Cornell product, Cornell/strain index and Framingham criterion; and risk of cardiovascular events and mortality in this population. Risk of cardiovascular events was estimated in 6913 adult patients with clinical manifest arterial disease originating from the Secondary Manifestations of ARTerial disease (SMART) cohort. Cox proportional regression analysis was used to estimate the risk of the four ECG-LVH criteria and the primary composite outcome: myocardial infarction (MI), stroke or cardiovascular death; and secondary outcomes: MI, stroke and all-cause mortality; adjusted for confounders. The highest prevalence of ECG-LVH was observed for Cornell product (10%) and Cornell/strain index (9%). All four ECG-LVH criteria were associated with an increased risk of the primary composite endpoint: Sokolow-Lyon (hazard ratio 1.37, 95% CI 1.13-1.66), Cornell product (hazard ratio 1.54, 95% CI 1.30-1.82), Cornell/strain index (hazard ratio 1.70, 95% CI 1.44-2.00) and Framingham criterion (hazard ratio 1.78, 95% CI 1.21-2.62). Cornell product, Cornell/strain index and Framingham criterion ECG-LVH were additionally associated with an elevated risk of secondary outcomes. Cardiovascular risk increased whenever two, or three or more ECG-LVH criteria were present concurrently. All four ECG-LVH criteria are associated with an increased risk of cardiovascular events. As Cornell/strain index is both highly prevalent and carries a high cardiovascular risk, this is likely the most relevant ECG-LVH criterion for clinical practice.

Thrombin-receptor antagonist vorapaxar in acute coronary syndromes.

PubMed

Tricoci, Pierluigi; Huang, Zhen; Held, Claes; Moliterno, David J; Armstrong, Paul W; Van de Werf, Frans; White, Harvey D; Aylward, Philip E; Wallentin, Lars; Chen, Edmond; Lokhnygina, Yuliya; Pei, Jinglan; Leonardi, Sergio; Rorick, Tyrus L; Kilian, Ann M; Jennings, Lisa H K; Ambrosio, Giuseppe; Bode, Christoph; Cequier, Angel; Cornel, Jan H; Diaz, Rafael; Erkan, Aycan; Huber, Kurt; Hudson, Michael P; Jiang, Lixin; Jukema, J Wouter; Lewis, Basil S; Lincoff, A Michael; Montalescot, Gilles; Nicolau, José Carlos; Ogawa, Hisao; Pfisterer, Matthias; Prieto, Juan Carlos; Ruzyllo, Witold; Sinnaeve, Peter R; Storey, Robert F; Valgimigli, Marco; Whellan, David J; Widimsky, Petr; Strony, John; Harrington, Robert A; Mahaffey, Kenneth W

2012-01-05

Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).

Risk of falling in a stroke unit after acute stroke: The Fall Study of Gothenburg (FallsGOT).

PubMed

Persson, Carina U; Kjellberg, Sigvar; Lernfelt, Bodil; Westerlind, Ellen; Cruce, Malin; Hansson, Per-Olof

2018-03-01

This study aimed to investigate incidence of falls and different baseline variables and their association with falling during hospitalization in a stroke unit among patients with acute stroke. Prospective observational study. A stroke unit at a university hospital. A consecutive sample of stroke patients, out of which 504 were included, while 101 declined participation. The patients were assessed a mean of 1.7 days after admission and 3.8 days after stroke onset. The primary end-point was any fall, from admission to the stroke unit to discharge. Factors associated with falling were analysed using univariable and multivariable Cox hazard regression analyses. Independent variables were related to function, activity and participation, as well as personal and environmental factors. In total, 65 patients (13%) fell at least once. Factors statistically significantly associated with falling in the multivariable analysis were male sex (hazard ratio (HR): 1.88, 95% confidence interval (CI): 1.13-3.14, P = 0.015), use of a walking aid (HR: 2.11, 95% CI: 1.24-3.60, P = 0.006) and postural control as assessed with the modified version of the Postural Assessment Scale for Stroke Patients (SwePASS). No association was found with age, cognition or stroke severity, the HR for low SwePASS scores (⩽24) was 9.33 (95% CI: 2.19-39.78, P = 0.003) and for medium SwePASS scores (25-30) was 6.34 (95% CI: 1.46-27.51, P = 0.014), compared with high SwePASS scores (⩾31). Postural control, male sex and use of a walking aid are associated with falling during hospitalization after acute stroke.

Sleep duration and risk of stroke mortality among Chinese adults: the Singapore Chinese Health Study

PubMed Central

Pan, An; De Silva, Deidre Anne; Yuan, Jian-Min; Koh, Woon-Puay

2014-01-01

Background and Purpose Prospective relation between sleep duration and stroke risk is less studied, particularly in Asians. We examined the association between sleep duration and stroke mortality among Chinese adults. Methods The Singapore Chinese Health Study is a population-based cohort of 63,257 Chinese adults aged 45-74 years enrolled during 1993 through 1998. Sleep duration at baseline was assessed via in-person interview, and death information during follow-up was ascertained via record linkage with the death registry up to December 31, 2011. Cox proportional hazard models were used to calculate hazard ratios (HRs) with adjustment for other comorbidities and lifestyle risk factors of stroke mortality. Results During 926,752 person-years of follow-up, we documented 1,381 stroke deaths (322 from hemorrhagic and 1,059 from ischemic or non-specified strokes). Compared to individuals with 7 hours/day of sleep, the multivariate-adjusted HR (95% confidence interval) of total stroke mortality was 1.25 (1.05-1.50) for ≤5 hours/day (short duration), 1.01 (0.87-1.18) for 6 hours/day, 1.09 (0.95-1.26) for 8 hours/day, and 1.54 (1.28-1.85) for ≥9 hours/day (long duration). The increased risk of stroke death with short (1.54; 1.16-2.03) and long duration of sleep (1.95; 1.48-2.57) was seen among subjects with a history of hypertension, but not in those without hypertension. These findings were limited to risk of death from ischemic or non-specified stroke, but not observed for hemorrhagic stroke. Conclusions Both short and long sleep durations are associated with increased risk of stroke mortality in a Chinese population, particularly among those with a history of hypertension. PMID:24743442

Physical Activity Frequency and Risk of Incident Stroke in a National US Study of Blacks and Whites

PubMed Central

McDonnell, Michelle N; Hillier, Susan L; Hooker, Steven P; Le, Anh; Judd, Suzanne E; Howard, Virginia J

2013-01-01

Background and Purpose Regular physical activity is an important recommendation for stroke prevention. We compared the associations of self-reported physical activity (PA) with incident stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Methods REGARDS recruited 30,239 US blacks (42%) and whites, aged ≥45 with follow-up every six months for stroke events. Excluding those with prior stroke, analysis involved27,348participants who reported their frequency of moderate-vigorous intensity PA at baseline according to three categories: none (physical inactivity), 1–3 times/week and ≥ 4 times/week. Stroke and TIA cases were identified during an average of 5.7 years of follow-up. Cox proportional hazards models were constructed to examine whether self-reported PA was associated with risk of incident stroke. Results Physical inactivity was reported by 33% of participants and was associated with a hazard ratio (HR) of 1.20 ([95% confidence intervals 1.02–1.42], p = 0.035). Adjustment for demographic and socioeconomic factors did not affect HR, but further adjustment for traditional stroke risk factors (diabetes, hypertension, body mass index, alcohol use and smoking) partially attenuated this risk (HR 1.14 [0.95–1.37], p = 0.17). There was no significant association between PA frequency and risk of stroke by sex groups although there was a trend towards increased risk for men reporting PA 0–3 times a week compared to 4 or more times a week. Conclusions Self-reported low PA frequency is associated with increased risk of incident stroke. Any effect of PA is likely to be mediated through reducing traditional risk factors. PMID:23868271

Metabolic syndrome and ischemic stroke risk: Northern Manhattan Study.

PubMed

Boden-Albala, Bernadette; Sacco, Ralph L; Lee, Hye-Sueng; Grahame-Clarke, Cairistine; Rundek, Tanja; Elkind, Mitchell V; Wright, Clinton; Giardina, Elsa-Grace V; DiTullio, Marco R; Homma, Shunichi; Paik, Myunghee C

2008-01-01

More than 47 million individuals in the United States meet the criteria for the metabolic syndrome. The relation between the metabolic syndrome and stroke risk in multiethnic populations has not been well characterized. As part of the Northern Manhattan Study, 3298 stroke-free community residents were prospectively followed up for a mean of 6.4 years. The metabolic syndrome was defined according to guidelines established by the National Cholesterol Education Program Adult Treatment Panel III. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs for ischemic stroke and vascular events (ischemic stroke, myocardial infarction, or vascular death). The etiologic fraction estimates the proportion of events attributable to the metabolic syndrome. More than 44% of the cohort had the metabolic syndrome (48% of women vs 38% of men, P<0.0001), which was more prevalent among Hispanics (50%) than whites (39%) or blacks (37%). The metabolic syndrome was associated with increased risk of stroke (HR=1.5; 95% CI, 1.1 to 2.2) and vascular events (HR=1.6; 95% CI, 1.3 to 2.0) after adjustment for sociodemographic and risk factors. The effect of the metabolic syndrome on stroke risk was greater among women (HR=2.0; 95% CI, 1.3 to 3.1) than men (HR=1.1; 95% CI, 0.6 to 1.9) and among Hispanics (HR=2.0; 95% CI, 1.2 to 3.4) compared with blacks and whites. The etiologic fraction estimates suggest that elimination of the metabolic syndrome would result in a 19% reduction in overall stroke, a 30% reduction of stroke in women; and a 35% reduction of stroke among Hispanics. The metabolic syndrome is an important risk factor for ischemic stroke, with differential effects by sex and race/ethnicity.

Greater Volume but not Higher Density of Abdominal Aortic Calcium Is Associated With Increased Cardiovascular Disease Risk: MESA (Multi-Ethnic Study of Atherosclerosis).

PubMed

Forbang, Nketi I; Michos, Erin D; McClelland, Robyn L; Remigio-Baker, Rosemay A; Allison, Matthew A; Sandfort, Veit; Ix, Joachim H; Thomas, Isac; Rifkin, Dena E; Criqui, Michael H

2016-11-01

Abdominal aortic calcium (AAC) and coronary artery calcium (CAC) independently and similarly predict cardiovascular disease (CVD) events. The standard AAC and CAC score, the Agatston method, upweights for greater calcium density, thereby modeling higher calcium density as a CVD hazard. Computed tomography scans were used to measure AAC and CAC volume and density in a multiethnic cohort of community-dwelling individuals, and Cox proportional hazard was used to determine their independent association with incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or CHD death), cardiovascular disease (CVD, defined as CHD plus stroke and stroke death), and all-cause mortality. In 997 participants with Agatston AAC and CAC scores >0, the mean age was 66±9 years, and 58% were men. During an average follow-up of 9 years, there were 77 CHD, 118 CVD, and 169 all-cause mortality events. In mutually adjusted models, additionally adjusted for CVD risk factors, an increase in ln(AAC volume) per standard deviation was significantly associated with increased all-cause mortality (hazard ratio=1.20; 95% confidence interval, 1.08-1.33; P<0.01) and an increased ln(CAC volume) per standard deviation was significantly associated with CHD (hazard ratio=1.17; 95% confidence interval, 1.04-1.59; P=0.02) and CVD (hazard ratio=1.20; 95% confidence interval, 1.05-1.36; P<0.01). In contrast, both AAC and CAC density were not significantly associated with CVD events. The Agatston method of upweighting calcium scores for greater density may be inappropriate for CVD risk prediction in both the abdominal aorta and coronary arteries. © 2016 American Heart Association, Inc.

Administrative data linkage to evaluate a quality improvement program in acute stroke care, Georgia, 2006-2009.

PubMed

Ido, Moges Seyoum; Bayakly, Rana; Frankel, Michael; Lyn, Rodney; Okosun, Ike S

2015-01-15

Tracking the vital status of stroke patients through death data is one approach to assessing the impact of quality improvement in stroke care. We assessed the feasibility of linking Georgia hospital discharge data with mortality data to evaluate the effect of participation in the Georgia Coverdell Acute Stroke Registry on survival rates among acute ischemic stroke patients. Multistage probabilistic matching, using a fine-grained record integration and linkage software program and combinations of key variables, was used to link Georgia hospital discharge data for 2005 through 2009 with mortality data for 2006 through 2010. Data from patients admitted with principal diagnoses of acute ischemic stroke were analyzed by using the extended Cox proportional hazard model. The survival times of patients cared for by hospitals participating in the stroke registry and of those treated at nonparticipating hospitals were compared. Average age of the 50,579 patients analyzed was 69 years, and 56% of patients were treated in Georgia Coverdell Acute Stroke Registry hospitals. Thirty-day and 365-day mortality after first admission for stroke were 8.1% and 18.5%, respectively. Patients treated at nonparticipating facilities had a hazard ratio for death of 1.14 (95% confidence interval, 1.03-1.26; P = .01) after the first week of admission compared with patients cared for by hospitals participating in the registry. Hospital discharge data can be linked with death data to assess the impact of clinical-level or community-level chronic disease control initiatives. Hospitals need to undertake quality improvement activities for a better patient outcome.

Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study.

PubMed

Smith, Ann; Patterson, Chris; Yarnell, John; Rumley, Ann; Ben-Shlomo, Yoav; Lowe, Gordon

2005-11-15

Few studies have examined whether hemostatic markers contribute to risk of coronary disease and ischemic stroke independently of conventional risk factors. This study examines 11 hemostatic markers that reflect different aspects of the coagulation process to determine which have prognostic value after accounting for conventional risk factors. A total of 2398 men aged 49 to 65 years were examined in 1984 to 1988, and the majority gave a fasting blood sample for assay of lipids and hemostatic markers. Men were followed up for a median of 13 years, and cardiovascular disease (CVD) events were recorded. There were 486 CVD events in total, 353 with prospective coronary disease and 133 with prospective ischemic stroke. On univariable analysis, fibrinogen, low activated protein C ratio, D-dimer, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were associated significantly with risk of CVD. On multivariable analyses with conventional risk factors forced into the proportional hazards model, fibrinogen, D-dimer, and PAI-1 were significantly associated with risk of CVD, whereas factor VIIc showed an inverse association (P=0.001). In a model that contained the conventional risk factors, the hazard ratio for subsequent CVD in the top third of the distribution of predicted risk relative to the bottom third was 2.7 for subjects without preexisting CVD. This ratio increased to 3.7 for the model that also contained the 4 hemostatic factors. Fibrinogen, D-dimer, PAI-1 activity, and factor VIIc each has potential to increase the prediction of coronary disease/ischemic stroke in middle-aged men, in addition to conventional risk factors.

Relations between dietary sodium and potassium intakes and mortality from cardiovascular disease: the Japan Collaborative Cohort Study for Evaluation of Cancer Risks.

PubMed

Umesawa, Mitsumasa; Iso, Hiroyasu; Date, Chigusa; Yamamoto, Akio; Toyoshima, Hideaki; Watanabe, Yoshiyuki; Kikuchi, Shogo; Koizumi, Akio; Kondo, Takaaki; Inaba, Yutaka; Tanabe, Naohito; Tamakoshi, Akiko

2008-07-01

Limited evidence is available about the relations between sodium and potassium intakes and cardiovascular disease in the general population. The objective was to investigate relations between sodium and potassium intakes and cardiovascular disease in Asian populations whose mean sodium intake is generally high. Between 1988 and 1990, a total of 58,730 Japanese subjects (n = 23,119 men and 35,611 women) aged 40-79 y with no history of stroke, coronary heart disease, or cancer completed a lifestyle questionnaire including food intake frequency under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Ministry of Education, Sports and Science. After 745,161 person-years of follow-up, we documented 986 deaths from stroke (153 subarachnoid hemorrhages, 227 intraparenchymal hemorrhages, and 510 ischemic strokes) and 424 deaths from coronary heart disease. Sodium intake was positively associated with mortality from total stroke, ischemic stroke, and total cardiovascular disease. The multivariable hazard ratio for the highest versus the lowest quintiles of sodium intake after adjustment for age, sex, and cardiovascular disease risk factors was 1.55 (95% CI: 1.21, 2.00; P for trend < 0.001) for total stroke, 2.04 (95% CI: 1.41, 2.94; P for trend < 0.001) for ischemic stroke, and 1.42 (95% CI: 1.20, 1.69; P for trend < 0.001) for total cardiovascular disease. Potassium intake was inversely associated with mortality from coronary heart disease and total cardiovascular disease. The multivariable hazard ratio for the highest versus the lowest quintiles of potassium intake was 0.65 (95% CI: 0.39, 1.06; P for trend = 0.083) for coronary heart disease and 0.73 (95% CI: 0.59, 0.92; P for trend = 0.018) for total cardiovascular disease, and these associations were more evident for women than for men. A high sodium intake and a low potassium intake may increase the risk of mortality from cardiovascular disease.

Development and Validation of a Predictive Model for Functional Outcome After Stroke Rehabilitation: The Maugeri Model.

PubMed

Scrutinio, Domenico; Lanzillo, Bernardo; Guida, Pietro; Mastropasqua, Filippo; Monitillo, Vincenzo; Pusineri, Monica; Formica, Roberto; Russo, Giovanna; Guarnaschelli, Caterina; Ferretti, Chiara; Calabrese, Gianluigi

2017-12-01

Prediction of outcome after stroke rehabilitation may help clinicians in decision-making and planning rehabilitation care. We developed and validated a predictive tool to estimate the probability of achieving improvement in physical functioning (model 1) and a level of independence requiring no more than supervision (model 2) after stroke rehabilitation. The models were derived from 717 patients admitted for stroke rehabilitation. We used multivariable logistic regression analysis to build each model. Then, each model was prospectively validated in 875 patients. Model 1 included age, time from stroke occurrence to rehabilitation admission, admission motor and cognitive Functional Independence Measure scores, and neglect. Model 2 included age, male gender, time since stroke onset, and admission motor and cognitive Functional Independence Measure score. Both models demonstrated excellent discrimination. In the derivation cohort, the area under the curve was 0.883 (95% confidence intervals, 0.858-0.910) for model 1 and 0.913 (95% confidence intervals, 0.884-0.942) for model 2. The Hosmer-Lemeshow χ 2 was 4.12 ( P =0.249) and 1.20 ( P =0.754), respectively. In the validation cohort, the area under the curve was 0.866 (95% confidence intervals, 0.840-0.892) for model 1 and 0.850 (95% confidence intervals, 0.815-0.885) for model 2. The Hosmer-Lemeshow χ 2 was 8.86 ( P =0.115) and 34.50 ( P =0.001), respectively. Both improvement in physical functioning (hazard ratios, 0.43; 0.25-0.71; P =0.001) and a level of independence requiring no more than supervision (hazard ratios, 0.32; 0.14-0.68; P =0.004) were independently associated with improved 4-year survival. A calculator is freely available for download at https://goo.gl/fEAp81. This study provides researchers and clinicians with an easy-to-use, accurate, and validated predictive tool for potential application in rehabilitation research and stroke management. © 2017 American Heart Association, Inc.

Associations between incident ischemic stroke events and stroke and cardiovascular disease-related genome-wide association studies single nucleotide polymorphisms in the Population Architecture Using Genomics and Epidemiology study.

PubMed

Carty, Cara L; Buzková, Petra; Fornage, Myriam; Franceschini, Nora; Cole, Shelley; Heiss, Gerardo; Hindorff, Lucia A; Howard, Barbara V; Mann, Sue; Martin, Lisa W; Zhang, Ying; Matise, Tara C; Prentice, Ross; Reiner, Alexander P; Kooperberg, Charles

2012-04-01

Genome-wide association studies (GWAS) have identified loci associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European-descent individuals, but their replication in different populations has been largely unexplored. Nine single nucleotide polymorphisms (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously associated with myocardial infarction and CVD risk factors, including blood lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], and triglycerides), type 2 diabetes, and body mass index (BMI), were investigated for associations with incident IS in European Americans (EA) N=26 276, African-Americans (AA) N=8970, and American Indians (AI) N=3570 from the Population Architecture using Genomics and Epidemiology Study. Ancestry-specific fixed effects meta-analysis with inverse variance weighting was used to combine study-specific log hazard ratios from Cox proportional hazards models. Two of 9 stroke SNPs (rs783396 and rs1804689) were significantly associated with [corrected] IS hazard in AA; none were significant in this large EA cohort. Of 73 CVD risk factor SNPs tested in EA, 2 (HDL and triglycerides SNPs) were associated with IS. In AA, SNPs associated with LDL, HDL, and BMI were significantly associated with IS (3 of 86 SNPs tested). Out of 58 SNPs tested in AI, 1 LDL SNP was significantly associated with IS. Our analyses showing lack of replication in spite of reasonable power for many stroke SNPs and differing results by ancestry highlight the need to follow up on GWAS findings and conduct genetic association studies in diverse populations. We found modest IS associations with BMI and lipids SNPs, though these findings require confirmation.

Association of Traditional Chinese Medicine Therapy and the Risk of Vascular Complications in Patients With Type II Diabetes Mellitus: A Nationwide, Retrospective, Taiwanese-Registry, Cohort Study.

PubMed

Lee, Ai-Lin; Chen, Bor-Chyuan; Mou, Chih-Hsin; Sun, Mao-Feng; Yen, Hung-Rong

2016-01-01

With an increasing use of traditional Chinese medicine (TCM) in type 2 diabetes mellitus (T2DM), evidence of long-term benefit with adjunctive TCM treatment is limited. This study investigated whether the concurrent TCM treatment reduces the risk of vascular complications in T2DM patients by using a large population from National Health Insurance Research Database (NHIRD).We identified 33,457 adult patients with newly diagnosed T2DM using anti-diabetic agents from a random sample of one million beneficiaries in the NHIRD between January 1, 2000 and December 31, 2011. We recruited 1049 TCM users (received TCM over 30 days with a diagnosis of T2DM) and randomly selected 4092 controls as the non-TCM cohort at a ratio of 1:4 frequency-matched by age, sex, hypertension, hyperlipidemia, and index year. We investigated the prescription pattern of TCM and conducted a Cox proportional hazards regression to calculate the hazard ratios (HRs) of stroke, chronic kidney diseases (CKD), and diabetic foot between the 2 cohorts.In the TCM cohort, the prescription pattern of TCM was different between insulin and noninsulin patients. The most common herbs were Dan-Shen (Radix Salviae Miltiorrhizae) in noninsulin group and Da-Huang (Radix et Rhizoma Rhei) in insulin group. The most common formulae were Liu-Wei-Di-Huang-Wan in noninsulin group and Yu-Quan-Wan in insulin group. Although no significant reduction in the hazard ratio of CKD and diabetic foot, the incidence rate of stroke was 7.19 per 1000 person-years in the TCM cohort and 10.66 per 1000 person-years in the control cohort, respectively. After adjustment of age, sex, hypertension, hyperlipidemia, and antidiabetes agent use (including sulfonylureas, α-glucosidase, metformin, meglitinide, thiazolidinediones, and insulin), TCM cohorts were found to have a 33% decreased risk of stroke (95% CI = 0.46-0.97; P < 0.05).This population-based retrospective study showed that the complementary TCM therapy might associate with the decreased risk of stroke in T2DM, suggesting TCM as an adjunctive therapy for T2DM to prevent subsequent stroke.

Apixaban in patients with atrial fibrillation.

PubMed

Connolly, Stuart J; Eikelboom, John; Joyner, Campbell; Diener, Hans-Christoph; Hart, Robert; Golitsyn, Sergey; Flaker, Greg; Avezum, Alvaro; Hohnloser, Stefan H; Diaz, Rafael; Talajic, Mario; Zhu, Jun; Pais, Prem; Budaj, Andrzej; Parkhomenko, Alexander; Jansky, Petr; Commerford, Patrick; Tan, Ru San; Sim, Kui-Hian; Lewis, Basil S; Van Mieghem, Walter; Lip, Gregory Y H; Kim, Jae Hyung; Lanas-Zanetti, Fernando; Gonzalez-Hermosillo, Antonio; Dans, Antonio L; Munawar, Muhammad; O'Donnell, Martin; Lawrence, John; Lewis, Gayle; Afzal, Rizwan; Yusuf, Salim

2011-03-03

Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients. In a double-blind study, we randomly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban (at a dose of 5 mg twice daily) or aspirin (81 to 324 mg per day), to determine whether apixaban was superior. The mean follow up period was 1.1 years. The primary outcome was the occurrence of stroke or systemic embolism. Before enrollment, 40% of the patients had used a vitamin K antagonist. The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban. There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI], 0.32 to 0.62; P<0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P=0.07). There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P=0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P<0.001). The treatment effects were consistent among important subgroups. In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable, apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00496769.).

Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure.

PubMed

Mehra, Mandeep R; Goldstein, Daniel J; Uriel, Nir; Cleveland, Joseph C; Yuzefpolskaya, Melana; Salerno, Christopher; Walsh, Mary N; Milano, Carmelo A; Patel, Chetan B; Ewald, Gregory A; Itoh, Akinobu; Dean, David; Krishnamoorthy, Arun; Cotts, William G; Tatooles, Antone J; Jorde, Ulrich P; Bruckner, Brian A; Estep, Jerry D; Jeevanandam, Valluvan; Sayer, Gabriel; Horstmanshof, Douglas; Long, James W; Gulati, Sanjeev; Skipper, Eric R; O'Connell, John B; Heatley, Gerald; Sood, Poornima; Naka, Yoshifumi

2018-04-12

In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure. In a randomized noninferiority and superiority trial, we compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal-flow pump group minus axial-flow pump group) was -10 percentage points. Of 366 patients, 190 were assigned to the centrifugal-flow pump group and 176 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal-flow pump group, as compared with 106 (60.2%) in the axial-flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (3 patients [1.6%] vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal-flow pump group than in the axial-flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02). In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Stroke After Radiation Therapy for Head and Neck Cancer: What Is the Risk?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arthurs, Erin; Hanna, Timothy P.; Department of Oncology, Queen's University, Kingston, Ontario

Purpose: A retrospective population-based cohort study was conducted to determine the risk of ischemic stroke with respect to time, associated with curative radiation therapy in head and neck squamous cell carcinomas (HNSCC). Methods and Materials: On the basis of data from the Ontario Cancer Registry and regional cancer treatment centers, 14,069 patients were identified with diagnoses of squamous cell carcinoma of the oral cavity, larynx, and pharynx who were treated for cure between 1990 and 2010. Hazards of stroke and time to stroke were examined, accounting for the competing risk of death. Stroke risk factors identified through diagnostic and proceduralmore » administrative codes were adjusted for in the comparison between treatment regimens, which included surgery alone versus radiation therapy alone and surgery alone versus any exposure to radiation therapy. Results: Overall, 6% of patients experienced an ischemic stroke after treatment, with 5% experiencing a stroke after surgery, 8% after radiation therapy alone, and 6% after any exposure to radiation therapy. The cause-specific hazard ratios of ischemic stroke after radiation therapy alone and after any exposure to radiation therapy compared with surgery were 1.70 (95% confidence interval [CI]: 1.41-2.05) and 1.46 (95% CI: 1.23-1.73), respectively, after adjustment for stroke risk factors, patient factors, and disease-related factors. Conclusions: Radiation therapy was associated with an increased risk of ischemic stroke compared with surgery alone: for both radiation therapy alone and after all treatment modalities that included any radiation treatment were combined. Because of a shift toward a younger HNSCC patient population, our results speak to the need for adequate follow-up and survivorship care among patients who have been treated with radiation therapy. Advances in treatment that minimize chronic morbidity also require further evaluation.« less

Relation of dietary glycemic load with ischemic and hemorrhagic stroke: a cohort study in Greece and a meta-analysis.

PubMed

Rossi, Marta; Turati, Federica; Lagiou, Pagona; Trichopoulos, Dimitrios; La Vecchia, Carlo; Trichopoulou, Antonia

2015-03-01

High glycemic load (GL) has been associated with excess stroke risk. Data suggest a different role of diet in the etiology of ischemic and hemorrhagic stroke. We analyzed data from 19,824 participants of the Greek cohort of the population-based European Prospective Investigation into Cancer and nutrition (EPIC), who were free of cardiovascular diseases, cancer, and diabetes at baseline and had not developed diabetes. Diet was assessed at enrollment through a validated, interviewer-administered semi-quantitative food frequency questionnaire. The average daily GL was derived using standard tables. We also conducted a meta-analysis on GL and stroke (overall, ischemic and hemorrhagic), using random-effects models. In the Greek EPIC cohort, 304 incident stroke cases were identified (67 ischemic, 49 hemorrhagic). Using Cox proportional hazards regression models adjusted for potential confounders, the hazard ratios for the highest versus the lowest GL tertiles were 1.07 [95 % confidence interval (CI) 0.74-1.54] for overall stroke, 1.55 (95 % CI 0.72-3.36) for ischemic and 0.48 (95 % CI 0.18-1.25) for hemorrhagic stroke (p-heterogeneity <0.01). The meta-analysis, including a total of 3,088 incident cases and 247 deaths from stroke (1,469 cases and 126 deaths ischemic; 576 cases and 94 deaths hemorrhagic), estimated pooled relative risks for the highest versus the lowest GL levels of 1.23 (95 % CI 1.07-1.41) for overall, 1.35 (95 % CI 1.06-1.72) for ischemic, and 1.09 (95 % CI 0.81-1.47) for hemorrhagic stroke (p-heterogeneity = 0.275). This study indicates that GL is an important determinant of the more common ischemic-though not of the hemorrhagic-stroke.

Decreased risk of pneumonia in stroke patients receiving acupuncture: A nationwide matched-pair retrospective cohort study

PubMed Central

Chang, Chuen-Chau; Chen, Ta-Liang; Lin, Chao-Shun; Chung, Chi-Li; Yeh, Chun-Chieh; Hu, Chaur-Jong; Lane, Hsin-Long

2018-01-01

Background Acupuncture treatment is common among stroke patients, but there is limited information available on whether acupuncture effectively prevents post-stroke pneumonia. The aim of this study was to analyze the differential risk of pneumonia after stroke between patients who did and did not receive acupuncture after discharge. Methods We used the Taiwan National Health Insurance Research Database to conduct a retrospective cohort study using propensity score matched-pairs of new stroke patients in 2000–2004 who did and did not receive acupuncture post-stroke. Both cohorts were followed up until the end of 2009 for new-onset pneumonia. After correcting for immortal time bias, the incidence and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of pneumonia associated with acupuncture use were calculated using multivariate Cox proportional hazard models. Results Overall, 12557 stroke patients with 12557 paired controls were included in the analysis; pneumonia was diagnosed in 6796 (27.1%). Stroke patients receiving acupuncture had a lower incidence of pneumonia than those without acupuncture (53.4 vs. 58.9 per 1000 person-years), with an adjusted HR of 0.86 (95% CI 0.82–0.90). The association between pneumonia risk and acupuncture use was significant in men (HR 0.92, 95% CI 0.86–0.98) and women (HR 0.79, 95% 0.70–0.82) and was also observed in every age group from 20–79 years. Conclusion Stroke patients receiving acupuncture had a lower risk of pneumonia than those who did not. Further randomized control studies are needed to validate the protective effect of acupuncture on the risk of pneumonia among stroke patients. PMID:29782526

Cognitive Impairment, Vulnerability, and Mortality Post Ischemic Stroke: A Five-Year Follow-Up of the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) Cohort.

PubMed

Gaynor, Eva; Rohde, Daniela; Large, Margaret; Mellon, Lisa; Hall, Patricia; Brewer, Linda; Conway, Orla; Hickey, Anne; Bennett, Kathleen; Dolan, Eamon; Callaly, Elizabeth; Williams, David

2018-05-23

The aim of this study was to examine predictors of mortality in patients 5 years after ischemic stroke, focusing on cognitive impairment, vulnerability, and vascular risk factors assessed at 6 months post stroke. Patients from the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) cohort were followed up 5 years post ischemic stroke. Vascular risk factors, cognitive impairment, and vulnerability were assessed at 6 months post stroke. Cognitive impairment was assessed using a cutoff score lower than 26 on the Montreal Cognitive Assessment (MoCA). Vulnerability was defined as a score of 3 or higher on the Vulnerable Elders Scale (VES). Mortality and date of death were ascertained using hospital records, death notifications, and contact with general practitioners. Predictors of mortality were explored using multivariate Cox proportional hazards models. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented. Sixty-three of 256 patients (24.6%) assessed at 6 months post stroke had died within 5 years. Cognitive impairment (HR [95% CI]: 2.19 [1.42-3.39]), vulnerability (HR [95% CI]: 5.23 [2.92-9.36]), atrial fibrillation (AF) (HR [95% CI]: 2.31 [1.80-2.96]), and dyslipidemia (HR [95% CI]: 1.90 [1.10-3.27]) were associated with increased risk of 5-year mortality. Vulnerability, cognitive impairment, AF, and dyslipidemia at 6 months were associated with increased risks of mortality 5 years post ischemic stroke. Identification and management of these risk factors should be emphasized in poststroke care. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Are migraine and non-migrainous headache risk factors for stroke in the elderly? Findings from a 12-year cohort follow-up

PubMed Central

Norton, Joanna; Portet, Florence; Gabelle, Audrey; Debette, Stephanie; Ritchie, Karen; Touchon, Jacques; Berr, Claudine

2016-01-01

Background There is evidence that migraine is a risk factor for stroke but little is known about this association in elderly people. Furthermore, non-migrainous headache (NMH) has received little attention as a potential risk factor, despite being the most frequently reported type of headache. Late-life migraine and NMH were examined as candidate risk factors for stroke in a community-dwelling elderly sample over a 12-year follow-up. Methods 1919 non-institutionalized subjects 65+, without dementia (DSM-IV criteria) and no stroke history at baseline were drawn from the 3C-Montpellier cohort (recruitment 1999–2001) for the longitudinal analysis. Ischemic and haemorrhagic stroke was reported at baseline, and at each of the 5 follow-ups, with ICD-10 cases validated by a panel of experts. Migraine and NMH were determined at baseline during a neurological interview and examination using 1988 IHS criteria. Results 110 (5.4%) cases of migraine and 179 (8.9%) cases of NMH were identified at baseline. During the median 8.8 year follow-up, incident stroke was observed in 1.9% of baseline migrainers, 6.2% of NMH and 3.6% of those with no lifetime history of headache. Cox proportional hazard models indicated that migraine was not a risk factor for stroke, however NMH sufferers were twice as likely to have a stroke (Hazard Ratio=2.00, 95% CI: 1.00–3.93, p=0.049). Conclusions This study is one of the first to suggest that late-life NMH rather than migraine could be an independent risk factor for stroke and warning sign. The incidence of stroke in elderly migrainers, seldom reported, is particularly low. PMID:27399611

Post-ischemic stroke rehabilitation is associated with a higher risk of fractures in older women: A population-based cohort study

PubMed Central

Yang, Clement Shih Hsien; Liang, Chung Chao

2017-01-01

Background Rehabilitation can improve physical activity after stroke. However, patients may be more prone to falls and fractures because of balance and gait deficits. Few reports have studied the relationship between rehabilitation and subsequent fractures after ischemic stroke. Objective To investigate whether post-stroke rehabilitation affects fracture risk. Methods We conducted a population-based retrospective cohort study based on the Taiwan National Health Insurance Research Database. Patients with a newly diagnosed ischemic stroke between 2000 and 2012 were included. After propensity score matching, a total of 8,384 patients were enrolled. Half of the patients (4,192) received post-stroke rehabilitation within 1 month; the other half did not receive any post-stroke rehabilitation. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) for fractures among patients with and without rehabilitation within 1 year after ischemic stroke. Patients were further stratified by sex and age (20–64 and ≥65 years). Results Patients receiving post-stroke rehabilitation had a higher incidence of fracture (6.2 per 100 person-years) than those who did not (4.1 per 100 person-years) after adjustment for sociodemographic and coexisting medical conditions [HR = 1.53, 95% confidence interval (CI) = 1.25–1.87, p < 0.001]. The analyses performed after stratifying for sex and age showed that only older women undergoing rehabilitation had a significantly higher risk of fracture (HR = 1.62, 95% CI = 1.21–2.17, p = 0.001). Conclusion Rehabilitation after ischemic stroke is associated with an increased fracture risk in older women. PMID:28414796

Effects of Transferring to the Rehabilitation Ward on Long-Term Mortality Rate of First-Time Stroke Survivors: A Population-Based Study.

PubMed

Chen, Chien-Min; Yang, Yao-Hsu; Chang, Chia-Hao; Chen, Pau-Chung

2017-12-01

To assess the long-term health outcomes of acute stroke survivors transferred to the rehabilitation ward. Long-term mortality rates of first-time stroke survivors during hospitalization were compared among the following sets of patients: patients transferred to the rehabilitation ward, patients receiving rehabilitation without being transferred to the rehabilitation ward, and patients receiving no rehabilitation. Retrospective cohort study. Patients (N = 11,419) with stroke from 2005 to 2008 were initially assessed for eligibility. After propensity score matching, 390 first-time stroke survivors were included. None. Cox proportional hazards regression model was used to assess differences in 5-year poststroke mortality rates. Based on adjusted hazard ratios (HRs), the patients receiving rehabilitation without being transferred to the rehabilitation ward (adjusted HR, 2.20; 95% confidence interval [CI], 1.36-3.57) and patients receiving no rehabilitation (adjusted HR, 4.00; 95% CI, 2.55-6.27) had significantly higher mortality risk than the patients transferred to the rehabilitation ward. Mortality rate of the stroke survivors was affected by age ≥65 years (compared with age <45y; adjusted HR, 3.62), being a man (adjusted HR, 1.49), having ischemic stroke (adjusted HR, 1.55), stroke severity (Stroke Severity Index [SSI] score≥20, compared with SSI score<10; adjusted HR, 2.68), and comorbidity (Charlson-Deyo Comorbidity Index [CCI] score≥3, compared with CCI score=0; adjusted HR, 4.23). First-time stroke survivors transferred to the rehabilitation ward had a 5-year mortality rate 2.2 times lower than those who received rehabilitation without transfer to the rehabilitation ward and 4 times lower than those who received no rehabilitation. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Duration of diabetes and risk of ischemic stroke: the Northern Manhattan Study.

PubMed

Banerjee, Chirantan; Moon, Yeseon P; Paik, Myunghee C; Rundek, Tatjana; Mora-McLaughlin, Consuelo; Vieira, Julio R; Sacco, Ralph L; Elkind, Mitchell S V

2012-05-01

Diabetes increases stroke risk, but whether diabetes status immediately before stroke improves prediction and whether duration is important are less clear. We hypothesized that diabetes duration independently predicts ischemic stroke. Among 3298 stroke-free participants in the Northern Manhattan Study, baseline diabetes and age at diagnosis were determined. Incident diabetes was assessed annually (median, 9 years). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% CI for incident ischemic stroke using baseline diabetes, diabetes as a time-dependent covariate, and duration of diabetes as a time-varying covariate; models were adjusted for demographic and cardiovascular risk factors. Mean age was 69 ± 10 years (52% Hispanic, 21% white, and 24% black); 22% had diabetes at baseline and 10% had development of diabetes. There were 244 ischemic strokes, and both baseline diabetes (HR, 2.5; 95% CI, 1.9-3.3) and diabetes considered as a time-dependent covariate (HR, 2.4; 95% CI, 1.8-3.2) were similarly associated with stroke risk. Duration of diabetes was associated with ischemic stroke (adjusted HR, 1.03 per year with diabetes; 95% CI, 1.02-1.04). Compared to nondiabetic participants, those with diabetes for 0 to 5 years (adjusted HR, 1.7; 95% CI, 1.1-2.7), 5 to 10 years (adjusted HR, 1.8; 95% CI, 1.1-3.0), and ≥ 10 years (adjusted HR, 3.2; 95% CI, 2.4-4.5) were at increased risk. Duration of diabetes is independently associated with ischemic stroke risk adjusting for risk factors. The risk increases 3% each year, and triples with diabetes ≥ 10 years.

Racial Differences in the Impact of Elevated Systolic Blood Pressure on Stroke Risk

PubMed Central

Howard, George; Lackland, Daniel T.; Kleindorfer, Dawn O.; Kissela, Brett M.; Moy, Claudia S.; Judd, Suzanne E.; Safford, Monika M.; Cushman, Mary; Glasser, Stephen P.; Howard, Virginia J.

2013-01-01

Background Between the ages 45 and 65 years, incident stroke is 2 to 3 times more common in blacks than in whites, a difference not explained by traditional stroke risk factors. Methods Stroke risk was assessed in 27 748 black and white participants recruited between 2003 and 2007, who were followed up through 2011, in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Racial differences in the impact of systolic blood pressure (SBP) was assessed using proportional hazards models. Racial differences in stroke risk were assessed in strata defined by age (<65 years, 65–74 years, and ≥75 years) and SBP (<120 mm Hg, 120–139 mm Hg, and 140–159 mm Hg). Results Over 4.5 years of follow-up, 715 incident strokes occurred. A 10–mm Hg difference in SBP was associated with an 8% (95% CI, 0%-16%) increase in stroke risk for whites, but a 24% (95% CI, 14%-35%) increase for blacks (P value for interaction, .02). For participants aged 45 to 64 years (where disparities are greatest), the black to white hazard ratio was 0.87 (95% CI, 0.48–1.57) for normotensive participants, 1.38 (95% CI, 0.94–2.02) for those with prehypertension, and 2.38 (95% CI, 1.19–4.72) for those with stage 1 hypertension. Conclusions These findings suggest racial differences in the impact of elevated blood pressure on stroke risk. When these racial differences are coupled with the previously documented higher prevalence of hypertension and poorer control of hypertension in blacks, they may account for much of the racial disparity in stroke risk. PMID:23229778

Effect of Exhaust- and Nonexhaust-Related Components of Particulate Matter on Long-Term Survival After Stroke.

PubMed

Desikan, Anita; Crichton, Siobhan; Hoang, Uy; Barratt, Benjamin; Beevers, Sean D; Kelly, Frank J; Wolfe, Charles D A

2016-12-01

Outdoor air pollution represents a potentially modifiable risk factor for stroke. We examined the link between ambient pollution and mortality up to 5 years poststroke, especially for pollutants associated with vehicle exhaust. Data from the South London Stroke Register, a population-based register covering an urban, multiethnic population, were used. Hazard ratios (HR) for a 1 interquartile range increase in particulate matter <2.5 µm diameter (PM 2.5 ) and PM <10 µm (PM 10 ) were estimated poststroke using Cox regression, overall and broken down into exhaust and nonexhaust components. Analysis was stratified for ischemic and hemorrhagic strokes and was further broken down by Oxford Community Stroke Project classification. The hazard of death associated with PM 2.5 up to 5 years after stroke was significantly elevated (P=0.006) for all strokes (HR=1.28; 95% confidence interval [CI], 1.08-1.53) and ischemic strokes (HR, 1.32; 95% CI, 1.08-1.62). Within ischemic subtypes, PM 2.5 pollution increased mortality risk for total anterior circulation infarcts by 2-fold (HR, 2.01; 95% CI, 1.17-3.48; P=0.012) and by 78% for lacunar infarcts (HR, 1.78; 95% CI, 1.18-2.66; P=0.006). PM 10 pollution was associated with 45% increased mortality risk for lacunar infarct strokes (HR, 1.45; 95% CI, 1.06-2.00; P=0.022). Separating PM 2.5 and PM 10 into exhaust and nonexhaust components did not show increased mortality. Exposure to certain outdoor PM pollution, particularly PM 2.5 , increased mortality risk poststroke up to 5 years after the initial stroke. © 2016 American Heart Association, Inc.

Southern Dietary Pattern is Associated With Hazard of Acute Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

PubMed

Shikany, James M; Safford, Monika M; Newby, P K; Durant, Raegan W; Brown, Todd M; Judd, Suzanne E

2015-09-01

The association of overall diet, as characterized by dietary patterns, with risk of incident acute coronary heart disease (CHD) has not been studied extensively in samples including sociodemographic and regional diversity. We used data from 17 418 participants in Reasons for Geographic and Racial Differences in Stroke (REGARDS), a national, population-based, longitudinal study of white and black adults aged ≥45 years, enrolled from 2003 to 2007. We derived dietary patterns with factor analysis and used Cox proportional hazards regression to examine hazard of incident acute CHD events - nonfatal myocardial infarction and acute CHD death - associated with quartiles of consumption of each pattern, adjusted for various levels of covariates. Five primary dietary patterns emerged: Convenience, Plant-based, Sweets, Southern, and Alcohol and Salad. A total of 536 acute CHD events occurred over a median (interquartile range) 5.8 (2.1) years of follow-up. After adjustment for sociodemographics, lifestyle factors, and energy intake, highest consumers of the Southern pattern (characterized by added fats, fried food, eggs, organ and processed meats, and sugar-sweetened beverages) experienced a 56% higher hazard of acute CHD (comparing quartile 4 with quartile 1: hazard ratio, 1.56; 95% confidence interval, 1.17-2.08; P for trend across quartiles=0.003). Adding anthropometric and medical history variables to the model attenuated the association somewhat (hazard ratio, 1.37; 95% confidence interval, 1.01-1.85; P=0.036). A dietary pattern characteristic of the southern United States was associated with greater hazard of CHD in this sample of white and black adults in diverse regions of the United States. © 2015 American Heart Association, Inc.

Efficacy and Safety of Ticagrelor in Relation to Aspirin Use Within the Week Before Randomization in the SOCRATES Trial.

PubMed

Wong, K S Lawrence; Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Himmelmann, Anders; Kasner, Scott E; Knutsson, Mikael; Ladenvall, Per; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Johnston, S Claiborne

2018-07-01

SOCRATES (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), comparing ticagrelor with aspirin in patients with acute cerebral ischemia, found a nonsignificant 11% relative risk reduction for stroke, myocardial infarction, or death ( P =0.07). Aspirin intake before randomization could enhance the effect of ticagrelor by conferring dual antiplatelet effect during a high-risk period for subsequent stroke. Therefore, we explored the efficacy and safety of ticagrelor versus aspirin in the patients who received any aspirin the week before randomization. A prespecified subgroup analysis in SOCRATES (n=13 199), randomizing patients with acute ischemic stroke (National Institutes of Health Stroke Scale score of ≤5) or transient ischemic attack (ABCD 2 score of ≥4) to 90-day treatment with ticagrelor or aspirin. Patients in the prior-aspirin group had received any aspirin within the week before randomization. Primary end point was time to stroke, myocardial infarction, or death. Safety end point was PLATO (Study of Platelet Inhibition and Patient Outcomes) major bleeding. The 4232 patients in the prior-aspirin group were older, had more vascular risk factors, and vascular disease than the other patients. In the prior-aspirin group, the primary end point occurred in 138/2130 (6.5%) of patients on ticagrelor and in 177/2102 (8.3%) on aspirin (hazard ratio, 0.76; 95% confidence interval, 0.61-0.95; P =0.02); in patients with no prior-aspirin usage an event occurred in 304/4459 (6.9%) and 320/4508 (7.1%) on ticagrelor and aspirin, respectively (hazard ratio, 0.96; 95% confidence interval, 0.82-1.12; P =0.59). The treatment-by-prior-aspirin interaction was not statistically significant ( P =0.10). In the prior-aspirin group, major bleeding occurred in 0.7% and 0.4% of patients on ticagrelor and aspirin, respectively (hazard ratio, 1.58; 95% confidence interval, 0.68-3.65; P =0.28). In this secondary analysis from SOCRATES, fewer primary end points occurred on ticagrelor treatment than on aspirin in patients receiving aspirin before randomization, but there was no significant treatment-by-prior-aspirin interaction. A new study will investigate the benefit-risk of combining ticagrelor and aspirin in patients with acute cerebral ischemia (URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429). URL: https://www.clinicaltrials.gov. Unique identifier: NCT01994720. © 2018 American Heart Association, Inc.

Recurrence risk after noncardioembolic mild ischemic stroke in a Japanese population.

PubMed

Kono, Yuji; Yamada, Sumio; Kamisaka, Kenta; Araki, Amane; Fujioka, Yusuke; Yasui, Keizo; Hasegawa, Yasuhiro; Koike, Yasuo

2011-01-01

This study aimed to identify the recurrence rate and risk factors or clinical variables predictive of vascular events after mild ischemic stroke (IS). From December 2006 to September 2007, patients with acute IS with a modified Rankin Scale of 0∼1 were consecutively enrolled in this study. Variables including sex, family history of vascular disease, age, height, weight, stroke subtype, blood pressure, lipid profile, fasting glucose, HbA1c, smoking, alcohol consumption, exercise habits, waist circumference, ankle-brachial pressure index, salt intake and physical activity were assessed. The primary outcome was stroke recurrence or other vascular events such as myocardial infarction, angina pectoris, and peripheral artery disease. Survival curves were calculated by Kaplan-Meier survival analysis, and hazard ratios for recurrence were determined by univariate and multivariate Cox proportional hazards regression models. A total of 102 mild IS patients (78 men and 24 women, mean age 64 years) were successfully followed for 3 years. Of those 102 patients, 25 (24.5%) had stroke recurrence, and 4 (3.9%) had a coronary event. Among the variables studied, abnormal ankle-brachial pressure index, metabolic syndrome, stroke subtypes, salt intake and poor lifestyle management were significant independent predictors of stroke recurrence or cardiovascular events. In mild IS patients within 3 years after onset, not only pathophysiological factors but also lifestyle factors can aid in the identification of patients at high risk for recurrence. Copyright © 2011 S. Karger AG, Basel.

C-reactive protein as a prognostic marker after lacunar stroke: levels of inflammatory markers in the treatment of stroke study.

PubMed

Elkind, Mitchell S V; Luna, Jorge M; McClure, Leslie A; Zhang, Yu; Coffey, Christopher S; Roldan, Ana; Del Brutto, Oscar H; Pretell, Edwin Javier; Pettigrew, L Creed; Meyer, Brett C; Tapia, Jorge; White, Carole; Benavente, Oscar R

2014-03-01

Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke. Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use. Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP>4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30-4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15-4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14-3.67). There was no interaction with randomized antiplatelet treatment. Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets. http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Risk of First and Recurrent Stroke in Childhood Cancer Survivors Treated With Cranial and Cervical Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, Sabine, E-mail: muellers@neuropeds.ucsf.edu; Department of Pediatrics, University of California, San Francisco, California; Department of Neurosurgery, University of California, San Francisco, California

Purpose: To assess, in a retrospective cohort study, rates and predictors of first and recurrent stroke in patients treated with cranial irradiation (CRT) and/or cervical irradiation at ≤18 years of age. Methods and Materials: We performed chart abstraction (n=383) and phone interviews (n=104) to measure first and recurrent stroke in 383 patients who received CRT and/or cervical radiation at a single institution between 1980 and 2009. Stroke was defined as a physician diagnosis and symptoms consistent with stroke. Incidence of first stroke was number of first strokes per person-years of observation after radiation. We used survival analysis techniques to determinemore » cumulative incidence of first and recurrent stroke. Results: Among 325 subjects with sufficient follow-up data, we identified 19 first strokes (13 ischemic, 4 hemorrhagic, 2 unknown subtype) occurring at a median age of 24 years (interquartile range 17-33 years) in patients treated with CRT. Imaging was reviewed when available (n=13), and the stroke was confirmed in 12. Overall rate of first stroke was 625 (95% confidence interval [CI] 378-977) per 100,000 person-years. The cumulative incidence of first stroke was 2% (95% CI 0.01%-5.3%) at 5 years and 4% (95% CI 2.0%-8.4%) at 10 years after irradiation. With each 100-cGy increase in the radiation dose, the stroke hazard increased by 5% (hazard ratio 1.05; 95% CI 1.01-1.09; P=.02). We identified 6 recurrent strokes; 5 had available imaging that confirmed the stroke. Median time to recurrence was 15 months (interquartile range 6 months-3.2 years) after first stroke. The cumulative incidence of recurrent stroke was 38% (95% CI 17%-69%) at 5 years and 59% (95% CI 27%-92%) at 10 years after first stroke. Conclusion: Cranial irradiation puts childhood cancer survivors at high risk of both first and recurrent stroke. Stroke prevention strategies for these survivors are needed.« less

Association of Lp-PLA2-A and early recurrence of vascular events after TIA and minor stroke.

PubMed

Lin, Jinxi; Zheng, Hongwei; Cucchiara, Brett L; Li, Jiejie; Zhao, Xingquan; Liang, Xianhong; Wang, Chunxue; Li, Hao; Mullen, Michael T; Johnston, S Claiborne; Wang, Yilong; Wang, Yongjun

2015-11-03

To determine the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) measured in the acute period and the short-term risk of recurrent vascular events in patients with TIA or minor stroke. We measured Lp-PLA2 activity (Lp-PLA2-A) in a subset of 3,201 participants enrolled in the CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) trial. Participants with TIA or minor stroke were enrolled within 24 hours of symptom onset and randomized to single or dual antiplatelet therapy. In the current analysis, the primary outcome was defined as the composite of ischemic stroke, myocardial infarction, or death within 90 days. The composite endpoint occurred in 299 of 3,021 participants (9.9%). The population average Lp-PLA2-A level was 209 ± 59 nmol/min/mL (95% confidence interval [CI] 207-211). Older age, male sex, and current smoking were associated with higher Lp-PLA2-A levels. Lp-PLA2-A was significantly associated with the primary endpoint (adjusted hazard ratio 1.07, 95% CI 1.01-1.13 for every 30 nmol/min/mL increase). Similar results were seen for ischemic stroke alone. Adjustment for low-density lipoprotein cholesterol attenuated the association between Lp-PLA2-A and the primary endpoint (adjusted hazard ratio 1.04, 95% CI 0.97-1.11 for every 30 nmol/min/mL increase). Higher levels of Lp-PLA2-A in the acute period are associated with increased short-term risk of recurrent vascular events. © 2015 American Academy of Neurology.

Ticagrelor Versus Aspirin in Acute Embolic Stroke of Undetermined Source.

PubMed

Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Hill, Michael D; Jonasson, Jenny; Kasner, Scott E; Ladenvall, Per; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

2017-09-01

Ticagrelor is an effective antiplatelet therapy among patients with atherosclerotic disease and, therefore, could be more effective than aspirin in preventing recurrent stroke and cardiovascular events among patients with embolic stroke of unknown source (ESUS), which includes patients with ipsilateral stenosis <50% and aortic arch atherosclerosis. We randomized 13 199 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90) within 24 hours of symptom onset. In all patients, investigators informed on the presence of ipsilateral stenosis ≥50%, small deep infarct <15 mm, and on cardiac source of embolism detected after enrollment or rare causes, which allowed to construct an ESUS category in all other patients with documented brain infarction. The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days. ESUS was identified in 4329 (32.8%) patients. There was no treatment-by-ESUS category interaction ( P =0.83). Hazard ratio in ESUS patients was 0.87 (95% confidence interval, 0.68-1.10; P =0.24). However, hazard ratio was 0.51 (95% confidence interval, 0.29-0.90; P =0.02) in ESUS patients with ipsilateral stenosis <50% or aortic arch atherosclerosis (n=961) and 0.98 (95% confidence interval, 0.76-1.27; P =0.89) in the remaining ESUS patients (n=3368; P for heterogeneity =0.04). In this post hoc, exploratory analysis, we found no treatment-by-ESUS category interaction. ESUS subgroups have heterogeneous response to treatment (Funded by AstraZeneca). URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720. © 2017 American Heart Association, Inc.

Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.

PubMed

Patel, Manesh R; Mahaffey, Kenneth W; Garg, Jyotsna; Pan, Guohua; Singer, Daniel E; Hacke, Werner; Breithardt, Günter; Halperin, Jonathan L; Hankey, Graeme J; Piccini, Jonathan P; Becker, Richard C; Nessel, Christopher C; Paolini, John F; Berkowitz, Scott D; Fox, Keith A A; Califf, Robert M

2011-09-08

The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin. In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism. In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group. In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).

Chocolate consumption and risk of stroke among men and women: A large population-based, prospective cohort study.

PubMed

Dong, Jia-Yi; Iso, Hiroyasu; Yamagishi, Kazumasa; Sawada, Norie; Tsugane, Shoichiro

2017-05-01

Chocolate consumption may have a beneficial effect on cardiovascular health, but evidence from prospective cohort studies is still limited. We aimed to examine the prospective associations between chocolate consumption and risk of stroke among men and women in a large population-based cohort. A total of 38,182 men and 46,415 women aged 44-76 years, and free of cardiovascular disease, diabetes, and cancer at baseline in 1995 and 1998, were followed up until the end of 2009 and 2010, respectively. We obtained data on chocolate consumption for each participant using a self-administrated food frequency questionnaire that included 138 food and beverage items. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of stroke in relation to chocolate consumption. During a median follow-up of 12.9 years, we identified 3558 incident strokes cases (2146 cerebral infarctions and 1396 hemorrhagic strokes). After adjustment for age, body mass index, life styles, dietary intakes, and other risk factors, chocolate consumption was associated with a significant lower risk of stroke in women (HR = 0.84; 95% CI, 0.71-0.99). However, the association in men was not significant (HR = 0.94; 95% CI, 0.80-1.10). In addition, the association did not vary by stroke subtypes in either men or women. Findings from this large Japanese cohort supported a significant inverse association between chocolate consumption and risk of developing stroke in women. However, residual confounding could not be excluded as an alternative explanation for our findings. Copyright © 2017 Elsevier B.V. All rights reserved.

N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation).

PubMed

Hijazi, Ziad; Wallentin, Lars; Siegbahn, Agneta; Andersson, Ulrika; Christersson, Christina; Ezekowitz, Justin; Gersh, Bernard J; Hanna, Michael; Hohnloser, Stefan; Horowitz, John; Huber, Kurt; Hylek, Elaine M; Lopes, Renato D; McMurray, John J V; Granger, Christopher B

2013-06-04

This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels. Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases. In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors. Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, >1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p < 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p < 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p = 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p < 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level. NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Outcomes After Percutaneous Coronary Intervention in Patients With a History of Cerebrovascular Disease: Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

PubMed

Song, Chris; Sukul, Devraj; Seth, Milan; Wohns, David; Dixon, Simon R; Slocum, Nicklaus K; Gurm, Hitinder S

2018-06-01

Because of shared risk factors between coronary artery disease and cerebrovascular disease, patients with a history of transient ischemic attack (TIA) or stroke are at greater risk of developing coronary artery disease, which may require percutaneous coronary intervention (PCI). However, there remains a paucity of research examining outcomes after PCI in these patients. We analyzed consecutive patients who underwent PCI between January 1, 2013, and March 31, 2016, at 47 Michigan hospitals and identified those with a history of TIA/stroke. We used propensity score matching to adjust for differences in baseline characteristics and compared in-hospital outcomes between patients with and without a history of TIA/stroke. We compared rates of 90-day readmission and long-term mortality in a subset of patients. Among 98 730 patients who underwent PCI, 10 915 had a history of TIA/stroke. After matching (n=10 618 per group), a history of TIA/stroke was associated with an increased risk of in-hospital stroke (adjusted odds ratio, 2.04; 95% confidence interval, 1.41-2.96; P <0.001). There were no differences in the risks of other in-hospital outcomes. In a subset of patients with postdischarge data, a history of TIA/stroke was associated with increased risks of 90-day readmission (adjusted odds ratio, 1.22; 95% confidence interval, 1.09-1.38; P <0.001) and long-term mortality (hazard ratio, 1.23; 95% confidence interval, 1.07-1.43; P =0.005). A history of TIA/stroke was common in patients who underwent PCI and was associated with increased risks of in-hospital stroke, 90-day readmission, and long-term mortality. Given the devastating consequences of post-PCI stroke, patients with a history of TIA/stroke should be counseled on this increased risk before undergoing PCI. © 2018 American Heart Association, Inc.

Microalbuminuria could improve risk stratification in patients with TIA and minor stroke.

PubMed

Elyas, Salim; Shore, Angela C; Kingwell, Hayley; Keenan, Samantha; Boxall, Leigh; Stewart, Jane; James, Martin A; Strain, William David

2016-09-01

Transient ischemic attacks (TIA) and minor strokes are important risk factors for recurrent strokes. Current stroke risk prediction scores such as ABCD2, although widely used, lack optimal sensitivity and specificity. Elevated urinary albumin excretion predicts cardiovascular disease, stroke, and mortality. We explored the role of microalbuminuria (using albumin creatinine ratio (ACR)) in predicting recurrence risk in patients with TIA and minor stroke. Urinary ACR was measured on a spot sample in 150 patients attending a daily stroke clinic with TIA or minor stroke. Patients were followed up at day 7, 30, and 90 to determine recurrent stroke, cardiovascular events, or death. Eligible patients had a carotid ultrasound Doppler investigation. High-risk patients were defined as those who had an event within 90 days or had >50% internal carotid artery (ICA) stenosis. Fourteen (9.8%) recurrent events were reported by day 90 including two deaths. Fifteen patients had severe ICA stenosis. In total, 26 patients were identified as high risk. These patients had a higher frequency of previous stroke or hypercholesterolemia compared to low-risk patients (P = 0.04). ACR was higher in high-risk patients (3.4 [95% CI 2.2-5.2] vs. 1.7 [1.5-2.1] mg/mmol, P = 0.004), independent of age, sex, blood pressure, diabetes, and previous stroke. An ACR greater than 1.5 mg/mmol predicted high-risk patients (Cox proportional hazard ratio 3.5 (95% CI 1.3-9.5, P = 0.01). After TIA or minor stroke, a higher ACR predicted recurrent events and significant ICA stenosis. Incorporation of urinary ACR from a spot sample in the acute setting could improve risk stratification in patients with TIA and minor stroke.

The intersection of sex, marital status, and cardiovascular risk factors in shaping stroke incidence: results from the health and retirement study.

PubMed

Maselko, Joanna; Bates, Lisa M; Avendaño, Mauricio; Glymour, M Maria

2009-12-01

To examine the role of sex and marital status in the distribution and consequences of cardiovascular risk factors for stroke. Longitudinal cohort. U.S. national sample, community based. U.S. adults aged 50 and older and their spouses. Health and Retirement Study (HRS) participants born between 1900 and 1947 (N=22,818), aged 50 and older, and stroke-free at baseline were followed an average of 9.4 years for self- or proxy-reported stroke (2,372 events). Financial resources, behavioral risk factors, and cardiovascular conditions were used to predict incident stroke in Cox proportional hazard models stratified according to sex and marital status (married, widowed, divorced or separated, or never married). Women were less likely to be married than men. The distribution of risk factors differed according to sex and marital status. Men had higher incident stroke rates than women, even after full risk factor adjustment (hazard ratio (HR)=1.22, 95% confidence interval (CI)=1.11-1.34). For both sexes, being never married or widowed predicted greater risk, associations that were attenuated after adjustment for financial resources. Widowed men had the highest risk (HR=1.40, 95% CI=1.12-1.74 vs married women). Lower income and wealth were associated with similarly high risk across subgroups, although this risk factor especially affected unmarried women, with this group reporting the lowest income and wealth levels. Most other risk factors had similar HRs across subgroups, although moderate alcohol use did not predict lower stroke risk in unmarried women. Stroke incidence and risk factors vary substantially according to sex and marital status. It is likely that gendered social experiences, such as marriage and socioeconomic disadvantage, mediate pathways linking sex and stroke.

"EMMA Study: a Brazilian community-based cohort study of stroke mortality and morbidity".

PubMed

Goulart, Alessandra Carvalho

2016-01-01

Stroke has a high burden of disability and mortality. The aim here was to evaluate epidemiology, risk factors and prognosis for stroke in the EMMA Study (Study of Stroke Mortality and Morbidity). Prospective community-based cohort carried out in Hospital Universitário, University of São Paulo, 2006-2014. Stroke data based on fatal and non-fatal events were assessed, including sociodemographic data, mortality and predictors, which were evaluated by means of logistic regression and survival analyses. Stroke subtype was better defined in the hospital setting than in the local community. In the hospital phase, around 70% were first events and the ischemic subtype. Among cerebrovascular risk factors, the frequency of alcohol intake was higher in hemorrhagic stroke (HS) than in ischemic stroke (IS) cases (35.4% versus 12.3%, P < 0.001). Low education was associated with higher risk of death, particularly after six months among IS cases (odds ratio, OR, 4.31; 95% confidence interval, CI, 1.34-13.91). The risk of death due to hemorrhagic stroke was greater than for ischemic stroke and reached its maximum 10 days after the event (OR: 3.31; 95% CI: 1.55-7.05). Four-year survival analysis on 665 cases of first stroke (82.6% ischemic and 17.4% hemorrhagic) showed an overall survival rate of 48%. At four years, the highest risks of death were in relation to ischemic stroke and illiteracy (hazard ratio, HR: 1.83; 95% CI: 1.26-2.68) and diabetes (HR: 1.45; 95% CI: 1.07-1.97). Major depression presented worse one-year survival (HR: 4.60; 95% CI: 1.36-15.55). Over the long term, the EMMA database will provide additional information for planning resources destined for the public healthcare system.

Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke.

PubMed

Saver, Jeffrey L; Carroll, John D; Thaler, David E; Smalling, Richard W; MacDonald, Lee A; Marks, David S; Tirschwell, David L

2017-09-14

Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown. In a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously; the current analysis of data from the extended follow-up period was considered to be exploratory. We enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3141 patient-years in the PFO closure group vs. 2669 patient-years in the medical-therapy group), owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (hazard ratio with PFO closure vs. medical therapy, 0.55; 95% confidence interval [CI], 0.31 to 0.999; P=0.046 by the log-rank test). Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% CI, 0.18 to 0.79; P=0.007). Venous thromboembolism (which comprised events of pulmonary embolism and deep-vein thrombosis) was more common in the PFO closure group than in the medical-therapy group. Among adults who had had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270 .).

Unprocessed red meat and processed meat consumption and risk of stroke in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).

PubMed

Amiano, P; Chamosa, S; Etxezarreta, N; Arriola, L; Sánchez, M-J; Ardanaz, E; Molina-Montes, E; Chirlaque, M-D; Moreno-Iribas, C; Huerta, J-M; Egües, N; Navarro, C; Requena, M; Quirós, J-R; Fonseca-Nunes, A; Jakszyn, P; González, C-A; Dorronsoro, M

2016-03-01

High intakes of unprocessed red or processed meat may increase the risk of stroke. We aimed to examine the association between unprocessed red meat, processed meat and total red meat consumption and risk of total stroke and ischaemic stroke. Cox proportional hazards regression analyses were conducted based on the data for 41,020 men and women aged 29-69 years at baseline. During a mean follow-up of 13.8 years, 674 incident cases of stroke (531 ischaemic strokes, 79 haemorrhagic strokes, 42 subarachnoid haemorrhages and 22 mixed or unspecified events) were identified. After multiple adjustment, unprocessed red meat, processed meat and total red meat consumption were not correlated with incidence of total stroke or ischaemic stroke in either men or women. The hazard ratios (HRs) for unprocessed red meat and processed meat and risk of total stroke comparing the highest with the lowest quintiles were, respectively, 0.81 (95% confidence interval (CI) 0.54-1.21; P-trend=0.15) and 0.92 (95% CI 0.64-1.32; P-trend=0.82) in men and 1.21 (95% CI 0.79-1.85; P-trend=0.10) and 0.81 (95% CI 0.51-1.27; P-trend=0.17) in women. The HRs for unprocessed red meat and processed meat and risk of ischaemic stroke were, respectively, 0.80 (95% CI 0.51-1.25; P-trend=0.51) and 0.86 (95% CI 0.57-1.29; P-trend=0.77) in men and 1.24 (95% CI 0.74-2.05; P-trend=0.13) and 0.82 (95% CI 0.47-1.42; P-trend=0.31) in women. In the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, unprocessed red meat and processed meat consumption were not associated with risk of stroke in men or women.

Young adult ischaemic stroke related acute symptomatic and late seizures: risk factors.

PubMed

Roivainen, R; Haapaniemi, E; Putaala, J; Kaste, M; Tatlisumak, T

2013-09-01

After first-ever ischaemic stroke, to assess the risk and baseline factors associated with acute symptomatic seizure (ASS) (occurring within 7 days) and late post-stroke seizure (LPS) (>7 days). All consecutive patients aged 15-49 with first-ever ischaemic stroke between 1994 and 2007 treated at the Helsinki University Central Hospital were included, using Cox proportional hazard models to identify factors associated with seizures. Adjustment was for age, gender, vascular risk factors, admission hyperglycemia (>6.1 mm) and hyponatremia (<137 mm), use of psychiatric medication, stroke severity (NIH Stroke Scale) and anatomical (Bamford criteria) and etiological (Trial of Org in Acute Stroke Treatment) stroke subtype. ASSs emerged in 35 (3.5%) patients. LPSs (n = 102) occurred at a cumulative rate of 6.1% at 1 year, 9.5% at 5 years and 11.5% at 10 years. In multivariate analysis, anxiolytic use at time of index stroke (hazard ratio 13.43, 95% confidence interval 3.91-46.14), moderate stroke severity (3.95, 1.86-8.41), cortical involvement (3.69, 1.66-8.18) and hyponatremia (3.26, 1.41-7.57) were independently associated with ASSs. Risk factors for LPSs were total anterior circulation infarct (15.94, 7.62-33.33), partial anterior circulation infarct (3.48, 1.52-7.93), history of ASS (3.94, 2.07-7.48), antidepressant use at the time of LPS (3.88, 2.46-6.11), hemorrhagic infarct (1.94, 1.19-3.15), male gender (1.79, 1.10-2.92) and hyperglycemia (1.62, 1.05-2.51). In young ischaemic stroke patients, the magnitude of seizure risk and the major risk factors were similar to older ischaemic stroke patients but risk factors for ASSs and LPSs differed. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Stenting for symptomatic vertebral artery stenosis: The Vertebral Artery Ischaemia Stenting Trial.

PubMed

Markus, Hugh S; Larsson, Susanna C; Kuker, Wilhelm; Schulz, Ursula G; Ford, Ian; Rothwell, Peter M; Clifton, Andrew

2017-09-19

To compare in the Vertebral Artery Ischaemia Stenting Trial (VIST) the risks and benefits of vertebral angioplasty and stenting with best medical treatment (BMT) alone for symptomatic vertebral artery stenosis. VIST was a prospective, randomized, open-blinded endpoint clinical trial performed in 14 hospitals in the United Kingdom. Participants with symptomatic vertebral stenosis ≥50% were randomly assigned (1:1) to vertebral angioplasty/stenting plus BMT or to BMT alone with randomization stratified by site of stenosis (extracranial vs intracranial). Because of slow recruitment and cessation of funding, recruitment was stopped after 182 participants. Follow-up was a minimum of ≥1 year for each participant. Three patients did not contribute any follow-up data and were excluded, leaving 91 patients in the stent group and 88 in the medical group. Mean follow-up was 3.5 (interquartile range 2.1-4.7) years. Of 61 patients who were stented, stenosis was extracranial in 48 (78.7%) and intracranial in 13 (21.3%). No periprocedural complications occurred with extracranial stenting; 2 strokes occurred during intracranial stenting. The primary endpoint of fatal or nonfatal stroke occurred in 5 patients in the stent group vs 12 in the medical group (hazard ratio 0.40, 95% confidence interval 0.14-1.13, p = 0.08), with an absolute risk reduction of 25 strokes per 1,000 person-years. The hazard ratio for stroke or TIA was 0.50 ( p = 0.05). Stenting in extracranial stenosis appears safe with low complication rates. Large phase 3 trials are required to determine whether stenting reduces stroke risk. ISRCTN95212240. This study provides Class I evidence that for patients with symptomatic vertebral stenosis, angioplasty with stenting does not reduce the risk of stroke. However, the study lacked the precision to exclude a benefit from stenting. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Obesity and Subtypes of Incident Cardiovascular Disease.

PubMed

Ndumele, Chiadi E; Matsushita, Kunihiro; Lazo, Mariana; Bello, Natalie; Blumenthal, Roger S; Gerstenblith, Gary; Nambi, Vijay; Ballantyne, Christie M; Solomon, Scott D; Selvin, Elizabeth; Folsom, Aaron R; Coresh, Josef

2016-07-28

Obesity is a risk factor for various subtypes of cardiovascular disease (CVD), including coronary heart disease (CHD), heart failure (HF), and stroke. Nevertheless, there are limited comparisons of the associations of obesity with each of these CVD subtypes, particularly regarding the extent to which they are unexplained by traditional CVD mediators. We followed 13 730 participants in the Atherosclerosis Risk in Communities (ARIC) study who had a body mass index ≥18.5 and no CVD at baseline (visit 1, 1987-1989). We compared the association of higher body mass index with incident HF, CHD, and stroke before and after adjusting for traditional CVD mediators (including systolic blood pressure, diabetes mellitus, and lipid measures). Over a median follow-up of 23 years, there were 2235 HF events, 1653 CHD events, and 986 strokes. After adjustment for demographics, smoking, physical activity, and alcohol intake, higher body mass index had the strongest association with incident HF among CVD subtypes, with hazard ratios for severe obesity (body mass index ≥35 versus normal weight) of 3.74 (95% CI 3.24-4.31) for HF, 2.00 (95% CI 1.67-2.40) for CHD, and 1.75 (95% CI 1.40-2.20) for stroke (P<0.0001 for comparisons of HF versus CHD or stroke). Further adjustment for traditional mediators fully explained the association of higher body mass index with CHD and stroke but not with HF (hazard ratio 2.27, 95% CI 1.94-2.64). The link between obesity and HF was stronger than those for other CVD subtypes and was uniquely unexplained by traditional risk factors. Weight management is likely critical for optimal HF prevention, and nontraditional pathways linking obesity to HF need to be elucidated. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study.

PubMed

Baumgartner, Christine; Fan, Dongjie; Fang, Margaret C; Singer, Daniel E; Witt, Daniel M; Schmelzer, John R; Williams, Marc S; Gurwitz, Jerry H; Sung, Sue Hee; Go, Alan S

2018-04-14

Anxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes. The Cardiovascular Research Network WAVE (Community-Based Control and Persistence of Warfarin Therapy and Associated Rates and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous Thromboembolism) Study included adults with AF newly starting warfarin between 2004 and 2007 within 5 health delivery systems in the United States. Diagnosed anxiety and depression and other patient characteristics were identified from electronic health records. We identified stroke and bleeding outcomes from hospitalization databases using validated International Classification of Diseases, Ninth Revision ( ICD-9 ), codes. We used multivariable Cox regression to assess the relation between anxiety and/or depression with outcomes after adjustment for stroke and bleeding risk factors. In 25 570 adults with AF initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52 events per 100 person-years). In multivariable analyses, diagnosed anxiety was associated with a higher adjusted rate of combined ischemic stroke and intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28). Results were not materially changed after additional adjustment for patient-level percentage of time in therapeutic anticoagulation range on warfarin (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36). In contrast, neither isolated depression nor combined depression and anxiety were significantly associated with outcomes. Diagnosed anxiety was independently associated with increased risk of combined ischemic stroke and intracranial hemorrhage in adults with AF initiating warfarin that was not explained by differences in risk factors or achieved anticoagulation quality. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis.

PubMed

Nave, Alexander H; Lange, Kristin S; Leonards, Christopher O; Siegerink, Bob; Doehner, Wolfram; Landmesser, Ulf; Steinhagen-Thiessen, Elisabeth; Endres, Matthias; Ebinger, Martin

2015-10-01

Lipoprotein (a) [Lp(a)] harbors atherogenic potential but its role as a risk factor for ischemic stroke remains controversial. We conducted a meta-analysis to determine the relative strength of the association between Lp(a) and ischemic stroke and identify potential subgroup-specific risk differences. A systematic search using the MeSH terms "lipoproteins" OR "lipoprotein a" AND "stroke" was performed in PubMed and ScienceDirect for case-control studies from June 2006 and prospective cohort studies from April 2009 until December 20th 2014. Data from eligible papers published before these dates were reviewed and extracted from previous meta-analyses. Studies that assessed the relationship between Lp(a) levels and ischemic stroke and reported generic data-i.e. odds ratio [OR], hazard ratio, or risk ratio [RR]-were eligible for inclusion. Studies that not distinguish between ischemic and hemorrhagic stroke and transient ischemic attack were excluded. Random effects meta-analyses with mixed-effects meta-regression were performed by pooling adjusted OR or RR. A total of 20 articles comprising 90,904 subjects and 5029 stroke events were eligible for the meta-analysis. Comparing high with low Lp(a) levels, the pooled estimated OR was 1.41 (95% CI, 1.26-1.57) for case-control studies (n = 11) and the pooled estimated RR was 1.29 (95% CI, 1.06-1.58) for prospective studies (n = 9). Sex-specific differences in RR were inconsistent between case-control and prospective studies. Study populations with a mean age of ≤55 years had an increased RR compared to older study populations. Reported Lp(a) contrast levels and ischemic stroke subtype significantly contributed to the heterogeneity observed in the analyses. Elevated Lp(a) is an independent risk factor for ischemic stroke and may be especially relevant for young stroke patients. Sex-specific risk differences remain conflicting. Further studies in these subgroups may be warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Apolipoprotein E and mortality in African-Americans and Yoruba.

PubMed

Lane, Kathleen A; Gao, Sujuan; Hui, Siu L; Murrell, Jill R; Hall, Kathleen S; Hendrie, Hugh C

2003-10-01

The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE epsilon4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 (hazard ratio: 2.00; 95% CI: 1.19-3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45-1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274).

Apolipoprotein E and mortality in African-Americans and Yoruba

PubMed Central

Lane, Kathleen A.; Gao, Sujuan; Hui, Siu L.; Murrell, Jill R.; Hall, Kathleen S.; Hendrie, Hugh C.

2011-01-01

The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE ε4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 ( hazard ratio: 2.00; 95% CI: 1.19–3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45–1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274). PMID:14646029

Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial.

PubMed

Diener, Hans-Christoph; Eikelboom, John; Connolly, Stuart J; Joyner, Campbell D; Hart, Robert G; Lip, Gregory Y H; O'Donnell, Martin; Hohnloser, Stefan H; Hankey, Graeme J; Shestakovska, Olga; Yusuf, Salim

2012-03-01

In the AVERROES study, apixaban, a novel factor Xa inhibitor, reduced the risk of stroke or systemic embolism in patients with atrial fibrillation who were at high risk of stroke but unsuitable for vitamin K antagonist therapy. We aimed to investigate whether the subgroup of patients with previous stroke or transient ischaemic attack (TIA) would show a greater benefit from apixaban compared with aspirin than would patients without previous cerebrovascular events. In AVERROES, 5599 patients (mean age 70 years) with atrial fibrillation who were at increased risk of stroke and unsuitable for vitamin K antagonist therapy were randomly assigned to receive apixaban (5 mg twice daily) or aspirin (81-324 mg per day). The mean follow-up was 1·1 years. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding. Patients and investigators were masked to study treatment. In this prespecified subgroup analysis, we used Kaplan-Meier estimates of 1-year event risk and Cox proportional hazards regression models to compare the effects of apixaban in patients with and without previous stroke or TIA. AVERROES is registered at ClinicalTrials.gov, number NCT00496769. In patients with previous stroke or TIA, ten events of stroke or systemic embolism occurred in the apixaban group (n=390, cumulative hazard 2·39% per year) compared with 33 in the aspirin group (n=374, 9·16% per year; hazard ratio [HR] 0·29, 95% CI 0·15-0·60). In those without previous stroke or TIA, 41 events occurred in the apixaban group (n=2417, 1·68% per year) compared with 80 in the aspirin group (n=2415, 3·06% per year; HR 0·51, 95% CI 0·35-0·74). The p value for interaction of the effects of aspirin and apixaban with previous cerebrovascular events was 0·17. Major bleeding was more frequent in patients with history of stroke or TIA than in patients without (HR 2·88, 95% CI 1·77-4·55) but risk of this event did not differ between treatment groups. In patients with atrial fibrillation, apixaban is similarly effective whether or not patients have had a previous stroke or TIA. Given that those with previous stroke or TIA have a higher risk of stroke, the absolute benefits might be greater in these patients. Bristol-Myers Squibb and Pfizer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.

PubMed

Marso, Steven P; Daniels, Gilbert H; Brown-Frandsen, Kirstine; Kristensen, Peter; Mann, Johannes F E; Nauck, Michael A; Nissen, Steven E; Pocock, Stuart; Poulter, Neil R; Ravn, Lasse S; Steinberg, William M; Stockner, Mette; Zinman, Bernard; Bergenstal, Richard M; Buse, John B

2016-07-28

The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.).

Ximelagatran compared with warfarin for the prevention of systemic embolism and stroke. An imputed placebo analysis.

PubMed

Berry, Colin; Norrie, John; McMurray, John J V

2005-03-01

The active control trials, SPORTIF III and SPORTIF V, compared the direct thrombin inhibitor ximelagatran to warfarin, where each was given as a treatment to prevent systemic embolism and stroke in patients with atrial fibrillation. Because warfarin has previously been compared to placebo in similar patients and ximelagatran has now been compared to warfarin, an indirect comparison between ximelagatran and placebo is possible (imputed placebo analysis). In this analysis, ximelagatran reduces the risk of stroke and systemic embolism by 66% (hazard ratio 0.338; 95% confidence interval [CI] 0.204-0.560). Ximelagatran preserves 102% (95% CI 72-132%) of the benefit of warfarin. Based on these data, ximelagatran may be an effective alternative to warfarin for the prevention of stroke and systemic embolism in high-risk patients with atrial fibrillation.

Ambulatory arterial stiffness index and 24-hour ambulatory pulse pressure as predictors of mortality in Ohasama, Japan.

PubMed

Kikuya, Masahiro; Staessen, Jan A; Ohkubo, Takayoshi; Thijs, Lutgarde; Metoki, Hirohito; Asayama, Kei; Obara, Taku; Inoue, Ryusuke; Li, Yan; Dolan, Eamon; Hoshi, Haruhisa; Hashimoto, Junichiro; Totsune, Kazuhito; Satoh, Hiroshi; Wang, Ji-Guang; O'Brien, Eoin; Imai, Yutaka

2007-04-01

Ambulatory arterial stiffness index (AASI) and pulse pressure (PP) are indexes of arterial stiffness and can be computed from 24-hour blood pressure recordings. We investigated the prognostic value of AASI and PP in relation to fatal outcomes. In 1542 Ohasama residents (baseline age, 40 to 93 years; 63.4% women), we applied Cox regression to relate mortality to AASI and PP while adjusting for sex, age, BMI, 24-hour MAP, smoking and drinking habits, diabetes mellitus, and a history of cardiovascular disease. During 13.3 years (median), 126 cardiovascular and 63 stroke deaths occurred. The sex- and age-standardized incidence rates of cardiovascular and stroke mortality across quartiles were U-shaped for AASI and J-shaped for PP. Across quartiles, the multivariate-adjusted hazard ratios for cardiovascular and stroke death significantly deviated from those in the whole population in a U-shaped fashion for AASI, whereas for PP, none of the HRs departed from the overall risk. The hazard ratios for cardiovascular mortality across ascending AASI quartiles were 1.40 (P=0.04), 0.82 (P=0.25), 0.64 (P=0.01), and 1.35 (P=0.03). Additional adjustment of AASI for PP and sensitivity analyses by sex, excluding patients on antihypertensive treatment or with a history of cardiovascular disease, or censoring deaths occurring within 2 years of enrollment, produced confirmatory results. In a Japanese population, AASI predicted cardiovascular and stroke mortality over and beyond PP and other risk factors, whereas in adjusted analyses, PP did not carry any prognostic information.

Where to Focus Efforts to Reduce the Black-White Disparity In Stroke Mortality: Incidence vs. Case-Fatality?

PubMed Central

Howard, George; Moy, Claudia S.; Howard, Virginia J.; McClure, Leslie A.; Kleindorfer, Dawn O.; Kissela, Brett M.; Judd, Suzanne E.; Unverzagt, Fredrick W.; Soliman, Elsayed Z.; Safford, Monika M.; Cushman, Mary; Flaherty, Matthew L.; Wadley, Virginia G.

2016-01-01

Background and Purpose At age 45, Blacks have a stroke mortality approximately 3-times greater than their White counterparts, with a declining disparity at older ages. We assess whether this Black-White disparity in stroke mortality is attributable to a Black-White disparity in stroke incidence versus a disparity in case-fatality. Methods We first assess if Black-White differences in stroke mortality within 29,681 participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort reflect national Black-White differences in stroke mortality, and then assess the degree to which Black-White differences in stroke incidence or 30-day case-fatality after stroke contribute to the disparities in stroke mortality. Results The pattern of stroke mortality within the study mirrors the national pattern, with the Black-to-White hazard ratio of approximately 4.0 at age 45 decreasing to approximately 1.0 at age 85. The pattern of Black-to-White disparities in stroke incidence shows a similar pattern, but no evidence of a corresponding disparity in stroke case-fatality. Discussion These findings show that the Black-White differences in stroke mortality are largely driven by differences in stroke incidence, with case fatality playing at most a minor role. Therefore to reduce the Black-White disparity in stroke mortality, interventions need to focus on prevention of stroke in Blacks. PMID:27256672

Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients.

PubMed

Wang, I-Kuan; Liu, Chung-Hsiang; Yen, Tzung-Hai; Jeng, Jiann-Shing; Hsu, Shih-Pin; Chen, Chih-Hung; Lien, Li-Ming; Lin, Ruey-Tay; Chen, An-Chih; Lin, Huey-Juan; Chi, Hsin-Yi; Lai, Ta-Chang; Sun, Yu; Lee, Siu-Pak; Sung, Sheng-Feng; Chen, Po-Lin; Lee, Jiunn-Tay; Chiang, Tsuey-Ru; Lin, Shinn-Kuang; Muo, Chih-Hsin; Ma, Henry; Wen, Chi-Pang; Sung, Fung-Chang; Hsu, Chung Y

2017-06-01

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients. From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013. Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of <120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of <120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or <120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Ching-Chih; Department of Otolaryngology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan; Tumor Center, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival ratemore » between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35-54 had a 1.66 times (95% CI, 1.16-2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55-64 years (hazard ratio = 0.87; 95% CI, 0.56-1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.« less

Associations of Stressful Life Events and Social Strain With Incident Cardiovascular Disease in the Women's Health Initiative

PubMed Central

Kershaw, Kiarri N.; Brenes, Gretchen A.; Charles, Luenda E.; Coday, Mace; Daviglus, Martha L.; Denburg, Natalie L.; Kroenke, Candyce H.; Safford, Monika M.; Savla, Tina; Tindle, Hilary A.; Tinker, Lesley F.; Van Horn, Linda

2014-01-01

Background Epidemiologic studies have yielded mixed findings on the association of psychosocial stressors with cardiovascular disease (CVD) risk. In this study, we examined associations of stressful life events (SLE) and social strain with incident coronary heart disease (CHD) and stroke (overall, and for hemorrhagic and ischemic strokes) independent of sociodemographic characteristics, and we evaluated whether these relationships were explained by traditional behavioral and biological risk factors. Methods and Results Data from approximately 82 000 Women's Health Initiative Observational Study participants were used for the SLE and social strain analyses, respectively. Participants were followed for events for up to 18.0 years (median, 14.0). Separate Cox proportional hazards models were generated to estimate associations of each stress measure with incident CVD. After adjusting for sociodemographic characteristics and depressive symptoms, higher SLE and social strain were associated with higher incident CHD and stroke (each P trend <0.05). Hazard ratios and 95% confidence intervals were 1.12 (1.01, 1.25) for incident CHD and 1.14 (1.01, 1.28) for incident stroke among participants reporting high versus low SLE. Findings were similar for social strain. Associations were attenuated with further adjustment for mediating behavioral and biological risk factors. Findings were similar for associations of SLE with ischemic stroke and hemorrhagic stroke, but social strain was only associated with ischemic stroke. Conclusions Higher SLE and social strain were associated with higher incident CVD independent of sociodemographic factors and depressive symptoms, but not behavioral and biological risk factors. PMID:24973226

Presence of intracranial artery calcification is associated with mortality and vascular events in patients with ischemic stroke after hospital discharge: a cohort study.

PubMed

Bugnicourt, Jean-Marc; Leclercq, Claire; Chillon, Jean-Marc; Diouf, Momar; Deramond, Hervé; Canaple, Sandrine; Lamy, Chantal; Massy, Ziad A; Godefroy, Olivier

2011-12-01

Although intracranial artery calcification (IAC) has been reported to be a risk factor for ischemic stroke, the prognostic implications of IAC in stroke outcome are unknown. The purpose of this study was to determine the association between IAC and risk of vascular events and death in patients with stroke after hospital discharge. All patients with ischemic stroke over a 1-year period were included (n=302). IAC, assessed by multidetector CT, was defined as hyperdense foci (peak density>130 Hounsfield units) and assessed in the 7 major cerebral arteries. The IAC scores ranged from 0 (no calcification) to 7. Follow-up information on major clinical events (including fatal or nonfatal ischemic stroke, cardiac and peripheral artery events, and all-cause death) was obtained by means of a structured phone interview. IAC was present in 260 patients (83%). With a mean follow-up of 773±223 days, 88 major clinical events occurred in 67 patients (22%): 45 new ischemic vascular events (ischemic stroke: n=22; cardiac event: n=15; peripheral artery event: n=8) and 43 deaths from any cause. Patients with the highest IAC scores had significantly higher rates of death and vascular events than those with the lowest IAC scores (log rank test, P=0.029). In the Cox proportional hazards regression model, the IAC score was significantly associated with major clinical events (hazard ratio, 1.34; 95% CI, 1.11-1.61; P=0.002). In patients with ischemic stroke, IAC detection may constitute a simple marker of a high risk of future major clinical events.

Influenza vaccination reduces hemorrhagic stroke risk in patients with atrial fibrillation: A population-based cohort study.

PubMed

Liu, Ju-Chi; Wang, Ta-Jung; Sung, Li-Chin; Kao, Pai-Feng; Yang, Tsung-Yeh; Hao, Wen-Rui; Chen, Chun-Chao; Hsu, Yi-Ping; Wu, Szu-Yuan

2017-04-01

The risk of hemorrhagic stroke in patients with atrial fibrillation (AF) is low but the consequences of its occurrence are extremely severe. In this study, we investigated the association of influenza vaccination with the risk of hemorrhagic stroke to develop an efficient strategy for reducing this risk in patients with AF. In this study, data were retrieved from the Taiwan National Health Insurance Research Database. The study cohort comprised all patients who received a diagnosis of AF (n=14,454) before January 1, 2005 (index date) and were followed until December 31, 2012. Propensity scores were calculated using a logistic regression model to determine the effects of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A time-dependent Cox proportional hazard model was used to calculate the hazard ratios (HRs) for hemorrhagic stroke in vaccinated and unvaccinated patients with AF. The study population comprised 6570 patients who did (2547 [38.77%]) and did not receive (4023 [61.23%]) influenza vaccination. The adjusted HRs (aHRs) for hemorrhagic stroke were lower in the vaccinated patients than in the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs=0.97 [0.59-1.60], 0.51 [0.30-0.87], and 0.72 [0.50-1.03], respectively). Influenza vaccination exerts dose-response and synergistic protective effects against hemorrhagic stroke in patients with AF who have a high risk of hemorrhagic stroke (i.e., male sex, age≥75years, Charlson comorbidity index ≥3, and hypertension) and reduces the incidence of hemorrhagic stroke. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Incidental Statin Use and the Risk of Stroke or Transient Ischemic Attack after Radiotherapy for Head and Neck Cancer

PubMed Central

Addison, Daniel; Lawler, Patrick R.; Emami, Hamed; Janjua, Sumbal A.; Staziaki, Pedro V.; Hallett, Travis R.; Hennessy, Orla; Lee, Hang; Szilveszter, Bálint; Lu, Michael; Mousavi, Negar; Nayor, Matthew G.; Delling, Francesca N.; Romero, Javier M.; Wirth, Lori J.; Chan, Annie W.; Hoffmann, Udo; Neilan, Tomas G.

2018-01-01

Background and Purpose Interventions to reduce the risk for cerebrovascular events (CVE; stroke and transient ischemic attack [TIA]) after radiotherapy (RT) for head and neck cancer (HNCA) are needed. Among broad populations, statins reduce CVEs; however, whether statins reduce CVEs after RT for HNCA is unclear. Therefore, we aimed to test whether incidental statin use at the time of RT is associated with a lower rate of CVEs after RT for HNCA. Methods From an institutional database we identified all consecutive subjects treated with neck RT from 2002 to 2012 for HNCA. Data collection and event adjudication was performed by blinded teams. The primary outcome was a composite of ischemic stroke and TIA. The secondary outcome was ischemic stroke. The association between statin use and events was determined using Cox proportional hazard models after adjustment for traditional and RT-specific risk factors. Results The final cohort consisted of 1,011 patients (59±13 years, 30% female, 44% hypertension) with 288 (28%) on statins. Over a median follow-up of 3.4 years (interquartile range, 0.1 to 14) there were 102 CVEs (89 ischemic strokes and 13 TIAs) with 17 in statin users versus 85 in nonstatins users. In a multivariable model containing known predictors of CVE, statins were associated with a reduction in the combination of stroke and TIA (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2 to 0.8; P=0.01) and ischemic stroke alone (HR, 0.4; 95% CI, 0.2 to 0.8; P=0.01). Conclusions Incidental statin use at the time of RT for HNCA is associated with a lower risk of stroke or TIA. PMID:29402065

Metabolic Syndrome and Ischemic Stroke Risk Northern Manhattan Study

PubMed Central

Boden-Albala, Bernadette; Sacco, Ralph L.; Lee, Hye-Sueng; Grahame-Clarke, Cairistine; Rundek, Tanja; Elkind, Mitchell V.; Wright, Clinton; Giardina, Elsa-Grace V.; DiTullio, Marco R.; Homma, Shunichi; Paik, Myunghee C.

2009-01-01

Background and Purpose More than 47 million individuals in the United States meet the criteria for the metabolic syndrome. The relation between the metabolic syndrome and stroke risk in multiethnic populations has not been well characterized. Methods As part of the Northern Manhattan Study, 3298 stroke-free community residents were prospectively followed up for a mean of 6.4 years. The metabolic syndrome was defined according to guidelines established by the National Cholesterol Education Program Adult Treatment Panel III. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs for ischemic stroke and vascular events (ischemic stroke, myocardial infarction, or vascular death). The etiologic fraction estimates the proportion of events attributable to the metabolic syndrome. Results More than 44% of the cohort had the metabolic syndrome (48% of women vs 38% of men, P<0.0001), which was more prevalent among Hispanics (50%) than whites (39%) or blacks (37%). The metabolic syndrome was associated with increased risk of stroke (HR=1.5; 95% CI, 1.1 to 2.2) and vascular events (HR=1.6; 95% CI, 1.3 to 2.0) after adjustment for sociodemographic and risk factors. The effect of the metabolic syndrome on stroke risk was greater among women (HR=2.0; 95% CI, 1.3 to 3.1) than men (HR=1.1; 95% CI, 0.6 to 1.9) and among Hispanics (HR=2.0; 95% CI, 1.2 to 3.4) compared with blacks and whites. The etiologic fraction estimates suggest that elimination of the metabolic syndrome would result in a 19% reduction in overall stroke, a 30% reduction of stroke in women; and a 35% reduction of stroke among Hispanics. Conclusions The metabolic syndrome is an important risk factor for ischemic stroke, with differential effects by sex and race/ethnicity. PMID:18063821

Modified creatinine index and risk for cardiovascular events and all-cause mortality in patients undergoing hemodialysis: The Q-Cohort study.

PubMed

Arase, Hokuto; Yamada, Shunsuke; Yotsueda, Ryusuke; Taniguchi, Masatomo; Yoshida, Hisako; Tokumoto, Masanori; Nakano, Toshiaki; Tsuruya, Kazuhiko; Kitazono, Takanari

2018-06-02

The modified creatinine (Cr) index, calculated by age, sex, pre-dialysis serum Cr levels, and Kt/V for urea, reflects skeletal muscle mass in patients on hemodialysis. Whether the modified Cr index is associated with cardiovascular events and all-cause mortality remains unknown. A total of 3027 patients registered in the Q-Cohort Study, a multicenter, prospective study of patients on hemodialysis in Japan, were analyzed. The main outcomes were cardiovascular events and all-cause mortality. Associations between sex-specific quartiles of the modified Cr index and outcomes were analyzed by the Cox proportional hazard models and the Fine-Gray proportional subdistribution hazards model. The modified Cr index was correlated with known nutritional and inflammatory markers. During a 4-year follow-up, 499 patients died of any cause, 372 experienced heart disease, and 194 developed stroke. The risk for all-cause mortality was significantly higher in the lower quartiles (Q1 and Q2) than in the highest quartile (Q4) as the reference group (hazard ratios and 95% confidence intervals: Q1, 2.65 [1.69-4.25], Q2, 1.92 [1.27-2.94], and Q3, 1.31 [0.87-2.02]). The risk of heart disease was significantly higher in Q1 than in Q4 (hazard ratios and 95% confidence intervals: Q1, 1.64 [1.04-2.61], Q2, 1.34 [0.91-2.00], and Q3, 1.04 [0.71-1.52]). The risk of stroke was not associated with the modified Cr index. A lower modified Cr index is associated with an increased risk for heart disease and all-cause mortality, but not with the risk for stroke in patients on hemodialysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Association of multiple ischemic strokes with mortality in incident hemodialysis patients: an application of multistate model to determine transition probabilities in a retrospective observational cohort.

PubMed

Wetmore, James B; Mahnken, Jonathan D; Phadnis, Milind A

2016-09-21

Little is known about the effect of multiple, or subsequent, ischemic strokes in patients receiving hemodialysis. We undertook a retrospective cohort study of incident hemodialysis patients with Medicare coverage who had experienced a first ischemic stroke. Factors associated with either a subsequent ischemic stroke or death following a first new stroke were modeled. A multistate model with Cox proportional hazards was used to predict transition probabilities from first ischemic stroke to either subsequent stroke or to death, and the demographic and clinical factors associated with the respective transition probabilities were determined. Effect of a subsequent ischemic stroke on survival was quantified. Overall, 12,054 individuals (mean age 69.7 years, 41.3 % male, 53.0 % Caucasian and 34.0 % African-American) experienced a first new ischemic stroke. Female sex was associated with an increased risk of having a subsequent ischemic stroke (adjusted hazard ratio 1.37, 95 % confidence intervals 1.20 - 1.56, P < 0.0001); African-Americans, as compared to Caucasians, had lower likelihood of dying after a first new ischemic stroke (0.81, 0.77 - 0.85, P < 0.0001). A subsequent stroke trended towards having a higher likelihood of transitioning to death compared to a first new ischemic stroke on dialysis (1.72, 0.96 - 3.09, P = 0.071). When a subsequent ischemic stroke occurs at 24 months, probability of survival dropped >15 %, in absolute terms, from 0.254 to 0.096, with substantial drops observed at subsequent time points such that the probability of survival was more than halved. Likelihood of subsequent ischemic stroke and of survival in hemodialysis patients appears to vary by sex and race: females are more likely than males to experience a subsequent ischemic stroke, and Caucasians are more likely than African-Americans to die after a first new ischemic stroke. The risk of a transitioning to a subsequent stroke (after having had a first) increases until about 1 year, then decreases. Subsequent strokes are associated with decreased probability of survival, an effect which increases as time since first stroke elapses. This information may be of assistance to clinicians when counseling hemodialysis patients about the implications of recurrent ischemic stroke.

Educational inequality in cardiovascular diseases: a sibling approach.

PubMed

Søndergaard, Grethe; Dalton, Susanne Oksbjerg; Mortensen, Laust Hvas; Osler, Merete

2018-02-01

Educational inequality in diseases in the circulatory system (here termed cardiovascular disease) is well documented but may be confounded by early life factors. The aim of this observational study was to examine whether the associations between education and all cardiovascular diseases, ischaemic heart disease and stroke, respectively, were explained by family factors shared by siblings. The study population included all individuals born in Denmark between 1950 and 1979 who had at least one full sibling born in the same period. Using Cox regression, data were analysed in conventional cohort and within-sibship analyses in which the association was examined within siblings discordant on education. Assuming that attenuation of associations in the within-sibship as compared with the cohort analyses would indicate confounding from factors shared within families. A lower educational status was associated with a higher risk of cardiovascular disease, ischaemic heart disease and stroke. All associations attenuated in the within-sibship analyses, in particular in the analyses on ischaemic heart disease before age 45 years. For instance, in the cohort analyses, the hazard rate of ischaemic heart disease among women less than 45 years who had a primary school education was 94% (hazard ratio 1.94 (1.78-2.12) higher than among those with a vocational education, while it attenuated to 51% (hazard ratio 1.51 (1.34-1.71)) in the within-sibship analysis. Confounding from factors shared by siblings explained the associations between education and the cardiovascular disease outcomes but to varying degrees. This should be taken into account when planning interventions aimed at reducing educational inequalities in the development of cardiovascular disease, ischaemic heart disease and stroke.

Mineralocorticoid Receptor Antagonism in Patients With Atrial Fibrillation: Findings From the ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) Registry.

PubMed

Fudim, Marat; Liu, Peter R; Shrader, Peter; Blanco, Rosalia G; Allen, Larry A; Fonarow, Gregg C; Gersh, Bernard J; Kowey, Peter R; Mahaffey, Kenneth W; Hylek, Elaine; Go, Alan S; Thomas, Laine; Peterson, Eric D; Piccini, Jonathan P

2018-04-13

Mineralocorticoid receptor antagonist (MRA) therapy may be beneficial to patients with atrial fibrillation (AF), but little is known about their use in patients with AF and subsequent outcomes. In order to better understand MRA use and subsequent outcomes, we performed a retrospective cohort study of the contemporary ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry. AF progression and cardiovascular outcomes were compared using propensity-matched Cox proportional hazards modeling according to MRA use at baseline and new MRA use at follow-up versus patients with no MRA use. Among 7012 patients with nonpermanent AF, 320 patients were taking MRA at enrollment, and 416 patients initiated MRA use during follow-up. The mean patient age was 72.5 years, 56.3% were men, and 70.4% had paroxysmal AF. Among all patients taking MRAs, 434 (59.0%) had heart failure, 655 (89.0%) had hypertension, and 380 (51.6%) had both. After adjustment, new MRA use was not associated with reduced AF progression (hazard ratio, 1.18; 95% confidence interval, 0.88-1.58; P =0.27) but showed a trend towards lower risk of stroke, transient ischemic attack, or systemic embolism (hazard ratio, 0.17; 95% confidence interval, 0.02-1.23; P =0.08). Results were similar for a comparison of new MRA users and baseline MRA users compared with nonusers. In community-based outpatients with AF, the majority of MRA use was for heart failure and hypertension. MRA use also trended towards lower adjusted stroke risk. Future studies should test the hypothesis that MRA use may decrease the risk of stroke in patients with AF. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Better outcomes for hospitalized patients with TIA when in stroke units

PubMed Central

Kim, Joosup; Lannin, Natasha A.; Levi, Christopher R.; Dewey, Helen M.; Hill, Kelvin; Faux, Steven; Andrew, Nadine E.; Kilkenny, Monique F.; Grimley, Rohan; Thrift, Amanda G.; Grabsch, Brenda; Middleton, Sandy; Anderson, Craig S.; Donnan, Geoffrey A.

2016-01-01

Objectives: To investigate differences in management and outcomes for patients admitted to the hospital with TIA according to care on a stroke unit (SU) or alternate ward setting up to 180 days post event. Methods: TIA admissions from 40 hospitals participating in the Australian Stroke Clinical Registry during 2010–2013 were assessed. Propensity score matching was used to assess outcomes by treatment group including Cox proportional hazards regression to compare survival differences and other appropriate multivariable regression models for outcomes including health-related quality of life and readmissions. Results: Among 3,007 patients with TIA (mean age 73 years, 54% male), 1,110 pairs could be matched. Compared to management elsewhere in hospitals, management in an SU was associated with improved cumulative survival at 180 days post event (hazard ratio 0.57, 95% confidence interval 0.35–0.94; p = 0.029), despite not being statistically significant at 90 days (hazard ratio 0.66, 95% confidence interval 0.33–1.31; p = 0.237). Overall, there were no differences for being discharged on antihypertensive medication or with a care plan, and the 90- to 180-day self-reported outcomes between these groups were similar. In subgroup analyses of 461 matched pairs treated in hospitals in one Australian state (Queensland), patients treated in an SU were more often prescribed aspirin within 48 hours (73% vs 62%, p < 0.001) and discharged on antithrombotic medications (84% vs 71%, p < 0.001) than those not treated in an SU. Conclusions: Hospitalized patients with TIA managed in SUs had better survival at 180 days than those treated in alternate wards, potentially through better management, but further research is needed. PMID:27164692

Comparison of BMSs with SES for Symptomatic Intracranial Disease of the Middle Cerebral Artery Stenosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yue Xuanye; Yin Qin; Xi Gangming

2011-02-15

This study was designed to compare the clinical and angiographic outcomes of patients with symptomatic atherosclerotic middle cerebral artery stenosis treated with balloon-mounted stents (BMS) and self-expandable Wingspan system (SES). We reviewed the 69 consecutive stent placement procedures for symptomatic atherosclerotic stenosis ({>=}70) in M1 segment of middle cerebral artery in 67 patients in 3 years. According to the stent types, the patients were classed as BMS and SES groups. The demographic characteristics, conventional risk factors of ischemic stroke, degree of stenosis, periprocedural complications, stent types, and clinical and angiographic outcomes were analyzed. There were 39 patients in the BMSmore » group and 28 patients in the SES group. The demographic characteristics, conventional risk factors, and periprocedural complications were similar but different in residual stenosis after stenting in both groups (5.9% {+-} 9.9% vs. 14.4% {+-} 14.6%; P = 0.01). For the overall cohort, the rate of stroke or death and restenosis was 10.9% (7/66) and 24.5% (14/57), respectively. The frequency of restenosis was higher in the SES group than in the BMS group (log-rank, P = 0.04; crude hazard ratio = 3.03; 95% confidence interval (CI), 1.01-9.15; P = 0.049; and adjusted hazard ratio = 3.61; 95% CI, 1.06-12.27; P = 0.04); however, there was no difference in clinical outcomes (log-rank, P = 0.51; crude hazard ratio = 1.66; 95% CI, 0.36-7.61; P = 0.51; and adjusted hazard ratio = 0.59; 95% CI, 0.04-7.89; P = 0.69). The corrected degree of restenosis was higher in the SES than the BMS group. The prevalence of restenosis was higher in the SES than the BMS group, but the perioperative complications and follow-up clinical outcomes had no significant difference.« less

Education, Socioeconomic Status, and Intelligence in Childhood and Stroke Risk in Later Life: A Meta-analysis.

PubMed

McHutchison, Caroline A; Backhouse, Ellen V; Cvoro, Vera; Shenkin, Susan D; Wardlaw, Joanna M

2017-07-01

Stroke is the second most common cause of death, and a common cause of dependency and dementia. Adult vascular risk factors and socioeconomic status (SES) are associated with increased risk, but less is known about early life risk factors, such as education, childhood SES, or intelligence (IQ). We comprehensively searched Medline, PsycINFO, and EMBASE from inception to November 2015. We included all studies reporting data on >50 strokes examining childhood/premorbid IQ, SES, and education. Two reviewers independently screened full texts and extracted and cross-checked data, including available risk factor adjustments. We meta-analyzed stroke risk using hazard ratios (HR), odds ratios (OR), and mean differences (MD). We tested effects of study and participant characteristics in sensitivity analyses and meta-regression, and assessed heterogeneity and publication bias. We identified 90 studies examining stroke risk and education (79), SES (10), or IQ (nine) including approximately 164,683 stroke and over 5 million stroke-free participants. Stroke risk increased with lower education (OR = 1.35, 95% CI = 1.24, 1.48), SES (OR = 1.28, 95% CI = 1.12, 1.46), and IQ (HR = 1.17, 95% CI = 1.00, 1.37) in studies reporting point estimates, with similar associations for MD. We found minimal publication bias. Between-study heterogeneity was partly explained by participant age and case ascertainment method. Education, childhood SES, and intelligence have modest but important associations with lifetime stroke, and hence dementia, risks. Future studies distinguishing between the individual and combined effects of education, childhood SES and intelligence are needed to determine the independent contribution of each factor to stroke risk. See video abstract at, http://links.lww.com/EDE/B210.

Non-high-density lipoprotein cholesterol on the risks of stroke: a result from the Kailuan study.

PubMed

Wu, Jianwei; Chen, Shengyun; Zhou, Yong; Wang, Chunxue; Wang, Anxin; Zhang, Qian; Gao, Xiang; Hu, Haitao; Wu, Shouling; Zhao, Xingquan

2013-01-01

To prospectively explore the association between non-high-density lipoprotein cholesterol (non-HDLC) and the risks of stroke and its subtypes. A total of 95,916 participants (18-98 years old; 76,354 men and 19,562 women) from a Chinese urban community who were free of myocardial infarction and stroke at baseline time point (2006-2007) were eligible and enrolled in the study. The serum non-HDLC levels of participants were determined by subtracting the high-density lipoprotein cholesterol (HDLC) from total serum cholesterol. The primary outcome was the first occurrence of stroke, which was diagnosed according to the World Health Organization criteria and classified into three subtypes: ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. The Cox proportional hazards models were used to estimate risk of stroke and its subtypes. During the four-year follow-up, we identified 1614 stroke events (1,156 ischemic, 416 intracerebral hemorrhagic and 42 subarachnoid hemorrhagic). Statistical analyses showed that hazard ratios (HR) (95% Confidence Interval: CI) of serum Non-HDLC level for total and subtypes of stroke were: 1.08 (1.03-1.12) (total), 1.10 (1.05-1.16) (ischemic), 1.03 (0.96-1.10) (intracerebral hemorrhage) and 0.83 (0.66-1.05) (subarachnoid hemorrhage). HR for non-HDLC refers to the increase per each 20 mg/dl. For total and ischemic stroke, the risks were significantly higher in the fourth and fifth quintiles of non-HDLC concentrations compared to the first quintile after adjusting the confounding factors (total stroke: 4(th) quintile HR=1.33 (1.12-1.59); 5(th) quintile HR = 1.36 (1.15-1.62); ischemic stroke: 4(th) quintile HR =1.34 (1.09-1.66); 5(th) quintile HR = 1.53 (1.24-1.88)). Our data suggest that serum non-HDLC level is an independent risk factor for total and ischemic stroke, and that higher serum non-HDLC concentrations are associated with increased risks for total stroke and ischemic stroke, but not for intracerebral and subarachnoid hemorrhage.

Migraine Headache and Ischemic Stroke Risk: An Updated Meta-analysis

PubMed Central

Spector, June T.; Kahn, Susan R.; Jones, Miranda R.; Jayakumar, Monisha; Dalal, Deepan; Nazarian, Saman

2010-01-01

Background Observational studies, including recent large cohort studies which were unavailable for prior meta-analysis, have suggested an association between migraine headache and ischemic stroke. We performed an updated meta-analysis to quantitatively summarize the strength of association between migraine and ischemic stroke risk. Methods We systematically searched electronic databases, including MEDLINE and EMBASE, through February 2009 for studies of human subjects in the English language. Study selection using a priori selection criteria, data extraction, and assessment of study quality were conducted independently by reviewer pairs using standardized forms. Results Twenty-one (60%) of 35 studies met the selection criteria, for a total of 622,381 participants (13 case-control, 8 cohort studies) included in the meta-analysis. The pooled adjusted odds ratio of ischemic stroke comparing migraineurs to non-migraineurs using a random effects model was 2.30 (95% confidence interval [CI], 1.91-2.76). The pooled adjusted effect estimates for studies that reported relative risks and hazard ratios, respectively, were 2.41 (95% CI, 1.81-3.20) and 1.52 (95% CI, 0.99-2.35). The overall pooled effect estimate was 2.04 (95% CI, 1.72-2.43). Results were robust to sensitivity analyses excluding lower quality studies. Conclusions Migraine is associated with increased ischemic stroke risk. These findings underscore the importance of identifying high-risk migraineurs with other modifiable stroke risk factors. Future studies of the effect of migraine treatment and modifiable risk factor reduction on stroke risk in migraineurs are warranted. PMID:20493462

Are migraine and non-migrainous headache risk factors for stroke in the elderly? Findings from a 12-year cohort follow-up.

PubMed

Norton, J; Portet, F; Gabelle, A; Debette, S; Ritchie, K; Touchon, J; Berr, C

2016-09-01

There is evidence that migraine is a risk factor for stroke but little is known about this association in elderly people. Furthermore, non-migrainous headache (NMH) has received little attention despite being the most frequently reported type of headache. Late-life migraine and NMH were examined as candidate risk factors for stroke in a community-dwelling elderly sample over a 12-year follow-up. One thousand nine hundred and nineteen non-institutionalized subjects aged 65+, without dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, DSM-IV criteria) and with no stroke history at baseline, were drawn from the Three-City Montpellier cohort (recruitment 1999-2001) for longitudinal analysis. Ischaemic and haemorrhagic stroke was reported at baseline and at each of the five follow-ups, with cases validated by a panel of experts, according to ICD-10 criteria (International Classification of Diseases, 10th revision). Migraine and NMH were determined at baseline during a neurological interview and examination using 1988 International Headache Society criteria. A total of 110 (5.4%) cases of migraine and 179 (8.9%) cases of NMH were identified at baseline. During the median 8.8-year follow-up, incident stroke was observed in 1.9% of baseline migrainers, 6.2% of NMH and 3.6% of those with no lifetime history of headache. Cox proportional hazard models indicated that migraine was not a risk factor for stroke; however, NMH sufferers were twice as likely to have a stroke (hazard ratio 2.00, 95% confidence interval 1.00-3.93, P = 0.049). This study is one of the first to suggest that late-life NMH rather than migraine could be an independent risk factor for stroke and a warning sign. The incidence of stroke in elderly migrainers, seldom reported, is particularly low. © 2016 EAN.

Substitutions of dairy product intake and risk of stroke: a Danish cohort study.

PubMed

Laursen, Anne Sofie Dam; Dahm, Christina Catherine; Johnsen, Søren Paaske; Tjønneland, Anne; Overvad, Kim; Jakobsen, Marianne Uhre

2018-02-01

Low fat dairy products are part of dietary guidelines to prevent stroke. However, epidemiological evidence is inconclusive with regard to the association between dairy products and stroke. We therefore investigated associations for substitutions between dairy product subgroups and risk of total stroke and stroke subtypes. We included 55,211 Danish men and women aged 50-64 years without previous stroke. Baseline diet was assessed by a food frequency questionnaire. Cases were identified through a national register and subsequently verified. The associations were analyzed using Cox proportional hazard regression. During a median follow-up of 13.4 years, we identified 2272 strokes, of which 1870 were ischemic (318 large artery atherosclerotic, 839 lacunar, 102 cardioembolic, 98 other determined types, 513 of unknown type), 389 were hemorrhages (273 intracerebral, 116 subarachnoid) and 13 of unknown etiology. Substitution of semi-skimmed fermented milk or cheese for whole-fat fermented milk was associated with a higher rate of ischemic stroke [semi-skimmed fermented milk: hazard ratio (HR) = 1.20 (95% confidence interval (CI) 0.99-1.45), cheese: HR = 1.14 (95% CI 0.98-1.31) per serving/day substituted] and substitutions of whole-fat fermented milk for low-fat milk, whole-fat milk or buttermilk were associated with a lower rate [low-fat milk: HR = 0.85 (95% CI 0.74-0.99), whole-fat milk: HR = 0.84 (95% CI 0.71-0.98) and buttermilk: HR = 0.83 (95% CI 0.70-0.99)]. We observed no associations for substitutions between dairy products and hemorrhagic stroke. Our results suggest that intake of whole-fat fermented milk as a substitution for semi-skimmed fermented milk, cheese, buttermilk or milk, regardless of fat content, is associated with a lower rate of ischemic stroke.

Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts.

PubMed

Saber, Hamidreza; Yakoob, Mohammad Yawar; Shi, Peilin; Longstreth, W T; Lemaitre, Rozenn N; Siscovick, David; Rexrode, Kathryn M; Willett, Walter C; Mozaffarian, Dariush

2017-10-01

The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke. We measured circulating phospholipid fatty acids at baseline in 3 separate US cohorts: CHS (Cardiovascular Health Study), NHS (Nurses' Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis. A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.58-0.92) and DHA (HR, 0.80; 95% CI, 0.64-1.00) but not eicosapentaenoic acid (HR, 0.94; 95% CI, 0.77-1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95% CI, 0.34-0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95% CI, 0.37-0.92). Findings in each individual cohort were consistent with pooled results. In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid. © 2017 American Heart Association, Inc.

Clopidogrel with aspirin in acute minor stroke or transient ischemic attack.

PubMed

Wang, Yongjun; Wang, Yilong; Zhao, Xingquan; Liu, Liping; Wang, David; Wang, Chunxue; Wang, Chen; Li, Hao; Meng, Xia; Cui, Liying; Jia, Jianping; Dong, Qiang; Xu, Anding; Zeng, Jinsheng; Li, Yansheng; Wang, Zhimin; Xia, Haiqin; Johnston, S Claiborne

2013-07-04

Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone. In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect. Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of hemorrhagic stroke was 0.3% in each group. Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage. (Funded by the Ministry of Science and Technology of the People's Republic of China; CHANCE ClinicalTrials.gov number, NCT00979589.).

Small Brain Lesions and Incident Stroke and Mortality: A Cohort Study.

PubMed

Windham, B Gwen; Deere, Bradley; Griswold, Michael E; Wang, Wanmei; Bezerra, Daniel C; Shibata, Dean; Butler, Kenneth; Knopman, David; Gottesman, Rebecca F; Heiss, Gerardo; Mosley, Thomas H

2015-07-07

Although cerebral lesions 3 mm or larger on imaging are associated with incident stroke, lesions smaller than 3 mm are typically ignored. To examine stroke risks associated with subclinical brain lesions (<3 mm only, ≥3 mm only, and both sizes) and white matter hyperintensities (WMHs). Community cohort from the ARIC (Atherosclerosis Risk in Communities) Study. Two ARIC sites with magnetic resonance imaging (MRI) data from 1993 to 1995. 1884 adults aged 50 to 73 years with MRI, no prior stroke, and average follow-up of 14.5 years. Lesions on MRI (by size), WMH score (scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality. Hazard ratios (HRs) were estimated with proportional hazards models. Compared with no lesions, stroke risk tripled with lesions smaller than 3 mm only (HR, 3.47 [95% CI, 1.86 to 6.49]), doubled with lesions 3 mm or larger only (HR, 1.94 [CI, 1.22 to 3.07]), was 8-fold higher with lesions of both sizes (HR, 8.59 [CI, 4.69 to 15.73]), and doubled with a WMH score of at least 3 (HR, 2.14 [CI, 1.45 to 3.16]). Risk for stroke-related death tripled with lesions smaller than 3 mm only (HR, 3.05 [CI, 1.04 to 8.94]) and was 7 times higher with lesions of both sizes (HR, 6.97 [CI, 2.03 to 23.93]). Few strokes (especially hemorrhagic) and few participants with lesions smaller than 3 mm only or lesions of both sizes. Very small cerebrovascular lesions may be associated with increased risks for stroke and death; presence of lesions smaller than 3 mm and 3 mm or larger may result in a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates. National Heart, Lung, and Blood Institute.

Brachial-ankle PWV for predicting clinical outcomes in patients with acute stroke.

PubMed

Ahn, Kye Taek; Jeong, Jin-Ok; Jin, Seon-Ah; Kim, Mijoo; Oh, Jin Kyung; Choi, Ung-Lim; Seong, Seok-Woo; Kim, Jun Hyung; Choi, Si Wan; Jeong, Hye Seon; Song, Hee-Jung; Kim, Jei; Seong, In-Whan

2017-08-01

Although brachial-ankle pulse wave velocity (baPWV) is well-known for predicting the cardiovascular mortality and morbidity, its anticipated value is not demonstrated well concerning acute stroke. Total 1557 patients with acute stroke who performed baPWV were enrolled. We evaluated the prognostic value of baPWV predicting all-cause death and vascular death in patients with acute stroke Results: Highest quartile of baPWV was ≥23.64 m/s. All-caused deaths (including vascular death; 71) were 109 patients during follow-up periods (median 905 days). Multivariate Cox regression analysis revealed that patients with the highest quartile of baPWV had higher risk for vascular death when they are compared with patients with all other three quartiles of baPWV (Hazard ratio with 95% confidence interval [CI] 1.879 [1.022-3.456], p = .042 for vascular death). High baPWV was a strong prognostic value of vascular death in patients with acute stroke.

Rheumatoid arthritis significantly increased recurrence risk after ischemic stroke/transient ischemic attack.

PubMed

Chen, Yih-Ru; Hsieh, Fang-I; Lien, Li-Ming; Hu, Chaur-Jong; Jeng, Jiann-Shing; Peng, Giia-Sheun; Tang, Sung-Chun; Chi, Nai-Fang; Sung, Yueh-Feng; Chiou, Hung-Yi

2018-06-02

The effect of RA on recurrent stroke is unknown. Therefore, we examined effects of rheumatoid arthritis (RA) on risk of stroke recurrence and investigated the interaction between RA and traditional cardiovascular risk factors on recurrence risk after ischemic stroke (IS) or transient ischemic attack (TIA). Of 3190 patients with IS or TIA recruited in this cohort study, 638 were comorbid with RA and 2552 without RA. Stroke recurrence, RA, lifestyle, lipid variables and other comorbidities were identified through linkage between a nationwide stroke database in Taiwan and the National Health Insurance claims database. Cox proportional hazard models with competing risk adjustment were used to evaluate the relationship between RA and recurrent stroke. Patients with RA showed a significantly increased risk of recurrent stroke, particular in recurrent IS/TIA. The increased risk of recurrent IS/TIA in RA patients may through the changes of triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio. A positive additive interaction was observed between RA and current smoking on the risk of recurrent IS/TIA. Significantly increased risks for recurrent IS/TIA were observed among RA patients who smoked > 40 years or those who smoked > 20 cigarettes/day. This study provides the first evidence that RA significantly increased recurrence IS/TIA risk. The changes of TG/HDL-C ratio may play some roles in the recurrence IS/TIA risk in RA patients. In addition, our results suggest that smoking increases the risk of recurrent IS/TIA in RA patients and reinforces the need for aggressive smoking cessation efforts in RA patients.

Impact of metabolic syndrome components on incident stroke subtypes: a Chinese cohort study.

PubMed

Chen, Y-C; Sun, C-A; Yang, T; Chu, C-H; Bai, C-H; You, S-L; Hwang, L-C; Chen, C-H; Wei, C-Y; Chou, Y-C

2014-11-01

Limited evidence is available on the risk differences in the development of stroke subtypes in relation to particular clustering patterns of the metabolic syndrome (MetS) components. A follow-up study of a Chinese cohort involving 10,292 individuals was performed to assess the roles of cluster patterns of the MetS components in the prediction of incident stroke subtypes. During follow-up, there were 161 incident cases of ischemic strokes and 41 incident cases of hemorrhagic strokes. Among MetS components, only the hypertensive trait was associated with significantly elevated risks of both ischemic and hemorrhagic strokes. Furthermore, MetS with hypertension as components was associated with increased risk of ischemic and hemorrhagic strokes (adjusted hazards ratio (95% confidence interval) was 2.96 (1.94-4.50) and 2.93 (1.25-6.90), respectively) as compared with those who had neither hypertension nor MetS. Notably, as the number of the MetS components increased, the risk of ischemic stroke significantly and dose-dependently increased. This implies a cumulative effect of MetS components in elevating the risk of ischemic stroke. These findings suggest that MetS comprises heterogenous clusters with respect to the risk of developing the subtype of stroke.

Relationship between Stroke and Mortality in Dialysis Patients

PubMed Central

Phadnis, Milind A.; Ellerbeck, Edward F.; Shireman, Theresa I.; Rigler, Sally K.; Mahnken, Jonathan D.

2015-01-01

Background and objectives Stroke is common in patients undergoing long-term dialysis, but the implications for mortality after stroke in these patients are not fully understood. Design, setting, participants, & measurements A large cohort of dually-eligible (Medicare and Medicaid) patients initiating dialysis from 2000 to 2005 and surviving the first 90 days was constructed. Medicare claims were used to ascertain ischemic and hemorrhagic strokes occurring after 90-day survival. A semi-Markov model with additive hazard extension was generated to estimate the association between stroke and mortality, to calculate years of life lost after a stroke, and to determine whether race was associated with differential survival after stroke. Results The cohort consisted of 69,371 individuals representing >112,000 person-years of follow-up. Mean age±SD was 60.8±15.5 years. There were 21.1 (99% confidence interval [99% CI], 20.0 to 22.3) ischemic strokes and 4.7 (99% CI, 4.2 to 5.3) hemorrhagic strokes after cohort entry per 1000 patient-years. At 30 days, mortality was 17.9% for ischemic stroke and 53.4% for hemorrhagic stroke. The adjusted hazard ratio (AHR) depended on time since entry into the cohort; for patients who experienced a stroke at 1 year after cohort entry, for example, the AHR of hemorrhagic stroke for mortality was 25.4 (99% CI, 22.4 to 28.4) at 1 week, 9.9 (99% CI, 8.4 to 11.6) at 3 months, 5.9 (99% CI, 5.0 to 7.0) at 6 months, and 1.8 (99% CI, 1.5 to 2.1) at 24 months. The corresponding AHRs for ischemic stroke were 11.7 (99% CI, 10.2 to 13.1) at 1 week, 6.6 (99% CI, 6.4 to 6.7) at 3 months, and 4.7 (99% CI, 4.5 to 4.9) at 6 months, remaining significantly >1.0 even at 48 months. Median months of life lost were 40.7 for hemorrhagic stroke and 34.6 for ischemic stroke. For both stroke types, mortality did not differ by race. Conclusions Dialysis recipients have high mortality after a stroke with corresponding decrements in remaining years of life. Poststroke mortality does not differ by race. PMID:25318759

Relationship between stroke and mortality in dialysis patients.

PubMed

Wetmore, James B; Phadnis, Milind A; Ellerbeck, Edward F; Shireman, Theresa I; Rigler, Sally K; Mahnken, Jonathan D

2015-01-07

Stroke is common in patients undergoing long-term dialysis, but the implications for mortality after stroke in these patients are not fully understood. A large cohort of dually-eligible (Medicare and Medicaid) patients initiating dialysis from 2000 to 2005 and surviving the first 90 days was constructed. Medicare claims were used to ascertain ischemic and hemorrhagic strokes occurring after 90-day survival. A semi-Markov model with additive hazard extension was generated to estimate the association between stroke and mortality, to calculate years of life lost after a stroke, and to determine whether race was associated with differential survival after stroke. The cohort consisted of 69,371 individuals representing >112,000 person-years of follow-up. Mean age±SD was 60.8±15.5 years. There were 21.1 (99% confidence interval [99% CI], 20.0 to 22.3) ischemic strokes and 4.7 (99% CI, 4.2 to 5.3) hemorrhagic strokes after cohort entry per 1000 patient-years. At 30 days, mortality was 17.9% for ischemic stroke and 53.4% for hemorrhagic stroke. The adjusted hazard ratio (AHR) depended on time since entry into the cohort; for patients who experienced a stroke at 1 year after cohort entry, for example, the AHR of hemorrhagic stroke for mortality was 25.4 (99% CI, 22.4 to 28.4) at 1 week, 9.9 (99% CI, 8.4 to 11.6) at 3 months, 5.9 (99% CI, 5.0 to 7.0) at 6 months, and 1.8 (99% CI, 1.5 to 2.1) at 24 months. The corresponding AHRs for ischemic stroke were 11.7 (99% CI, 10.2 to 13.1) at 1 week, 6.6 (99% CI, 6.4 to 6.7) at 3 months, and 4.7 (99% CI, 4.5 to 4.9) at 6 months, remaining significantly >1.0 even at 48 months. Median months of life lost were 40.7 for hemorrhagic stroke and 34.6 for ischemic stroke. For both stroke types, mortality did not differ by race. Dialysis recipients have high mortality after a stroke with corresponding decrements in remaining years of life. Poststroke mortality does not differ by race. Copyright © 2015 by the American Society of Nephrology.

Changes in the living arrangement and risk of stroke in Japan; does it matter who lives in the household? Who among the family matters?

PubMed

Eshak, Ehab Salah; Iso, Hiroyasu; Honjo, Kaori; Noda, Ai; Sawada, Norie; Tsugane, Shoichiro

2017-01-01

Previous studies have suggested associations of family composition with morbidity and mortality; however, the evidence of associations with risk of stroke is limited. We sought to examine the impact of changes in the household composition on risk of stroke and its types in Japanese population. Cox proportional hazard modelling was used to assess the risk of incident stroke and stroke types within a cohort of 77,001 Japanese men and women aged 45-74 years who experienced addition and/or loss of family members [spouse, child(ren), parent(s) and others] to their households over a five years interval (between 1990-1993 and 1995-1998). During 1,043,446 person-years of the follow-up for 35,247 men and 41,758 women, a total of 3,858 cases of incident stroke (1485 hemorrhagic and 2373 ischemic) were documented. When compared with a stable family composition, losing at least one family member was associated with 11-15% increased risk of stroke in women and men; hazard ratios (95% confidence interval) were 1.11 (1.01-1.22) and 1.15 (1.05-1.26), respectively. The increased risk was associated with the loss of a spouse, and was evident for ischemic stroke in men and hemorrhagic stroke in women. The addition of any family members to the household was not associated with risk of stroke in men, whereas the addition of a parent (s) to the household was associated with increased risk in women: 1.49 (1.09-2.28). When the loss of a spouse was accompanied by the addition of other family members to the household, the increased risk of stroke disappeared in men: 1.18 (0.85-1.63), but exacerbated in women: 1.58 (1.19-2.10). In conclusion, men who have lost family members, specifically a spouse have higher risk of ischemic stroke, and women who gained family members; specifically a parent (s) had the higher risk of hemorrhagic stroke than those with a stable family composition.

C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease.

PubMed

Arenillas, Juan F; Alvarez-Sabín, José; Molina, Carlos A; Chacón, Pilar; Montaner, Joan; Rovira, Alex; Ibarra, Bernardo; Quintana, Manuel

2003-10-01

The role of inflammation in intracranial large-artery occlusive disease is unclear. We sought to investigate the relationship between high-sensitivity C-reactive protein (CRP) levels and the risk of further ischemic events in first-ever transient ischemic attack (TIA) or stroke patients with intracranial large-artery occlusive disease. Of a total of 127 consecutive first-ever TIA or ischemic stroke patients with intracranial stenoses detected by transcranial Doppler ultrasonography, 71 fulfilled all inclusion criteria, which included angiographic confirmation. Serum high-sensitivity CRP level was determined a minimum of 3 months after the qualifying event. Patients were followed up during 1 year after blood sampling. Thirteen patients (18.3%) with intracranial large-artery occlusive disease experienced an end point event: 9 cerebral ischemic events, 7 of which were attributable to intracranial large-artery occlusive disease, and 4 myocardial infarctions. Patients in the highest quintile of high-sensitivity CRP level had a significantly higher adjusted odds ratio for new events compared with those in the first quintile (odds ratio, 8.66; 95% CI, 1.39 to 53.84; P=0.01). A high-sensitivity CRP level above the receiver operating characteristic curve cutoff value of 1.41 mg/dL emerged as an independent predictor of new end point events (hazard ratio, 7.14; 95% CI, 1.77 to 28.73; P=0.005) and of further intracranial large-artery occlusive disease-related ischemic events (hazard ratio, 30.67; 95% CI, 3.6 to 255.5; P=0.0015), after adjustment for age, sex, and risk factors. Kaplan-Meier curves showed that a significantly lower proportion of patients with a high-sensitivity CRP >1.41 mg/dL remained free of a new ischemic event (P<0.0001). High-sensitivity CRP serum level predicts further intracranial large-artery occlusive disease-related and any major ischemic events in patients with first-ever TIA or stroke with intracranial large-artery occlusive disease. These findings are consistent with the hypothesis that inflammation may be involved in the progression and complication of intracranial large-artery occlusive disease.

Computational Fluid Dynamics Modeling of Symptomatic Intracranial Atherosclerosis May Predict Risk of Stroke Recurrence

PubMed Central

Leng, Xinyi; Scalzo, Fabien; Ip, Hing Lung; Johnson, Mark; Fong, Albert K.; Fan, Florence S. Y.; Chen, Xiangyan; Soo, Yannie O. Y.; Miao, Zhongrong; Liu, Liping; Feldmann, Edward; Leung, Thomas W. H.; Liebeskind, David S.; Wong, Ka Sing

2014-01-01

Background Patients with symptomatic intracranial atherosclerosis (ICAS) of ≥70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset. Methods Patients with a symptomatic ICAS lesion of 70–99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year. Results Overall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (−2.46–0.79), 4.5 (2.2–20.6), and 7.4 (5.2–12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004–1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002–1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594–0.903; P = 0.014) and 0.776 (95% CI, 0.594–0.903; P = 0.002) in receiver operating characteristic analysis. Conclusions Hemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70–99% luminal stenosis. PMID:24818753

Association of Progression of Carotid Artery Wall Volume and Recurrent Transient Ischemic Attack or Stroke: A Magnetic Resonance Imaging Study.

PubMed

Lu, Mingming; Peng, Peng; Cui, Yuanyuan; Qiao, Huiyu; Li, Dongye; Cai, Jianming; Zhao, Xihai

2018-03-01

This study aimed to investigate the association between carotid plaque progression and subsequent recurrent events using magnetic resonance imaging. Sixty-three symptomatic patients with ipsilateral carotid atherosclerotic stenosis (30%-69% stenosis) determined by ultrasound underwent first and second carotid artery magnetic resonance imaging for carotid artery at baseline and ≥6 months after the first scan, respectively. All the patients had clinical follow-up after the second magnetic resonance scan for ≤5 years until the onset of recurrent transient ischemic attack or stroke. Presence/absence of carotid plaque compositional features, particularly intraplaque hemorrhage and fibrous cap rupture was identified. The annual progression of carotid wall volume between 2 magnetic resonance scans was measured. Univariate and multivariate Cox regression was used to calculate the hazard ratio and corresponding 95% confidence interval of carotid plaque features in discriminating recurrent events. Receiver-operating-characteristic-curve analysis was conducted to determine the area-under-the-curve of carotid plaque features in predicting recurrent events. Sixty-three patients (mean age: 66.5±10.0 years old; 54 males) were eligible for final statistics analysis. During a mean follow-up duration of 55.1±13.6 months, 14.3% of patients (n=9) experienced ipsilateral recurrent transient ischemic attack/stroke. The annual progression of carotid wall volume was significantly associated with recurrent events before (hazard ratio, 1.14 per 10 mm 3 ; 95% confidence interval, 1.02-1.27; P =0.019) and after (hazard ratio, 1.19 per 10 mm3; 95% confidence interval, 1.03-1.37; P =0.022) adjusted for confounding factors. In discriminating the recurrence of transient ischemia attack/stroke, receiver-operator curve analysis indicated that combined with annual progression of wall volume, there was a significant incremental improvement in the area-under-the-curve of intraplaque hemorrhage (area-under-the-curve: 0.69-0.81) and fibrous cap rupture (area-under-the-curve: 0.73-0.84). The annual progression of carotid wall volume is independently associated with recurrent ischemic cerebrovascular events, and this measurement has added value for intraplaque hemorrhage and fibrous cap rupture in predicting future events. © 2018 American Heart Association, Inc.

Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects.

PubMed

James, W Philip T; Caterson, Ian D; Coutinho, Walmir; Finer, Nick; Van Gaal, Luc F; Maggioni, Aldo P; Torp-Pedersen, Christian; Sharma, Arya M; Shepherd, Gillian M; Rode, Richard A; Renz, Cheryl L

2010-09-02

The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.)

Five-year Prognosis after Mild to Moderate Ischemic Stroke by Stroke Subtype: A Multi-Clinic Registry Study

PubMed Central

Lv, Yumei; Fang, Xianghua; Asmaro, Karam; Liu, Hongjun; Zhang, Xinqing; Zhang, Hongmei; Qin, Xiaoming; Ji, Xunming

2013-01-01

Background and Purpose Mild to moderate ischemic stroke is a common presentation in the outpatient setting. Among the various subtypes of stroke, lacunar infarction (LI) is generally very common. Currently, little is known about the long-term prognosis and factors associated with the prognosis between LI and non-LI. This study aims to compare the risk of death and acute cardiovascular events between patients with LI and non-LI, and identify potential risk factors associated with these outcomes. Methods A total of 710 first-ever ischemic stroke patients (LI: 474, non-LI: 263) from 18 clinics were recruited consecutively from 2003 to 2004. They were prospectively followed-up until the end of 2008. Hazard ratios and 95% confidence intervals were calculated using multivariable Cox proportional hazards regression. Results After a 5-year follow up, 54 deaths and 96 acute cardiovascular events occurred. Recurrent stroke was the most common cause of death (19 cases, 35.18%) and new acute cardiovascular events (75 cases, 78.13%). There were no significant differences between patients with LI and non-LI in their risks of death, new cardiovascular events, and recurrent stroke after adjusting for age, sex, hypertension, diabetes, cardiac diseases, body mass index, dyslipidemia, smoking, alcohol consumption, ADL dependence, and depressive symptoms. Among the modifiable risk factors, diabetes, hypertension, ADL dependency, and symptoms of depression were independent predictors of poor outcomes in patients with LI. In non-LI patients, however, no modifiable risk factors were detected for poor outcomes. Conclusion Long-term outcomes did not differ significantly between LI and non-LI patients. Detecting and managing vascular risk factors and depression as well as functional rehabilitation may improve the prognoses of LI patients. PMID:24223696

A prospective cohort study of stroke mortality and arsenic in drinking water in Bangladeshi adults

PubMed Central

2014-01-01

Background Arsenic in drinking water causes increased coronary artery disease (CAD) and death from CAD, but its association with stroke is not known. Methods Prospective cohort study with arsenic exposure measured in well water at baseline. 61074 men and women aged 18 years or older on January 2003 were enrolled in 2003. The cohort was actively followed for an average of 7 years (421,754 person-years) through December 2010. Based on arsenic concentration the population was categorized in three groups and stroke mortality HR was compared to the referent. The risk of stroke mortality Hazard Ratio (HR) and 95% Confidence Interval was calculated in relation to arsenic exposure was estimated by Cox proportional hazard models with adjustment for potential confounders. Results A total of 1033 people died from stroke during the follow-up period, accounting for 23% of the total deaths. Multivariable adjusted HRs (95% confidence interval) for stroke for well water arsenic concentrations <10, 10-49, and ≥50 μg/L were 1.0 (reference), 1.20 (0.92 to 1.57), and 1.35 (1.04 to 1.75) respectively (Ptrend=0.00058). For men, multivariable adjusted HRs (95%) for well water arsenic concentrations <10, 10-49, and ≥50 μg/L were 1.0 (reference), 1.12 (0.78 to 1.60), and 1.07 (0.75 to 1.51) respectively (Ptrend=0.45) and for women 1.0 (reference),1.31 (0.87 to 1.98), and 1.72 (1.15 to 2.57) respectively (Ptrend=0.00004). Conclusion The result suggests that arsenic exposure was associated with increased stroke mortality risk in this population, and was more significant in women compared to men. PMID:24548416

Role of APOE ε4 Allele and Incident Stroke on Cognitive Decline and Mortality.

PubMed

Rajan, Kumar B; Aggarwal, Neelum T; Schneider, Julie A; Wilson, Robert S; Everson-Rose, Susan A; Evans, Denis A

2016-01-01

The apolipoprotein E (APOE) ε4 allele and stroke increase the risk of cognitive decline. However, the association of the APOE ε4 allele before and after stroke is not well understood. Using a prospective sample of 3444 (66% African Americans, 61% females, mean age=71.9 y) participants, we examined cognitive decline relative to stroke among those with and without the APOE ε4 allele. In our sample, 505 (15%) had incident stroke. Among participants without stroke, the ε4 allele was associated with increased cognitive decline compared to noncarriers (0.080 vs. 0.036 units/year; P<0.0001). Among participants without the ε4 allele, cognitive decline increased significantly after stroke compared to before stroke (0.115 vs. 0.039 units/year; P<0.0001). Interestingly, cognitive decline before and after stroke was not significantly different among those with the ε4 allele (0.091 vs. 0.102 units/year; P=0.32). Poor cognitive function was associated with higher risk of stroke (hazard ratio=1.41, 95% confidence interval, 1.25-1.58), but the APOE ε4 allele was not (P=0.66). The APOE ε4 allele, cognitive function, and incident stroke were associated with mortality. The association of stroke with cognitive decline appears to differ by the presence of the APOE ε4 allele, but no such interaction was observed for mortality.

Years of disability-adjusted life gained as a result of thrombolytic therapy for acute ischemic stroke.

PubMed

Hong, Keun-Sik; Saver, Jeffrey L

2010-03-01

Disability-adjusted life year (DALY) metric reflects years of healthy life lost because of living with disability and years of life lost because of premature mortality. Widely used in epidemiological analyses, DALY has not been applied to acute stroke trials. From previous studies, we derived, for each modified Rankin Scale level, disability weights, disability-linked mortality hazard ratios, and age-specific life expectancies. We then analyzed patient level data from the 2 publicly available National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator trials. For each subject, we abstracted age, treatment assignment, and 3-month modified Rankin Scale outcome and calculated the DALYs lost resulting from the qualifying stroke. The disability-linked hazard ratios for premature annual mortality for a modified Rankin Scale score of 0 to 5 were 1.53, 1.52, 2.17, 3.18, 4.55, and 6.55, respectively. In the NINDS recombinant tissue plasminogen activator trials, DALYs (mean+/-SE) lost as a result of the qualifying stroke were substantially less with recombinant tissue plasminogen activator than with placebo (4.64+/-0.17 versus 5.91+/-0.21; P<0.0001), a finding that remained robust after adjustment for baseline prognostic factors. When DALYs gained were apportioned to the 29% of patients experiencing any benefit from lytic therapy, each patient gained an average of 4.4 DALYs. DALY analysis showed greater power than dichotomized modified Rankin Scale analysis in discriminating treatment effects overall and in patients >or=70 years of age. For patients who benefit from treatment, <3-hour thrombolytic therapy adds the equivalent of 4.4 years of healthy life, free of disability. The DALY metric provides a continuous scale that increases statistical power, is intuitively understandable, and is applicable to a wide range of conditions and treatments.

Differences in the role of black race and stroke risk factors for first vs. recurrent stroke.

PubMed

Howard, George; Kissela, Brett M; Kleindorfer, Dawn O; McClure, Leslie A; Soliman, Elsayed Z; Judd, Suzanne E; Rhodes, J David; Cushman, Mary; Moy, Claudia S; Sands, Kara A; Howard, Virginia J

2016-02-16

To assess whether black race and other cerebrovascular risk factors have a differential effect on first vs. recurrent stroke events. Estimate the differences in the magnitude of the association of demographic (age, back race, sex) or stroke risk factors (hypertension, diabetes, cigarette smoking, atrial fibrillation, left ventricular hypertrophy, or heart disease) for first vs. recurrent stroke from a longitudinal cohort study of 29,682 black or white participants aged 45 years and older. Over an average 6.8 years follow-up, 301 of 2,993 participants with a previous stroke at baseline had a recurrent stroke, while 818 of 26,689 participants who were stroke-free at baseline had a first stroke. Among those stroke-free at baseline, there was an age-by-race interaction (p = 0.0002), with a first stroke risk 2.70 (95% confidence interval: 1.86-3.91) times greater for black than white participants at age 45, but no racial disparity at age 85 (hazard ratio = 0.91; 95% confidence interval: 0.70-1.18). In contrast, there was no evidence of a higher risk of recurrent stroke at any age for black participants (p > 0.05). The association of traditional stroke risk factors was generally similar for first and recurrent stroke. The association of age and black race differs substantially on first vs. recurrent stroke risk, with risk factors playing a similar role. © 2016 American Academy of Neurology.

"Ikigai", Subjective Wellbeing, as a Modifier of the Parity-Cardiovascular Mortality Association　- The Japan Collaborative Cohort Study.

PubMed

Yasukawa, Sumiyo; Eguchi, Eri; Ogino, Keiki; Tamakoshi, Akiko; Iso, Hiroyasu

2018-04-25

Nulliparity is associated with an excess risk of cardiovascular disease (CVD). "Ikigai", subjective wellbeing in Japan, is associated with reduced risk of CVD. The impact of ikigai on the association between parity and the risk of CVD, however, has not been reported.Methods and Results:A total of 39,870 Japanese women aged 40-79 years without a history of CVD, cancer or insufficient information at baseline in 1988-1990, were enrolled and followed until the end of 2009. They were categorized into 7 groups according to parity number 0-≥6. Using Cox regression hazard modeling, the associations between parity and mortality from stroke, coronary artery disease, and total CVD were investigated. During the follow-up period, 2,121 total CVD deaths were documented. No association was observed between parity and stroke and CVD mortality in women with ikigai, but there was an association in those without ikigai. The multivariable hazard ratios of stroke and total CVD mortality for nulliparous women without ikigai vs. those with 1 child were 1.87 (95% CI: 1.15-3.05) and 1.46 (95% CI: 1.07-2.01), respectively, and that for stroke mortality in high parity women without ikigai was 1.56 (95% CI: 1.00-2.45). Nulliparous or high parity women without ikigai had higher mortality from stroke and/or total CVD, suggesting that ikigai attenuated the association between parity and CVD mortality in Japanese women.

Benefits of off-pump coronary artery bypass grafting in high-risk patients.

PubMed

Marui, Akira; Okabayashi, Hitoshi; Komiya, Tatsuhiko; Tanaka, Shiro; Furukawa, Yutaka; Kita, Toru; Kimura, Takeshi; Sakata, Ryuzo

2012-09-11

The benefits of off-pump coronary artery bypass graft (OPCAB) compared with conventional on-pump coronary artery bypass graft (CCAB) remain controversial. Thus, it is important to investigate which patient subgroups may benefit the most from OPCAB rather than CCAB. Among the patients undergoing first coronary revascularization enrolled in the CREDO-Kyoto Registry (a registry of first-time percutaneous coronary intervention and coronary artery bypass graft patients in Japan), 2468 patients undergoing coronary artery bypass graft were entered into the study (mean age, 67 ± 9 years). Predicted risk of operative mortality (PROM) of each patient was calculated by logistic EuroSCORE. Patients were divided into tertile based on their PROM. Mortality rates and the incidences of cardiovascular events were compared between CCAB and OPCAB within each PROM tertile using propensity score analysis. A total of 1377 patients received CCAB whereas 1091 received OPCAB. Adjusted 30-day mortality was not significantly different between CCAB and OPCAB patients regardless of their PROM range. However, the odds ratio of 30-day stroke in CCAB compared with OPCAB in the high-risk tertile was 8.30 (95% confidence interval, 2.25-30.7; P<0.01). Regarding long-term outcomes, hazard ratio of stroke in CCAB compared with OPCAB in the high-risk tertile was 1.80 (95% confidence interval, 1.07-3.02; P=0.03). Nevertheless, hazard ratio of overall mortality in the high-risk tertile was 1.44 (95% confidence interval, 0.98-2.11; P=0.06), indicating no statistically significant difference between the 2 procedures. OPCAB as opposed to CCAB is associated with short-term and long-term benefits in stroke prevention in patients at higher risk as estimated by EuroSCORE. No survival benefit of OPCAB was shown regardless of preoperative risk level.

A History of Falls is Associated with a Significant Increase in Acute Mortality in Women after Stroke.

PubMed

Foster, Emma J; Barlas, Raphae S; Wood, Adrian D; Bettencourt-Silva, Joao H; Clark, Allan B; Metcalf, Anthony K; Bowles, Kristian M; Potter, John F; Myint, Phyo K

2017-10-01

The risks of falls and fractures increase after stroke. Little is known about the prognostic significance of previous falls and fractures after stroke. This study examined whether having a history of either event is associated with poststroke mortality. We analyzed stroke register data collected prospectively between 2003 and 2015. Eight sex-specific models were analyzed, to which the following variables were incrementally added to examine their potential confounding effects: age, type of stroke, Oxfordshire Community Stroke Project classification, previous comorbidities, frailty as indicated by the prestroke modified Rankin Scale score, and acute illness parameters. Logistic regression was applied to investigate in-hospital and 30-day mortality, and Cox proportional-hazards models were applied to investigate longer-term outcomes of mortality. In total, 10,477 patients with stroke (86.1% ischemic) were included in the analysis. They were aged 77.7±11.9 years (mean±SD), and 52.2% were women. A history of falls was present in 8.6% of the men (n=430) and 20.2% of the women (n=1,105), while 3.8% (n=189) of the men and 12.9% of the women (n=706) had a history of both falls and fractures. Of the outcomes examined, a history of falls alone was associated with increased in-hospital mortality [odds ratio (OR)=1.33, 95% confidence interval (CI)=1.03-1.71] and 30-day mortality (OR=1.34, 95% CI=1.03-1.73) in women in the fully adjusted models. The Cox proportional-hazards models for longer-term outcomes and the history of falls and fractures combined showed no significant results. The history of falls is an important factor for acute stroke mortality in women. A previous history of falls may therefore be an important factor to consider in the short-term stroke prognosis, particularly in women. Copyright © 2017 Korean Neurological Association

Dose comparisons of clopidogrel and aspirin in acute coronary syndromes.

PubMed

Mehta, Shamir R; Bassand, Jean-Pierre; Chrolavicius, Susan; Diaz, Rafael; Eikelboom, John W; Fox, Keith A A; Granger, Christopher B; Jolly, Sanjit; Joyner, Campbell D; Rupprecht, Hans-Jurgen; Widimsky, Petr; Afzal, Rizwan; Pogue, Janice; Yusuf, Salim

2010-09-02

Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). However, evidence-based guidelines for dosing have not been established for either agent. We randomly assigned, in a 2-by-2 factorial design, 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600-mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily). The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. The primary outcome occurred in 4.2% of patients assigned to double-dose clopidogrel as compared with 4.4% assigned to standard-dose clopidogrel (hazard ratio, 0.94; 95% confidence interval [CI], 0.83 to 1.06; P=0.30). Major bleeding occurred in 2.5% of patients in the double-dose group and in 2.0% in the standard-dose group (hazard ratio, 1.24; 95% CI, 1.05 to 1.46; P=0.01). Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI (1.6% vs. 2.3%; hazard ratio, 0.68; 95% CI, 0.55 to 0.85; P=0.001). There was no significant difference between higher-dose and lower-dose aspirin with respect to the primary outcome (4.2% vs. 4.4%; hazard ratio, 0.97; 95% CI, 0.86 to 1.09; P=0.61) or major bleeding (2.3% vs. 2.3%; hazard ratio, 0.99; 95% CI, 0.84 to 1.17; P=0.90). In patients with an acute coronary syndrome who were referred for an invasive strategy, there was no significant difference between a 7-day, double-dose clopidogrel regimen and the standard-dose regimen, or between higher-dose aspirin and lower-dose aspirin, with respect to the primary outcome of cardiovascular death, myocardial infarction, or stroke. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00335452.)

Nitrous Oxide and Serious Long-term Morbidity and Mortality in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II Trial.

PubMed

Leslie, Kate; Myles, Paul S; Kasza, Jessica; Forbes, Andrew; Peyton, Philip J; Chan, Matthew T V; Paech, Michael J; Sessler, Daniel I; Beattie, W Scott; Devereaux, P J; Wallace, Sophie

2015-12-01

The Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II trial randomly assigned 7,112 noncardiac surgery patients at risk of perioperative cardiovascular events to 70% N2O or 70% N2 groups. The aim of this follow-up study was to determine the effect of nitrous oxide on a composite primary outcome of death and major cardiovascular events at 1 yr after surgery. One-year follow-up was conducted via a medical record review and telephone interview. Disability was defined as a Katz index of independence in activities of daily living score less than 8. Adjusted odds ratios and hazard ratios were calculated as appropriate for primary and secondary outcomes. Among 5,844 patients evaluated at 1 yr, 435 (7.4%) had died, 206 (3.5%) had disability, 514 (8.8%) had a fatal or nonfatal myocardial infarction, and 111 (1.9%) had a fatal or nonfatal stroke during the 1-yr follow-up period. Exposure to nitrous oxide did not increase the risk of the primary outcome (odds ratio, 1.08; 95% CI, 0.94 to 1.25; P = 0.27), disability or death (odds ratio, 1.07; 95% CI, 0.90 to 1.27; P = 0.44), death (hazard ratio, 1.17; 95% CI, 0.97 to 1.43; P = 0.10), myocardial infarction (odds ratio, 0.97; 95% CI, 0.81 to 1.17; P = 0.78), or stroke (odds ratio, 1.08; 95% CI, 0.74 to 1.58; P = 0.70). These results support the long-term safety of nitrous oxide administration in noncardiac surgical patients with known or suspected cardiovascular disease.

Depression and young age impact on hip fracture subsequent to stroke: A population-based cohort study.

PubMed

Yeh, Hui-Fang; Hsu, Yao-Chun; Clinciu, Daniel L; Tung, Heng-Hsin; Yen, Yung-Chieh; Kuo, Hung-Chang

2018-06-03

The purpose of this study is to identify whether depression and other associated factors in stroke are related to subsequent hip fracture. There are very few studies that focus on depression and demographic impact on subsequent hip fracture after a stroke. This a retrospective cohort study design. The Taiwan Longitudinal Health Insurance Database between 1997 and 2010 was used. Two stroke patient cohorts were analysed: (1) depression within 1 year after newly diagnosed strokes; (2) without depression within 1 year after newly diagnosed strokes. Demographic characteristics, comorbidities, and hip fracture were compared using the Fine and Gray regression model for subdistribution hazard ratios. Patients with depression showed a higher risk of hip fracture (95% CI, 0.99-1.66). Depression was associated with increased risk of hip fracture for patients below 50 years old (95% CI, 1.45-7.34). Comorbidities and gender showed no significant correlation with hip fracture risk in the depressed or nondepressed groups. Poststroke depression was a significant contributor to hip fracture in patients who suffered strokes and had more negative impact on the younger population, regardless of the gender and presence of comorbidities. © 2018 John Wiley & Sons Australia, Ltd.

Higher Education Is Associated with a Lower Risk of Dementia after a Stroke or TIA. The Rotterdam Study.

PubMed

Mirza, Saira Saeed; Portegies, Marileen L P; Wolters, Frank J; Hofman, Albert; Koudstaal, Peter J; Tiemeier, Henning; Ikram, M Arfan

2016-01-01

Higher education is associated with a lower risk of dementia, possibly because of a higher tolerance to subclinical neurodegenerative pathology. Whether higher education also protects against dementia after clinical stroke or transient ischemic attack (TIA) remains unknown. Within the population-based Rotterdam Study, 12,561 participants free of stroke, TIA and dementia were followed for occurrence of stroke, TIA and dementia. Across the levels of education, associations of incident stroke or TIA with subsequent development of dementia and differences in cognitive decline following stroke or TIA were investigated. During 124,862 person-years, 1,463 persons suffered a stroke or TIA, 1,158 persons developed dementia, of whom 186 developed dementia after stroke or TIA. Risk of dementia after a stroke or TIA, compared to no stroke or TIA, was highest in the low education category (hazards ratio [HR] 1.46, 95% CI 1.18-1.81) followed by intermediate education category (HR 1.36, 95% CI 1.03-1.81). No significant association was observed in the high education category (HR 0.62, 95% CI 0.25-1.54). In gender stratified analyses, decrease in risk of dementia with increasing education was significant only in men. Higher education is associated with a lower risk of dementia after stroke or TIA, particularly in men, which might be explained by a higher cognitive reserve. © 2016 S. Karger AG, Basel.

Increased Risk of Stroke in Patients of Concussion: A Nationwide Cohort Study.

PubMed

Liu, Shih-Wei; Huang, Liang-Chung; Chung, Wu-Fu; Chang, Hsuan-Kan; Wu, Jau-Ching; Chen, Li-Fu; Chen, Yu-Chun; Huang, Wen-Cheng; Cheng, Henrich; Lo, Su-Shun

2017-02-25

Long-term morbidities can develop after traumatic brain injury (TBI). Some studies have suggested that the risk of stroke is higher after TBI, but the association between concussion and stroke remains unclear. Using a national cohort, the authors analyzed the incidence of both hemorrhagic and ischemic strokes in patients with previous concussion. A representative cohort of approximately one million people was followed up for four years. Patients with new-onset concussion were identified ( n = 13,652) as the concussion group. Subsequently, the incidence rates of later stroke events in the concussion group were compared to a sex-, age- and propensity score-matched comparison group ( n = 13,652). The overall incidence rate of stroke in the concussion group was higher than that of the comparison group (9.63 versus 6.52 per 1000 person-years, p < 0.001). Significantly higher stroke risk was observed in the concussion group than in the comparison group (crude hazard ratio 1.48, p < 0.001; adjusted HR 1.65, p < 0.001). In the concussion group, the cumulative incidence rates of both ischemic stroke and hemorrhagic stroke were higher than those of the comparison group (8.9% vs. 5.8% and 2.7% vs. 1.6%, respectively, both p < 0.001). Concussion is an independent risk factor for both ischemic and hemorrhagic strokes. Prevention and monitoring strategies of stroke are therefore suggested for patients who have experienced concussion.

Alcohol consumption and risk of stroke and coronary heart disease among Japanese women: the Japan Public Health Center-based prospective study.

PubMed

Ikehara, Satoyo; Iso, Hiroyasu; Yamagishi, Kazumasa; Kokubo, Yoshihiro; Saito, Isao; Yatsuya, Hiroshi; Inoue, Manami; Tsugane, Shoichiro

2013-11-01

The study aims to examine the association between a wide range of alcohol consumption and risk of stroke and coronary heart disease. The Japan Public Health Center-based prospective study was initiated in 1990 in Cohort I and in 1993 in Cohort II, with follow-up until 2009. The sample consisted of 47,100 women aged 40-69 years. During an average of 16.7-years, the incidence of 1846 strokes and 292 coronary heart diseases was observed. Heavy drinking (≥ 300 gethanol/week) was associated with increased risk of total stroke. The multivariable hazard ratios for heavy versus occasional drinkers were 2.19 (95% confidence interval: 1.45-3.30) for total stroke, 2.25 (1.29-3.91) for hemorrhagic stroke, 2.24 (1.05-4.76) for intraparenchymal hemorrhage, 2.26 (1.01-5.09) for subarachnoid hemorrhage and 2.04 (1.09-3.82) for ischemic stroke. In the exposure-updated analysis, the positive association between heavy drinking and risks of total stroke, hemorrhagic stroke and intraparenchymal hemorrhage became more evident. Light drinking (<150 gethanol/week) was not associated with risk of ischemic stroke. There was also no association between alcohol consumption and risk of coronary heart disease. Heavy drinking was associated with increased risk of hemorrhagic and ischemic strokes among Japanese women. © 2013.

Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke.

PubMed

Barsic, Bruno; Dickerman, Stuart; Krajinovic, Vladimir; Pappas, Paul; Altclas, Javier; Carosi, Giampiero; Casabé, José H; Chu, Vivian H; Delahaye, Francois; Edathodu, Jameela; Fortes, Claudio Querido; Olaison, Lars; Pangercic, Ana; Patel, Mukesh; Rudez, Igor; Tamin, Syahidah Syed; Vincelj, Josip; Bayer, Arnold S; Wang, Andrew

2013-01-01

The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.

Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation.

PubMed

Hankey, Graeme J; Stevens, Susanna R; Piccini, Jonathan P; Lokhnygina, Yuliya; Mahaffey, Kenneth W; Halperin, Jonathan L; Patel, Manesh R; Breithardt, Günter; Singer, Daniel E; Becker, Richard C; Berkowitz, Scott D; Paolini, John F; Nessel, Christopher C; Hacke, Werner; Fox, Keith A A; Califf, Robert M

2014-05-01

Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation. We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used. During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10(9)/L (1.08; 1.02-1.13 per 10×10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73). Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.

Stroke and long-term exposure to outdoor air pollution from nitrogen dioxide: a cohort study.

PubMed

Andersen, Zorana J; Kristiansen, Luise C; Andersen, Klaus K; Olsen, Tom S; Hvidberg, Martin; Jensen, Steen S; Ketzel, Matthias; Loft, Steffen; Sørensen, Mette; Tjønneland, Anne; Overvad, Kim; Raaschou-Nielsen, Ole

2012-02-01

Years of exposure to tobacco smoke substantially increase the risk for stroke. Whether long-term exposure to outdoor air pollution can lead to stroke is not yet established. We examined the association between long-term exposure to traffic-related air pollution and incident and fatal stroke in a prospective cohort study. We followed 57,053 participants of the Danish Diet, Cancer and Health cohort in the Hospital Discharge Register for the first-ever hospital admission for stroke (incident stroke) between baseline (1993-1997) and 2006 and defined fatal strokes as death within 30 days of admission. We associated the estimated mean levels of nitrogen dioxide at residential addresses since 1971 to incident and fatal stroke by Cox regression analyses and examined the effects by stroke subtypes: ischemic, hemorrhagic, and nonspecified stroke. Over a mean follow-up of 9.8 years of 52,215 eligible subjects, there were 1984 (3.8%) first-ever (incident) hospital admissions for stroke of whom 142 (7.2%) died within 30 days. We detected borderline significant associations between mean nitrogen dioxide levels at residence since 1971 and incident stroke (hazard ratio, 1.05; 95% CI, 0.99-1.11, per interquartile range increase) and stroke hospitalization followed by death within 30 days (1.22; 1.00-1.50). The associations were strongest for nonspecified and ischemic strokes, whereas no association was detected with hemorrhagic stroke. Long-term exposure to traffic-related air pollution may contribute to the development of ischemic but not hemorrhagic stroke, especially severe ischemic strokes leading to death within 30 days.

Small brain lesions and incident stroke and mortality: A cohort study

PubMed Central

Windham, B Gwen; Deere, Bradley; Griswold, Michael E.; Wang, Wanmei; Bezerra, Daniel C; Shibata, Dean; Butler, Kenneth; Knopman, David; Gottesman, Rebecca F; Heiss, Gerardo; Mosley, Thomas H

2015-01-01

Background Although cerebral lesions ≥3mm on imaging are associated with incident stroke, lesions < 3mm are typically ignored. Objective To examine stroke risks associated with subclinical brain lesions by size (< 3 mm only, lesions ≥3 mm only, both < 3 mm and ≥3 mm) and white matter hyperintensities (WMH). Design Community cohort, Atherosclerosis Risk in Communities (ARIC) Study Setting Two ARIC sites with magnetic resonance imaging (MRI) data (1993–95) Participants 1,884 (99%) adults (50–73 years, 40% men; 50% black) with MRI and no prior stroke; average 14.5 years follow-up. Measurements MRI lesions: none (n=1611), < 3 mm only (n=50), ≥3 mm only (n=185), or both < 3 and ≥3 mm lesions (n=35); WMH score (0–9 scale). Outcomes: incident stroke (n=157), overall mortality (n=576), stroke mortality (n=50). Hazard Ratios (HR) estimated with proportional hazards models. Results Compared to no lesions, stroke risk was tripled with lesions < 3mm only (HR=3.47, 95% CI:1.86-6.49), doubled with lesions ≥3 mm only (HR=1.94, 95% CI:1.22-3.07), and was 8-fold higher with both < 3 mm and ≥3 mm-sized lesions (HR=8.59, 95% CI:4.69-15.73). Stroke risk doubled with WMH ≥3 (HR=2.14, 95% CI:1.45-3.16). Stroke mortality risk tripled with lesions < 3 mm only (HR=3.05, 95% CI:1.04-8.94), doubled with lesions ≥3 mm (HR=1.9, 95% CI:1.48-2.44) and was seven-times higher with both lesion sizes (HR=6.97, 95% CI:2.03-23.93). Limitations Few stroke events (n=147), especially hemorrhagic (n=15); limited numbers of participants with only lesions ≤3mm (n=50) or with both lesions ≤3mm and 3–20mm (n=35). Conclusions Very small cerebrovascular lesions may be associated with increased risks of stroke and mortality; having both < 3 mm and ≥3 mm lesions may represent a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates. PMID:26148278

Decreased risk of stroke in patients receiving traditional Chinese medicine for vertigo: A population-based cohort study.

PubMed

Tsai, Tzung-Yi; Li, Chung-Yi; Livneh, Hanoch; Lin, I-Hsin; Lu, Ming-Chi; Yeh, Chia-Chou

2016-05-26

Patients with vertigo are reported to exhibit a higher risk of subsequent stroke. However, it remains unclear if Traditional Chinese Medicine (TCM), the most common form of complementary and alternative medicine, can help lower the risk of stroke for these patients. So the aim of the study was to investigate the effects of TCM on stroke risk among patients with vertigo. This longitudinal cohort study used the Taiwanese National Health Insurance Research Database to identify 112,458 newly diagnosed vertigo patients aged ≥20 years who received treatment between 1998 and 2007. Among these patients, 53,203 (47.31%) received TCM after vertigo onset (TCM users), and the remaining 59,201 patients were designated as a control group (non-TCM users). All enrollees received follow-up until the end of 2012 to measure stroke incidence. Cox proportional hazards regression was used to compute the hazard ratio (HR) of stroke in recipients of TCM services. During 15-year follow-up, 5532 TCM users and 12,295 non-TCM users developed stroke, representing an incidence rate of 13.10% and 25.71% per 1000 person-years. TCM users had a significantly reduced risk of stroke compared to non-TCM users (adjusted HR=0.64; 95% confidence interval CI=0.59-0.74). The predominant effect was observed for those receiving TCM for more than 180 days (adjusted HR=0.52; 95% CI=0.49-0.56). Commonly used TCM formulae, including Ban-Xia-Bai-Zhu-Tian-Ma-Tang, Ling-Gui-Zhu-Gan-Tang, Bai Zhi (Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., root), Ge Gen (Pueraria lobata (Willd.) Ohwi, root) and Hai Piao Xiao (Endoconcha Sepiae, Cuttlefish Bone) were significantly associated with lower risk of stroke. Results of this population-based study support the effects of TCM on reducing stroke risk, and may provide a reference for stroke prevention strategies. The study results may also help to integrate TCM into clinical intervention programs that provide a favorable prognosis for vertigo patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Antithrombotic therapy use and clinical outcomes following thrombo-embolic events in patients with atrial fibrillation: insights from ARISTOTLE.

PubMed

Goto, Shinya; Merrill, Peter; Wallentin, Lars; Wojdyla, Daniel M; Hanna, Michael; Avezum, Alvaro; Easton, J Donald; Harjola, Veli-Pekka; Huber, Kurt; Lewis, Basil S; Parkhomenko, Alexander; Zhu, Jun; Granger, Christopher B; Lopes, Renato D; Alexander, John H

2018-04-01

We investigated baseline characteristics, antithrombotic use, and clinical outcomes of patients with atrial fibrillation (AF) and a thrombo-embolic event in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study to better inform the care of these high-risk patients. Thrombo-embolic events were defined as stroke (ischaemic or unknown cause) or systemic embolism (SE). Clinical outcomes were estimated using the Kaplan-Meier method. All-cause mortality and International Society on Thrombosis and Haemostasis (ISTH) major bleeding after events were analysed using a Cox proportional hazards model with time-dependent covariates. Of 18 201 patients in ARISTOTLE, 365 experienced a thrombo-embolic event [337 strokes (ischaemic or unknown cause), 28 SE]; 46 (12.6%) of which were fatal. In the 30 days before and after a thrombo-embolic event, 11% and 37% of patients, respectively, were not taking an oral anticoagulant. During follow-up (median 1.8 years), 22 patients (7.1%/year) had a recurrent stroke, 97 (30.1%/year) died, and 10 (6.7%/year) had major bleeding. Compared with patients without a thrombo-embolic event, the short- and long-term adjusted hazards of death in patients with a thrombo-embolic event were high [≤30 days: hazard ratio (HR) 54.3%, 95% confidence interval (95% CI) 41.4-71.3; >30 days: HR 3.5, 95% CI 2.5-4.8; both P < 0.001]. The adjusted hazards of major bleeding were also high short-term (HR 10.37, 95% CI 3.87-27.78; P < 0.001) but not long-term (HR 1.7, 95% CI: 0.77-3.88; P = 0.18). Thrombo-embolic events were rare but associated with high short- and long-term morbidity and mortality. Substantial numbers of patients are not receiving oral anticoagulattherapy before and, despite this risk, after a first thrombo-embolic event. ClinicalTrials.gov (NCT00412984).

Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium.

PubMed

Chen, Yu; Copeland, Wade K; Vedanthan, Rajesh; Grant, Eric; Lee, Jung Eun; Gu, Dongfeng; Gupta, Prakash C; Ramadas, Kunnambath; Inoue, Manami; Tsugane, Shoichiro; Tamakoshi, Akiko; Gao, Yu-Tang; Yuan, Jian-Min; Shu, Xiao-Ou; Ozasa, Kotaro; Tsuji, Ichiro; Kakizaki, Masako; Tanaka, Hideo; Nishino, Yoshikazu; Chen, Chien-Jen; Wang, Renwei; Yoo, Keun-Young; Ahn, Yoon-Ok; Ahsan, Habibul; Pan, Wen-Harn; Chen, Chung-Shiuan; Pednekar, Mangesh S; Sauvaget, Catherine; Sasazuki, Shizuka; Yang, Gong; Koh, Woon-Puay; Xiang, Yong-Bing; Ohishi, Waka; Watanabe, Takashi; Sugawara, Yumi; Matsuo, Keitaro; You, San-Lin; Park, Sue K; Kim, Dong-Hyun; Parvez, Faruque; Chuang, Shao-Yuan; Ge, Wenzhen; Rolland, Betsy; McLerran, Dale; Sinha, Rashmi; Thornquist, Mark; Kang, Daehee; Feng, Ziding; Boffetta, Paolo; Zheng, Wei; He, Jiang; Potter, John D

2013-10-01

To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. Pooled analyses of 20 prospective cohorts in Asia, including data from 835,082 east Asians and 289,815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). 1,124,897 men and women (mean age 53.4 years at baseline). Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. 49,184 cardiovascular deaths (40,791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12). Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

Atrial fibrillation and risk of stroke in dialysis patients

PubMed Central

Wetmore, James B.; Ellerbeck, Edward F.; Mahnken, Jonathan D.; Phadnis, Milind; Rigler, Sally K.; Mukhopadhyay, Purna; Spertus, John A.; Zhou, Xinhua; Hou, Qingjiang; Shireman, Theresa I.

2013-01-01

Purpose Both stroke and chronic atrial fibrillation (AF) are common in dialysis patients, but uncertainty exists in the incidence of new strokes and the risk conferred by chronic AF. Methods A cohort of dually-eligible (Medicare & Medicaid) incident dialysis patients was constructed. Medicare claims were used to determine the onset of chronic AF, which was specifically treated as a time-dependent covariate. Cox proportional hazards models were used to model time to stroke. Results Of 56,734 patients studied, 5629 (9.9%) developed chronic AF. There were 22.8 ischemic and 5.0 hemorrhagic strokes per 1000 patient-years, a ratio of approximately 4.5:1. Chronic AF was independently associated with time to ischemic (HR 1.26, 99% CI’s 1.06 – 1.49, P = 0.0005), but not hemorrhagic, stroke. Race was strongly associated with hemorrhagic stroke: African-Americans (HR 1.46, 99% CI’s 1.08 – 1.96), Hispanics (HR 1.64, 99% CI’s 1.16 – 2.31), and others (HR 1.76, 99% CI’s 1.16 – 2.78) had higher rates than did Caucasians (P < 0.001 for all). Conclusions Chronic AF has a significant, but modest, association with ischemic stroke. Race/ethnicity is strongly associated with hemorrhagic strokes. The proportion of strokes due to hemorrhage is much higher than in the general population. PMID:23332588

Time Trends of Aspirin and Warfarin Use on Stroke and Bleeding Events in Chinese Patients With New-Onset Atrial Fibrillation

PubMed Central

Guo, Yutao; Wang, Hao; Tian, Yingchun; Wang, Yutang

2015-01-01

BACKGROUND: Much of the clinical epidemiology and treatment patterns for patients with atrial fibrillation (AF) are derived from Western populations. Limited data are available on antithrombotic therapy use over time and its impact on the stroke or bleeding events in newly diagnosed Chinese patients with AF. The present study investigates time trends in warfarin and aspirin use in China in relation to stroke and bleeding events in a Chinese population. METHODS: We used a medical insurance database involving > 10 million individuals for the years 2001 to 2012 in Yunnan, a southwestern province of China, and performed time-trend analysis on those with newly diagnosed AF. Cox proportional hazards time-varying exposures were used to determine the risk of stroke or bleeding events associated with antithrombotic therapy among patients with AF. RESULTS: Among the randomly sampled 471,446 participants, there were 1,237 patients with AF, including 921 newly diagnosed with AF, thus providing 4,859 person-years of experience (62% men; mean attained age, 70 years). The overall rate of antithrombotic therapy was 37.7% (347 of 921 patients), with 4.1% (38 of 921) on warfarin and 32.3% (298 of 921) on aspirin. Antithrombotic therapy was not related to stroke/bleeding risk scores (CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke (doubled)] score, P = .522; CHA2DS2-VASc [congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (doubled), vascular disease, age 65 to 74 years, and female sex] score, P = .957; HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 years), drugs/alcohol concomitantly] score, P = .095). The use of antithrombotic drugs (mainly aspirin) increased in both women and men over time, with the rate of aspirin increasing from 4.0% in 2007 to 46.1% in 2012 in the former, and from 7.7% in 2007 to 61.9% in 2012 in the latter (P for trend for both, < .005). In the overall cohort, the annual stroke rate was approximately 6% and the annual major bleeding rate was about 1%. Compared with nonantithrombotic therapy, the hazard ratio for ischemic stroke was 0.68 (95% CI, 0.39-1.18) for aspirin and 1.39 (0.54-3.59) for warfarin. CONCLUSIONS: Aspirin use increased among Chinese patients newly diagnosed with AF, with no relationship to the patient’s stroke or bleeding risk. Warfarin use was very low. Given the health-care burden of AF and its complications, our study has major implications for health-care systems in non-Western countries, given the global burden of this common arrhythmia. PMID:25501045

The influence of the day of the week of hospital admission on the prognosis of stroke patients.

PubMed

Barros, Juliana B; Goulart, Alessandra Carvalho; Alencar, Airlane P; Lotufo, Paulo A; Bensenor, Isabela M

2013-04-01

This study aimed to evaluate the weekday and weekend distribution of stroke case hospital admissions and their respective prognosis based on a sample from the Estudo de Mortalidade e Morbidade do Acidente Vascular Cerebral (EMMA), a cohort of stroke patients admitted to a community hospital in the city of São Paulo, Brazil. We ascertained all consecutive cases of first-time strokes between April 2006 and December 2008 and performed a subsequent one-year follow-up. No association was found between frequency of hospital admissions due to ischemic and hemorrhagic strokes and the specific day of the week on which the admission occurred. However, ten-day and twelve-month case-fatality was higher in hemorrhagic stroke patients admitted at the weekend. We also found that intracerebral hemorrhage patients admitted on weekends had a worse survival rate (50%) compared with those admitted during weekdays (25.6%, P log-rank = 0.03). We found a multivariate hazard ratio of 2.49 (95%CI: 1.10-5.81, P trend = 0.03) for risk of death at the weekend compared to weekdays for intracerebral hemorrhage cases. No difference in survival was observed with respect to the overall sample of stroke or ischemic stroke patients.

An ensemble survival model for estimating relative residual longevity following stroke: Application to mortality data in the chronic dialysis population

PubMed Central

Phadnis, Milind A; Wetmore, James B; Shireman, Theresa I; Ellerbeck, Edward F; Mahnken, Jonathan D

2016-01-01

Time-dependent covariates can be modeled within the Cox regression framework and can allow both proportional and nonproportional hazards for the risk factor of research interest. However, in many areas of health services research, interest centers on being able to estimate residual longevity after the occurrence of a particular event such as stroke. The survival trajectory of patients experiencing a stroke can be potentially influenced by stroke type (hemorrhagic or ischemic), time of the stroke (relative to time zero), time since the stroke occurred, or a combination of these factors. In such situations, researchers are more interested in estimating lifetime lost due to stroke rather than merely estimating the relative hazard due to stroke. To achieve this, we propose an ensemble approach using the generalized gamma distribution by means of a semi-Markov type model with an additive hazards extension. Our modeling framework allows stroke as a time-dependent covariate to affect all three parameters (location, scale, and shape) of the generalized gamma distribution. Using the concept of relative times, we answer the research question by estimating residual life lost due to ischemic and hemorrhagic stroke in the chronic dialysis population. PMID:26403934

An ensemble survival model for estimating relative residual longevity following stroke: Application to mortality data in the chronic dialysis population.

PubMed

Phadnis, Milind A; Wetmore, James B; Shireman, Theresa I; Ellerbeck, Edward F; Mahnken, Jonathan D

2017-12-01

Time-dependent covariates can be modeled within the Cox regression framework and can allow both proportional and nonproportional hazards for the risk factor of research interest. However, in many areas of health services research, interest centers on being able to estimate residual longevity after the occurrence of a particular event such as stroke. The survival trajectory of patients experiencing a stroke can be potentially influenced by stroke type (hemorrhagic or ischemic), time of the stroke (relative to time zero), time since the stroke occurred, or a combination of these factors. In such situations, researchers are more interested in estimating lifetime lost due to stroke rather than merely estimating the relative hazard due to stroke. To achieve this, we propose an ensemble approach using the generalized gamma distribution by means of a semi-Markov type model with an additive hazards extension. Our modeling framework allows stroke as a time-dependent covariate to affect all three parameters (location, scale, and shape) of the generalized gamma distribution. Using the concept of relative times, we answer the research question by estimating residual life lost due to ischemic and hemorrhagic stroke in the chronic dialysis population.

Relationship of right- to left-sided ventricular filling pressures in advanced heart failure: insights from the ESCAPE trial.

PubMed

Drazner, Mark H; Velez-Martinez, Mariella; Ayers, Colby R; Reimold, Sharon C; Thibodeau, Jennifer T; Mishkin, Joseph D; Mammen, Pradeep P A; Markham, David W; Patel, Chetan B

2013-03-01

Although right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) are correlated in heart failure, in a sizeable minority of patients, the RAP and PCWP are not tightly coupled. The basis of this variability in the RAP/PCWP ratio, and whether it conveys prognostic value, is not known. We analyzed the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial database. Baseline characteristics, including echocardiographic assessment of right ventricular (RV) structure and function, and invasively measured hemodynamic parameters, were compared among tertiles of the RAP/PCWP ratio. Multivariable Cox proportional hazard models assessed the association of RAP/PCWP ratio with the primary ESCAPE outcome (6-month death or hospitalization [days]) adjusting for systolic blood pressure, blood urea nitrogen, 6-minute walk distance, and PCWP. The RAP/PCWP tertiles were 0.27 to 0.4 (tertile 1); 0.41 to 0.615 (tertile 2), and 0.62 to 1.21 (tertile 3). Increasing RAP/PCWP was associated with increasing median right atrial area (23, 26, 29 cm2, respectively; P<0.005), RV area in diastole (21, 27, 27 cm2, respectively; P<0.005), and pulmonary vascular resistance (2.4, 2.9, 3.6 woods units, respectively; P=0.003), and lower RV stroke work index (8.6, 8.4, 5.5 g·m/m2 per beat, respectively; P<0.001). RAP/PCWP ratio was associated with death or hospitalization within 6 months (hazard ratio, 1.16 [1, 1.4]; P<0.05). Increased RAP/PCWP ratio was associated with higher pulmonary vascular resistance, reduced RV function (manifest as a larger right atrium and ventricle and lower RV stroke work index), and an increased risk of adverse outcomes in patients with advanced heart failure.

A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease.

PubMed

Pfeffer, Marc A; Burdmann, Emmanuel A; Chen, Chao-Yin; Cooper, Mark E; de Zeeuw, Dick; Eckardt, Kai-Uwe; Feyzi, Jan M; Ivanovich, Peter; Kewalramani, Reshma; Levey, Andrew S; Lewis, Eldrin F; McGill, Janet B; McMurray, John J V; Parfrey, Patrick; Parving, Hans-Henrik; Remuzzi, Giuseppe; Singh, Ajay K; Solomon, Scott D; Toto, Robert

2009-11-19

Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested. In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease. Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95% confidence interval [CI], 0.94 to 1.17; P=0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P=0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95% CI, 1.38 to 2.68; P<0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P<0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group. The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits. (ClinicalTrials.gov number, NCT00093015.) 2009 Massachusetts Medical Society

Insulin-like growth factor 1 as a predictor of ischemic stroke outcome in the elderly.

PubMed

Denti, Licia; Annoni, Valentina; Cattadori, Evelina; Salvagnini, Maria Angela; Visioli, Sandra; Merli, Maria Francesca; Corradi, Francesco; Ceresini, Graziano; Valenti, Giorgio; Hoffman, Andrew R; Ceda, Gian Paolo

2004-09-01

To examine whether serum insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) concentrations, determined early after the onset of stroke, are predictive of clinical outcome in elderly patients. The sample comprised 85 patients (mean [+/- SD] age, 83 +/- 7.4 years; range, 67 to 99 years; 34% male) who were admitted with acute stroke to a geriatric ward between January 1998 and June 2000, and 88 control patients who were similar in age and sex. Clinical and laboratory assessments, computed tomographic scan of the head, carotid ultrasonography, and electrocardiography were employed to define the clinical and etiologic stroke subtype. Fasting blood samples were collected within 24 hours of admission for IGF-I and IGFBP-3 measurement. Univariate and multiple logistic regression analyses, with adjustment for other related clinical covariates, were used to assess the relation of IGF-I and IGFBP-3 to poor outcome, defined as severe disability (Barthel index <60/100) or death, at 1 month (or at discharge), 3 months, and 6 months. Mean (+/- SD) IGF-1 levels were lower in patients with stroke than in controls (69 +/- 45 ng/mL vs. 102 +/- 67 ng/mL, P adjusted for age = 0.001). The mean IGF-1/IGFBP-3 molar ratio was also lower in stroke patients (0.12 +/- 0.07 vs. 0.19 +/- 0.09, P adjusted for age <0.0001). However, there was no relation of hormone levels to either the clinical subtype of stroke or the extent of neurologic impairment. IGF-1 levels were inversely related to poor outcome (mainly death) at 3 and 6 months, independent of other clinical covariates that were highly predictive of outcome, such as age and stroke scale score on admission (hazard ratio for death at 6 months for each 20-ng/mL increase = 0.7; 95% confidence interval: 0.5 to 0.9). An independent association of the molar ratio with death at 3 and 6 months was also found. Low levels of circulating IGF-1 may predict the clinical outcome of stroke in elderly patients.

Angiotensin-Converting Enzyme Inhibitor Use and Major Cardiovascular Outcomes in Type 2 Diabetes Mellitus Treated With the Dipeptidyl Peptidase 4 Inhibitor Alogliptin.

PubMed

White, William B; Wilson, Craig A; Bakris, George L; Bergenstal, Richard M; Cannon, Christopher P; Cushman, William C; Heller, Simon K; Mehta, Cyrus R; Nissen, Steven E; Zannad, Faiez; Kupfer, Stuart

2016-09-01

Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of high-dose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62%) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4% versus 11.8%; hazard ratio, 0.97; 95% confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8% of patients on alogliptin versus 7.2% on placebo (hazard ratio, 0.93; 95% confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors. © 2016 American Heart Association, Inc.

Urinary cadmium concentration and the risk of ischemic stroke.

PubMed

Chen, Cheng; Xun, Pengcheng; Tsinovoi, Cari; McClure, Leslie A; Brockman, John; MacDonald, Leslie; Cushman, Mary; Cai, Jianwen; Kamendulis, Lisa; Mackey, Jason; He, Ka

2018-06-22

To examine the association between urinary cadmium levels and the incidence of ischemic stroke and to explore possible effect modifications. A case-cohort study was designed nested in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including 680 adjudicated incident cases of ischemic stroke and 2,540 participants in a randomly selected subcohort. Urinary creatinine-corrected cadmium concentration was measured at baseline. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated with the Barlow weighting method for the Cox proportional hazards regression model. The median urinary cadmium concentration was 0.42 (interquartile range 0.27-0.68) μg/g creatinine. After adjustment for potential confounders, urinary cadmium was associated with increased incidence of ischemic stroke (quintile 5 vs quintile 1: HR 1.50, 95% CI 1.01-2.22, p for trend = 0.02). The observed association was more pronounced among participants in the lowest serum zinc tertile (tertile 3 vs tertile 1: HR 1.82, 95% CI 1.06-3.11, p for trend = 0.004, p for interaction = 0.05) but was attenuated and became nonsignificant among never smokers (tertile 3 vs tertile 1: never smokers: HR 1.27, 95% CI 0.80-2.03, p for trend = 0.29; ever smokers: HR 1.60, 95% CI 1.06-2.43, p for trend = 0.07, p for interaction = 0.51). Findings from this study suggest that cadmium exposure may be an independent risk factor for ischemic stroke in the US general population. Never smoking and maintaining a high serum zinc level may ameliorate the potential adverse effects of cadmium exposure. © 2018 American Academy of Neurology.

Endocardial Device Leads in Patients with Patent Foramen Ovale: Echocardiographic Correlates of Stroke/TIA and Mortality.

PubMed

Ponamgi, Shiva P; Vaidya, Vaibhav R; Desimone, Christopher V; Noheria, Amit; Hodge, David O; Slusser, Joshua P; Ammash, Naser M; Bruce, Charles J; Rabinstein, Alejandro A; Friedman, Paul A; Asirvatham, Samuel J

2017-03-01

Echocardiographically detected patent foramen ovale (PFO) has been associated with stroke/transient ischemic attack (TIA) in patients with cardiac implantable electronic devices (CIEDs). We sought to evaluate the relationship between echocardiographic characteristics and risk of stroke/TIA and mortality in CIED patients with PFO. In 6,086 device patients, PFO was detected in 319 patients. A baseline echocardiogram was present in 250 patients, with 186 having a follow-up echocardiogram. Of 250 patients with a baseline echocardiogram, 9.6% (n = 24) had a stroke/TIA during mean follow-up of 5.3 ± 3.1 years; and 42% (n = 105) died over 7.1 ± 3.7 years. Atrial septal aneurysm, prominent Eustachian valve, visible shunting across PFO, baseline or change in estimated right ventricular systolic pressure (RVSP)/tricuspid regurgitation (TR), or maximum RVSP were not associated with postimplant stroke/TIA (P > 0.05). An exploratory multivariate analysis using time-dependent Cox models showed increased hazard of death in patients with increase in TR ≥2 grades (hazard ratio [HR] 1.780, 95% confidence interval [CI] 1.447-2.189, P < 0.0001), or increase in RVSP by >10 mm Hg (HR 2.018, 95% CI 1.593-2.556, P < 0.0001), or maximum RVSP in follow-up (HR 1.432, 95% CI 1.351-1.516, P < 0.0001). A significant increase (P < 0.001) in TR was also noted during follow-up. In patients with CIED and PFO, structural and hemodynamic echocardiographic markers did not predict future stroke/TIA. However, a significantly higher TR or RVSP was associated with higher mortality. © 2016 Wiley Periodicals, Inc.

Junctional bradycardia is a potential risk factor of stroke.

PubMed

Kim, Gwang Sil; Uhm, Jae-Sun; Kim, Tae-Hoon; Lee, Hancheol; Park, Junbeom; Park, Jin-Kyu; Joung, Boyoung; Pak, Hui-Nam; Lee, Moon-Hyoung

2016-07-25

This study aimed to determine the risk of thromboembolic events in patients with junctional bradycardia(JB). We retrospectively reviewed electrocardiograms(ECGs) for 380,682 patients. Those with JB on an ECG at least twice over a ≥3-month interval were included for analysis. We additionally included 138 CHADS2 score-matched patients(age, 68.4 ± 15.7 years; male, 52.2%) in sinus rhythm as a control group. Between the JB patients(with or without retrograde P wave) and controls, we compared incidences of ischemic stroke and a composite of ischemic stroke, renal infarction, ischemic colitis, acute limb ischemia, and pulmonary embolism. Among 380,682 patients (age, 47.6 ± 19.9 years; male, 49.3%), 69 patients (age, 68.5 ± 16.5 years; male, 50.7%) exhibited JB on an ECG at least twice over a ≥3-month interval; the overall prevalence of JB was 0.02%. The mean follow-up period was 27.2 ± 26.2 months. Forty-five patients (65.2%) in the JB group had no retrograde P wave. Ischemic stroke incidence was significantly higher in JB patients without a retrograde P wave than in controls (6/45 patients [13.3%] and 3/138 patients [2.2%], respectively; P = 0.007). The incidence of composite thromboembolic events was also significantly higher in JB patients without a retrograde P wave than in controls (8/45 patients [17.8%] and 4/138 patients [2.9%], respectively; P = 0.011). In a Cox proportional hazards model, JB patients without a P wave showed a greater incidence of stroke (hazard ratio, 8.89 [2.20-33.01], P = 0.007) than controls and JB patients with a P wave. Junctional bradycardia is potentially associated with ischemic stroke, particularly in the absence of an identifiable retrograde P wave.

Clopidogrel With Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) Trial: One-Year Outcomes.

PubMed

Wang, Yilong; Pan, Yuesong; Zhao, Xingquan; Li, Hao; Wang, David; Johnston, S Claiborne; Liu, Liping; Meng, Xia; Wang, Anxin; Wang, Chunxue; Wang, Yongjun

2015-07-07

The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone, but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial. The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy (loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for 90 days, plus 75 mg of aspirin per day for the first 21 days) or to the aspirin-alone group (75 mg/d for 90 days). The primary outcome was stroke event (ischemic or hemorrhagic) during 1-year follow-up. Differences in outcomes between groups were assessed by using the Cox proportional hazards model. Stroke occurred in 275 (10.6%) patients in the clopidogrel-aspirin group, in comparison with 362 (14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93; P=0.006). Moderate or severe hemorrhage occurred in 7 (0.3%) patients in the clopidogrel-aspirin group and in 9 (0.4%) patients in the aspirin group (P=0.44). The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2015 American Heart Association, Inc.

A gender-stratified comparative analysis of various definitions of metabolic syndrome and cardiovascular risk in a multiethnic U.S. population.

PubMed

Hari, Pawan; Nerusu, Kamalakar; Veeranna, Vikas; Sudhakar, Rajeev; Zalawadiya, Sandip; Ramesh, Krithi; Afonso, Luis

2012-02-01

We sought to evaluate the ability of various metabolic syndrome definitions in predicting primary cardiovascular disease (CVD) outcomes in a vast multiethnic U.S. cohort. This study included 6,814 self-identified men and women aged 45-84 years enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. Gender-stratified analyses were performed to calculate hazard ratios of CVD, stroke, and mortality associated with various metabolic syndrome definitions and their individual constructs. The hazard ratios [95% confidence interval (CI)] for all-cause CVD in men were 2.90 (2.18-3.85), 2.64 (1.98-3.51), 2.16 (1.62-2.88), 2.56 (1.91-3.44), 1.82 (1.35-2.46), and 2.92 (2.15-3.95) for the National Cholesterol Education Program (NCEP), American Heart Association (AHA), World Health Organization (WHO), International Diabetes Federation (IDF), European Group for the Study of Insulin Resistance (EGIR), and the newly defined consensus criteria. Hazard ratios in women were 2.11 (1.41-3.15), 2.17 (1.45-3.27), 2.04 (1.37-3.06), 1.91 (1.27-2.88), 1.85 (1.23-2.79), and 2.08 (1.37-3.14), respectively. Metabolic syndrome was strongly associated with stroke risk only in males. In men, all constitutive metabolic syndrome components were continuously and strongly associated with CVD. In women, high-density lipoprotein and triglycerides did not appear to be associated with short term CVD risk. We found the newly defined consensus criteria for metabolic syndrome to be similarly predictive of cardiovascular events when compared to existing definitions. Significant gender differences exist in the association between metabolic syndrome, its individual components, and CVD.

Premature Atrial Contractions on the Screening Electrocardiogram and Risk of Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

PubMed

O'Neal, Wesley T; Kamel, Hooman; Kleindorfer, Dawn; Judd, Suzanne E; Howard, George; Howard, Virginia J; Soliman, Elsayed Z

2016-01-01

It is currently unknown if premature atrial contractions (PACs) detected on the routine screening electrocardiogram are associated with an increased risk of ischemic stroke. We examined the association between PACs and ischemic stroke in 22,975 (mean age 64 ± 9.2; 56% women; 40% black) participants from the Reasons for Geographic and Racial Differences in Stroke study. Participants who were free of stroke at baseline were included. PACs were detected from centrally read electrocardiograms at baseline. Cox regression was used to examine the association between PACs and ischemic stroke events through March 31, 2014. PACs were present in 1,687 (7.3%) participants at baseline. In a Cox regression model adjusted for stroke risk factors and potential confounders, PACs were associated with an increased risk of ischemic stroke (hazards ratio (HR) 1.34, 95% CI 1.04-1.74). The relationship was limited to non-lacunar infarcts (HR 1.42, 95% CI 1.08-1.87), and not lacunar strokes (HR 1.01, 95% CI 0.51-2.03). An interaction by sex was detected, with the association between PACs and ischemic stroke being stronger among women (HR 1.82, 95% CI 1.29-2.56) than men (HR 1.03, 95% CI 0.69-1.52; p-interaction = 0.0095). PACs detected on the routine electrocardiogram are associated with an increased risk for non-lacunar ischemic strokes, especially in women. © 2016 S. Karger AG, Basel.

Association between obstructive sleep apnea and optic neuropathy: a Taiwanese population-based cohort study.

PubMed

Sun, Ming-Hui; Liao, Yaping Joyce; Lin, Che-Chen; Chiang, Rayleigh Ping-Ying; Wei, James Cheng-Chung

2018-04-26

Obstructive sleep apnea (OSA) is associated with many systemic diseases including diabetes, hypertension, stroke, and cardiovascular disease. The aim of our study was to investigate the association between OSA and optic neuropathy (ON), and to evaluate the efficacy of treatment for OSA on the risk of ON. We used the data from the Longitudinal Health Insurance Database, which involved one million insurants from Taiwan National Health Insurance program (Taiwan NHI). OSA patients had a 1.95-fold higher risk of ON compared with non-OSA patients in all age group. The risk was significantly higher (adjusted hazard ratio: 4.21) in the group aged <45 years and male individuals (adjusted hazard ratio: 1.93). Meanwhile, sleep apnea was associated with ON regardless of the existence of comorbidity or not. OSA patients treated with continuous positive airway pressure (CPAP) had an adjusted 2.31-fold higher hazard of developing ON compared to controls, and those without any treatment had an adjusted 1.82-fold higher hazard of developing ON compared to controls. Moreover, ON patients had a 1.45-fold higher risk of OSA, and those aged between 45 and 64 years (hazard ratio: 1.76) and male individuals (hazard ratio: 1.55) had highest risk. Our study showed that OSA increased the risk of developing ON after controlling the comorbidities; however, treatment with CPAP did not reduce the risk of ON. Further large population study accessing to medical records about the severity of OSA and treatment for OSA is needed to clarify the efficacy of treatment for OSA in reducing the risk of ON.

Predictors of early and late stroke following cardiac surgery

PubMed Central

Whitlock, Richard; Healey, Jeff S.; Connolly, Stuart J.; Wang, Julie; Danter, Matthew R.; Tu, Jack V.; Novick, Richard; Fremes, Stephen; Teoh, Kevin; Khera, Vikas; Yusuf, Salim

2014-01-01

Background: Much is known about the short-term risks of stroke following cardiac surgery. We examined the rate and predictors of long-term stroke in a cohort of patients who underwent cardiac surgery. Methods: We obtained linked data for patients who underwent cardiac surgery in the province of Ontario between 1996 and 2006. We analyzed the incidence of stroke and death up to 2 years postoperatively. Results: Of 108 711 patients, 1.8% (95% confidence interval [CI] 1.7%–1.9%) had a stroke perioperatively, and 3.6% (95% CI 3.5%–3.7%) had a stroke within the ensuing 2 years. The strongest predictors of both early and late stroke were advanced age (≥ 65 year; adjusted hazard ratio [HR] for all stroke 1.9, 95% CI 1.8–2.0), a history of stroke or transient ischemic attack (adjusted HR 2.1, 95% CI 1.9–2.3), peripheral vascular disease (adjusted HR 1.6, 95% CI 1.5–1.7), combined coronary bypass grafting and valve surgery (adjusted HR 1.7, 95% CI 1.5–1.8) and valve surgery alone (adjusted HR 1.4, 95% CI 1.2–1.5). Preoperative need for dialysis (adjusted odds ratio [OR] 2.1, 95% CI 1.6–2.8) and new-onset postoperative atrial fibrillation (adjusted OR 1.5, 95% CI 1.3–1.6) were predictors of only early stroke. A CHADS2 score of 2 or higher was associated with an increased risk of stroke or death compared with a score of 0 or 1 (19.9% v. 9.3% among patients with a history of atrial fibrillation, 16.8% v. 7.8% among those with new-onset postoperative atrial fibrillation and 14.8% v. 5.8% among those without this condition). Interpretation: Patients who had cardiac surgery were at highest risk of stroke in the early postoperative period and had continued risk over the ensuing 2 years, with similar risk factors over these periods. New-onset postoperative atrial fibrillation was a predictor of only early stroke. The CHADS2 score predicted stroke risk among patients with and without atrial fibrillation. PMID:25047983

Better adherence to antithyroid drug is associated with decreased risk of stroke in hyperthyroidism patients.

PubMed

Tsai, M-S; Chuang, P-Y; Huang, C-H; Shih, S-R; Chang, W-T; Chen, N-C; Yu, P-H; Cheng, H-J; Tang, C-H; Chen, W-J

2015-12-01

An increased risk for ischaemic stroke has been reported in young hyperthyroidism patients independent of atrial fibrillation (AF). However, whether the use of antithyroid drugs in hyperthyroidism patients can reduce the occurrence of ischaemic stroke remains unclear. A total of 36,510 newly diagnosed hyperthyroidism patients during 2003-2006 were identified from the Taiwan National Health Insurance Research database. Each patient was individually tracked for 5 years from their index date (beginning the antithyroid drugs) to identify those who suffered from new episode of ischaemic stroke. Medication possession ratio (MPR) was used to represent the antithyroid drug compliance. The association between the MPR and the risk of stroke was examined. The stroke incidence rates for hyperthyroidism patients with age < 45 years and age ≥ 45 years were 0.42 and 3.76 per 1000 person-years, respectively. The patients aged < 45 years with MPR < 0.2 (adjusted hazard ratio, HR, 2.30; 95% CI, 1.13-4.70; p = 0.02) and 0.2 ≤ MPR < 0.4 (adjusted HR, 2.24; 95% CI, 1.06-4.72; p = 0.035) had a significantly increased risk of ischaemic stroke as compared to those with ≥ 0.6. In patients of the age ≥ 45 years, only the patients with MPR < 0.2 (adjusted HR, 1.44; 95% CI, 1.03-2.01; p = 0.036) had a significantly higher risk of ischaemic stroke as compared to those with MPR ≥ 0.6. In hyperthyroidism patients without AF, good antithyroid drugs compliance also reduced the incidence of stroke significantly (adjusted HR, range: 1.52-1.61; p = 0.02); but not in hyperthyroidism with AF. Hyperthyroidism patients with good antithyroid drug compliance had a lower risk of ischaemic stroke than patients with poor compliance. © 2015 John Wiley & Sons Ltd.

Blood Pressure Control and Risk of Stroke or Systemic Embolism in Patients With Atrial Fibrillation: Results From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.

PubMed

Rao, Meena P; Halvorsen, Sigrun; Wojdyla, Daniel; Thomas, Laine; Alexander, John H; Hylek, Elaine M; Hanna, Michael; Bahit, M Cecilia; Lopes, Renato D; De Caterina, Raffaele; Erol, Cetin; Goto, Shinya; Lanas, Fernando; Lewis, Basil S; Husted, Steen; Gersh, Bernard J; Wallentin, Lars; Granger, Christopher B

2015-12-01

Patients with atrial fibrillation (AF) and hypertension are at high risk for stroke. Previous studies have shown elevated risk of stroke in patients with AF who have a history of hypertension (regardless of blood pressure [BP] control) and in patients with elevated BP. We assessed the association of hypertension and BP control on clinical outcomes. In ARISTOTLE (n=18 201), BP was evaluated as history of hypertension requiring treatment and elevated BP (systolic ≥140 and/or diastolic ≥90 mm Hg) at study entry and any point during the trial. Hazard ratios (HRs) were derived from Cox proportional hazards models including BP as a time-dependent covariate. A total of 15 916 (87.5%) patients had a history of hypertension requiring treatment. In patients with elevated BP measurement at any point during the trial, the rate of stroke or systemic embolism was significantly higher (HR, 1.53; 95% confidence interval [CI], 1.25-1.86), as was hemorrhagic stroke (HR 1.85; 95% CI, 1.26-2.72) and ischemic stroke (HR, 1.50; 95% CI, 1.18-1.90). Rates of major bleeding were lower in patients with a history of hypertension (HR, 0.80; 95% CI, 0.66-0.98) and nonsignificantly lower in patients with elevated BP at study entry (HR, 0.89; 95% CI, 0.77-1.03). The benefit of apixaban versus warfarin on preventing stroke or systemic embolism was consistent among patients with and without a history of hypertension (P interaction=0.27), BP control at baseline (P interaction=0.43), and BP control during the trial (P interaction=0.97). High BP measurement at any point during the trial was independently associated with a substantially higher risk of stroke or systemic embolism. These results strongly support efforts to treat elevated BP as an important strategy to optimally lower risk of stroke in patients with AF. URL: https://ClinicalTrials.gov/. Unique identifier: NCT00412984. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Primary closure after carotid endarterectomy is not inferior to other closure techniques.

PubMed

Avgerinos, Efthymios D; Chaer, Rabih A; Naddaf, Abdallah; El-Shazly, Omar M; Marone, Luke; Makaroun, Michel S

2016-09-01

Primary closure after carotid endarterectomy (CEA) has been much maligned as an inferior technique with worse outcomes than in patch closure. Our purpose was to compare perioperative and long-term results of different CEA closure techniques in a large institutional experience. A consecutive cohort of CEAs between January 1, 2000, and December 31, 2010, was retrospectively analyzed. Closure technique was used to divide patients into three groups: primary longitudinal arteriotomy closure (PRC), patch closure (PAC), and eversion closure (EVC). End points were perioperative events, long-term strokes, and restenosis ≥70%. Multivariate regression models were used to assess the effect of baseline predictors. There were 1737 CEA cases (bilateral, 143; mean age, 71.4 ± 9.3 years; 56.2% men; 35.3% symptomatic) performed during the study period with a mean clinical follow-up of 49.8 ± 36.4 months (range, 0-155 months). More men had primary closure, but other demographic and baseline symptoms were similar between groups. Half the patients had PAC, with the rest evenly distributed between PRC and EVC. The rate of nerve injury was 2.7%, the rate of reintervention for hematoma was 1.5%, and the length of hospital stay was 2.4 ± 3.0 days, with no significant differences among groups. The combined stroke and death rate was 2.5% overall and 3.9% and 1.7% in the symptomatic and asymptomatic cohort, respectively. Stroke and death rates were similar between groups: PRC, 11 (2.7%); PAC, 19 (2.2%); EVC, 13 (2.9%). Multivariate analysis showed baseline symptomatic disease (odds ratio, 2.4; P = .007) and heart failure (odds ratio, 3.1; P = .003) as predictors of perioperative stroke and death, but not the type of closure. Cox regression analysis demonstrated, among other risk factors, no statin use (hazard ratio, 2.1; P = .008) as a predictor of ipsilateral stroke and severe (glomerular filtration rate <30 mL/min/1.73 m(2)) renal insufficiency (hazard ratio, 2.6; P = .032) as the only predictor of restenosis ≥70%. Type of closure did not have any predictive value. In our study, baseline risk factors and statin use, but not the type of closure, affect perioperative and long-term outcomes after CEA. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.

PubMed

Scirica, Benjamin M; Bhatt, Deepak L; Braunwald, Eugene; Steg, P Gabriel; Davidson, Jaime; Hirshberg, Boaz; Ohman, Peter; Frederich, Robert; Wiviott, Stephen D; Hoffman, Elaine B; Cavender, Matthew A; Udell, Jacob A; Desai, Nihar R; Mosenzon, Ofri; McGuire, Darren K; Ray, Kausik K; Leiter, Lawrence A; Raz, Itamar

2013-10-03

The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the "on-treatment" analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively). DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. (Funded by AstraZeneca and Bristol-Myers Squibb; SAVOR-TIMI 53 ClinicalTrials.gov number, NCT01107886.).

Predictive Value of Cumulative Blood Pressure for All-Cause Mortality and Cardiovascular Events

NASA Astrophysics Data System (ADS)

Wang, Yan Xiu; Song, Lu; Xing, Ai Jun; Gao, Ming; Zhao, Hai Yan; Li, Chun Hui; Zhao, Hua Ling; Chen, Shuo Hua; Lu, Cheng Zhi; Wu, Shou Ling

2017-02-01

The predictive value of cumulative blood pressure (BP) on all-cause mortality and cardiovascular and cerebrovascular events (CCE) has hardly been studied. In this prospective cohort study including 52,385 participants from the Kailuan Group who attended three medical examinations and without CCE, the impact of cumulative systolic BP (cumSBP) and cumulative diastolic BP (cumDBP) on all-cause mortality and CCEs was investigated. For the study population, the mean (standard deviation) age was 48.82 (11.77) years of which 40,141 (76.6%) were male. The follow-up for all-cause mortality and CCEs was 3.96 (0.48) and 2.98 (0.41) years, respectively. Multivariate Cox proportional hazards regression analysis showed that for every 10 mm Hg·year increase in cumSBP and 5 mm Hg·year increase in cumDBP, the hazard ratio for all-cause mortality were 1.013 (1.006, 1.021) and 1.012 (1.006, 1.018); for CCEs, 1.018 (1.010, 1.027) and 1.017 (1.010, 1.024); for stroke, 1.021 (1.011, 1.031) and 1.018 (1.010, 1.026); and for MI, 1.013 (0.996, 1.030) and 1.015 (1.000, 1.029). Using natural spline function analysis, cumSBP and cumDBP showed a J-curve relationship with CCEs; and a U-curve relationship with stroke (ischemic stroke and hemorrhagic stroke). Therefore, increases in cumSBP and cumDBP were predictive for all-cause mortality, CCEs, and stroke.

Neighborhood income and stroke care and outcomes

PubMed Central

Fang, Jiming; Chan, Crystal; Alter, David A.; Bronskill, Susan E.; Hill, Michael D.; Manuel, Douglas G.; Tu, Jack V.; Anderson, Geoffrey M.

2012-01-01

Objective: To evaluate factors that may contribute to the increased stroke case fatality rates observed in individuals from low-income areas. Methods: We conducted a cohort study on a population-based sample of all patients with stroke or TIA seen at 153 acute care hospitals in the province of Ontario, Canada, between April 1, 2002, and March 31, 2003, and April 1, 2004, and March 31, 2005. Socioeconomic status measured as income quintiles was imputed from median neighborhood income. In the study sample of 7,816 patients we determined 1-year mortality by grouped income quintile and used multivariable analyses to assess whether differences in survival were explained by cardiovascular risk factors, stroke severity, stroke management, or other prognostic factors. Results: There was no significant gradient across income groups for stroke severity or stroke management. However, 1-year mortality rates were higher in those from the lowest income group compared to those from the highest income group, even after adjustment for age, sex, stroke type and severity, comorbid conditions, hospital and physician characteristics, and processes of care (adjusted hazard ratio for low- vs high-income groups, 1.18; 95 confidence interval 1.03 to 1.29). Conclusions: In Ontario, 1-year survival rates after an index stroke are higher for those from the richest compared to the least wealthy areas, and this is only partly explained by age, sex, comorbid conditions, and other baseline risk factors. PMID:22895592

Effects of Concurrent Depressive Symptoms and Perceived Stress on Cardiovascular Risk in Low- and High-Income Participants: Findings From the Reasons for Geographical and Racial Differences in Stroke (REGARDS) Study.

PubMed

Sumner, Jennifer A; Khodneva, Yulia; Muntner, Paul; Redmond, Nicole; Lewis, Marquita W; Davidson, Karina W; Edmondson, Donald; Richman, Joshua; Safford, Monika M

2016-10-10

Psychosocial risk for cardiovascular disease (CVD) may be especially deleterious in persons with low socioeconomic status. Most work has focused on psychosocial factors individually, but emerging research suggests that the confluence of psychosocial risk may be particularly harmful. Using data from the Reasons for Geographical and Racial Differences in Stroke (REGARDS) study, we examined associations among depressive symptoms and stress, alone and in combination, and incident CVD and all-cause mortality as a function of socioeconomic status. At baseline, 22 658 participants without a history of CVD (58.8% female, 41.7% black, mean age 63.9±9.3 years) reported on depressive symptoms, stress, annual household income, and education. Participants were classified into 1 of 3 psychosocial risk groups at baseline: (1) neither depressive symptoms nor stress, (2) either depressive symptoms or stress, or (3) both depressive symptoms and stress. Cox proportional hazards models were used to predict physician-adjudicated incident total CVD events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and all-cause mortality over a median of 7.0 years (interquartile range 5.4-8.3 years) of follow-up. In fully adjusted models, participants with both depressive symptoms and stress had the greatest elevation in risk of developing total CVD (hazard ratio 1.48, 95% CI 1.21-1.81) and all-cause mortality (hazard ratio 1.33, 95% CI 1.13-1.56) but only for those with low income (<$35 000) and not high (≥$35 000) income. This pattern of results was not observed in models stratified by education. Findings suggest that screening for a combination of elevated depressive symptoms and stress in low-income persons may help identify those at increased risk of incident CVD and mortality. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Dietary fibre intake and risk of ischaemic and haemorrhagic stroke in the UK Women's Cohort Study.

PubMed

Threapleton, D E; Burley, V J; Greenwood, D C; Cade, J E

2015-04-01

Stroke risk is modifiable through many risk factors, one being healthy dietary habits. Fibre intake was associated with a reduced stroke risk in recent meta-analyses; however, data were contributed by relatively few studies, and few examined different stroke types. A total of 27,373 disease-free women were followed up for 14.4 years. Diet was assessed with a 217-item food frequency questionnaire and stroke cases were identified using English Hospital Episode Statistics and mortality records. Survival analysis was applied to assess the risk of total, ischaemic or haemorrhagic stroke in relation to fibre intake. A total of 135 haemorrhagic and 184 ischaemic stroke cases were identified in addition to 138 cases where the stroke type was unknown or not recorded. Greater intake of total fibre, higher fibre density and greater soluble fibre, insoluble fibre and fibre from cereals were associated with a significantly lower risk for total stroke. For total stroke, the hazard ratio per 6 g/day total fibre intake was 0.89 (95% confidence intervals: 0.81-0.99). Different findings were observed for haemorrhagic and ischaemic stroke in healthy-weight or overweight women. Total fibre, insoluble fibre and cereal fibre were inversely associated with haemorrhagic stroke risk in overweight/obese participants, and in healthy-weight women greater cereal fibre was associated with a lower ischaemic stroke risk. In non-hypertensive women, higher fibre density was associated with lower ischaemic stroke risk. Greater total fibre and fibre from cereals are associated with a lower stroke risk, and associations were more consistent with ischaemic stroke. The different observations by stroke type, body mass index group or hypertensive status indicates potentially different mechanisms.

Risk and mortality of traumatic brain injury in stroke patients: two nationwide cohort studies.

PubMed

Chou, Yi-Chun; Yeh, Chun-Chieh; Hu, Chaur-Jong; Meng, Nai-Hsin; Chiu, Wen-Ta; Chou, Wan-Hsin; Chen, Ta-Liang; Liao, Chien-Chang

2014-01-01

Patients with stroke had higher incidence of falls and hip fractures. However, the risk of traumatic brain injury (TBI) and post-TBI mortality in patients with stroke was not well defined. Our study is to investigate the risk of TBI and post-TBI mortality in patients with stroke. Using reimbursement claims from Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study of 7622 patients with stroke and 30 488 participants without stroke aged 20 years and older as reference group. Data were collected on newly developed TBI after stroke with 5 to 8 years' follow-up during 2000 to 2008. Another nested cohort study including 7034 hospitalized patients with TBI was also conducted to analyze the contribution of stroke to post-TBI in-hospital mortality. Compared with the nonstroke cohort, the adjusted hazard ratio of TBI risk among patients with stroke was 2.80 (95% confidence interval = 2.58-3.04) during the follow-up period. Patients with stroke had higher mortality after TBI than those without stroke (10.2% vs 3.2%, P < .0001) with an adjusted relative risk (RR) of 1.46 (95% confidence interval = 1.15-1.84). Recurrent stroke (RR = 1.60), hemorrhagic stroke (RR = 1.68), high medical expenditure for stroke (RR = 1.80), epilepsy (RR = 1.79), neurosurgery (RR = 1.94), and hip fracture (RR = 2.11) were all associated with significantly higher post-TBI mortality among patients with stroke. Patients with stroke have an increased risk of TBI and in-hospital mortality after TBI. Various characteristics of stroke severity were all associated with higher post-TBI mortality. Special attention is needed to prevent TBI among these populations.

Higher total serum cholesterol levels are associated with less severe strokes and lower all-cause mortality: ten-year follow-up of ischemic strokes in the Copenhagen Stroke Study.

PubMed

Olsen, Tom Skyhøj; Christensen, Rune Haubo Bojesen; Kammersgaard, Lars Peter; Andersen, Klaus Kaae

2007-10-01

Evidence of a causal relation between serum cholesterol and stroke is inconsistent. We investigated the relation between total serum cholesterol and both stroke severity and poststroke mortality to test the hypothesis that hypercholesterolemia is primarily associated with minor stroke. In the study, 652 unselected patients with ischemic stroke arrived at the hospital within 24 hours of stroke onset. A measure of total serum cholesterol was obtained in 513 (79%) within the 24-hour time window. Stroke severity was measured with the Scandinavian Stroke Scale (0=worst, 58=best); a full cardiovascular risk profile was established for all. Death within 10 years after stroke onset was obtained from the Danish Registry of Persons. Mean+/-SD age of the 513 patients was 75+/-10 years, 54% were women, and the mean+/-SD Scandinavian Stroke Scale score was 39+/-17. Serum cholesterol was inversely and almost linearly related to stroke severity: an increase of 1 mmol/L in total serum cholesterol resulted in an increase in the Scandinavian Stroke Scale score of 1.32 (95% CI, 0.28 to 2.36, P=0.013), meaning that higher cholesterol levels are associated with less severe strokes. A survival analysis revealed an inverse linear relation between serum cholesterol and mortality, meaning that an increase of 1 mmol/L in cholesterol results in a hazard ratio of 0.89 (95% CI, 0.82 to 0.97, P=0.01). The results of our study support the hypothesis that a higher cholesterol level favors development of minor strokes. Because of selection, therefore, major strokes are more often seen in patients with lower cholesterol levels. Poststroke mortality, therefore, is inversely related to cholesterol.

Association of high waist-to-height ratio with functional outcomes in patients with acute ischemic stroke

PubMed Central

Yu, Ping; Pan, Yuesong; Zheng, Huaguang; Wang, Xianwei; Yan, Hongyi; Tong, Xu; Jing, Jing; Zhang, Xiao; Guo, Li; Wang, Yilong

2017-01-01

Abstract The aim of our study was to investigate the relationship between the waist-to-height ratio (WHR) and all-cause mortality and functional outcomes after acute ischemic stroke in a prospective cohort study. A total of 2076 patients (36.66% females) with ischemic stroke were analyzed from ACROSS-China, which is a nationwide, prospective, hospital-based stroke registry aimed to detect the glucose abnormality in China. One-year follow-up evaluation was done by telephone interview. Outcome measures were all-cause mortality and functional outcome defined as modified Rankin score being 6 and from 0 to 6, respectively. We identified predictors for functional outcomes using logistic regression analysis, and mortality outcome using Cox proportional hazards model which incorporated covariates with P value of < 0.2 in the univariate analysis and those of clinical importance. The higher WHR was associated with worse functional outcome, but not predictive of the patients’ mortality outcomes. Compared with the first quartile (≤0.48), the fourth quartile of the WHR was more likely to be associated with poor functional recovery (fourth quartile (≥0.56), OR = 1.38, CI: 1.08–1.77, P = 0.01; third quartile OR = 1.10, CI: 0.86–1.40, P = 0.45; second quartile OR = 1.05, CI: 0.83–1.33, P = 0.71). Our findings suggest that abdominal fat accumulation may be associated with functional recovery after stroke, and is not associated with mortality after stroke. Compared with the lowest quartile, the highest quartile of WHR at admission was possibly associated with worse postacute ischemic stroke functional recovery. PMID:28353610

Association of high waist-to-height ratio with functional outcomes in patients with acute ischemic stroke: A report from the ACROSS-China study.

PubMed

Yu, Ping; Pan, Yuesong; Zheng, Huaguang; Wang, Xianwei; Yan, Hongyi; Tong, Xu; Jing, Jing; Zhang, Xiao; Guo, Li; Wang, Yilong

2017-03-01

The aim of our study was to investigate the relationship between the waist-to-height ratio (WHR) and all-cause mortality and functional outcomes after acute ischemic stroke in a prospective cohort study.A total of 2076 patients (36.66% females) with ischemic stroke were analyzed from ACROSS-China, which is a nationwide, prospective, hospital-based stroke registry aimed to detect the glucose abnormality in China. One-year follow-up evaluation was done by telephone interview. Outcome measures were all-cause mortality and functional outcome defined as modified Rankin score being 6 and from 0 to 6, respectively. We identified predictors for functional outcomes using logistic regression analysis, and mortality outcome using Cox proportional hazards model which incorporated covariates with P value of < 0.2 in the univariate analysis and those of clinical importance.The higher WHR was associated with worse functional outcome, but not predictive of the patients' mortality outcomes. Compared with the first quartile (≤0.48), the fourth quartile of the WHR was more likely to be associated with poor functional recovery (fourth quartile (≥0.56), OR = 1.38, CI: 1.08-1.77, P = 0.01; third quartile OR = 1.10, CI: 0.86-1.40, P = 0.45; second quartile OR = 1.05, CI: 0.83-1.33, P = 0.71).Our findings suggest that abdominal fat accumulation may be associated with functional recovery after stroke, and is not associated with mortality after stroke. Compared with the lowest quartile, the highest quartile of WHR at admission was possibly associated with worse postacute ischemic stroke functional recovery.

Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

PubMed

Westenbrink, B Daan; Alings, Marco; Granger, Christopher B; Alexander, John H; Lopes, Renato D; Hylek, Elaine M; Thomas, Laine; Wojdyla, Daniel M; Hanna, Michael; Keltai, Matyas; Steg, P Gabriel; De Caterina, Raffaele; Wallentin, Lars; van Gilst, Wiek H

2017-03-01

Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes. We performed a post hoc analysis of the ARISTOTLE trial, which included >18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin <13.0 in men and <12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality. Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS 2 and HAS-BLED scores, and were more likely to have experienced previous bleeding events. Anemia was associated with major bleeding (adjusted hazard ratio [HR], 1.92; 95% CI, 1.62-2.28; P<.0001) and all-cause mortality (adjusted HR, 1.68; 95% CI, 1.46-1.93; P<.0001) but not stroke or systemic embolism (adjusted HR, 0.92; 95% CI, 0.70-1.21). The benefits of apixaban compared with warfarin on the rates of stroke, mortality, and bleeding events were consistent in patients with and without anemia. Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Impact of gender-age interaction on the outcome of ischemic stroke in an Italian cohort of patients treated according to a standardized clinical pathway.

PubMed

Denti, Licia; Artoni, Andrea; Scoditti, Umberto; Caminiti, Caterina; Giambanco, Fabiola; Casella, Monica; Ceda, Gian Paolo

2013-12-01

Stroke outcome has been reported as worse in women, especially in terms of disability. As for mortality, the data are conflicting, with some reports suggesting a female advantage. Our objective was to explore such issues in an Italian cohort of patients managed by a standardized clinical pathway (CPW) and, as such, homogeneous in terms of clinical management. Data from a cohort of 1993 patients (987 women and 1006 men) with first-ever ischemic stroke, consecutively referred to an in-hospital Clinical Pathway Program from January 1, 2001 to December 31, 2009, were retrospectively analyzed. The relationship between female gender and one-month outcome was assessed with adjustment for age, stroke severity and premorbid disability. The outcome was worse in women in terms of disability (age-adjusted odds ratio 2.03, 95% CI 1.69-2.46), while no difference was found for mortality. In multivariate models, female gender turned out to be associated with a lower case-fatality rate (adjusted hazard ratio 0.65, 95% CI 0.48-0.89, P=0.007), whereas the odds ratio for disability decreased but remained significant (OR 1.30; 95% CI 1.01-1.69). We found a significant interaction between gender and age in the case-fatality rate, and a female survival advantage was apparent only below 50 years. Our study confirms the excess risk of disability after stroke in women, although it is mostly explained by the occurrence of the most severe clinical syndromes. As for mortality, female gender seems to play a protective role, at least in the short-term and in younger patients. © 2013.

The poor outcome of ischemic stroke in very old people: a cohort study of its determinants.

PubMed

Denti, Licia; Scoditti, Umberto; Tonelli, Claudio; Saccavini, Marsilio; Caminiti, Caterina; Valcavi, Rita; Benatti, Mario; Ceda, Gian Paolo

2010-01-01

To assess how much of the excess risk of poor outcome from stroke in people aged 80 and older aging per se explains, independent of other prognostic determinants. Cohort, observational. University hospital. One thousand five hundred fifty-five patients with first-ever ischemic stroke consecutively referred to an in-hospital Clinical Pathway program were studied. The relationship between age and 1-month outcome (death, disability (modified Rankin Scale 3-5), and poor outcome (modified Rankin Scale 3-6)) was assessed, with adjustment for several prognostic factors. Six hundred twelve patients aged 80 and older showed worse outcome after 1 month than those who were younger, in terms of mortality (19% vs 5%, hazard ratio (HR)=3.85, 95% confidence interval (CI)=2.8-5.4) and disability (51% vs 33%, odds ratio (OR)=3.16, 95% CI=2.5-4.0), although in multivariate models, the adjusted HR for mortality decreased to 1.47 (95% CI=1.0-2.16) and the ORs for disability and poor outcome decreased to 1.76 (95% CI=1.32-2.3.) and 1.83 (95% CI=137-2.43), respectively. Stroke severity, the occurrence of at least one medical complication, and premorbid disability explained most of the risk excess in the oldest-old. Stroke outcome is definitely worse in very old people, and most of the excess risk of death and disability is attributable to the higher occurrences of the most-severe clinical stroke syndromes and of medical complications in the acute phase. These represent potential targets for preventive and therapeutical strategies specifically for elderly people.

Early-Life Origins of Adult Disease: National Longitudinal Population-Based Study of the United States

PubMed Central

Schoeni, Robert F.

2011-01-01

Objectives. We examined the relation between low birth weight and childhood family and neighborhood socioeconomic disadvantage and disease onset in adulthood. Methods. Using US nationally representative longitudinal data, we estimated hazard models of the onset of asthma, hypertension, diabetes, and stroke, heart attack, or heart disease. The sample contained 4387 children who were members of the Panel Study of Income Dynamics in 1968; they were followed up to 2007, when they were aged 39 to 56 years. Our research design included sibling comparisons of disease onset among siblings with different birth weights. Results. The odds ratios of having asthma, hypertension, diabetes, and stroke, heart attack, or heart disease by age 50 years for low–birth weight babies vs others were 1.64 (P < .01), 1.51 (P < .01), 2.09 (P < .01), and 2.16 (P < .01), respectively. Adult disease prevalence differed substantially by childhood socioeconomic status (SES). After accounting for childhood socioeconomic factors, we found a substantial hazard ratio of disease onset associated with low birth weight, which persisted for sibling comparisons. Conclusions. Childhood SES is strongly associated with the onset of chronic disease in adulthood. Low birth weight plays an important role in disease onset; this relation persists after an array of childhood socioeconomic factors is accounted for. PMID:22021306

Heterogeneity in Early Responses in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

PubMed

Dhruva, Sanket S; Huang, Chenxi; Spatz, Erica S; Coppi, Andreas C; Warner, Frederick; Li, Shu-Xia; Lin, Haiqun; Xu, Xiao; Furberg, Curt D; Davis, Barry R; Pressel, Sara L; Coifman, Ronald R; Krumholz, Harlan M

2017-07-01

Randomized trials of hypertension have seldom examined heterogeneity in response to treatments over time and the implications for cardiovascular outcomes. Understanding this heterogeneity, however, is a necessary step toward personalizing antihypertensive therapy. We applied trajectory-based modeling to data on 39 763 study participants of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) to identify distinct patterns of systolic blood pressure (SBP) response to randomized medications during the first 6 months of the trial. Two trajectory patterns were identified: immediate responders (85.5%), on average, had a decreasing SBP, whereas nonimmediate responders (14.5%), on average, had an initially increasing SBP followed by a decrease. Compared with those randomized to chlorthalidone, participants randomized to amlodipine (odds ratio, 1.20; 95% confidence interval [CI], 1.10-1.31), lisinopril (odds ratio, 1.88; 95% CI, 1.73-2.03), and doxazosin (odds ratio, 1.65; 95% CI, 1.52-1.78) had higher adjusted odds ratios associated with being a nonimmediate responder (versus immediate responder). After multivariable adjustment, nonimmediate responders had a higher hazard ratio of stroke (hazard ratio, 1.49; 95% CI, 1.21-1.84), combined cardiovascular disease (hazard ratio, 1.21; 95% CI, 1.11-1.31), and heart failure (hazard ratio, 1.48; 95% CI, 1.24-1.78) during follow-up between 6 months and 2 years. The SBP response trajectories provided superior discrimination for predicting downstream adverse cardiovascular events than classification based on difference in SBP between the first 2 measurements, SBP at 6 months, and average SBP during the first 6 months. Our findings demonstrate heterogeneity in response to antihypertensive therapies and show that chlorthalidone is associated with more favorable initial response than the other medications. © 2017 American Heart Association, Inc.

Retinal vein occlusion and the risk of stroke development: a 9-year nationwide population-based study.

PubMed

Rim, Tyler Hyungtaek; Kim, Dong Wook; Han, John Seungsoo; Chung, Eun Jee

2015-06-01

To evaluate the risk of stroke development after retinal vein occlusion (RVO). Nationwide, population-based 9-year longitudinal study. National registry data were collected from the Korean National Health Insurance Research Database, comprising 1 025 340 (∼2.2%) random subjects who were selected from 46 605 433 Korean residents in 2002. Patients diagnosed with RVO or stroke in 2002 were excluded. The RVO group was composed of patients with an initial diagnosis of central or branch RVO between January 2003 and December 2005 (n = 344 in 2003, 375 in 2004, and 312 in 2005). The comparison group was composed of randomly selected patients (5 per patient with RVO; n = 1696 in 2003, 1854 in 2004, and 1524 in 2005) who were matched to the RVO group according to age, sex, residential area, household income, and year of RVO diagnosis. Each sampled patient was tracked until 2010. Cox proportional hazard regressions were used to calculate the overall survival rate for stroke development after adjusting for potential confounders, including hypertension, diabetes mellitus, and chronic kidney disease. Retinal vein occlusion and ischemic or hemorrhagic stroke based on the International Classification of Disease codes. Stroke developed in 16.8% of the RVO group and in 10.7% of the comparison group. Retinal vein occlusion was associated with an increased risk of stroke development (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.24-1.76). Hypertension, diabetes mellitus, and chronic kidney disease also increased the risk of stroke development. In addition, RVO increased the risk of both ischemic stroke (HR, 1.51; 95% CI, 1.24-1.84) and hemorrhagic stroke (HR, 1.30; 95% CI, 0.83-2.05), although this result was not significant for hemorrhagic stroke. In terms of age, the effect size of the HR was largest among younger adults, aged <50 years (HR, 2.69), compared with middle-aged adults, aged 50 to 69 years (HR, 1.33), and older adults, aged ≥70 years (HR, 1.46). Retinal vein occlusion was significantly associated with stroke development after adjusting for potential confounders. These findings are limited by uncontrolled confounding and need to be replicated by other observational studies. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Prescription Opioid Use and Risk of Coronary Heart Disease, Stroke, and Cardiovascular Death Among Adults from a Prospective Cohort (REGARDS Study).

PubMed

Khodneva, Yulia; Muntner, Paul; Kertesz, Stefan; Kissela, Brett; Safford, Monika M

2016-03-01

Despite unknown risks, prescription opioid use (POU) for nonmalignant chronic pain has grown in the US over the last decade. The objective of this study was to examine associations between POU and coronary heart disease (CHD), stroke, and cardiovascular disease (CVD) death in a large cohort. POU was assessed in the prospective cohort study of 29,025 participants of the REasons for Geographic and Racial Differences in Stroke study, enrolled between 2003 and 2007 from the continental United States and followed through December 31, 2010. CHD, stroke, and CVD death were expert adjudicated outcome measures. Cox proportional hazards models adjusted for CVD risk factors were used. Over a median (SD) of 5.2 (1.8) years of follow-up, 1,362 CHD events, 749 strokes, and 1,120 CVD death occurred (105, 55, and 104, respectively, in the 1,851 opioid users). POU was not associated with CHD (adjusted hazard ratio [aHR]) 1.03 [95% CI 0.83-1.26] or stroke (aHR 1.04 [95% CI 0.78-1.38]), but was associated with CVD death (aHR 1.24 [95% CI 1.00-1.53]) in the overall sample. In the sex-stratified analyses, POU was associated with increased risk of CHD (aHR 1.38 [95% CI 1.05-1.82]) and CVD death (aHR 1.66 [95% CI 1.27-2.17]) among females but not males (aHR 0.70 [95% CI 0.50-0.97] for CHD and 0.78 [95% CI 0.54-1.11] for CVD death). Female but not male POU were at higher risk of CHD and CVD death. POU was not associated with stroke in overall or sex-stratified analyses. © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population.

PubMed

Amin, Alpesh; Keshishian, Allison; Trocio, Jeffrey; Dina, Oluwaseyi; Le, Hannah; Rosenblatt, Lisa; Liu, Xianchen; Mardekian, Jack; Zhang, Qisu; Baser, Onur; Vo, Lien

2017-09-01

To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients. Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts. Of the 186,132 eligible patients, 20,803 apixaban-warfarin pairs, 52,476 rivaroxaban-warfarin pairs, and 16,731 dabigatran-warfarin pairs were matched. Apixaban (hazard ratio [HR] = 0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR = 0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.51; 95% CI 0.44, 0.58) and dabigatran (HR = 0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR = 1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs. Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.

Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.

PubMed

Avezum, Alvaro; Lopes, Renato D; Schulte, Phillip J; Lanas, Fernando; Gersh, Bernard J; Hanna, Michael; Pais, Prem; Erol, Cetin; Diaz, Rafael; Bahit, M Cecilia; Bartunek, Jozef; De Caterina, Raffaele; Goto, Shinya; Ruzyllo, Witold; Zhu, Jun; Granger, Christopher B; Alexander, John H

2015-08-25

Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves. We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.97 and HR, 0.84; 95%, CI 0.67-1.04; interaction P=0.38), causing less major bleeding (HR, 0.79; 95% CI, 0.61-1.04 and HR, 0.65; 95% CI, 0.55-0.77; interaction P=0.23), and reducing mortality (HR, 1.01; 95% CI, 0.84-1.22 and HR, 0.84; 95% CI, 0.73-0.96; interaction P=0.10). More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2015 American Heart Association, Inc.

Cross-level interaction between individual socioeconomic status and regional deprivation on overall survival after onset of ischemic stroke: National health insurance cohort sample data from 2002 to 2013.

PubMed

Shin, Jaeyong; Choi, Young; Kim, Seung Woo; Lee, Sang Gyu; Park, Eun-Cheol

2017-08-01

The literature on stroke mortality and neighborhood effect is characterized by studies that are often Western society-oriented, with a lack of racial and cultural diversity. We estimated the effect of cross-level interaction between individual and regional socioeconomic status on the survival after onset of ischemic stroke. We selected newly diagnosed ischemic stroke patients from 2002 to 2013 using stratified representative sampling data of 1,025,340 subjects. A total of 37,044 patients over the 10 years from 2004 to 2013 had newly diagnosed stroke. We calculated hazard ratios (HR) of 12- and 36-month mortality using the Cox proportional hazard model, with the reference group as stroke patients with high income in advantaged regions. For the middle income level, the patients in advantaged regions showed low HRs for overall mortality (12-month HR 1.27; 95% confidence interval [CI], 1.13-1.44; 36-month HR 1.25; 95% CI, 1.14-1.37) compared to the others in disadvantaged regions (12-month HR 1.36; 95% CI, 1.19-1.56; 36-month HR 1.30; 95% CI, 1.17-1.44). Interestingly, for the low income level, the patients in advantaged regions showed high HRs for overall mortality (12-month HR 1.27; 95% CI, 1.13-1.44; 36-month HR 1.33; 95% CI, 1.22-1.46) compared to the others in disadvantaged regions (12-month HR 1.25; 95% CI, 1.09-1.43; 36-month HR 1.30; 95% CI, 1.18-1.44). Although we need to perform further investigations to determine the exact mechanisms, regional deprivation, as well as medical factors, might be associated with survival after onset of ischemic stroke in low-income patients. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Association between polymorphisms in the β2-adrenergic receptor gene with myocardial infarction and ischemic stroke in women

PubMed Central

Schürks, Markus; Kurth, Tobias; Ridker, Paul M; Buring, Julie E.; Zee, Robert Y. L.

2008-01-01

Summary Results from studies investigating the association between polymorphisms in the β2-adrenergic receptor gene (ADRB2) and cardiovascular disease (CVD) are controversial. Using haplotype-based analysis, we have previously shown a protective effect of the Gly16-Gln27-Ile164 haplotype on myocardial infarction in men. We sought to replicate these findings in women and further investigated, whether the gene variants exert differential effects on myocardial infarction and ischemic stroke. We performed a prospective study among 25,224 women, participating in the Women's Health Study and free of CVD at study entry. We had information on polymorphisms Gly16Arg, Gln27Glu, and Thr164Ile in the ADRB2. Incident CVD was self-reported and confirmed after medical record review. We used proportional hazards models to investigate the association between genotypes and haplotypes with any myocardial infarction, any ischemic stroke, and CVD death. During a mean of 11.8 years of follow-up, 274 myocardial infarctions, 299 ischemic strokes, and 159 CVD deaths occurred. Among the whole cohort genotype- and haplotype-based analyses did not show an association for any of the gene variants with any of the CVD outcomes. When we focused on Caucasian women, the haplotype-based analysis, however, suggested an inverse association of the haplotype Gly16-Gln27-Thr164 with incident myocardial infarction (multivariable-adjusted hazard ratio 0.75; 95%CI 0.58−0.97; p=0.03). We did not find associations in the haplotype-based analyses with incident ischemic stroke or CVD death. Our results suggest that the haplotype Gly16-Gln27-Thr164 is associated with reduced risk of incident myocardial infarction but not ischemic stroke in Caucasian women and suggests differential pathophysiologies for myocardial infarction and stroke. PMID:19190821

The impact of preadmission oral bisphosphonate use on 30-day mortality following stroke: a population-based cohort study of 100,043 patients

PubMed Central

Christensen, Diana Hedevang; Horváth-Puhó, Erzsébet; Schmidt, Morten; Christiansen, Christian Fynbo; Pedersen, Lars; Langdahl, Bente Lomholt; Thomsen, Reimar Wernich

2015-01-01

Purpose Bisphosphonate use has been associated with increased risk of fatal stroke. We examined the association between preadmission use of oral bisphosphonates and 30-day mortality following hospitalization for stroke. Patients and methods We conducted a nationwide population-based cohort study using medical databases and identified all patients in Denmark with a first-time hospitalization for stroke between 1 July 2004 and 31 December 2012 (N=100,043). Cox regression was used to compute adjusted hazard ratios as a measure of 30-day mortality rate ratios (MRRs) associated with bisphosphonate current use (prescription filled within 90 days prior to the stroke) or recent use (prescription filled in the 90–180 days prior to the stroke). Current use was further classified as new or long-term use. Results We found 51,982 patients with acute ischemic stroke (AIS), 11,779 with intracerebral hemorrhage (ICH), 4,528 with subarachnoid hemorrhage (SAH), and 31,754 with unspecified stroke. Absolute 30-day mortality risks were increased among current vs nonusers of bisphosphonates for AIS (11.9% vs 8.5%), ICH (43.2% vs 34.5%), SAH (40.3% vs 23.2%), and unspecified strokes (18.8% vs 14.0%). However, in adjusted analyses, current bisphosphonate use did not increase 30-day mortality from AIS (MRR, 0.87; 95% confidence interval [CI]: 0.75, 1.01); ICH (MRR, 1.05; 95% CI: 0.90, 1.23); SAH (MRR, 1.15; 95% CI: 0.83, 1.61); or unspecified stroke (MRR, 0.94; 95% CI: 0.81, 1.09). Likewise, no association with mortality was found for recent use. Adjusted analyses by type of bisphosphonate showed increased mortality following stroke among new users of etidronate (MRR, 1.40; 95% CI: 1.01, 1.93) and reduced mortality after AIS among current users of alendronate (MRR, 0.87; 95% CI: 0.74, 1.02). Conclusion We found no overall evidence that preadmission bisphosphonate use increases 30-day mortality following stroke. PMID:26346502

Smoking cessation and outcome after ischemic stroke or TIA.

PubMed

Epstein, Katherine A; Viscoli, Catherine M; Spence, J David; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Gerstenhaber, Brett; Guarino, Peter D; Dixit, Anand; Furie, Karen L; Kernan, Walter N

2017-10-17

To assess whether smoking cessation after an ischemic stroke or TIA improves outcomes compared to continued smoking. We conducted a prospective observational cohort study of 3,876 nondiabetic men and women enrolled in the Insulin Resistance Intervention After Stroke (IRIS) trial who were randomized to pioglitazone or placebo within 180 days of a qualifying stroke or TIA and followed up for a median of 4.8 years. A tobacco use history was obtained at baseline and updated during annual interviews. The primary outcome, which was not prespecified in the IRIS protocol, was recurrent stroke, myocardial infarction (MI), or death. Cox regression models were used to assess the differences in stroke, MI, and death after 4.8 years, with correction for adjustment variables prespecified in the IRIS trial: age, sex, stroke (vs TIA) as index event, history of stroke, history of hypertension, history of coronary artery disease, and systolic and diastolic blood pressures. At the time of their index event, 1,072 (28%) patients were current smokers. By the time of randomization, 450 (42%) patients had quit smoking. Among quitters, the 5-year risk of stroke, MI, or death was 15.7% compared to 22.6% for patients who continued to smoke (adjusted hazard ratio 0.66, 95% confidence interval 0.48-0.90). Cessation of cigarette smoking after an ischemic stroke or TIA was associated with significant health benefits over 4.8 years in the IRIS trial cohort. © 2017 American Academy of Neurology.

Mortality Reduction for Fever, Hyperglycemia, and Swallowing Nurse-Initiated Stroke Intervention: QASC Trial (Quality in Acute Stroke Care) Follow-Up.

PubMed

Middleton, Sandy; Coughlan, Kelly; Mnatzaganian, George; Low Choy, Nancy; Dale, Simeon; Jammali-Blasi, Asmara; Levi, Chris; Grimshaw, Jeremy M; Ward, Jeanette; Cadilhac, Dominique A; McElduff, Patrick; Hiller, Janet E; D'Este, Catherine

2017-05-01

Implementation of nurse-initiated protocols to manage fever, hyperglycemia, and swallowing dysfunction decreased death and disability 90 days poststroke in the QASC trial (Quality in Acute Stroke Care) conducted in 19 Australian acute stroke units (2005-2010). We now examine long-term all-cause mortality. Mortality was ascertained using Australia's National Death Index. Cox proportional hazards regression compared time to death adjusting for correlation within stroke units using the cluster sandwich (Huber-White estimator) method. Primary analyses included treatment group only unadjusted for covariates. Secondary analysis adjusted for age, sex, marital status, education, and stroke severity using multiple imputation for missing covariates. One thousand and seventy-six participants (intervention n=600; control n=476) were followed for a median of 4.1 years (minimum 0.3 to maximum 70 months), of whom 264 (24.5%) had died. Baseline demographic and clinical characteristics were generally well balanced by group. The QASC intervention group had improved long-term survival (>20%), but this was only statistically significant in adjusted analyses (unadjusted hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.58-1.07; P =0.13; adjusted HR, 0.77; 95% CI, 0.59-0.99; P =0.045). Older age (75-84 years; HR, 4.9; 95% CI, 2.8-8.7; P <0.001) and increasing stroke severity (HR, 1.5; 95% CI, 1.3-1.9; P <0.001) were associated with increased mortality, while being married (HR, 0.70; 95% CI, 0.49-0.99; P =0.042) was associated with increased likelihood of survival. Cardiovascular disease (including stroke) was listed either as the primary or secondary cause of death in 80% (211/264) of all deaths. Our results demonstrate the potential long-term and sustained benefit of nurse-initiated multidisciplinary protocols for management of fever, hyperglycemia, and swallowing dysfunction. These protocols should be a routine part of acute stroke care. URL: http://www.anzctr.org.au. Unique identifier: ACTRN12608000563369. © 2017 American Heart Association, Inc.

Association of Vagotomy and Decreased Risk of Subsequent Ischemic Stroke in Complicated Peptic Ulcer Patients: an Asian Population Study.

PubMed

Fang, Chu-Wen; Tseng, Chun-Hung; Wu, Shih-Chi; Chen, William Tzu-Liang; Muo, Chih-Hsin

2017-12-01

The primary management of peptic ulcers is medical treatment. Persistent exacerbation of a peptic ulcer may lead to complications (perforation and/or bleeding). There has been a trend toward the use of a less invasive surgical simple suture, simple local suture or non-operative (endoscopic/angiography) hemostasis rather than acid-reducing vagotomy (i.e., vagus nerve severance) for treating complicated peptic ulcers. Other studies have shown the relationship between high vagus nerve activity and survival in cancer patients via reduced levels of inflammation, indicating the essential role of the vagus nerve. We were interested in the role of the vagus nerve and attempted to assess the long-term systemic effects after vagus nerve severance. Complicated peptic ulcer patients who underwent truncal vagotomy may represent an appropriate study population for investigating the association between vagus nerve severance and long-term effects. Therefore, we assessed the risks of subsequent ischemic stroke using different treatment methods in complicated peptic ulcer patients who underwent simple suture/hemostasis or truncal vagotomy/pyloroplasty. We selected 299,742 peptic ulcer patients without a history of stroke and Helicobacter pylori infection and an additional 299,742 matched controls without ulcer, stroke, and Helicobacter pylori infection from the National Health Insurance database. The controls were frequency matched for age, gender, Charlson comorbidity index (CCI) score, hypertension, hyperlipidemia history, and index year. Then, we measured the incidence of overall ischemic stroke in the two cohorts. The hazard ratio (HR) and the 95% confidence intervals (CIs) were estimated by Cox proportional hazard regression. Compared to the controls, peptic ulcer patients had a 1.86-fold higher risk of ischemic stroke. There were similar results in gender, age, CCI, hypertension, and hyperlipidemia stratified analyses. In complicated peptic ulcer patients, those who received truncal vagotomy and pyloroplasty had a lower risk of ischemic stroke than patients who received simple suture/hemostasis (HR = 0.70, 95% CI = 0.60-0.81). Our findings suggest that patients with peptic ulcers have an elevated risk of subsequent ischemic stroke. Moreover, there were associations between vagotomy and a decreased risk of subsequent ischemic stroke in complicated peptic ulcer patients.

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.

PubMed

Hart, Robert G; Pearce, Lesly A; Bakheet, Majid F; Benavente, Oscar R; Conwit, Robin A; McClure, Leslie A; Talbert, Robert L; Anderson, David C

2014-04-01

Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high versus low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. Multivariable analyses of 3020 participants with recent magnetic resonance imaging-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. Prior symptomatic lacunar stroke or transient ischemic attack (TIA) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.6, 2.9), diabetes (HR 2.0, 95% CI 1.5, 2.5), black race (HR 1.7, 95% CI 1.3, 2.3), and male sex (HR 1.5, 95% CI 1.1, 1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3% per year (95% CI 3.4, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1% per year (95% CI 2.6, 3.9) in those with more than 1 of the other 3 risk factors (27% of the cohort), and 1.3% per year (95% CI 1.0, 1.7) in those with 0-1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, black race, and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk. Copyright © 2014 National Stroke Association. All rights reserved.

Smoking and hemorrhagic stroke mortality in a prospective cohort study of older Chinese.

PubMed

Xu, Lin; Schooling, Catherine Mary; Chan, Wai Man; Lee, Siu Yin; Leung, Gabriel M; Lam, Tai Hing

2013-08-01

Hemorrhagic stroke is more common in non-Western settings and does not always share risk factors with other cardiovascular diseases. The association of smoking with hemorrhagic stroke subtypes has not been established. We examined the association of cigarette smoking with hemorrhagic stroke, by subtype (intracerebral hemorrhage and subarachnoid hemorrhage), in a large cohort of older Chinese from Hong Kong. Multivariable Cox regression analysis was used to assess the adjusted associations of smoking at baseline with death from hemorrhagic stroke and its subtypes, using a population-based prospective cohort of 66 820 Chinese aged>65 years enrolled from July 1998 to December 2001 at all the 18 Elderly Health Centers of the Hong Kong Government Department of Health and followed until May 31, 2012. After follow-up for an average of 10.9 years (SD=3.1), 648 deaths from hemorrhagic stroke had occurred, of which 530 (82%) were intracerebral hemorrhage. Current smoking was associated with a higher risk of hemorrhagic stroke (hazard ratio, 2.19; 95% confidence interval, 1.49-3.22), intracerebral hemorrhage (1.94; 1.25-3.01), and subarachnoid hemorrhage (3.58; 1.62-7.94), adjusted for age, sex, education, public assistance, housing type, monthly expenditure, alcohol use, and exercise. Further adjustment for hypertension and body mass index slightly changed the estimates. Smoking is strongly associated with hemorrhagic stroke mortality, particularly for subarachnoid hemorrhage.

Diabetes is an Independent Risk Factor for Stroke Recurrence in Stroke Patients: A Meta-analysis.

PubMed

Shou, Juan; Zhou, Li; Zhu, Shanzhu; Zhang, Xiangjie

2015-09-01

This study aimed to assess the association between diabetes and risk of stroke recurrence (especially ischemic stroke recurrence) and to evaluate whether diabetes was an independent predictor for stroke recurrence in stroke patients with diabetes. The relevant studies were identified through searching databases of PubMed, EMBASE, and Cochrane library. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to evaluate the association between diabetes and risk of stroke recurrence. Funnel plot and Egger's regression tests were used to assess publication bias. All statistical analyses were conducted in Stata 12.0. Eighteen studies containing totally 43,899 participants were included in the meta-analysis. The results showed that stroke recurrence risk of all stroke patients with diabetes was significantly higher than those without diabetes (HR, 1.45; 95% CI, 1.32-1.59), similar results were achieved in ischemic stroke patients (HR, 1.44; 95% CI, 1.28-1.61), and there were no regional differences (Europe: HR, 1.28; 95% CI, 1.13-1.44; USA: HR, 1.89; 95% CI, 1.53-2.33; Asia: HR, 1.57, 95% CI, 1.28-1.92, respectively) and age differences (mean age <70 years: HR, 1.58; 95% CI, 1.34-1.86; mean age ≥70 years: HR, 1.27; 95% CI, 1.11-1.45, respectively). The heterogeneity of all included studies was not statistically significant, and no publication bias was observed. This meta-analysis shows that diabetes is an independent risk factor for stroke recurrence in stroke patients. Copyright © 2015. Published by Elsevier Inc.

Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF).

PubMed

Sherwood, Matthew W; Douketis, James D; Patel, Manesh R; Piccini, Jonathan P; Hellkamp, Anne S; Lokhnygina, Yuliya; Spyropoulos, Alex C; Hankey, Graeme J; Singer, Daniel E; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Becker, Richard C

2014-05-06

During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32). TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Sleep Duration and the Risk of Mortality From Stroke in Japan: The Takayama Cohort Study.

PubMed

Kawachi, Toshiaki; Wada, Keiko; Nakamura, Kozue; Tsuji, Michiko; Tamura, Takashi; Konishi, Kie; Nagata, Chisato

2016-01-01

Few studies have assessed the associations between sleep duration and stroke subtypes. We examined whether sleep duration is associated with mortality from total stroke, ischemic stroke, and hemorrhagic stroke in a population-based cohort of Japanese men and women. Subjects included 12 875 men and 15 021 women aged 35 years or older in 1992, who were followed until 2008. The outcome variable was stroke death (ischemic stroke, hemorrhagic stroke, and total stroke). During follow-up, 611 stroke deaths (354 from ischemic stroke, 217 from hemorrhagic stroke, and 40 from undetermined stroke) were identified. Compared with 7 h of sleep, ≥9 h of sleep was significantly associated with an increased risk of total stroke and ischemic stroke mortality after controlling for covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were 1.51 (95% CI, 1.16-1.97) and 1.65 (95% CI, 1.16-2.35) for total stroke mortality and ischemic stroke mortality, respectively. Short sleep duration (≤6 h of sleep) was associated with a decreased risk of mortality from total stroke (HR 0.77; 95% CI, 0.59-1.01), although this association was of borderline significance (P = 0.06). The trends for total stroke and ischemic stroke mortality were also significant (P < 0.0001 and P = 0.0002, respectively). There was a significant risk reduction of hemorrhagic stroke mortality for ≤6 h of sleep as compared with 7 h of sleep (HR 0.64; 95% CI, 0.42-0.98; P for trend = 0.08). The risk reduction was pronounced for men (HR 0.31; 95% CI, 0.16-0.64). Data suggest that longer sleep duration is associated with increased mortality from total and ischemic stroke. Short sleep duration may be associated with a decreased risk of mortality from hemorrhagic stroke in men.

Meta-Analysis of Effectiveness and Safety of Oral Anticoagulants in Atrial Fibrillation With Focus on Apixaban.

PubMed

Bai, Ying; Shi, Xu-Bo; Ma, Chang-Sheng; Lip, Gregory Y H

2017-11-01

We performed a meta-analysis of data on the effectiveness and safety of apixaban compared with other oral anticoagulants (warfarin or rivaroxaban or dabigatran or edoxaban) for stroke prevention in atrial fibrillation (AF) in different settings of randomized controlled trials, real-world studies, and radiofrequency ablation (RFA). Thirty studies were searched in PubMed, the Cochrane Library, and Clinicaltrials.gov databases reporting comparative effectiveness and safety of apixaban with warfarin (n = 23), rivaroxaban (n = 12), dabigatran (n = 13), or edoxaban (n = 2) for stroke prevention in AF. In real-world estimates, apixaban was similar to warfarin for the prevention of stroke or systematic thromboembolism (hazard ratio 0.93, 95% CI 0.71 to 1.14, I 2  = 82.9%, N = 7), and safer than warfarin in the risks of major bleeding (hazard ratio 0.62, 95% CI 0.54 to 0.70, I 2  = 18.7%, N = 9) in patients with AF. The risk of stroke or thromboembolism with apixaban was similar to rivaroxaban, dabigatran, and edoxaban in the settings of real-world studies and RFA. Major bleeding with apixaban was generally lower than rivaroxaban (relative risks 0.45, 95% CI 0.38 to 0.53, I 2  = 0%, N = 5) and similar to dabigatran in real-world studies (relative risks 1.44, 95% CI 0.33 to 6.30, I 2  = 97.7%, N = 5), but similar to rivaroxaban, dabigatran, and edoxaban in RFA. In conclusion, our meta-analysis provides a comprehensive estimate of the effectiveness and safety of apixaban compared with other oral anticoagulants (warfarin, rivaroxaban, dabigatran, and edoxaban) in patients with AF in different settings of randomized controlled trial, real-world studies, and RFA. Copyright © 2017 Elsevier Inc. All rights reserved.

Alcohol consumption and risk of recurrent cardiovascular events and mortality in patients with clinically manifest vascular disease and diabetes mellitus: the Second Manifestations of ARTerial (SMART) disease study.

PubMed

Beulens, J W J; Algra, A; Soedamah-Muthu, S S; Visseren, F L J; Grobbee, D E; van der Graaf, Y

2010-09-01

This study investigated the relation between alcohol consumption and specific vascular events and mortality in a high risk population of patients with clinical manifestations of vascular disease and diabetes. Patients with clinically manifest vascular disease or diabetes (n=5447) from the SMART study were followed for cardiovascular events and mortality. Alcohol consumption was assessed with a baseline questionnaire and analysed in relation with coronary heart disease (CHD), amputations, stroke, and all-cause and vascular death. After a follow up of 4.7 years, we documented 363 cases of CHD, 187 cases of stroke, 79 amputations and 641 cases of all-cause death, of which 382 were vascular. In multivariate-adjusted models, alcohol consumption was inversely associated with CHD (p(linear trend)=0.007) and stroke (p(linear trend)=0.051) with respective hazard ratios of 0.39 (95%CI: 0.20-0.76) and 0.67 (0.31-1.46) for consuming 10-20 drinks/week compared with abstainers. We observed significant U-shaped associations between alcohol consumption and amputations (p(quadratic trend)=0.001), all-cause death (p(quadratic trend)=0.001) and vascular death (p(quadratic trend)=0.013). Hazard ratios for consuming 10-20 drinks/week were 0.29 (0.07-1.30) for amputations, 0.40 (0.24-0.69) for all-cause death and 0.34 (0.16-0.71) for vascular death compared with abstainers. Similar associations were observed for red wine consumption only. Moderate alcohol consumption (1-2 drinks/day) is not only associated with a reduced risk of vascular and all-cause death in a high risk patients with clinical manifestations of vascular disease, but also with reduced risks of non-fatal events like CHD, stroke and possibly amputations. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients.

PubMed

Leon, Martin B; Smith, Craig R; Mack, Michael J; Makkar, Raj R; Svensson, Lars G; Kodali, Susheel K; Thourani, Vinod H; Tuzcu, E Murat; Miller, D Craig; Herrmann, Howard C; Doshi, Darshan; Cohen, David J; Pichard, Augusto D; Kapadia, Samir; Dewey, Todd; Babaliaros, Vasilis; Szeto, Wilson Y; Williams, Mathew R; Kereiakes, Dean; Zajarias, Alan; Greason, Kevin L; Whisenant, Brian K; Hodson, Robert W; Moses, Jeffrey W; Trento, Alfredo; Brown, David L; Fearon, William F; Pibarot, Philippe; Hahn, Rebecca T; Jaber, Wael A; Anderson, William N; Alu, Maria C; Webb, John G

2016-04-28

Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial.

PubMed

Saito, Yoshihiko; Okada, Sadanori; Ogawa, Hisao; Soejima, Hirofumi; Sakuma, Mio; Nakayama, Masafumi; Doi, Naofumi; Jinnouchi, Hideaki; Waki, Masako; Masuda, Izuru; Morimoto, Takeshi

2017-02-14

The long-term efficacy and safety of low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus are still inconclusive. The JPAD trial (Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes) was a randomized, open-label, standard care-controlled trial examining whether low-dose aspirin affected cardiovascular events in 2539 Japanese patients with type 2 diabetes mellitus and without preexisting cardiovascular disease. Patients were randomly allocated to receive aspirin (81 or 100 mg daily; aspirin group) or no aspirin (no-aspirin group) in the JPAD trial. After that trial ended in 2008, we followed up with the patients until 2015, with no attempt to change the previously assigned therapy. Primary end points were cardiovascular events, including sudden death, fatal or nonfatal coronary artery disease, fatal or nonfatal stroke, and peripheral vascular disease. For the safety analysis, hemorrhagic events, consisting of gastrointestinal bleeding, hemorrhagic stroke, and bleeding from any other sites, were also analyzed. The primary analysis was conducted for cardiovascular events among patients who retained their original allocation (a per-protocol cohort). Analyses on an intention-to-treat cohort were conducted for hemorrhagic events and statistical sensitivity. The median follow-up period was 10.3 years; 1621 patients (64%) were followed up throughout the study; and 2160 patients (85%) retained their original allocation. Low-dose aspirin did not reduce cardiovascular events in the per-protocol cohort (hazard ratio, 1.14; 95% confidence interval, 0.91-1.42). Multivariable Cox proportional hazard model adjusted for age, sex, glycemic control, kidney function, smoking status, hypertension, and dyslipidemia showed similar results (hazard ratio, 1.04; 95% confidence interval, 0.83-1.30), with no heterogeneity of efficacy in subgroup analyses stratified by each of these factors (all interaction P >0.05). Sensitivity analyses on the intention-to-treat cohort yielded consistent results (hazard ratio, 1.01; 95% confidence interval, 0.82-1.25). Gastrointestinal bleeding occurred in 25 patients (2%) in the aspirin group and 12 (0.9%) in the no-aspirin group ( P =0.03), and the incidence of hemorrhagic stroke was not different between groups. Low-dose aspirin did not affect the risk for cardiovascular events but increased risk for gastrointestinal bleeding in patients with type 2 diabetes mellitus in a primary prevention setting. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00110448. © 2016 American Heart Association, Inc.

Abnormal P-Wave Axis and Ischemic Stroke: The ARIC Study (Atherosclerosis Risk In Communities).

PubMed

Maheshwari, Ankit; Norby, Faye L; Soliman, Elsayed Z; Koene, Ryan J; Rooney, Mary R; O'Neal, Wesley T; Alonso, Alvaro; Chen, Lin Y

2017-08-01

Abnormal P-wave axis (aPWA) has been linked to incident atrial fibrillation and mortality; however, the relationship between aPWA and stroke has not been reported. We hypothesized that aPWA is associated with ischemic stroke independent of atrial fibrillation and other stroke risk factors and tested our hypothesis in the ARIC study (Atherosclerosis Risk In Communities), a community-based prospective cohort study. We included 15 102 participants (aged 54.2±5.7 years; 55.2% women; 26.5% blacks) who attended the baseline examination (1987-1989) and without prevalent stroke. We defined aPWA as any value outside 0 to 75° using 12-lead ECGs obtained during study visits. Each case of incident ischemic stroke was classified in accordance with criteria from the National Survey of Stroke by a computer algorithm and adjudicated by physician review. Multivariable Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of aPWA with stroke. During a mean follow-up of 20.2 years, there were 657 incident ischemic stroke cases. aPWA was independently associated with a 1.50-fold (95% confidence interval, 1.22-1.85) increased risk of ischemic stroke in the multivariable model that included atrial fibrillation. When subtyped, aPWA was associated with a 2.04-fold (95% confidence interval, 1.42-2.95) increased risk of cardioembolic stroke and a 1.32-fold (95% confidence interval, 1.03-1.71) increased risk of thrombotic stroke. aPWA is independently associated with ischemic stroke. This association seems to be stronger for cardioembolic strokes. Collectively, our findings suggest that alterations in atrial electric activation may predispose to cardiac thromboembolism independent of atrial fibrillation. © 2017 American Heart Association, Inc.

Self-Reported Sleep Duration in Relation to Incident Stroke Symptoms: Nuances by Body Mass and Race from the REGARDS Study

PubMed Central

Ruiter Petrov, Megan E.; Letter, Abraham J.; Howard, Virginia J.; Kleindorfer, Dawn

2013-01-01

Objectives Determine, amongst employed persons with low risk for obstructive sleep apnea (OSA), if sleep duration is associated with incident stroke symptoms, independent of body mass index (BMI), and if sleep duration mediates racial differences in stroke symptoms. Methods In 2008, 5,666 employed participants (US blacks and whites, ≥45years) from the longitudinal and nationally-representative REasons for Geographic And Racial Differences in Stroke (REGARDS) study, self-reported their average sleep duration. Participants had no history of stroke, transient ischemic attack, or stroke symptoms, and were low risk for OSA. After the sleep assessment, self-reported stroke symptoms were collected at six-month intervals, up to 3 years (M=751 days). Interval-censored, parametric survival models were conducted to estimate hazard ratios predicting time from sleep duration measurement (<6, 6-6.9, 7-7.9(reference), 8-8.9, ≥9 hours) to first stroke symptom. Adjusted models included demographics, stroke risk factors, psychological symptoms, health behaviors, and diet. Results During follow-up, 224 participants reported ≥1 stroke symptom. In the unadjusted model, short sleep (<6hrs) significantly predicted increased risk of stroke symptoms, but not in adjusted models. Stratification by BMI revealed a significant association between short sleep duration and stroke symptoms only for normal BMI persons in unadjusted (HR: 2.93, 95%CI: 1.38-6.22) and fully adjusted models (HR: 4.19, 95%CI: 1.62-10.84). The mediating effect of sleep duration on the relationship between race and stroke symptoms was borderline significant in normal weight participants. Conclusions Among middle-aged to older employed individuals of normal weight and low risk of OSA, self-reported short sleep duration is prospectively associated with increased risk of stroke symptoms. PMID:24119626

Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium

PubMed Central

Copeland, Wade K; Vedanthan, Rajesh; Grant, Eric; Lee, Jung Eun; Gu, Dongfeng; Gupta, Prakash C; Ramadas, Kunnambath; Inoue, Manami; Tsugane, Shoichiro; Tamakoshi, Akiko; Gao, Yu-Tang; Yuan, Jian-Min; Shu, Xiao-Ou; Ozasa, Kotaro; Tsuji, Ichiro; Kakizaki, Masako; Tanaka, Hideo; Nishino, Yoshikazu; Wang, Renwei; Yoo, Keun-Young; Ahn, Yoon-Ok; Ahsan, Habibul; Pan, Wen-Harn; Pednekar, Mangesh S; Sauvaget, Catherine; Sasazuki, Shizuka; Yang, Gong; Koh, Woon-Puay; Xiang, Yong-Bing; Ohishi, Waka; Watanabe, Takashi; Sugawara, Yumi; Matsuo, Keitaro; You, San-Lin; Park, Sue K; Kim, Dong-Hyun; Parvez, Faruque; Chuang, Shao-Yuan; Ge, Wenzhen; Rolland, Betsy; McLerran, Dale; Sinha, Rashmi; Thornquist, Mark; Kang, Daehee; Feng, Ziding; Boffetta, Paolo; Zheng, Wei

2013-01-01

Objective To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. Design Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. Setting General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). Participants 1 124 897 men and women (mean age 53.4 years at baseline). Main outcome measures Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. Results 49 184 cardiovascular deaths (40 791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12). Conclusions Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians. PMID:24473060

Aortic Arch Plaques and Risk of Recurrent Stroke and Death

PubMed Central

Di Tullio, Marco R.; Russo, Cesare; Jin, Zhezhen; Sacco, Ralph L.; Mohr, J.P.; Homma, Shunichi

2010-01-01

Background Aortic arch plaques are a risk factor for ischemic stroke. Although the stroke mechanism is conceivably thromboembolic, no randomized studies have evaluated the efficacy of antithrombotic therapies in preventing recurrent events. Methods and Results The relationship between arch plaques and recurrent events was studied in 516 patients with ischemic stroke, double–blindly randomized to treatment with warfarin or aspirin as part of the Patent Foramen Ovale in Cryptogenic Stroke Study (PICSS), based on the Warfarin-Aspirin Recurrent Stroke Study (WARSS). Plaque thickness and morphology was evaluated by transesophageal echocardiography. End-points were recurrent ischemic stroke or death over a 2-year follow-up. Large plaques (≥4mm) were present in 19.6% of patients, large complex plaques (those with ulcerations or mobile components) in 8.5 %. During follow-up, large plaques were associated with a significantly increased risk of events (adjusted Hazard Ratio 2.12, 95% Confidence Interval 1.04-4.32), especially those with complex morphology (HR 2.55, CI 1.10-5.89). The risk was highest among cryptogenic stroke patients, both for large plaques (HR 6.42, CI 1.62-25.46) and large-complex plaques (HR 9.50, CI 1.92-47.10). Event rates were similar in the warfarin and aspirin groups in the overall study population (16.4% vs. 15.8%; p=0.43). Conclusions In patients with stroke, and especially cryptogenic stroke, large aortic plaques remain associated with an increased risk of recurrent stroke and death at two years despite treatment with warfarin or aspirin. Complex plaque morphology confers a slight additional increase in risk. PMID:19380621

Geomagnetic storms can trigger stroke: evidence from 6 large population-based studies in Europe and Australasia.

PubMed

Feigin, Valery L; Parmar, Priya G; Barker-Collo, Suzanne; Bennett, Derrick A; Anderson, Craig S; Thrift, Amanda G; Stegmayr, Birgitta; Rothwell, Peter M; Giroud, Maurice; Bejot, Yannick; Carvil, Phillip; Krishnamurthi, Rita; Kasabov, Nikola

2014-06-01

Although the research linking cardiovascular disorders to geomagnetic activity is accumulating, robust evidence for the impact of geomagnetic activity on stroke occurrence is limited and controversial. We used a time-stratified case-crossover study design to analyze individual participant and daily geomagnetic activity (as measured by Ap Index) data from several large population-based stroke incidence studies (with information on 11 453 patients with stroke collected during 16 031 764 person-years of observation) in New Zealand, Australia, United Kingdom, France, and Sweden conducted between 1981 and 2004. Hazard ratios and corresponding 95% confidence intervals (CIs) were calculated. Overall, geomagnetic storms (Ap Index 60+) were associated with 19% increase in the risk of stroke occurrence (95% CI, 11%-27%). The triggering effect of geomagnetic storms was most evident across the combined group of all strokes in those aged <65 years, increasing stroke risk by >50%: moderate geomagnetic storms (60-99 Ap Index) were associated with a 27% (95% CI, 8%-48%) increased risk of stroke occurrence, strong geomagnetic storms (100-149 Ap Index) with a 52% (95% CI, 19%-92%) increased risk, and severe/extreme geomagnetic storms (Ap Index 150+) with a 52% (95% CI, 19%-94%) increased risk (test for trend, P<2×10(-16)). Geomagnetic storms are associated with increased risk of stroke and should be considered along with other established risk factors. Our findings provide a framework to advance stroke prevention through future investigation of the contribution of geomagnetic factors to the risk of stroke occurrence and pathogenesis. © 2014 American Heart Association, Inc.

Association of cerebral microbleeds with mortality in stroke patients having atrial fibrillation.

PubMed

Song, Tae-Jin; Kim, Jinkwon; Song, Dongbeom; Nam, Hyo Suk; Kim, Young Dae; Lee, Hye Sun; Heo, Ji Hoe

2014-10-07

We investigated the association of cerebral microbleeds (CMBs) with long-term mortality in patients with nonvalvular atrial fibrillation (NVAF) according to burden and distribution of CMBs. This was a retrospective, hospital-based, observational study. In total, 504 consecutive ischemic stroke patients with NVAF who underwent brain T2-weighted, gradient-recalled echo MRI were included. Data for the date and causes of death were based on the death certificates from the Korean National Statistical Office. We determined the association of the presence, burden, and distribution of CMBs with mortality from all-cause, ischemic heart disease, ischemic stroke, and hemorrhagic stroke. CMBs were found in 30.7% of patients (155/504). During a median follow-up of 2.5 years, 176 patients (34.9%) died (ischemic stroke, 81; hemorrhagic stroke, 12; ischemic heart disease, 32). Patients with CMBs died more frequently than those without (41.9% vs 31.8%, p = 0.028). After adjusting for age, sex, and other significant variables, the presence of multiple (≥5) CMBs was as an independent predictor for all-cause (hazard ratio [HR]: 1.99) and ischemic stroke (HR: 3.39) mortality. Patients with strictly lobar CMBs had an increased risk of hemorrhagic stroke mortality (HR: 5.91). The presence and burden of CMBs were associated with increased mortality in stroke patients with NVAF. Patients with lobar CMBs were at increased risk of death due to hemorrhagic stroke. The diagnosis of CMBs is of value in predicting long-term prognosis in stroke patients with NVAF. © 2014 American Academy of Neurology.

Social network, social support, and risk of incident stroke: Atherosclerosis Risk in Communities study.

PubMed

Nagayoshi, Mako; Everson-Rose, Susan A; Iso, Hiroyasu; Mosley, Thomas H; Rose, Kathryn M; Lutsey, Pamela L

2014-10-01

Having a small social network and lack of social support have been associated with incident coronary heart disease; however, epidemiological evidence for incident stroke is limited. We assessed the longitudinal association of a small social network and lack of social support with risk of incident stroke and evaluated whether the association was partly mediated by vital exhaustion and inflammation. The Atherosclerosis Risk in Communities study measured social network and social support in 13 686 men and women (mean, 57 years; 56% women; 24% black; 76% white) without a history of stroke. Social network was assessed by the 10-item Lubben Social Network Scale and social support by a 16-item Interpersonal Support Evaluation List-Short Form. During a median follow-up of 18.6 years, 905 incident strokes occurred. Relative to participants with a large social network, those with a small social network had a higher risk of stroke (hazard ratio [95% confidence interval], 1.44 [1.02-2.04]) after adjustment for demographics, socioeconomic variables, marital status, behavioral risk factors, and major stroke risk factors. Vital exhaustion, but not inflammation, partly mediated the association between a small social network and incident stroke. Social support was unrelated to incident stroke. In this sample of US community-dwelling men and women, having a small social network was associated with excess risk of incident stroke. As with other cardiovascular conditions, having a small social network may be associated with a modestly increased risk of incident stroke. © 2014 American Heart Association, Inc.

Childhood Stature and Growth in Relation to First Ischemic Stroke or Intracerebral Hemorrhage.

PubMed

Gjærde, Line Klingen; Truelsen, Thomas Clement; Baker, Jennifer Lyn

2018-03-01

Attained height, an indicator of genetic potential and childhood growth environment, is inversely associated with stroke, but the mechanisms are poorly understood. We investigated whether childhood height and growth are associated with ischemic stroke (IS) and intracerebral hemorrhage (ICH). In a cohort of Danish schoolchildren born 1930 to 1989, with measured height from 7 to 13 years, we investigated associations of childhood stature and growth with risks of adult IS and ICH. Cox proportional hazards regressions were performed to estimate hazard ratios (HRs) with CIs separately for women and men. Among 311 009 individuals, 10 412 were diagnosed with IS and 2546 with ICH. Height at 7 years was inversely and significantly associated with IS in both sexes (per z score, equivalent to ≈5.2 cm in women and 5.1 cm in men; women: HR=0.89 [95% CI: 0.87-0.92]; men: HR=0.90 [95% CI: 0.88-0.92]) and with ICH in men (HR=0.89 [95% CI: 0.84-0.94]) but not in women (HR=0.97 [95% CI: 0.91-1.04]). Associations were similar at older childhood ages and were stable throughout the study period. No statistically significant associations for growth from 7 to 13 years were observed for IS or ICH. Short stature at 7 to 13 years is significantly associated with increased risks of IS in both sexes and with ICH in men. Growth during this period of childhood is not significantly associated with either of these stroke subtypes, suggesting that underlying mechanisms linking height with risks of stroke may exert their influence already by early childhood. © 2018 American Heart Association, Inc.

Long-term exposure to air pollution and cardiorespiratory disease in the California teachers study cohort.

PubMed

Lipsett, Michael J; Ostro, Bart D; Reynolds, Peggy; Goldberg, Debbie; Hertz, Andrew; Jerrett, Michael; Smith, Daniel F; Garcia, Cynthia; Chang, Ellen T; Bernstein, Leslie

2011-10-01

Several studies have linked long-term exposure to particulate air pollution with increased cardiopulmonary mortality; only two have also examined incident circulatory disease. To examine associations of individualized long-term exposures to particulate and gaseous air pollution with incident myocardial infarction and stroke, as well as all-cause and cause specific mortality. We estimated long-term residential air pollution exposure for more than 100,000 participants in the California Teachers Study, a prospective cohort of female public school professionals.We linked geocoded residential addresses with inverse distance-weighted monthly pollutant surfaces for two measures of particulate matter and for several gaseous pollutants. We examined associations between exposure to these pollutants and risks of incident myocardial infarction and stroke, and of all-cause and cause-specific mortality, using Cox proportional hazards models. We found elevated hazard ratios linking long-term exposure to particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5), scaled to an increment of 10 μg/m3 with mortality from ischemic heart disease (IHD) (1.20; 95% confidence interval [CI], 1.02-1.41) and, particularly among postmenopausal women, incident stroke (1.19; 95% CI, 1.02-1.38). Long-term exposure to particulate matter less than 10 μm in aerodynamic diameter (PM10) was associated with elevated risks for IHD mortality (1.06; 95% CI, 0.99-1.14) and incident stroke (1.06; 95% CI, 1.00-1.13), while exposure to nitrogen oxides was associated with elevated risks for IHD and all cardiovascular mortality. This study provides evidence linking long-term exposure to PM2.5 and PM10 with increased risks of incident stroke as well as IHD mortality; exposure to nitrogen oxides was also related to death from cardiovascular diseases.

Early and late mortality of spontaneous hemorrhagic transformation of ischemic stroke.

PubMed

D'Amelio, Marco; Terruso, Valeria; Famoso, Giorgia; Di Benedetto, Norma; Realmuto, Sabrina; Valentino, Francesca; Ragonese, Paolo; Savettieri, Giovanni; Aridon, Paolo

2014-04-01

Hemorrhagic transformation (HT), a complication of ischemic stroke (IS), might influence patient's prognosis. Our aim is to evaluate, in a hospital-based series of patients not treated with thrombolysis, the relationship between HT and mortality. We compared mortality of individuals with spontaneous HT with that of individuals without. Medical records of patients diagnosed with anterior IS were retrospectively reviewed. Outcome measures were 30- and 90-day survival after IS onset. Kaplan-Meier estimates were used to construct survival curves. Cox proportional hazards model was used to estimate hazard ratio (HR) for the main outcome measure (death). HT was stratified in hemorrhagic infarction and parenchymal hematoma (PH). We also evaluated the relationship between HT and the main mortality risk factors (gender, age, premorbid status, severity of stroke, and radiological features). Thirty days from stroke onset, 8.1% (19 of 233) of patients died. At multivariate analysis, PH (HR: 7.7, 95% confidence interval [CI]: 2.1, 27.8) and low level of consciousness at admission (HR: 5.0, 95% CI: 1.3, 18.6) were significantly associated with death. At 3-month follow-up, mortality rate was 12.1% (28 of 232). At multivariate analysis, large infarct size (HR: 2.7, 95% CI: 1.2, 6.0) and HT (HR: 2.3, 95% CI: 1.0, 5.4) were independent risk factors for mortality. Parenchymal hematoma was, however, the strongest predictor of late mortality (HR: 7.9, 95% CI: 2.9, 21.4). Neurological status and infarct size play a significant role, respectively, in early and late mortality after IS. Parenchymal hematoma independently predicts both early and late mortality. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Antidepressant Medication Use and Its Association With Cardiovascular Disease and All-Cause Mortality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

PubMed

Hansen, Richard A; Khodneva, Yulia; Glasser, Stephen P; Qian, Jingjing; Redmond, Nicole; Safford, Monika M

2016-04-01

Mixed evidence suggests that second-generation antidepressants may increase the risk of cardiovascular and cerebrovascular events. To assess whether antidepressant use is associated with acute coronary heart disease (CHD), stroke, cardiovascular disease (CVD) death, and all-cause mortality. Secondary analyses of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) longitudinal cohort study were conducted. Use of selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, bupropion, nefazodone, and trazodone was measured during the baseline (2003-2007) in-home visit. Outcomes of CHD, stroke, CVD death, and all-cause mortality were assessed every 6 months and adjudicated by medical record review. Cox proportional hazards time-to-event analysis followed patients until their first event on or before December 31, 2011, iteratively adjusting for covariates. Among 29 616 participants, 3458 (11.7%) used an antidepressant of interest. Intermediate models adjusting for everything but physical and mental health found an increased risk of acute CHD (hazard ratio [HR] = 1.21; 95% CI = 1.04-1.41), stroke (HR = 1.28; 95% CI = 1.02-1.60), CVD death (HR = 1.29; 95% CI = 1.09-1.53), and all-cause mortality (HR = 1.27; 95% CI = 1.15-1.41) for antidepressant users. Risk estimates trended in this direction for all outcomes in the fully adjusted model but only remained statistically associated with increased risk of all-cause mortality (HR = 1.12; 95% CI = 1.01-1.24). This risk was attenuated in sensitivity analyses censoring follow-up time at 2 years (HR = 1.37; 95% CI = 1.11-1.68). In fully adjusted models, antidepressant use was associated with a small increase in all-cause mortality. © The Author(s) 2016.

Effect of Statin Intensity on the Risk of Epilepsy After Ischaemic Stroke: Real-World Evidence from Population-Based Health Claims.

PubMed

Lin, Fang-Ju; Lin, Hung-Wei; Ho, Yunn-Fang

2018-04-01

Statins possess neuroprotective effects. However, real-world evidence supporting their utility in post-stroke epilepsy (PSE) prevention is limited. The association between statin use, including timing of prescribing (pre-stroke vs post-stroke), type (lipophilicity, intensity of therapy) and dose intensity, and risk of developing PSE were investigated by studying Taiwanese health claims (2003-2013). Patients with new-onset ischaemic stroke were identified. The main outcome was a diagnosis of epilepsy after ischaemic stroke. According to pre-stroke statin use, groups of current users, former users, and non-users were compared using ANOVA. An extended Cox regression model was utilized to estimate the hazard ratio (HR) of PSE, with post-stroke statin use and certain comedications as time-dependent variables. Serial sensitivity analyses were performed to ensure study robustness. Of the 20,858 ischaemic stroke patients, 954 (4.6%) developed PSE. Post-stroke statin use (adjusted HR (aHR) 0.55; 95% confidence interval 0.46-0.67, p < 0.001), but not pre-stroke statin use was associated with a significantly reduced risk of developing PSE. A dose-response correlation was also observed between PSE risk reduction and quartiles of the statin cumulative defined daily dose (cDDD) (aHR 0.84, 0.67, 0.53, and 0.50 for the lowest, second, third, and highest quartiles of cDDD, respectively). Risk predictors and protectors against PSE were also characterized. The post-stroke use of statins after ischaemic stroke was associated with PSE risk reduction in a cDDD-dependent manner. Further clinical studies on the potential applications of statins for PSE prophylaxis, particularly among at-risk patients, are warranted.

Racial differences in mortality among patients with acute ischemic stroke: an observational study.

PubMed

Xian, Ying; Holloway, Robert G; Noyes, Katia; Shah, Manish N; Friedman, Bruce

2011-02-01

Black patients are commonly believed to have higher stroke mortality. However, several recent studies have reported better survival in black patients with stroke. To examine racial differences in stroke mortality and explore potential reasons for these differences. Observational cohort study. 164 hospitals in New York. 5319 black and 18 340 white patients aged 18 years or older who were hospitalized with acute ischemic stroke between January 2005 and December 2006. Influence of race on mortality, examined by using propensity score analysis. Secondary outcomes were selected aspects of end-of-life treatment, use of tissue plasminogen activator, hospital spending, and length of stay. Patients were followed for mortality for 1 year after admission. Overall in-hospital mortality was lower for black patients than for white patients (5.0% vs. 7.4%; P < 0.001), as was all-cause mortality at 30 days (6.1% vs. 11.4%; P < 0.001) and 1 year (16.5% vs. 24.4%; P < 0.001). After propensity score adjustment, black race was independently associated with lower in-hospital mortality (odds ratio [OR], 0.77 [95% CI, 0.61 to 0.98]) and all-cause mortality up to 1 year (OR, 0.86 [CI, 0.77 to 0.96]). The adjusted hazard ratio was 0.87 (CI, 0.79 to 0.96). After adjustment for the probability of dying in the hospital, black patients with stroke were more likely to receive life-sustaining interventions (OR, 1.22 [CI, 1.09 to 1.38]) but less likely to be discharged to hospice (OR, 0.25 [CI, 0.14 to 0.46]). The study used hospital administrative data that lacked a stroke severity measure. The study design precluded determination of causality. Among patients with acute ischemic stroke, black patients had lower mortality than white patients. This could be the result of differences in receipt of life-sustaining interventions and end-of-life care.

Recurrent Pregnancy Loss and Cardiovascular Disease Mortality in Japanese Women: A Population-Based, Prospective Cohort Study.

PubMed

Yamada, Keiko; Iso, Hiroyasu; Cui, Renzhe; Tamakoshi, Akiko

2017-05-01

This study aimed to examine the association between recurrent pregnancy loss and the risk of cardiovascular disease mortality. We identified 54,652 women who were pregnant during the Japan Collaborative Cohort Study. These women were 40-79 years at the date of cohort entry between 1988 and 1990. Participants received municipal health screening examinations and completed self-administered questionnaires. The cause of death was confirmed by annual or biannual follow-up surveys for a median of 18 years. The exposure was the number of pregnancy loss. The outcome was mortality from total cardiovascular disease and its subtypes according to the International Classification of Diseases, 10th Revision. Adjustment variables included age, number of deliveries, education, body mass index, physical activity, smoking status, and drinking status. Kaplan-Meier survival curves were used to estimate the cumulative mortality. The number of pregnancy loss tended to be inversely associated with the risk of mortality from total stroke, intracerebral hemorrhage, and total cardiovascular disease. The multivariable hazard ratio of total cardiovascular disease for ≥2 pregnancy losses versus no pregnancy loss was .84 (95% confidence interval, .74-0.95). A 2-fold excess risk of mortality from ischemic stroke associated with ≥2 pregnancy losses was observed in women aged 40-59 years, with a multivariable hazard ratio of 2.19 (95% confidence interval, 1.06-4.49), but not in older women. Recurrentpregnancy loss tends to be associated with a lower risk of mortality from cardiovascular disease at 40-79 years. Younger women have an excess risk of ischemic stroke mortality associated with recurrent pregnancy loss. Copyright © 2017. Published by Elsevier Inc.

VISIT-TO-VISIT VARIABILITY OF BLOOD PRESSURE AND DEATH, ESRD AND CARDIOVASCULAR EVENTS IN PATIENTS WITH CHRONIC KIDNEY DISEASE

PubMed Central

CHANG, Tara I.; TABADA, Grace H.; YANG, Jingrong; TAN, Thida X.; GO, Alan S.

2016-01-01

OBJECTIVES Visit-to-visit variability of blood pressure is an important independent risk factor for premature death and cardiovascular events, but relatively little is known about this phenomenon in patients with chronic kidney disease not yet on dialysis. METHODS We conducted a retrospective study in a community-based cohort of 114,900 adults with chronic kidney disease stages 3–4 (estimated glomerular filtration rate 15–59 mL/min per 1.73 m2). We hypothesized that visit-to-visit variability of blood pressure would be independently associated with higher risks of death, incident treated end-stage renal disease, and cardiovascular events. We defined systolic visit-to-visit variability of blood pressure using three metrics: (1) coefficient of variation (2) standard deviation of the mean systolic blood pressure, and (3) average real variability. RESULTS The highest versus the lowest quintile of the coefficient of variation was associated with higher adjusted rates of death (hazard ratio 1.22; 95% confidence interval 1.11–1.34) and hemorrhagic stroke (hazard ratio 1.91, confidence interval 1.36–2.68). Visit-to-visit variability of blood pressure was inconsistently associated with heart failure, and was not significantly associated with acute coronary syndrome and ischemic stroke. Results were similar when using the other two visit-to-visit variability of blood pressure. Visit-to-visit variability of blood pressure had inconsistent associations with end-stage renal disease, perhaps due to the relatively low incidences of this outcome. CONCLUSIONS Higher visit-to-visit variability of blood pressure is independently associated with higher rates of death and hemorrhagic stroke in patients with moderate to advanced chronic kidney disease not yet on dialysis. PMID:26599220

Anticoagulation Use and Clinical Outcomes Following Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation

PubMed Central

Hernandez, Inmaculada; Zhang, Yuting; Brooks, Maria M.; Chin, Paul K.L.; Saba, Samir

2016-01-01

Background and Purpose Little is known about the clinical outcomes associated with post-hemorrhage anticoagulation resumption for atrial fibrillation. This study had two objectives: first, to evaluate anticoagulation use after a first major bleed on warfarin or dabigatran; and second, to compare effectiveness and safety outcomes between patients discontinuing anticoagulation after a major bleed and patients restarting warfarin or dabigatran. Methods Using 2010-2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding event while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their post-hemorrhage use of anticoagulation. We followed them until an ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors impacting anticoagulation resumption, and Cox Proportional Hazard models to compare the combined risk of ischemic stroke and all-cause mortality, and the risk of recurrent bleeding between treatment groups. Results Resumption of anticoagulation with warfarin (hazard ratio (HR) 0.76; 95%CI, 0.59-0.97) or dabigatran (HR0.66; 95%CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients prescribed warfarin after the event than for those prescribed dabigatran (HR2.31; 95%CI, 1.19-4.76) or whose anticoagulation ceased (HR1.56; 95%CI, 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation (HR0.66; 95% CI, 0.32-1.33). Conclusions Dabigatran was associated with a superior benefit/risk ratio than warfarin and anticoagulation discontinuation in the treatment of atrial fibrillation patients who have survived a major bleed. PMID:27909200

Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study.

PubMed

Dennis, Michael; Shine, Laura; John, Ann; Marchant, Amanda; McGregor, Joanna; Lyons, Ronan A; Brophy, Sinead

2017-06-01

Over recent years there has been growing evidence of increased risk of mortality associated with antipsychotic use in older people with dementia. Although this concern combined with limited evidence of efficacy has informed guidelines restricting antipsychotic prescription in this population, the use of antipsycotics remains common. Many published studies only report short-term outcomes, are restricted to examining mortality and stroke risk or have other limitations. The aim of this study was to assess adverse outcomes associated with the use of antipsychotics in older people living with dementia in Wales (UK). This was a retrospective study of a population-based dementia cohort using the Welsh Secure Anonymised Information Linkage databank. The prior event rate ratio (PERR) was used to estimate the influence of exposure to antipsychotic medication on acute cardiac events, venous thromboembolism, stroke and hip fracture, and adjusted Cox proportional hazard models were used to compare all-cause mortality. A total of 10,339 people aged ≥65 years were identified with newly diagnosed dementia. After excluding those who did not meet the inclusion criteria, 9674 people remained in the main cohort of whom 3735 were exposed to antipsychotic medication. An increased risk of a venous thromboembolic episode [PERR 1.95, 95% confidence interval (CI) 1.83-2.0], stroke (PERR 1.41, 95% CI 1.4-1.46) and hip fracture (PERR 1.62, 95% CI 1.59-1.65) was associated with antipsychotic use. However, there was no long-term increased mortality in people exposed to antipsychotics (adjusted hazard ratio 1.06, 95% CI 0.99-1.13). The increase in adverse medical events supports guidelines restricting antipsychotic use in this population.

Long-term outcome of vertebral artery origin stenosis in patients with acute ischemic stroke

PubMed Central

2013-01-01

Background Vertebral artery origin (VAO) stenosis is occasionally observed in patients who have acute ischemic stroke. We investigated the long-term outcomes and clinical significance of VAO stenosis in patients with acute ischemic stroke. Methods We performed a prospective observational study using a single stroke center registry to investigate the risk of recurrent stroke and vascular outcomes in patients with acute ischemic stroke and VAO stenosis. To relate the clinical significance of VAO stenosis to the vascular territory of the index stroke, patients were classified into an asymptomatic VAO stenosis group and a symptomatic VAO stenosis group. Results Of the 774 patients who had acute ischemic stroke, 149 (19.3%) of them had more than 50% stenosis of the VAO. During 309 patient-years of follow-up (mean, 2.3 years), there were 7 ischemic strokes, 6 hemorrhagic strokes, and 2 unknown strokes. The annual event rates were 0.97% for posterior circulation ischemic stroke, 4.86% for all stroke, and 6.80% for the composite cardiovascular outcome. The annual event rate for ischemic stroke in the posterior circulation was significantly higher in patients who had symptomatic VAO stenosis than in patients who had asymptomatic stenosis (1.88% vs. 0%, p = 0.046). In a multivariate analysis, the hazard ratio, per one point increase of the Essen Stroke Risk Score (ESRS) for the composite cardiovascular outcome, was 1.46 (95% CI, 1.02-2.08, p = 0.036). Conclusions Long-term outcomes of more than 50% stenosis of the VAO in patients with acute ischemic stroke were generally favorable. Additionally, ESRS was a predictor for the composite cardiovascular outcome. Asymptomatic VAO stenosis may not be a specific risk factor for recurrent ischemic stroke in the posterior circulation. However, VAO stenosis may require more clinical attention as a potential source of recurrent stroke when VAO stenosis is observed in patients who have concurrent ischemic stroke in the posterior circulation. PMID:24215371

Predictors of short- and long-term mortality in first-ever ischaemic older stroke patients.

PubMed

Hsu, Chia-Yu; Hu, Gwo-Chi; Chen, Yi-Min; Chen, Chiu-Hsiang; Hu, Yu-Ning

2013-12-01

Predictors of short- and long-term all-cause mortality of older stroke patients were explored. Cox regression models were used to estimate the relative risk and 95% confidence intervals (CI) in the database entries of 636 older stroke patients aged 70 years and over. National Institutes of Health Stroke Scale (NIHSS) score on admission, age and coronary heart disease were significantly associated with 28-day death. The hazard ratios for the predictors of long-term mortality were as follows: NIHSS score, 1.1 (95% CI: 1.07-1.1); serum glucose level, 1.08 (95% CI: 1.01-1.2); serum triglyceride level, 0.6 (95% CI: 0.4-0.8); age, 1.04 (95% CI: 1.01-1.08); and coronary heart disease, 2.7 (95% CI: 1.4-5.4). NIHSS score on admission, age and coronary heart disease are independent predictors of short- and long-term mortality. Higher glucose and lower triglyceride level are significantly associated with the long-term mortality. © 2013 The Authors. Australasian Journal on Ageing © 2013 ACOTA.

The Short-term Prognostic Value of the Triglyceride-to-high-density Lipoprotein Cholesterol Ratio in Acute Ischemic Stroke

PubMed Central

Wang, Huan; Lei, Leix; Zhang, Han-Qing; Gu, Zheng-Tian; Xing, Fang-Lan; Yan, Fu-Ling

2018-01-01

The triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) is a simple approach to predicting unfavorable outcomes in cardiovascular disease. The influence of TG/HDL-C on acute ischemic stroke remains elusive. The purpose of this study was to investigate the precise effect of TG/HDL-C on 3-month mortality after acute ischemic stroke (AIS). Patients with AIS were enrolled in the present study from 2011 to 2017. A total of 1459 participants from a single city in China were divided into retrospective training and prospective test cohorts. Medical records were collected periodically to determine the incidence of fatal events. All participants were followed for 3 months. Optimal cutoff values were determined using X-tile software to separate the training cohort patients into higher and lower survival groups based on their lipid levels. A survival analysis was conducted using Kaplan-Meier curves and a Cox proportional hazards regression model. A total of 1459 patients with AIS (median age 68.5 years, 58.5% male) were analyzed. Univariate Cox regression analysis confirmed that TG/HDL-C was a significant prognostic factor for 3-month survival. X-tile identified 0.9 as an optimal cutoff for TG/HDL-C. In the univariate analysis, the prognosis of the TG/HDL-C >0.9 group was markedly superior to that of TG/HDL-C ≤0.9 group (P<0.001). A multivariate Cox regression analysis showed that TG/HDL-C was independently correlated with a reduced risk of mortality (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.62; P<0.001). These results were confirmed in the 453 patients in the test cohort. A nomogram was constructed to predict 3-month case-fatality, and the c-indexes of predictive accuracy were 0.684 and 0.670 in the training and test cohorts, respectively (P<0.01). The serum TG/HDL-C ratio may be useful for predicting short-term mortality after AIS. PMID:29896437

The Short-term Prognostic Value of the Triglyceride-to-high-density Lipoprotein Cholesterol Ratio in Acute Ischemic Stroke.

PubMed

Deng, Qi-Wen; Li, Shuo; Wang, Huan; Lei, Leix; Zhang, Han-Qing; Gu, Zheng-Tian; Xing, Fang-Lan; Yan, Fu-Ling

2018-06-01

The triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) is a simple approach to predicting unfavorable outcomes in cardiovascular disease. The influence of TG/HDL-C on acute ischemic stroke remains elusive. The purpose of this study was to investigate the precise effect of TG/HDL-C on 3-month mortality after acute ischemic stroke (AIS). Patients with AIS were enrolled in the present study from 2011 to 2017. A total of 1459 participants from a single city in China were divided into retrospective training and prospective test cohorts. Medical records were collected periodically to determine the incidence of fatal events. All participants were followed for 3 months. Optimal cutoff values were determined using X-tile software to separate the training cohort patients into higher and lower survival groups based on their lipid levels. A survival analysis was conducted using Kaplan-Meier curves and a Cox proportional hazards regression model. A total of 1459 patients with AIS (median age 68.5 years, 58.5% male) were analyzed. Univariate Cox regression analysis confirmed that TG/HDL-C was a significant prognostic factor for 3-month survival. X-tile identified 0.9 as an optimal cutoff for TG/HDL-C. In the univariate analysis, the prognosis of the TG/HDL-C >0.9 group was markedly superior to that of TG/HDL-C ≤0.9 group (P<0.001). A multivariate Cox regression analysis showed that TG/HDL-C was independently correlated with a reduced risk of mortality (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.62; P<0.001). These results were confirmed in the 453 patients in the test cohort. A nomogram was constructed to predict 3-month case-fatality, and the c-indexes of predictive accuracy were 0.684 and 0.670 in the training and test cohorts, respectively (P<0.01). The serum TG/HDL-C ratio may be useful for predicting short-term mortality after AIS.

Comparative risk of ischemic stroke among users of clopidogrel together with individual proton pump inhibitors.

PubMed

Leonard, Charles E; Bilker, Warren B; Brensinger, Colleen M; Flockhart, David A; Freeman, Cristin P; Kasner, Scott E; Kimmel, Stephen E; Hennessy, Sean

2015-03-01

There is controversy and little information about whether individual proton pump inhibitors (PPIs) differentially alter the effectiveness of clopidogrel in reducing ischemic stroke risk. We, therefore, aimed to elucidate the risk of ischemic stroke among concomitant users of clopidogrel and individual PPIs. We conducted a propensity score-adjusted cohort study of adult new users of clopidogrel, using 1999 to 2009 Medicaid claims from 5 large states. Exposures were defined by prescriptions for esomeprazole, lansoprazole, omeprazole, rabeprazole, and pantoprazole-with pantoprazole serving as the referent. The end point was hospitalization for acute ischemic stroke, defined by International Classification of Diseases Ninth Revision Clinical Modification codes in the principal position on inpatient claims, within 180 days of concomitant therapy initiation. Among 325 559 concomitant users of clopidogrel and a PPI, we identified 1667 ischemic strokes for an annual incidence of 2.4% (95% confidence interval, 2.3-2.5). Adjusted hazard ratios for ischemic stroke versus pantoprazole were 0.98 (0.82-1.17) for esomeprazole; 1.06 (0.92-1.21) for lansoprazole; 0.98 (0.85-1.15) for omeprazole; and 0.85 (0.63-1.13) for rabeprazole. PPIs of interest did not increase the rate of ischemic stroke among clopidogrel users when compared with pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel. © 2015 American Heart Association, Inc.

Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study.

PubMed

Patorno, Elisabetta; Goldfine, Allison B; Schneeweiss, Sebastian; Everett, Brendan M; Glynn, Robert J; Liu, Jun; Kim, Seoyoung C

2018-02-06

To evaluate the cardiovascular safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus, in direct comparisons with DPP-4 inhibitors (DPP-4i), GLP-1 receptor agonists (GLP-1RA), or sulfonylureas, as used in routine practice. Population based retrospective cohort study. Nationwide sample of patients with type 2 diabetes from a large de-identified US commercial healthcare database (Optum Clinformatics Datamart). Three pairwise 1:1 propensity score matched cohorts of patients with type 2 diabetes 18 years and older who initiated canagliflozin or a comparator non-gliflozin antidiabetic agent (ie, a DPP-4i, a GLP-1RA, or a sulfonylurea) between April 2013 and September 2015. The primary outcomes were heart failure admission to hospital and a composite cardiovascular endpoint (comprised of being admitted to hospital for acute myocardial infarction, ischemic stroke, or hemorrhagic stroke). Hazard ratios and 95% confidence intervals were estimated in each propensity score matched cohort controlling for more than 100 baseline characteristics. During a 30 month period, the hazard ratio for heart failure admission to hospital associated with canagliflozin was 0.70 (95% confidence interval 0.54 to 0.92) versus a DPP-4i (n=17 667 pairs), 0.61 (0.47 to 0.78) versus a GLP-1RA (20 539), and 0.51 (0.38 to 0.67) versus a sulfonylurea (17 354 ). The hazard ratio for the composite cardiovascular endpoint associated with canagliflozin was 0.89 (0.68 to 1.17) versus a DPP-4i, 1.03 (0.79 to 1.35) versus a GLP-1RA, and 0.86 (0.65 to 1.13) versus a sulfonylurea. Results were similar in sensitivity analyses further adjusting for baseline hemoglobin A1c levels and in subgroups of patients with and without prior cardiovascular disease or heart failure. In this large cohort study, canagliflozin was associated with a lower risk of heart failure admission to hospital and with a similar risk of myocardial infarction or stroke in direct comparisons with three different classes of non-gliflozin diabetes treatment alternatives as used in routine care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Embolic Strokes of Undetermined Source in the Athens Stroke Registry: An Outcome Analysis.

PubMed

Ntaios, George; Papavasileiou, Vasileios; Milionis, Haralampos; Makaritsis, Konstantinos; Vemmou, Anastasia; Koroboki, Eleni; Manios, Efstathios; Spengos, Konstantinos; Michel, Patrik; Vemmos, Konstantinos

2015-08-01

Information about outcomes in Embolic Stroke of Undetermined Source (ESUS) patients is unavailable. This study provides a detailed analysis of outcomes of a large ESUS population. Data set was derived from the Athens Stroke Registry. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group criteria. End points were mortality, stroke recurrence, functional outcome, and a composite cardiovascular end point comprising recurrent stroke, myocardial infarction, aortic aneurysm rupture, systemic embolism, or sudden cardiac death. We performed Kaplan-Meier analyses to estimate cumulative probabilities of outcomes by stroke type and Cox-regression to investigate whether stroke type was outcome predictor. 2731 patients were followed-up for a mean of 30.5±24.1months. There were 73 (26.5%) deaths, 60 (21.8%) recurrences, and 78 (28.4%) composite cardiovascular end points in the 275 ESUS patients. The cumulative probability of survival in ESUS was 65.6% (95% confidence intervals [CI], 58.9%-72.2%), significantly higher compared with cardioembolic stroke (38.8%, 95% CI, 34.9%-42.7%). The cumulative probability of stroke recurrence in ESUS was 29.0% (95% CI, 22.3%-35.7%), similar to cardioembolic strokes (26.8%, 95% CI, 22.1%-31.5%), but significantly higher compared with all types of noncardioembolic stroke. One hundred seventy-two (62.5%) ESUS patients had favorable functional outcome compared with 280 (32.2%) in cardioembolic and 303 (60.9%) in large-artery atherosclerotic. ESUS patients had similar risk of composite cardiovascular end point as all other stroke types, with the exception of lacunar strokes, which had significantly lower risk (adjusted hazard ratio, 0.70 [95% CI, 0.52-0.94]). Long-term mortality risk in ESUS is lower compared with cardioembolic strokes, despite similar rates of recurrence and composite cardiovascular end point. Recurrent stroke risk is higher in ESUS than in noncardioembolic strokes. © 2015 American Heart Association, Inc.

Association Between Markers of Inflammation and Total Stroke by Hypertensive Status Among Women

PubMed Central

Rexrode, Kathryn M.; Kotler, Gregory; Everett, Brendan M.; Glynn, Robert J.; Lee, I-Min; Buring, Julie E.; Ridker, Paul M.; Sesso, Howard D.

2016-01-01

BACKGROUND Markers of systemic inflammation (high-sensitivity C-reactive protein [hsCRP], soluble intercellular adhesion molecule 1 [sICAM-1], and fibrinogen) have been associated with a greater risk of total and ischemic stroke, in addition to elevated blood pressure. However, the role of these inflammatory markers on stroke pathophysiology by hypertension status is uncertain. METHODS Blood samples were collected and assayed for hsCRP, sICAM-1, and fibrinogen among 27,330 initially healthy women from the Women’s Health Study, and women were followed up from 1992 to 2013. Prior to randomization, the baseline questionnaire collected self-reported hypertension status, cardiovascular risk factors, and lifestyle factors. New cases of total, ischemic, and hemorrhagic stroke were updated annually through questionnaires and confirmed by medical records according to the National Survey of Stroke criteria. Multivariable Cox models estimated overall associations between each inflammatory marker and stroke and separately stratified by hypertension status. RESULTS We observed 629 incident total strokes over 477,278 person-years. In adjusted analyses, extreme quartiles of hsCRP and sICAM-1 were each associated with a significantly greater risk of total stroke (hsCRP: hazard ratios [HR] = 1.77, 95% confidence interval [CI]: 1.39–2.26; sICAM-1: HR = 1.28, 95% CI: 1.00–1.63). Fibrinogen was not associated with a significantly greater stroke risk. In analyses stratified by hypertension status, elevated hsCRP was associated with a nonstatistically significant greater risk of total stroke among prehypertensive and hypertensive women. CONCLUSIONS These data indicate that hsCRP and sICAM-1 are associated with hypertension status and stroke risk among women. Further work should examine the role of inflammatory markers on ischemic stroke subtypes and clarify mechanisms. PMID:27235695

Silent Brain Infarction and Risk of Future Stroke: A Systematic Review and Meta-Analysis

PubMed Central

Gupta, Ajay; Giambrone, Ashley E.; Gialdini, Gino; Finn, Caitlin; Delgado, Diana; Gutierrez, Jose; Wright, Clinton; Beiser, Alexa S.; Seshadri, Sudha; Pandya, Ankur; Kamel, Hooman

2016-01-01

Background and Purpose Silent brain infarction (SBI) on magnetic resonance imaging (MRI) has been proposed as a subclinical risk marker for future symptomatic stroke. We performed a systematic review and meta-analysis to summarize the association between MRI-defined SBI and future stroke risk. Methods We searched the medical literature to identify cohort studies involving adults with MRI detection of SBI who were subsequently followed for incident clinically-defined stroke. Study data and quality assessment were recorded in duplicate with disagreements in data extraction resolved by a third reader. Strength association between MRI detected SBI and future symptomatic stroke measured by a hazard ratio (HR). Results The meta-analysis included 13 studies (14,764 subjects) with a mean follow-up ranging from 25.7 to 174 months. SBI predicted the occurrence of stroke with a random effects crude relative risk of 2.94 (95% CI 2.24–3.86, P<0.001; Q=39.65, P<0.001). In the eight studies of 10,427 subjects providing HR adjusted for cardiovascular risk factors, SBI was an independent predictor of incident stroke (HR 2.08 [95% CI 1.69–2.56, P<0.001]; Q=8.99, P=0.25). In a subgroup analysis pooling 9,483 stroke-free individuals from large population-based studies, SBI was present in ~18% of participants and remained a strong predictor of future stroke (HR 2.06 [95% CI 1.64–2.59], p<0.01). Conclusions SBI is present in approximately one in five stroke-free older adults and is associated with a 2-fold increased risk of future stroke. Future studies of in-depth stroke risk evaluations and intensive prevention measures are warranted in patients with clinically unrecognized radiologically evident brain infarctions. PMID:26888534

Acute-Phase Blood Pressure Levels Correlate With a High Risk of Recurrent Strokes in Young-Onset Ischemic Stroke.

PubMed

Mustanoja, Satu; Putaala, Jukka; Gordin, Daniel; Tulkki, Lauri; Aarnio, Karoliina; Pirinen, Jani; Surakka, Ida; Sinisalo, Juha; Lehto, Mika; Tatlisumak, Turgut

2016-06-01

High blood pressure (BP) in acute stroke has been associated with a poor outcome; however, this has not been evaluated in young adults. The relationship between BP and long-term outcome was assessed in 1004 consecutive young, first-ever ischemic stroke patients aged 15 to 49 years enrolled in the Helsinki Young Stroke Registry. BP parameters included systolic (SBP) and diastolic BP, pulse pressure, and mean arterial pressure at admission and 24 hours. The primary outcome measure was recurrent stroke in the long-term follow-up. Adjusted for demographics and preexisting comorbidities, Cox regression models were used to assess independent BP parameters associated with outcome. Of our patients (63% male), 393 patients (39%) had prestroke hypertension and 358 (36%) used antihypertensive treatment. The median follow-up period was 8.9 years (interquartile range 5.7-13.2). Patients with a recurrent stroke (n=142, 14%) had significantly higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure (P<0.001) and 24-h SBP, diastolic BP, and mean arterial pressure compared with patients without the recurrent stroke. Patients with SBP ≥160 mm Hg compared with those with SBP <160 mm Hg had significantly more recurrent strokes (hazard ratio 3.3 [95% confidence interval, 2.05-4.55]; P<0.001) occurring earlier (13.9 years [13.0-14.6] versus 16.2 [15.8-16.6]; P<0.001) within the follow-up period. In multivariable analyses, higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure were independently associated with the risk of recurrent stroke, while the 24-hour BP levels were not. In young ischemic stroke patients, high acute phase BP levels are independently associated with a high risk of recurrent strokes. © 2016 American Heart Association, Inc.

Population-based study of blood biomarkers in prediction of sub-acute recurrent stroke

PubMed Central

Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Silver, Louise E; Rothwell, Peter M

2017-01-01

Background and purpose Risk of recurrent stroke is high in the first few weeks after TIA or stroke and clinic risk prediction tools have only limited accuracy, particularly after the hyper-acute phase. Previous studies of the predictive value of biomarkers have been small, been done in selected populations and have not concentrated on the acute phase or on intensively treated populations. We aimed to determine the predictive value of a panel of blood biomarkers in intensively treated patients early after TIA and stroke. Methods We studied 14 blood biomarkers related to inflammation, thrombosis, atherogenesis and cardiac or neuronal cell damage in early TIA or ischaemic stroke in a population-based study (Oxford Vascular Study). Biomarker levels were related to 90-day risk of recurrent stroke as Hazard Ratio (95%CI) per decile increase, adjusted for age and sex. Results Among 1292 eligible patients there were 53 recurrent ischaemic strokes within 90 days. There were moderate correlations (r>0.40; p<0001) between the inflammatory biomarkers and between the cell damage and thrombotic subsets. However, associations with risk of early recurrent stroke were weak, with significant associations limited to Interleukin-6 (HR=1.12, 1.01-1.24; p=0.035) and C-reactive protein (1.16, 1.02-1.30; p=0.019). When stratified by type of presenting event, P-selectin predicted stroke after TIA (1.31, 1.03-1.66; p=0.028) and C-reactive protein predicted stroke after stroke (1.16, 1.01-1.34; p=0.042). These associations remained after fully adjusting for other vascular risk factors. Conclusion In the largest study to date, we found very limited predictive utility for early recurrent stroke for a panel of inflammatory, thrombotic and cell damage biomarkers. PMID:25158774

Allopurinol use and the risk of acute cardiovascular events in patients with gout and diabetes.

PubMed

Singh, Jasvinder A; Ramachandaran, Rekha; Yu, Shaohua; Curtis, Jeffrey R

2017-03-14

Few studies, if any, have examined cardiovascular outcomes in patients with diabetes and gout. Both diabetes and gout are risk factors for cardiovascular disease. The objective of this study was to examine the effect of allopurinol on the risk of incident acute cardiovascular events in patients with gout and diabetes. We used the 2007-2010 Multi-Payer Claims Database (MPCD) that linked health plan data from national commercial and governmental insurances, representing beneficiaries with United Healthcare, Medicare, or Medicaid coverage. In patients with gout and diabetes, we assessed the current allopurinol use, defined as a new filled prescription for allopurinol, as the main predictor of interest. Our outcome of interest was the occurrence of the first Incident hospitalized myocardial infarction (MI) or stroke (composite acute cardiovascular event), after which observations were censored. We employed multivariable-adjusted Cox proportional hazards models that simultaneously adjusted for patient demographics, cardiovascular risk factors and other medical comorbidities. We calculated hazard ratios [HR] (95% confidence intervals [CI]) for incident composite (MI or stroke) acute cardiovascular events. We performed sensitivity analyses that additionally adjusted for the presence of immune diseases and colchicine use, as potential confounders. There were 2,053,185 person days (5621.3 person years) of current allopurinol use and 1,671,583 person days (4576.5 person years) of prior allopurinol use. There were 158 incident MIs or strokes in current and 151 in prior allopurinol users, respectively. Compared to previous allopurinol users, current allopurinol users had significantly lower adjusted hazard of incident acute cardiovascular events (incident stroke or MI), with an HR of 0.67 (95% CI, 0.53, 0.84). Sensitivity analyses, additionally adjusted for immune diseases or colchicine use, confirmed this association. Current allopurinol use protected against the occurrence of acute cardiovascular events in patients with gout and diabetes. The underlying mechanisms for this potential cardio-protective effect of allopurinol need further exploration.

Accelerated death rate in population-based cohort of persons with traumatic brain injury.

PubMed

Selassie, Anbesaw W; Cao, Yue; Church, Elizabeth C; Saunders, Lee L; Krause, James

2014-01-01

To determine the influence of preexisting heart, liver, kidney, cancer, stroke, and mental health problems and examine the influence of low socioeconomic status on mortality after discharge from acute care facilities for individuals with traumatic brain injury. Population-based retrospective cohort study of 33695 persons discharged from acute care hospital with traumatic brain injury in South Carolina, 1999-2010. Days elapsing from the dates of injury to death established the survival time (T). Data were censored at the 145th month. Multivariable Cox regression was used to examine the independent effect of the variables on death. Age-adjusted cumulative probability of death for each chronic disease of interest was plotted. By the 70th month of follow-up, rate of death was accelerated from 10-fold for heart diseases to 2.5-fold for mental health problems. Adjusted hazard ratios for diseases of the heart (2.13), liver-renal (3.25), cancer (2.64), neurological diseases and stroke (2.07), diabetes (1.89), hypertension (1.43), and mental health problems (1.59) were highly significant (each with P < .001). Compared with persons with private insurance, the hazard ratio was significantly elevated with Medicaid (1.67), Medicare (1.54), and uninsured (1.27) (each with P < .001). Specific chronic diseases strongly influenced postdischarge mortality after traumatic brain injury. Low socioeconomic status as measured by the type of insurance elevated the risk of death.

Nocturnal periodic limb movements decrease antioxidant capacity in post-stroke women.

PubMed

Chen, C-Y; Yu, C-C; Chen, C-L

2016-04-01

Considerable evidence suggests that periodic limb movements during sleep (PLMS) are associated with cardiovascular risk and poor stroke outcome. However, the pathogenesis for this association in stroke patients remains largely unknown. This cross-sectional study enrolled 112 consecutive patients who were admitted to rehabilitation ward due to ischemic stroke. Polysomnography and laboratory tests for oxidative stress and inflammatory biomarkers including C-reactive protein, interleukin 6, total antioxidant capacity (TAC), and urinary 8-hydroxy-2-deoxyguanosine were conducted. Patients were stratified into three categories according to their PLMS index. Patients in the PLMS index ≥15 group were significantly older (P = 0.011), presented a significantly higher National Institute of Health Stroke Scale at stroke onset (P = 0.032), and lower Barthel index (P = 0.035) than patients in the PLMS index <5 group. The level of TAC differed significantly (P = 0.018) among the three groups. Multivariate linear regression analyses show that the PLMS index was negatively and independently correlated with TAC (P = 0.024) in women. Besides, multivariate logistic regression analyses also reveal that patients with a PLMS index ≥15 compared with the referent PLMS index <5 had a 7.58-fold increased relative hazard for stroke recurrence (odds ratio 7.58, [1.31-43.88], P = 0.024). This study suggests that PLMS was independently associated with decreased antioxidant capacity in women with ischemic stroke. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association between the volume of inpatient rehabilitation therapy and the risk of all-cause and cardiovascular mortality in patients with ischemic stroke.

PubMed

Hu, Gwo-Chi; Hsu, Chia-Yu; Yu, Hui-Kung; Chen, Jiann-Perng; Chang, Yu-Ju; Chien, Kuo-Liong

2014-02-01

To investigate the relationship between the volume of inpatient rehabilitation therapy and mortality among patients with acute ischemic stroke, as well as to assess whether the association varies with respect to stroke severity. A retrospective study with a cohort of consecutive patients who had acute ischemic stroke between January 1, 2008, and June 30, 2009. Referral medical center. Adults with acute ischemic stroke (N=1277) who were admitted to a tertiary hospital. Not applicable. Stroke-related mortality. During the median follow-up period of 12.3 months (ranging from January 1, 2008, to December 31, 2009), 163 deaths occurred. Greater volume of rehabilitation therapy was associated with a reduced risk of all-cause and cardiovascular mortality (P for trend <.001 for both). Compared with the first tertile, the third tertile of rehabilitation volume was associated with a 55% lower risk of all-cause mortality (hazard ratio [HR]=.45; 95% confidence interval [CI], .30-.65) and a 50% lower risk of cardiovascular mortality (HR=.50; 95% CI, .31-.82). The association did not vary with respect to stroke severity (P for interaction = .45 and .73 for all-cause and cardiovascular mortality, respectively). The volume of inpatient rehabilitation therapy and mortality were significantly inversely related in the patients with ischemic stroke. Thus, further programs aimed at promoting greater use of rehabilitation services are warranted. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Five-year outcomes in patients with left main disease treated with either percutaneous coronary intervention or coronary artery bypass grafting in the synergy between percutaneous coronary intervention with taxus and cardiac surgery trial.

PubMed

Morice, Marie-Claude; Serruys, Patrick W; Kappetein, A Pieter; Feldman, Ted E; Ståhle, Elisabeth; Colombo, Antonio; Mack, Michael J; Holmes, David R; Choi, James W; Ruzyllo, Witold; Religa, Grzegorz; Huang, Jian; Roy, Kristine; Dawkins, Keith D; Mohr, Friedrich

2014-06-10

Current guidelines recommend coronary artery bypass graft surgery (CABG) when treating significant de novo left main coronary artery (LM) stenosis; however, percutaneous coronary intervention (PCI) has a class IIa indication for unprotected LM disease in selected patients. This analysis compares 5-year clinical outcomes in PCI- and CABG-treated LM patients in the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) trial, the largest trial in this group to date. The SYNTAX trial randomly assigned 1800 patients with LM or 3-vessel disease to receive either PCI (with TAXUS Express paclitaxel-eluting stents) or CABG. The unprotected LM cohort (N=705) was predefined and powered. Major adverse cardiac and cerebrovascular event rates at 5 years was 36.9% in PCI patients and 31.0% in CABG patients (hazard ratio, 1.23 [95% confidence interval, 0.95-1.59]; P=0.12). Mortality rate was 12.8% and 14.6% in PCI and CABG patients, respectively (hazard ratio, 0.88 [95% confidence interval, 0.58-1.32]; P=0.53). Stroke was significantly increased in the CABG group (PCI 1.5% versus CABG 4.3%; hazard ratio, 0.33 [95% confidence interval, 0.12-0.92]; P=0.03) and repeat revascularization in the PCI arm (26.7% versus 15.5%; hazard ratio, 1.82 [95% confidence interval, 1.28-2.57]; P<0.01). Major adverse cardiac and cerebrovascular events were similar between arms in patients with low/intermediate SYNTAX scores but significantly increased in PCI patients with high scores (≥33). At 5 years, no difference in overall major adverse cardiac and cerebrovascular events was found between treatment groups. PCI-treated patients had a lower stroke but a higher revascularization rate versus CABG. These results suggest that both treatments are valid options for LM patients. The extent of disease should accounted for when choosing between surgery and PCI, because patients with high SYNTAX scores seem to benefit more from surgery compared with those in the lower tertiles. http://www.clinicaltrials.gov. Unique identifier: NCT00114972. © 2014 American Heart Association, Inc.

Admission Low Magnesium Level Is Associated with In-Hospital Mortality in Acute Ischemic Stroke Patients.

PubMed

You, Shoujiang; Zhong, Chongke; Du, Huaping; Zhang, Yu; Zheng, Danni; Wang, Xia; Qiu, Chenhong; Zhao, Hongru; Cao, Yongjun; Liu, Chun-Feng

2017-01-01

Low magnesium levels are associated with an elevated risk of stroke. In this study, we investigated the association between magnesium levels on hospital admission and in-hospital mortality in acute ischemic stroke (AIS) patients. A total of 2,485 AIS patients, enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city, were included in this study. The patients were divided into 4 groups according to their level of admission magnesium: Q1 (<0.82 mmol/L), Q2 (0.82-0.89 mmol/L), Q3 (0.89-0.98 mmol/L), and Q4 (≥0.98 mmol/L). Cox proportional hazard model was used to estimate the effect of magnesium on all-cause in-hospital mortality in AIS patients. During hospitalization, 92 patients (3.7%) died from all causes. The lowest serum magnesium level (Q1) was associated with a 2.66-fold increase in the risk of in-hospital mortality in comparison to Q4 (hazard ratio [HR] 2.66; 95% CI 1.55-4.56; p-trend < 0.001). After adjusting for age, sex, time from onset to hospital admission, baseline National Institutes of Health Stroke Scale score, and other potential covariates, HR for Q1 was 2.03 (95% CI 1.11-3.70; p-trend = 0.014). Sensitivity and subgroup analyses further confirmed a significant association between lower magnesium levels and a high risk of in-hospital mortality. Decreased serum magnesium levels at admission were independently associated with in-hospital mortality in AIS patients. © 2017 S. Karger AG, Basel.

Beyond Volume: Hospital-Based Healthcare Technology for Better Outcomes in Cerebrovascular Surgical Patients Diagnosed With Ischemic Stroke: A Population-Based Nationwide Cohort Study From 2002 to 2013.

PubMed

Kim, Jae-Hyun; Park, Eun-Cheol; Lee, Sang Gyu; Lee, Tae-Hyun; Jang, Sung-In

2016-03-01

We examined whether the level of hospital-based healthcare technology was related to the 30-day postoperative mortality rates, after adjusting for hospital volume, of ischemic stroke patients who underwent a cerebrovascular surgical procedure. Using the National Health Insurance Service-Cohort Sample Database, we reviewed records from 2002 to 2013 for data on patients with ischemic stroke who underwent cerebrovascular surgical procedures. Statistical analysis was performed using Cox proportional hazard models to test our hypothesis. A total of 798 subjects were included in our study. After adjusting for hospital volume of cerebrovascular surgical procedures as well as all for other potential confounders, the hazard ratio (HR) of 30-day mortality in low healthcare technology hospitals as compared to high healthcare technology hospitals was 2.583 (P < 0.001). We also found that, although the HR of 30-day mortality in low healthcare technology hospitals with high volume as compared to high healthcare technology hospitals with high volume was the highest (10.014, P < 0.0001), cerebrovascular surgical procedure patients treated in low healthcare technology hospitals had the highest 30-day mortality rate, irrespective of hospital volume. Although results of our study provide scientific evidence for a hospital volume/30-day mortality rate relationship in ischemic stroke patients who underwent cerebrovascular surgical procedures, our results also suggest that the level of hospital-based healthcare technology is associated with mortality rates independent of hospital volume. Given these results, further research into what components of hospital-based healthcare technology significantly impact mortality is warranted.

Risk of Suicide Attempt in Poststroke Patients: A Population-Based Cohort Study.

PubMed

Harnod, Tomor; Lin, Cheng-Li; Kao, Chia-Hung

2018-01-10

This nationwide population-based cohort study evaluated the risk of and risk factors for suicide attempt in poststroke patients in Taiwan. The poststroke and nonstroke cohorts consisted of 713 690 patients and 1 426 009 controls, respectively. Adults (aged >18 years) who received new stroke diagnoses according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM ; codes 430-438) between 2000 and 2011 were included in the poststroke cohort. We calculated the adjusted hazard ratio for suicide attempt ( ICD-9-CM codes E950-E959) after adjustment for age, sex, monthly income, urbanization level, occupation category, and various comorbidities. Kaplan-Meier analysis was used to measure the cumulative incidence of suicide attempt, and the Fine and Gray method was used as a competing event when estimating death subhazard ratios and 95% confidence intervals between groups. The cumulative incidence of suicide attempt was higher in the poststroke cohort, and the adjusted hazard ratio of suicide attempt was 2.20 (95% confidence interval, 2.04-2.37) compared with that of the controls. The leading risk factors for poststroke suicide attempt were earning low monthly income (<660 US dollars), living in less urbanized regions, doing manual labor, and having a stroke before age 50 years. The attempted suicide risk did not differ significantly between male and female patients in this study. These results convey crucial information to clinicians and governments for preventing suicide attempt in poststroke patients in Taiwan and other Asian countries. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

A Gender-Stratified Comparative Analysis of Various Definitions of Metabolic Syndrome and Cardiovascular Risk in a Multiethnic U.S. Population

PubMed Central

Hari, Pawan; Nerusu, Kamalakar; Veeranna, Vikas; Sudhakar, Rajeev; Zalawadiya, Sandip; Ramesh, Krithi

2012-01-01

Abstract Introduction We sought to evaluate the ability of various metabolic syndrome definitions in predicting primary cardiovascular disease (CVD) outcomes in a vast multiethnic U.S. cohort. Methods This study included 6,814 self-identified men and women aged 45–84 years enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. Gender-stratified analyses were performed to calculate hazard ratios of CVD, stroke, and mortality associated with various metabolic syndrome definitions and their individual constructs. Results The hazard ratios [95% confidence interval (CI)] for all-cause CVD in men were 2.90 (2.18–3.85), 2.64 (1.98–3.51), 2.16 (1.62–2.88), 2.56 (1.91–3.44), 1.82 (1.35–2.46), and 2.92 (2.15–3.95) for the National Cholesterol Education Program (NCEP), American Heart Association (AHA), World Health Organization (WHO), International Diabetes Federation (IDF), European Group for the Study of Insulin Resistance (EGIR), and the newly defined consensus criteria. Hazard ratios in women were 2.11 (1.41–3.15), 2.17 (1.45–3.27), 2.04 (1.37–3.06), 1.91 (1.27–2.88), 1.85 (1.23–2.79), and 2.08 (1.37–3.14), respectively. Metabolic syndrome was strongly associated with stroke risk only in males. In men, all constitutive metabolic syndrome components were continuously and strongly associated with CVD. In women, high-density lipoprotein and triglycerides did not appear to be associated with short term CVD risk. Conclusion We found the newly defined consensus criteria for metabolic syndrome to be similarly predictive of cardiovascular events when compared to existing definitions. Significant gender differences exist in the association between metabolic syndrome, its individual components, and CVD. PMID:21999397

Body-Weight Fluctuations and Outcomes in Coronary Disease.

PubMed

Bangalore, Sripal; Fayyad, Rana; Laskey, Rachel; DeMicco, David A; Messerli, Franz H; Waters, David D

2017-04-06

Body-weight fluctuation is a risk factor for death and coronary events in patients without cardiovascular disease. It is not known whether variability in body weight affects outcomes in patients with coronary artery disease. We determined intraindividual fluctuations in body weight from baseline weight and follow-up visits and performed a post hoc analysis of the Treating to New Targets trial, which involved assessment of the efficacy and safety of lowering low-density lipoprotein cholesterol levels with atorvastatin. The primary outcome was any coronary event (a composite of death from coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, revascularization, or angina). Secondary outcomes were any cardiovascular event (a composite of any coronary event, a cerebrovascular event, peripheral vascular disease, or heart failure), death, myocardial infarction, or stroke. Among 9509 participants, after adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body-weight variability (measured according to average successive variability and used as a time-dependent covariate) was associated with an increase in the risk of any coronary event (2091 events; hazard ratio, 1.04; 95% confidence interval [CI], 1.01 to 1.07; P=0.01), any cardiovascular event (2727 events; hazard ratio, 1.04; 95% CI, 1.02 to 1.07; P<0.001), and death (487 events; hazard ratio,1.09; 95% CI, 1.07 to 1.12; P<0.001). Among patients in the quintile with the highest variation in body weight, the risk of a coronary event was 64% higher, the risk of a cardiovascular event 85% higher, death 124% higher, myocardial infarction 117% higher, and stroke 136% higher than it was among those in the quintile with the lowest variation in body weight in adjusted models. Among participants with coronary artery disease, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events independent of traditional cardiovascular risk factors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00327691 .).

Prediction of cardiovascular outcome by estimated glomerular filtration rate and estimated creatinine clearance in the high-risk hypertension population of the VALUE trial.

PubMed

Ruilope, Luis M; Zanchetti, Alberto; Julius, Stevo; McInnes, Gordon T; Segura, Julian; Stolt, Pelle; Hua, Tsushung A; Weber, Michael A; Jamerson, Ken

2007-07-01

Reduced renal function is predictive of poor cardiovascular outcomes but the predictive value of different measures of renal function is uncertain. We compared the value of estimated creatinine clearance, using the Cockcroft-Gault formula, with that of estimated glomerular filtration rate (GFR), using the Modification of Diet in Renal Disease (MDRD) formula, as predictors of cardiovascular outcome in 15 245 high-risk hypertensive participants in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. For the primary end-point, the three secondary end-points and for all-cause death, outcomes were compared for individuals with baseline estimated creatinine clearance and estimated GFR < 60 ml/min and > or = 60 ml/min using hazard ratios and 95% confidence intervals. Coronary heart disease, left ventricular hypertrophy, age, sex and treatment effects were included as covariates in the model. For each end-point considered, the risk in individuals with poor renal function at baseline was greater than in those with better renal function. Estimated creatinine clearance (Cockcroft-Gault) was significantly predictive only of all-cause death [hazard ratio = 1.223, 95% confidence interval (CI) = 1.076-1.390; P = 0.0021] whereas estimated GFR was predictive of all outcomes except stroke. Hazard ratios (95% CIs) for estimated GFR were: primary cardiac end-point, 1.497 (1.332-1.682), P < 0.0001; myocardial infarction, 1.501 (1.254-1.796), P < 0.0001; congestive heart failure, 1.699 (1.435-2.013), P < 0.0001; stroke, 1.152 (0.952-1.394) P = 0.1452; and all-cause death, 1.231 (1.098-1.380), P = 0.0004. These results indicate that estimated glomerular filtration rate calculated with the MDRD formula is more informative than estimated creatinine clearance (Cockcroft-Gault) in the prediction of cardiovascular outcomes.

Darapladib for preventing ischemic events in stable coronary heart disease.

PubMed

White, Harvey D; Held, Claes; Stewart, Ralph; Tarka, Elizabeth; Brown, Rebekkah; Davies, Richard Y; Budaj, Andrzej; Harrington, Robert A; Steg, P Gabriel; Ardissino, Diego; Armstrong, Paul W; Avezum, Alvaro; Aylward, Philip E; Bryce, Alfonso; Chen, Hong; Chen, Ming-Fong; Corbalan, Ramon; Dalby, Anthony J; Danchin, Nicolas; De Winter, Robbert J; Denchev, Stefan; Diaz, Rafael; Elisaf, Moses; Flather, Marcus D; Goudev, Assen R; Granger, Christopher B; Grinfeld, Liliana; Hochman, Judith S; Husted, Steen; Kim, Hyo-Soo; Koenig, Wolfgang; Linhart, Ales; Lonn, Eva; López-Sendón, José; Manolis, Athanasios J; Mohler, Emile R; Nicolau, José C; Pais, Prem; Parkhomenko, Alexander; Pedersen, Terje R; Pella, Daniel; Ramos-Corrales, Marco A; Ruda, Mikhail; Sereg, Mátyás; Siddique, Saulat; Sinnaeve, Peter; Smith, Peter; Sritara, Piyamitr; Swart, Henk P; Sy, Rody G; Teramoto, Tamio; Tse, Hung-Fat; Watson, David; Weaver, W Douglas; Weiss, Robert; Viigimaa, Margus; Vinereanu, Dragos; Zhu, Junren; Cannon, Christopher P; Wallentin, Lars

2014-05-01

Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease.

PubMed

Larsen, Sanne Bøjet; Grove, Erik Lerkevang; Neergaard-Petersen, Søs; Würtz, Morten; Hvas, Anne-Mette; Kristensen, Steen Dalby

2017-08-05

Increased platelet aggregation during antiplatelet therapy may predict cardiovascular events in patients with coronary artery disease. The majority of these patients receive aspirin monotherapy. We aimed to investigate whether high platelet-aggregation levels predict cardiovascular events in stable coronary artery disease patients treated with aspirin. We included 900 stable coronary artery disease patients with either previous myocardial infarction, type 2 diabetes mellitus, or both. All patients received single antithrombotic therapy with 75 mg aspirin daily. Platelet aggregation was evaluated 1 hour after aspirin intake using the VerifyNow Aspirin Assay (Accriva Diagnostics) and Multiplate Analyzer (Roche; agonists: arachidonic acid and collagen). Adherence to aspirin was confirmed by serum thromboxane B 2 . The primary end point was the composite of nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At 3-year follow-up, 78 primary end points were registered. The primary end point did not occur more frequently in patients with high platelet-aggregation levels (first versus fourth quartile) assessed by VerifyNow (hazard ratio: 0.5 [95% CI, 0.3-1.1], P =0.08) or Multiplate using arachidonic acid (hazard ratio: 1.0 [95% CI, 0.5-2.1], P =0.92) or collagen (hazard ratio: 1.4 [95% CI, 0.7-2.8], P =0.38). Similar results were found for the composite secondary end point (nonfatal myocardial infarction, ischemic stroke, stent thrombosis, and all-cause death) and the single end points. Thromboxane B 2 levels did not predict any end points. Renal insufficiency was the only clinical risk factor predicting the primary and secondary end points. This study is the largest to investigate platelet aggregation in stable coronary artery disease patients receiving aspirin as single antithrombotic therapy. We found that high platelet-aggregation levels did not predict cardiovascular events. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Anxiety disorders and risk of stroke: A systematic review and meta-analysis.

PubMed

Pérez-Piñar, M; Ayerbe, L; González, E; Mathur, R; Foguet-Boreu, Q; Ayis, S

2017-03-01

Anxiety disorders are the most common mental health problem worldwide. However, the evidence on the association between anxiety disorders and risk of stroke is limited. This systematic review and meta-analysis presents a critical appraisal and summary of the available evidence on the association between anxiety disorders and risk of stroke. Cohort studies reporting risk of stroke among patients with anxiety disorders were searched in PubMed, Embase, PsycINFO, Scopus, and the Web of Science, from database inception to June 2016. The quality of the studies was assessed using standard criteria. A meta-analysis was undertaken to obtain pooled estimates of the risk of stroke among patients with anxiety disorders. Eight studies, including 950,759 patients, from the 11,764 references initially identified, were included in this review. A significantly increased risk of stroke for patients with anxiety disorders was observed, with an overall hazard ratio: 1.24 (1.09-1.41), P=0.001. No significant heterogeneity between studies was detected and the funnel plot suggested that publication bias was unlikely. Limited evidence suggests that the risk of stroke is increased shortly after the diagnosis of anxiety and that risk of stroke may be higher for patients with severe anxiety. Anxiety disorders are a very prevalent modifiable condition associated with risk of stroke increased by 24%. This evidence could inform the development of interventions for the management of anxiety and the prevention of stroke. Further studies on the risk of stroke in patients with anxiety, and the explanatory factors for this association, are required. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Advanced interatrial block and ischemic stroke: The Atherosclerosis Risk in Communities Study.

PubMed

O'Neal, Wesley T; Kamel, Hooman; Zhang, Zhu-Ming; Chen, Lin Y; Alonso, Alvaro; Soliman, Elsayed Z

2016-07-26

Given that recent reports have suggested left atrial disease to be an independent risk factor for ischemic stroke, we sought to examine if advanced interatrial block (aIAB) is an independent stroke risk factor. We examined the association between aIAB and incident ischemic stroke in 14,716 participants (mean age 54 ± 5.8 years; 55% female; 26% black) from the Atherosclerosis Risk in Communities Study (ARIC). Cases of aIAB were identified from digital ECGs recorded during the baseline ARIC visit (1987-1989) and the first 3 follow-up study visits (1990-1992, 1993-1995, and 1996-1998). Adjudicated ischemic stroke events were ascertained through December 31, 2010. There were 266 (1.8%) participants who had evidence of aIAB. Over a median follow-up of 22 years, 916 (6.2%) ischemic stroke events were detected. The incidence rate (per 1,000 person-years) of ischemic stroke among those with aIAB (incidence rate 8.05, 95% confidence interval [CI] 5.7, 11.4) was more than twice the rate in those without aIAB (incidence rate 3.14, 95% CI 2.94, 3.35). In a multivariable Cox regression analysis adjusted for stroke risk factors and potential confounders, aIAB was associated with an increased risk of ischemic stroke (hazard ratio 1.63, 95% CI 1.13, 2.34). The results were consistent across subgroups of participants stratified by age, sex, and race. In the ARIC, aIAB was associated with incident ischemic stroke, which strengthens the hypothesis that left atrial disease should be considered an independent stroke risk factor. © 2016 American Academy of Neurology.

Revised Framingham Stroke Risk Profile to Reflect Temporal Trends.

PubMed

Dufouil, Carole; Beiser, Alexa; McLure, Leslie A; Wolf, Philip A; Tzourio, Christophe; Howard, Virginia J; Westwood, Andrew J; Himali, Jayandra J; Sullivan, Lisa; Aparicio, Hugo J; Kelly-Hayes, Margaret; Ritchie, Karen; Kase, Carlos S; Pikula, Aleksandra; Romero, Jose R; D'Agostino, Ralph B; Samieri, Cécilia; Vasan, Ramachandran S; Chêne, Genevieve; Howard, George; Seshadri, Sudha

2017-03-21

Age-adjusted stroke incidence has decreased over the past 50 years, likely as a result of changes in the prevalence and impact of various stroke risk factors. An updated version of the Framingham Stroke Risk Profile (FSRP) might better predict current risks in the FHS (Framingham Heart Study) and other cohorts. We compared the accuracy of the standard (old) and of a revised (new) version of the FSRP in predicting the risk of all-stroke and ischemic stroke and validated this new FSRP in 2 external cohorts, the 3C (3 Cities) and REGARDS (Reasons for Geographic and Racial Differences in Stroke) studies. We computed the old FSRP as originally described and a new model that used the most recent epoch-specific risk factor prevalence and hazard ratios for individuals ≥55 years of age and for the subsample ≥65 years of age (to match the age range in REGARDS and 3C studies, respectively) and compared the efficacy of these models in predicting 5- and 10-year stroke risks. The new FSRP was a better predictor of current stroke risks in all 3 samples than the old FSRP (calibration χ 2 of new/old FSRP: in men: 64.0/12.1, 59.4/30.6, and 20.7/12.5; in women: 42.5/4.1, 115.4/90.3, and 9.8/6.5 in FHS, REGARDS, and 3C, respectively). In the REGARDS, the new FSRP was a better predictor among whites compared with blacks. A more contemporaneous, new FSRP better predicts current risks in 3 large community samples and could serve as the basis for examining geographic and racial differences in stroke risk and the incremental diagnostic utility of novel stroke risk factors. © 2017 American Heart Association, Inc.

Stroke Patients with a Past History of Cancer Are at Increased Risk of Recurrent Stroke and Cardiovascular Mortality

PubMed Central

Lau, Kui-Kai; Wong, Yuen-Kwun; Teo, Kay-Cheong; Chang, Richard Shek-Kwan; Hon, Sonny Fong-Kwong; Chan, Koon-Ho; Cheung, Raymond Tak-Fai; Li, Leonard Sheung-Wai; Tse, Hung-Fat; Ho, Shu-Leong; Siu, Chung-Wah

2014-01-01

Background and Purpose Cancer patients are at increased risk of cardiovascular and cerebrovascular events. It is unclear whether cancer confers any additional risk for recurrent stroke or cardiovascular mortality after stroke. Methods This was a single center, observational study of 1,105 consecutive Chinese ischemic stroke patients recruited from a large stroke rehabilitation unit based in Hong Kong. We sought to determine whether patients with cancer are at higher risk of recurrent stroke and cardiovascular mortality. Results Amongst 1,105 patients, 58 patients (5.2%) had cancer, of whom 74% were in remission. After a mean follow-up of 76±18 months, 241 patients developed a recurrent stroke: 22 in patients with cancer (38%, annual incidence 13.94%/year), substantially more than those without cancer (21%, 4.65%/year) (p<0.01). In a Cox regression model, cancer, age and atrial fibrillation were the 3 independent predictors of recurrent stroke with a hazard ratio (HR) of 2.42 (95% confidence interval (CI): 1.54–3.80), 1.01 (1.00–1.03) and 1.35 (1.01–1.82) respectively. Likewise, patients with cancer had a higher cardiovascular mortality compared with those without cancer (4.30%/year vs. 2.35%/year, p = 0.08). In Cox regression analysis, cancer (HR: 2.08, 95% CI: 1.08–4.02), age (HR: 1.04, 95% CI 1.02–1.06), heart failure (HR: 3.06, 95% CI 1.72–5.47) and significant carotid atherosclerosis (HR: 1.55, 95% CI 1.02–2.36) were independent predictors for cardiovascular mortality. Conclusions Stroke patients with a past history of cancer are at increased risk of recurrent stroke and cardiovascular mortality. PMID:24523883

Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study

PubMed Central

Grove, Erik L; Hansen, Peter Riis; Olesen, Jonas B; Ahlehoff, Ole; Selmer, Christian; Lindhardsen, Jesper; Madsen, Jan Kyst; Køber, Lars; Torp-Pedersen, Christian; Gislason, Gunnar H

2011-01-01

Objective To examine the effect of proton pump inhibitors on adverse cardiovascular events in aspirin treated patients with first time myocardial infarction. Design Retrospective nationwide propensity score matched study based on administrative data. Setting All hospitals in Denmark. Participants All aspirin treated patients surviving 30 days after a first myocardial infarction from 1997 to 2006, with follow-up for one year. Patients treated with clopidogrel were excluded. Main outcome measures The risk of the combined end point of cardiovascular death, myocardial infarction, or stroke associated with use of proton pump inhibitors was analysed using Kaplan-Meier analysis, Cox proportional hazard models, and propensity score matched Cox proportional hazard models. Results 3366 of 19 925 (16.9%) aspirin treated patients experienced recurrent myocardial infarction, stroke, or cardiovascular death. The hazard ratio for the combined end point in patients receiving proton pump inhibitors based on the time dependent Cox proportional hazard model was 1.46 (1.33 to 1.61; P<0.001) and for the propensity score matched model based on 8318 patients it was 1.61 (1.45 to 1.79; P<0.001). A sensitivity analysis showed no increase in risk related to use of H2 receptor blockers (1.04, 0.79 to 1.38; P=0.78). Conclusion In aspirin treated patients with first time myocardial infarction, treatment with proton pump inhibitors was associated with an increased risk of adverse cardiovascular events. PMID:21562004

Statin therapy in lower limb peripheral arterial disease: Systematic review and meta-analysis.

PubMed

Antoniou, George A; Fisher, Robert K; Georgiadis, George S; Antoniou, Stavros A; Torella, Francesco

2014-11-01

To investigate and analyse the existing evidence supporting statin therapy in patients with lower limb atherosclerotic arterial disease. A systematic search of electronic information sources was undertaken to identify studies comparing cardiovascular outcomes in patients with lower limb peripheral arterial disease treated with a statin and those not receiving a statin. Estimates were combined applying fixed- or random-effects models. Twelve observational cohort studies and two randomised trials reporting 19,368 patients were selected. Statin therapy was associated with reduced all-cause mortality (odds ratio 0.60, 95% confidence interval 0.46-0.78) and incidence of stroke (odds ratio 0.77, 95% confidence interval 0.67-0.89). A trend towards improved cardiovascular mortality (odds ratio 0.62, 95% confidence interval 0.35-1.11), myocardial infarction (odds ratio 0.62, 95% confidence interval 0.38-1.01), and the composite of death/myocardial infarction/stroke (odds ratio 0.91, 95% confidence interval 0.81-1.03), was identified. Meta-analyses of studies performing adjustments showed decreased all-cause mortality in statin users (hazard ratio 0.77, 95% confidence interval 0.68-0.86). Evidence supporting statins' protective role in patients with lower limb peripheral arterial disease is insufficient. Statin therapy seems to be effective in reducing all-cause mortality and the incidence cerebrovascular events in patients diagnosed with peripheral arterial disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Non-high-density lipoprotein cholesterol vs low-density lipoprotein cholesterol as a risk factor for ischemic stroke: a result from the Kailuan study.

PubMed

Wu, Jianwei; Chen, Shengyun; Liu, Liping; Gao, Xiang; Zhou, Yong; Wang, Chunxue; Zhang, Qian; Wang, Anxin; Hussain, Mohammed; Sun, Baoying; Wu, Shouling; Zhao, Xingquan

2013-06-01

To compare the predictive value of serum low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol levels for ischemic stroke in the Chinese population. We performed a four-year cohort study of 95 778 men and women, aged 18-98 years, selected from the Kailuan study (2006-2007). Baseline LDL cholesterol levels were estimated using direct test method. Total cholesterol levels were estimated using endpoint test method. The predictive values of LDL cholesterol and non-HDL cholesterol for ischemic stroke were compared. During the follow-up period, there were 1153 incident cases of ischemic stroke. The hazard ratio (HR) for ischemic stroke in the top quintile of LDL cholesterol was the highest among five quintiles (HR: 1·25; 95% confidence interval (CI), 1·01-1·53). The HR in the top quintile of non-HDL cholesterol for ischemic stroke was also the highest among five quintiles (HR: 1·53; 95% CI, 1·24-1·88). Analysis of trends showed a significant positive relationship between ischemic stroke incidence and serum LDL cholesterol level, and non-HDL cholesterol level, respectively (both P < 0·05). The area under the curve of LDL cholesterol and non-HDL cholesterol for ischemic stroke was 0·51 and 0·56, respectively (P < 0·05 for the difference). Serum Non-HDL cholesterol level is a stronger predictor for the risk of ischemic stroke than serum LDL cholesterol level in the Chinese population.

Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: Individual-patient-data meta-analysis of randomized trials.

PubMed

Hacke, Werner; Lyden, Patrick; Emberson, Jonathan; Baigent, Colin; Blackwell, Lisa; Albers, Gregory; Bluhmki, Erich; Brott, Thomas; Cohen, Geoffrey; Davis, Stephen M; Donnan, Geoffrey A; Grotta, James C; Howard, George; Kaste, Markku; Koga, Masatoshi; von Kummer, Rüdiger; Lansberg, Maarten G; Lindley, Richard I; Olivot, Jean-Marc; Parsons, Mark; Sandercock, Peter Ag; Toni, Danilo; Toyoda, Kazunori; Wahlgren, Nils; Wardlaw, Joanna M; Whiteley, William N; Del Zoppo, Gregory; Lees, Kennedy R

2018-02-01

Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0-1) at 3-6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0-1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21-1.68 and 1.43, 1.23-1.65, respectively), but not in those outside the age-revised label (1.06, 0.90-1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76-1.25 and 1.01, 0.86-1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99-1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19-2.01 and 1.37, 1.17-1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97-1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77-1.26 and 1.02, 0.87-1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98-1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

PubMed

Bonati, Leo H; Ederle, Jörg; Dobson, Joanna; Engelter, Stefan; Featherstone, Roland L; Gaines, Peter A; Beard, Jonathan D; Venables, Graham S; Markus, Hugh S; Clifton, Andrew; Sandercock, Peter; Brown, Martin M

2014-04-01

The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Validity of the modified Charlson Comorbidity Index as predictor of short-term outcome in older stroke patients.

PubMed

Denti, Licia; Artoni, Andrea; Casella, Monica; Giambanco, Fabiola; Scoditti, Umberto; Ceda, Gian Paolo

2015-02-01

The modified Charlson Comorbidity Index (MCCI) has been proposed as a tool for adjusting the outcomes of stroke for comorbidity, but its validity in such a context has been evaluated in only a few studies and needs to be further explored, especially in elderly patients. We aimed to retrospectively assess the validity of the MCCI as a predictor of the short-term outcomes in a cohort of 297 patients with first-ever ischemic stroke, older than 60 years, and managed according to a clinical pathway. The poor outcome (PO) at 1 month, defined as a modified Rankin Scale score of 3-6, was the primary end point. Furthermore, a new comorbidity index has been developed, specific to our cohort, according to the same statistical approach used for the original CCI. The MCCI showed a positive association with PO (odds ratio [OR] 1.62; 95% confidence interval [CI] .98-2.68) and mortality (hazard ratio [HR] 1.85; 95% CI .94-3.61), not statistically significant and totally dependent on its association with the severity of neurologic impairment at onset. The new comorbidity index showed, as expected, a significant association with the PO and mortality with higher point estimates of OR (2.74; 95% CI 1.64-4.59) and HR (2.73; 95% CI 1.51-4.94), but this association was also dependent on stroke severity and premorbid disability. Our results do not support the validity of the MCCI as a predictor of the short-term outcomes in elderly stroke patients nor could we develop a more valid index from the available data. This suggests the need for development of disease- and age-specific indexes, possibly according to a prospective design. In any case, initial stroke severity, a strong predictor of outcome, is associated with the degree of comorbidity. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Risk of stroke in patients with patent foramen ovale: an updated meta-analysis of observational studies.

PubMed

Ma, Bing; Liu, Guangcong; Chen, Xin; Zhang, Jianming; Liu, Yiting; Shi, Jingpu

2014-01-01

Although patent foramen ovale (PFO) is considered to be associated with cryptogenic stroke (CS), there remains an ongoing disputation on this issue because of unstable results from randomized controlled trials. The aim of this study was to reassess the PFO effect on stroke through observational data. An electronic search of PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) were finished. Only case-control studies and cohort studies in Chinese or English were included in the analysis. Then random-effected meta-analysis models were performed to assess the association between PFO and stroke. Twelve case-control studies and 6 cohort studies were eligible. Case-control studies showed strong association between PFO and CS (odds ratio [OR]: 2.94, 95% confidence interval [CI]: 2.06, 4.20; P < .001), but cohort studies failed to demonstrate a significant association (hazard ratio [HR]: 1.28, 95% CI: .91, 1.80; P = .155). Subgroup analysis revealed that the pooled OR decreased significantly when the region was limited to the United States (OR: 1.52, 95% CI: 1.00, 2.32; P = .083). OR of studies that adjusted major confounders was 1.74 (95% CI: 1.22, 2.47; P = .119) and high-quality studies was 1.68 (95% CI: 1.14, 2.47; P = .072). For cohort studies, a weak statistical association was observed in using transesophageal echocardiography (TEE) studies (HR: 1.45, 95% CI: 1.06, 2.01; P = .138) and follow-up years less than 4 years' studies (HR: 1.45, 95% CI: 1.00, 2.09; P = .064). Although case-control studies still show a positive effect of PFO on stroke, the results of cohort challenged the credibility. Further trial data are needed to confirm the effect of PFO on stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: Data From ROCKET AF.

PubMed

Pokorney, Sean D; Piccini, Jonathan P; Stevens, Susanna R; Patel, Manesh R; Pieper, Karen S; Halperin, Jonathan L; Breithardt, Günter; Singer, Daniel E; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Berkowitz, Scott D; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M

2016-03-08

Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS2 score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P<0.0001) were associated with higher all-cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C-index 0.677). In a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Women's Health Initiative estrogen plus progestin clinical trial: a study that does not allow establishing relevant clinical risks.

PubMed

Aedo, Sócrates; Cavada, Gabriel; Blümel, Juan E; Chedraui, Peter; Fica, Juan; Barriga, Patricio; Brantes, Sergio; Irribarra, Cristina; Vallejo, María; Campodónico, Ítalo

2015-12-01

This study aims to determine time differences (differences in restricted mean survival times [RMSTs]) in the onset of invasive breast cancer, coronary heart disease, stroke, pulmonary embolism, colorectal cancer, and hip fracture between the placebo group and the conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg group of the Women's Health Initiative (WHI) trial based on survival curves of the original report and to provide adequate interpretation of the clinical effects of a given intervention. Distribution of survival function was obtained from cumulative hazard plots of the WHI report; Monte Carlo simulation was performed to obtain censored observations for each outcome, in which assumptions of the Cox model were evaluated once corresponding hazard ratios had been estimated. Using estimation methods such as numerical integration, pseudovalues, and flexible parametric modeling, we determined differences in RMSTs for each outcome. Obtained cumulative hazard plots, hazard ratios, and outcome rates from the simulated model did not show differences in relation to the original WHI report. The differences in RMST between placebo and conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg (in flexible parametric modeling) were 1.17 days (95% CI, -2.25 to 4.59) for invasive breast cancer, 7.50 days (95% CI, 2.90 to 12.11) for coronary heart disease, 2.75 days (95% CI, -0.84 to 6.34) for stroke, 4.23 days (95% CI, 1.82 to 6.64) for pulmonary embolism, -2.73 days (95% CI, -5.32 to -0.13) for colorectal cancer, and -2.77 days (95% CI, -5.44 to -0.1) for hip fracture. The differences in RMST for the outcomes of the WHI study are too small to establish clinical risks related to hormone therapy use.

New diagnosis of cancer and the risk of subsequent cerebrovascular events.

PubMed

Navi, Babak B; Howard, George; Howard, Virginia J; Zhao, Hong; Judd, Suzanne E; Elkind, Mitchell S V; Iadecola, Costantino; DeAngelis, Lisa M; Kamel, Hooman; Okin, Peter M; Gilchrist, Susan; Soliman, Elsayed Z; Cushman, Mary; Muntner, Paul

2018-06-05

We aimed to evaluate the association between cancer and cerebrovascular disease in a prospective cohort study with adjudicated cerebrovascular diagnoses. We analyzed participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were 45 years and older and had Medicare coverage for 365 days before their baseline study visit. Participants with a history of cancer or cerebrovascular events were excluded. The time-dependent exposure was a new diagnosis of malignant cancer identified through Medicare claims algorithms. Participants were prospectively followed from their baseline study visit (2003-2007) through 2014 for the outcome of a neurologist-adjudicated cerebrovascular event defined as a composite of stroke (ischemic or hemorrhagic) or TIA. Cox regression was used to evaluate the association between a new cancer diagnosis and subsequent cerebrovascular events. Follow-up time was modeled in discrete time periods to fulfill the proportional hazard assumption. Among 6,602 REGARDS participants who met eligibility criteria, 1,149 were diagnosed with cancer during follow-up. Compared to no cancer, a new cancer diagnosis was associated with subsequent cerebrovascular events in the first 30 days after diagnosis (hazard ratio 6.1, 95% confidence interval 2.7-13.7). This association persisted after adjustment for demographics, region of residence, and vascular risk factors (hazard ratio 6.6, 95% confidence interval 2.7-16.0). There was no association between cancer diagnosis and incident cerebrovascular events beyond 30 days. Cancers considered high risk for venous thromboembolism demonstrated the strongest associations with cerebrovascular event risk. A new diagnosis of cancer is associated with a substantially increased short-term risk of cerebrovascular events. © 2018 American Academy of Neurology.

Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: the Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF Trial).

PubMed

Bansilal, Sameer; Bloomgarden, Zachary; Halperin, Jonathan L; Hellkamp, Anne S; Lokhnygina, Yuliya; Patel, Manesh R; Becker, Richard C; Breithardt, Günter; Hacke, Werner; Hankey, Graeme J; Nessel, Christopher C; Singer, Daniel E; Berkowitz, Scott D; Piccini, Jonathan P; Mahaffey, Kenneth W; Fox, Keith A A

2015-10-01

The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial. We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non-central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding. The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS2 score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio [HR] 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively; interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09; interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72; interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients. The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Pet Ownership and the Risk of Dying from Cardiovascular Disease Among Adults Without Major Chronic Medical Conditions.

PubMed

Ogechi, Imala; Snook, Kassandra; Davis, Bionca M; Hansen, Andrew R; Liu, Fengqi; Zhang, Jian

2016-09-01

In a recent statement, the American Heart Association stated "There are scant data on pet ownership and survival in people without established cardiovascular disease (CVD)". This study sought to fill this gap. We analyzed nationally representative data of 3964 adults aged ≥50 who were free from major physical illnesses. Pet ownership was assessed at baseline between 1988 and 1994. Vital status was followed through December 31st 2006. With dogs being most popular pets owned by 22.0 (standard error 0.34) % of the participants, 34.6 % of the study population owned a pet. Pet ownership was associated with low rates of CVD deaths [hazard ratio (HR) = 0.69 (95 % CI 0.45-1.07)] and stroke [0.54 (0.28-1.01)] at borderline significant levels among women. These associations were adjusted for physical activity and largely attributed to having a cat rather than a dog. Among cat owners, the HR of all CVD deaths was 0.62 (0.36-1.05) and the HR of dying from stroke was 0.22 (0.07-0.68) compared with non-cat owners. The corresponding HRs among dog owners were 0.82 (0.51-1.34) and 0.76 (0.34-1.71) respectively. No similar associations were observed among men. The hazard of dying from hypertension was not associated with pet ownership for both men and women. Owning a cat rather than a dog was significantly associated with a reduced hazard of dying from CVD events, in particular, stroke. The protection pets confer may not be from physical activities, but possibly due to personality of the pet owners or stress-relieving effects of animal companionship.

[Time-series analysis on effect of air pollution on stroke mortality in Tianjin, China].

PubMed

Wang, De-zheng; Gu, Qing; Jiang, Guo-hong; Yang, De-yi; Zhang, Hui; Song, Gui-de; Zhang, Ying

2012-12-01

To investigate the effect of air pollution on stroke mortality in Tianjin, China, and to provide basis for stroke control and prevention. Total data of mortality surveillance were collected by Tianjin Centers for Disease Control and Prevention. Meteorological data and atmospheric pollution data were from Tianjin Meteorological Bureau and Tianjin Environmental Monitoring Center, respectively. Generalized additive Poisson regression model was used in time-series analysis on the relationship between air pollution and stroke mortality in Tianjin. Single-pollutant analysis and multi-pollutant analysis were performed after adjustment for confounding factors such as meteorological factors, long-term trend of death, "days of the week" effect and population. The crude death rates of stroke in Tianjin were from 136.67 in 2001 to 160.01/100000 in 2009, with an escalating trend (P = 0.000), while the standardized mortality ratios of stroke in Tianjin were from 138.36 to 99.14/100000, with a declining trend (P = 0.000). An increase of 10 µg/m³ in daily average concentrations of atmospheric SO₂, NO₂ and PM₁₀ led to 1.0105 (95%CI: 1.0060 ∼ 1.0153), 1.0197 (95%CI: 1.0149 ∼ 1.0246) and 1.0064 (95%CI: 1.0052 ∼ 1.0077), respectively, in relative risks of stroke mortality. SO₂ effect peaked after 1-day exposure, while NO₂ and PM₁₀ effects did within 1 day. Air pollution in Tianjin may increase the risk of stroke mortality in the population and induce acute onset of stroke. It is necessary to carry out air pollution control and allocate health resources rationally to reduce the hazard of stroke mortality.

Increased risk of brain cancer incidence in stroke patients: a clinical case series, population-based and longitudinal follow-up study.

PubMed

Chen, Chih-Wei; Cheng, Tain-Junn; Ho, Chung-Han; Wang, Jhi-Joung; Weng, Shih-Feng; Hou, Ya-Chin; Cheng, Hung-Chi; Chio, Chung-Ching; Shan, Yan-Shen; Chang, Wen-Tsan

2017-12-12

Stroke and brain cancer are two distinct diseases. However, the relationship between both diseases has rarely been examined. This study investigated the longitudinal risk for developing brain cancer in stroke patients. To study this, we first reviewed the malignant gliomas previously with or without stroke using brain magnetic resonance imaging (MRI) images and the past histories. Two ischemic stroke patients before the malignant glioma were identified and belonged to the glioblastoma mutiforme (GBM). Particularly, both GBM specimens displayed strong hypoxia-inducible factor 1α (HIF-1α) expression in immunohistochemical (IHC) staining. To elucidate the significance of this relationship, we then used a nationwide population-based cohort in Taiwan to investigate the risk for the incidence of brain cancer in patients previously with or without stroke. The incidence of all tumors in the stroke group was lower than that in the control group with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI]: 0.74-0.84) in both gender and age older than 60 years. But the stroke patients had higher risk of developing only brain cancer with an adjusted HR of 3.09 (95% CI: 1.80-5.30), and otherwise had lower risk of developing head and neck, digestive, respiratory, bone and skin, as well as other tumors, all with p<0.05. After stratification by gender and age, the female and aged 40-60 year old stroke patients had higher risk of developing brain cancer with an adjusted HR of 7.41 (95% CI: 3.30-16.64) and 16.34 (95% CI: 4.45-62.13), respectively, both with p<0.05. Patients with stroke, in particular female and age 40-60 years old, have an increased risk for developing brain cancer.

Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study.

PubMed

Kunutsor, Setor K; Khan, Hassan; Zaccardi, Francesco; Laukkanen, Tanjaniina; Willeit, Peter; Laukkanen, Jari A

2018-05-29

To assess the association between frequency of sauna bathing and risk of future stroke. Baseline habits of sauna bathing were assessed in 1,628 adult men and women aged 53-74 years (mean age, 62.7 years) without a known history of stroke in the Finnish Kuopio Ischemic Heart Disease prospective cohort study. Three sauna bathing frequency groups were defined: 1, 2-3, and 4-7 sessions per week. Hazard ratios (HRs) (95% confidence intervals [CIs]) were estimated for incident stroke. During a median follow-up of 14.9 years, 155 incident stroke events were recorded. Compared with participants who had one sauna bathing session per week, the age- and sex-adjusted HR (95% CI) for stroke was 0.39 (0.18-0.83) for participants who had 4-7 sauna sessions per week. After further adjustment for established cardiovascular risk factors and other potential confounders, the corresponding HR (95% CI) was 0.39 (0.18-0.84) and this remained persistent on additional adjustment for physical activity and socioeconomic status at 0.38 (0.18-0.81). The association between frequency of sauna bathing and risk of stroke was not modified by age, sex, or other clinical characteristics ( p for interaction > 0.10 for all subgroups). The association was similar for ischemic stroke but modest for hemorrhagic stroke, which could be attributed to the low event rate (n = 34). This long-term follow-up study shows that middle-aged to elderly men and women who take frequent sauna baths have a substantially reduced risk of new-onset stroke. © 2018 American Academy of Neurology.

Vertebrobasilar ectasia in patients with lacunar stroke: the secondary prevention of small subcortical strokes trial.

PubMed

Nakajima, Makoto; Pearce, Lesly A; Ohara, Nobuyuki; Field, Thalia S; Bazan, Carlos; Anderson, David C; Hart, Robert G; Benavente, Oscar R

2015-05-01

The clinical implications of vertebrobasilar ectasia (VBE) in patients with cerebral small-artery disease are not well defined. We investigated whether VBE is associated with recurrent stroke, major hemorrhage, and death in a large cohort of patients with recent lacunar stroke. Maximum diameters of the vertebral and basilar arteries were measured by magnetic resonance angiography and computed tomographic angiography in 2621 participants in the Secondary Prevention of Small Subcortical Strokes trial. VBE was defined a priori as basilar artery greater than 4.5 mm and/or vertebral artery greater than 4.0 mm. Patient characteristics and risks of stroke recurrence and mortality during follow-up (median, 3.5 years) were compared between patients with and without VBE. VBE affecting 1 or more arteries was present in 200 (7.6%) patients. Patient features independently associated with VBE were increasing age, male sex, white race ethnicity, hypertension, and higher baseline diastolic blood pressure. Baseline systolic blood pressure was inversely associated with VBE. After adjustment for other risk factors, VBE was not predictive of recurrent stroke (hazard ratio [HR], 1.3; 95% confidence interval [CI], .85-1.9) or major hemorrhage (HR, 1.5; CI, .94-2.6), but was of death (HR, 1.7; CI, 1.1-2.7). In this large well-characterized cohort of patients with recent lacunar stroke, VBE was predictive of death but not of recurrent stroke or major hemorrhage. In these exploratory analyses, the frequency of VBE was directly related to diastolic blood pressure but inversely related to systolic blood pressure. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A Revised Framingham Stroke Risk Profile to Reflect Temporal Trends

PubMed Central

Dufouil, Carole; Beiser, Alexa; McLure, Leslie A.; Wolf, Philip A.; Tzourio, Christophe; Howard, Virginia J; Westwood, Andrew J.; Himali, Jayandra J.; Sullivan, Lisa; Aparicio, Hugo J.; Kelly-Hayes, Margaret; Ritchie, Karen; Kase, Carlos S.; Pikula, Aleksandra; Romero, Jose R.; D’Agostino, Ralph B.; Samieri, Cécilia; Vasan, Ramachandran S.; Chêne, Genevieve; Howard, George; Seshadri, Sudha

2017-01-01

Background Age-adjusted stroke incidence has decreased over the past 50 years, likely due to changes in the prevalence and impact of various stroke risk factors. An updated version of the Framingham Stroke Risk Profile (FSRP) might better predict current risks in the Framingham Heart Study (FHS) and other cohorts. We compared the accuracy of the standard (Old), and of a revised (New) version of the FSRP in predicting the risk of all-stroke and ischemic stroke, and validated this new FSRP in two external cohorts, the 3 Cities (3C) and REGARDS studies. Methods We computed the old FSRP as originally described, and a new model that used the most recent epoch-specific risk factors' prevalence and hazard-ratios for persons ≥ 55 years and for the subsample ≥ 65 years (to match the age range in REGARDS and 3C studies respectively), and compared the efficacy of these models in predicting 5- and 10-year stroke risks. Results The new FSRP was a better predictor of current stroke risks in all three samples than the old FSRP (Calibration chi-squares of new/old FSRP: in men 64.0/12.1, 59.4/30.6 and 20.7/12.5; in women 42.5/4.1, 115.4/90.3 and 9.8/6.5 in FHS, REGARDS and 3C, respectively). In the REGARDS, the new FSRP was a better predictor among whites compared to blacks. Conclusions A more contemporaneous, new FSRP better predicts current risks in 3 large community samples and could serve as the basis for examining geographic and racial differences in stroke risk and the incremental diagnostic utility of novel stroke risk factors. PMID:28159800

Hyperuricemia and the risk of ischemic stroke in patients with atrial fibrillation--could it refine clinical risk stratification in AF?

PubMed

Chao, Tze-Fan; Liu, Chia-Jen; Chen, Su-Jung; Wang, Kang-Ling; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Chen, Tzeng-Ji; Tsao, Hsuan-Ming; Chen, Shih-Ann

2014-01-01

Although hyperuricemia has been reported to be a risk factor of stroke, the relationship between hyperuricemia and stroke in patients with atrial fibrillation (AF) remains uncertain. The goal of the present study was to investigate whether hyperuricemia could potentially refine clinical risk stratification in AF. This study used the "National Health Insurance Research Database" in Taiwan. A total of 7601 AF patients who did not receive antiplatelet agents or oral anticoagulants were identified as the study population. Hyperuricemia was defined as having at least one episode of gout attack necessitating long-term treatment with uric acid-lowering agents. The association between hyperuricemia and ischemic stroke was analyzed. During the follow up of 3.0±2.7 years, 1116 patients (14.7%) experienced ischemic stroke with an annual rate of around 4.9%. Hyperuricemia significantly predicts stroke, with a hazard ratio (HR) of 1.280 after adjusting for CHA2DS2-VASc score and other comorbidities. Among the 376 patients with a CHA2DS2VASc score of 0, hyperuricemia can further stratify them into 2 groups with different stroke rates (7.1% versus 1.3%, p=0.020). The adjusted HR of hyperuricemia in predicting ischemic stroke diminished from 7.491 for patients with a CHA2DS2-VASc score of 0 to 1.659 for those with a score of 3, and became insignificant for patients with a score ≥4. Hyperuricemia was a significant risk factor of stroke which could potentially refine the clinical risk stratification in AF. It deserves a prospective trial to investigate whether it would change the current strategy for stroke preventions using oral anticoagulants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?

PubMed

Go, Alan S; Hylek, Elaine M; Chang, Yuchiao; Phillips, Kathleen A; Henault, Lori E; Capra, Angela M; Jensvold, Nancy G; Selby, Joe V; Singer, Daniel E

2003-11-26

Warfarin has been shown to be highly efficacious for preventing thromboembolism in atrial fibrillation in randomized trials, but its effectiveness and safety in clinical practice is less clear. To evaluate the effect of warfarin on risk of thromboembolism, hemorrhage, and death in atrial fibrillation within a usual care setting. Cohort study assembled between July 1, 1996, and December 31, 1997, and followed up through August 31, 1999. Large integrated health care system in Northern California. Of 13,559 adults with nonvalvular atrial fibrillation, 11,526 were studied, 43% of whom were women, mean age 71 years, with no known contraindications to anticoagulation at baseline. Ischemic stroke, peripheral embolism, hemorrhage, and death according to warfarin use and comorbidity status, as determined by automated databases, review of medical records, and state mortality files. Among 11,526 patients, 397 incident thromboembolic events (372 ischemic strokes, 25 peripheral embolism) occurred during 25,341 person-years of follow-up, and warfarin therapy was associated with a 51% (95% confidence interval [CI], 39%-60%) lower risk of thromboembolism compared with no warfarin therapy (either no antithrombotic therapy or aspirin) after adjusting for potential confounders and likelihood of receiving warfarin. Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke. A nested case-control analysis estimated a 64% reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy. Warfarin was also associated with a reduced risk of all-cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial hemorrhage was uncommon, but the rate was moderately higher among those taking vs those not taking warfarin (0.46 vs 0.23 per 100 person-years, respectively; P =.003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However, warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage. The effects of warfarin were similar when patients with contraindications at baseline were analyzed separately or combined with those without contraindications (total cohort of 13,559). Warfarin is very effective for preventing ischemic stroke in patients with atrial fibrillation in clinical practice while the absolute increase in the risk of intracranial hemorrhage is small. Results of randomized trials of anticoagulation translate well into clinical care for patients with atrial fibrillation.

Biomarkers and mortality after transient ischemic attack and minor ischemic stroke: population-based study.

PubMed

Greisenegger, Stefan; Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Rothwell, Peter M

2015-03-01

Premature death after transient ischemic attack or stroke is more often because of heart disease or cancer than stroke. Previous studies found blood biomarkers not usefully predictive of nonfatal stroke but possibly of all-cause death. This association might be explained by potentially treatable occult cardiac disease or cancer. We therefore aimed to validate the association of a panel of biomarkers with all-cause death, particularly cardiac death and cancer death, despite the absence of associations with risk of nonfatal vascular events. Fifteen biomarkers were measured in 929 consecutive patients in a population-based study (Oxford Vascular Study), recruited from 2002 and followed up to 2013. Associations were determined by Cox regression. Model discrimination was assessed by c-statistic and the integrated discrimination improvement. During 5560 patient-years of follow-up, none of the biomarkers predicted risk of nonfatal vascular events. However, soluble tumor necrosis factor α receptor-1, von Willebrand factor, heart-type fatty-acid-binding protein, and N-terminal pro-B-type natriuretic peptide were independently predictive of all-cause death (n=361; adjusted hazard ratio per SD, 95% confidence interval: heart-type fatty-acid-binding protein: 1.31, 1.12-1.56, P=0.002; N-terminal pro-B-type natriuretic peptide: 1.34, 1.11-1.62, P=0.002; soluble tumor necrosis factor α receptor-1: 1.45, 1.26-1.66, P=0.02; von Willebrand factor: 1.19, 1.04-1.36, P=0.01). The independent contribution of the four biomarkers taken together added prognostic information and improved model discrimination (integrated discrimination improvement=0.028, P=0.0001). N-terminal pro-B-type natriuretic peptide was most predictive of vascular death (adjusted hazard ratio=1.80, 95% confidence interval, 1.34-2.41, P<0.0001), whereas heart-type fatty-acid-binding protein predicted cancer deaths (1.64, 1.26-2.12, P=0.0002). Associations were strongest in patients without known prior cardiac disease or cancer. Several biomarkers predicted death of any cause after transient ischemic attack and minor stroke. N-terminal pro-B-type natriuretic peptide and heart-type fatty-acid-binding protein might improve patient selection for additional screening for occult cardiac disease or cancer, respectively. However, our results require validation in future studies. © 2015 American Heart Association, Inc.

Comparative risk of ischemic stroke among users of clopidogrel together with individual proton pump inhibitors

PubMed Central

Bilker, Warren B.; Brensinger, Colleen M.; Flockhart, David A.; Freeman, Cristin P.; Kasner, Scott E.; Kimmel, Stephen E.; Hennessy, Sean

2015-01-01

Background and Purpose There is controversy and little information concerning whether individual proton pump inhibitors (PPIs) differentially alter the effectiveness of clopidogrel in reducing ischemic stroke risk. We therefore aimed to elucidate the risk of ischemic stroke among concomitant users of clopidogrel and individual PPIs. Methods We conducted a propensity score-adjusted cohort study of adult new users of clopidogrel, using 1999–2009 Medicaid claims from 5 large states. Exposures were defined by prescriptions for esomeprazole, lansoprazole, omeprazole, rabeprazole and pantoprazole—with pantoprazole serving as the referent. The endpoint was hospitalization for acute ischemic stroke, defined by International Classification of Diseases 9th Revision Clinical Modification codes in the principal position on inpatient claims, within 180 days of concomitant therapy initiation. Results Among 325,559 concomitant users of clopidogrel and a PPI, we identified 1,667 ischemic strokes for an annual incidence of 2.4% (95% confidence interval: 2.3–2.5). Adjusted hazard ratios for ischemic stroke vs. pantoprazole were: 0.98 (0.82–1.17) for esomeprazole; 1.06 (0.92–1.21) for lansoprazole; 0.98 (0.85–1.15) for omeprazole; and 0.85 (0.63–1.13) for rabeprazole. Conclusions PPIs of interest did not increase the rate of ischemic stroke among clopidogrel users when compared to pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel. PMID:25657176

Social networks and incident stroke among women with suspected myocardial ischemia.

PubMed

Rutledge, Thomas; Linke, Sarah E; Olson, Marian B; Francis, Jennifer; Johnson, B Delia; Bittner, Vera; York, Kaki; McClure, Candace; Kelsey, Sheryl F; Reis, Steven E; Cornell, Carol E; Vaccarino, Viola; Sheps, David S; Shaw, Leslee J; Krantz, David S; Parashar, Susmita; Merz, C Noel Bairey

2008-04-01

To describe the prospective relationship between social networks and nonfatal stroke events in a sample of women with suspected myocardial ischemia. Social networks are an independent predictor of all-cause and cardiovascular mortality, but their relationship with stroke events in at-risk populations is largely unknown. A total of 629 women (mean age = 59.6 +/- 11.6 years) were evaluated at baseline for cardiovascular disease risk factors as part of a protocol including coronary angiography; the subjects were followed over a median 5.9 years to track the incidence of cardiovascular events including stroke. Participants also completed the Social Network Index (SNI), measuring the presence/absence of 12 types of common social relationships. Stroke events occurred among 5.1% of the sample over follow-up. More isolated women were older and less educated, with higher rates of smoking and hypertension, and increased use of cardiovascular medications. Women with smaller social networks were also more likely to show elevations (scores of > or =10) on the Beck Depression Inventory (54% versus 41%, respectively; p = .003). Relative to women with higher SNI scores, Cox regression results indicated that more isolated women experienced strokes at greater than twice the rate of those with more social relationships after adjusting for covariates (hazard ratio = 2.7; 95% Confidence Interval = 1.1-6.7). Smaller social networks are a robust predictor of stroke in at-risk women, and the magnitude of the association rivals that of conventional risk factors.

Genetic variants influencing elevated myeloperoxidase levels increase risk of stroke.

PubMed

Phuah, Chia-Ling; Dave, Tushar; Malik, Rainer; Raffeld, Miriam R; Ayres, Alison M; Goldstein, Joshua N; Viswanathan, Anand; Greenberg, Steven M; Jagiella, Jeremiasz M; Hansen, Björn M; Norrving, Bo; Jimenez-Conde, Jordi; Roquer, Jaume; Pichler, Alexander; Enzinger, Christian; Montaner, Joan; Fernandez-Cadenas, Israel; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Biffi, Alessandro; Rost, Natalia; Langefeld, Carl D; Markus, Hugh S; Mitchell, Braxton D; Worrall, Brad B; Kittner, Steven J; Woo, Daniel; Dichgans, Martin; Rosand, Jonathan; Anderson, Christopher D

2017-10-01

Primary intracerebral haemorrhage and lacunar ischaemic stroke are acute manifestations of progressive cerebral microvascular disease. Current paradigms suggest atherosclerosis is a chronic, dynamic, inflammatory condition precipitated in response to endothelial injury from various environmental challenges. Myeloperoxidase plays a central role in initiation and progression of vascular inflammation, but prior studies linking myeloperoxidase with stroke risk have been inconclusive. We hypothesized that genetic determinants of myeloperoxidase levels influence the development of vascular instability, leading to increased primary intracerebral haemorrhage and lacunar stroke risk. We used a discovery cohort of 1409 primary intracerebral haemorrhage cases and 1624 controls from three studies, an extension cohort of 12 577 ischaemic stroke cases and 25 643 controls from NINDS-SiGN, and a validation cohort of 10 307 ischaemic stroke cases and 29 326 controls from METASTROKE Consortium with genome-wide genotyping to test this hypothesis. A genetic risk score reflecting elevated myeloperoxidase levels was constructed from 15 common single nucleotide polymorphisms identified from prior genome-wide studies of circulating myeloperoxidase levels (P < 5 × 10-6). This genetic risk score was used as the independent variable in multivariable regression models for association with primary intracerebral haemorrhage and ischaemic stroke subtypes. We used fixed effects meta-analyses to pool estimates across studies. We also used Cox regression models in a prospective cohort of 174 primary intracerebral haemorrhage survivors for association with intracerebral haemorrhage recurrence. We present effects of myeloperoxidase elevating single nucleotide polymorphisms on stroke risk per risk allele, corresponding to a one allele increase in the myeloperoxidase increasing genetic risk score. Genetic determinants of elevated circulating myeloperoxidase levels were associated with both primary intracerebral haemorrhage risk (odds ratio, 1.07, P = 0.04) and recurrent intracerebral haemorrhage risk (hazards ratio, 1.45, P = 0.006). In analysis of ischaemic stroke subtypes, the myeloperoxidase increasing genetic risk score was strongly associated with lacunar subtype only (odds ratio, 1.05, P = 0.0012). These results, demonstrating that common genetic variants that increase myeloperoxidase levels increase risk of primary intracerebral haemorrhage and lacunar stroke, directly implicate the myeloperoxidase pathway in the pathogenesis of cerebral small vessel disease. Because genetic variants are not influenced by environmental exposures, these results provide new support for a causal rather than bystander role for myeloperoxidase in the progression of cerebrovascular disease. Furthermore, these results support a rationale for chronic inflammation as a potential modifiable stroke risk mechanism, and suggest that immune-targeted therapies could be useful for treatment and prevention of cerebrovascular disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Counterclockwise and Clockwise Rotation of QRS Transitional Zone: Prospective Correlates of Change and Time-Varying Associations With Cardiovascular Outcomes.

PubMed

Patel, Siddharth; Kwak, Lucia; Agarwal, Sunil K; Tereshchenko, Larisa G; Coresh, Josef; Soliman, Elsayed Z; Matsushita, Kunihiro

2017-11-03

A few studies have recently reported clockwise and counterclockwise rotations of QRS transition zone as predictors of mortality. However, their prospective correlates and associations with individual cardiovascular disease (CVD) outcomes are yet to be investigated. Among 13 567 ARIC (Atherosclerosis Risk in Communities) study participants aged 45 to 64 years, we studied key correlates of changes in the status of clockwise and counterclockwise rotation over time as well as the association of rotation status with incidence of coronary heart disease (2408 events), heart failure (2196 events), stroke (991 events), composite CVD (4124 events), 898 CVD deaths, and 3469 non-CVD deaths over 23 years of follow-up. At baseline, counterclockwise rotation was most prevalent (52.9%), followed by no (40.5%) and clockwise (6.6%) rotation. Of patients with no rotation, 57.9% experienced counterclockwise or clockwise rotation during follow-up, with diabetes mellitus and black race significantly predicting clockwise and counterclockwise conversion, respectively. Clockwise rotation was significantly associated with higher risk of heart failure (hazard ratio, 1.20; 95% confidence interval [CI], 1.02-1.41) and non-CVD death (hazard ratio, 1.28; 95% CI, 1.12-1.46) after adjusting for potential confounders including other ECG parameters. On the contrary, counterclockwise rotation was significantly related to lower risk of composite CVD (hazard ratio, 0.93; 95% CI, 0.87-0.99]), CVD mortality (hazard ratio, 0.76; 95% CI, 0.65-0.88), and non-CVD deaths (hazard ratio, 0.92; 95% CI, 0.85-0.99 [borderline significance with heart failure]). Counterclockwise rotation, the most prevalent QRS transition zone pattern, demonstrated the lowest risk of CVD and mortality, whereas clockwise rotation was associated with the highest risk of heart failure and non-CVD mortality. These results have implications on how to interpret QRS transition zone rotation when ECG was recorded. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Heart rate and ischemic stroke: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

PubMed

O'Neal, Wesley T; Qureshi, Waqas T; Judd, Suzanne E; Meschia, James F; Howard, Virginia J; Howard, George; Soliman, Elsayed Z

2015-12-01

The association between resting heart rate and ischemic stroke remains unclear. To examine the association between resting heart rate and ischemic stroke. A total of 24 730 participants (mean age: 64 ± 9·3 years; 59% women; 41% blacks) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were free of stroke at the time of enrollment (2003-2007) were included in this analysis. Resting heart rate was determined from baseline electrocardiogram data. Heart rate was examined as a continuous variable per 10 bpm increase and also as a categorical variable using tertiles ( <61 bpm, 61 to 70 bpm, and >70 bpm). First-time ischemic stroke events were identified during follow-up and adjudicated by physician review. Over a median follow-up of 7·6 years, a total of 646 ischemic strokes occurred. In a Cox regression model adjusted for socio-demographics, cardiovascular risk factors, and potential confounders, each 10 bpm increase in heart rate was associated with a 10% increase in the risk of ischemic stroke (hazard ratio = 1·10, 95% confidence interval = 1·02, 1·18). In the categorical model, an increased risk of ischemic stroke was observed for heart rates in the middle (hazard ratio = 1·29, 95% confidence interval = 1·06, 1·57) and upper (hazard ratio = 1·37, 95% confidence interval = 1·12, 1·67) tertiles compared with the lower tertile. The results were consistent when the analysis was stratified by age, gender, race, exercise habits, hypertension, and coronary heart disease. In REGARDS, high resting heart rates were associated with an increased risk of ischemic stroke compared with low heart rates. Further research is needed to examine whether interventions aimed to reduce heart rate decrease stroke risk. © 2015 World Stroke Organization.

Psychosocial work environment and risk of ischemic stroke and coronary heart disease: a prospective longitudinal study of 75 236 construction workers.

PubMed

Schiöler, Linus; Söderberg, Mia; Rosengren, Annika; Järvholm, Bengt; Torén, Kjell

2015-05-01

The present study aimed to investigate whether different dimensions of psychosocial stress, as measured by the job demand-control model (JDC), were associated with increased risks of ischemic stroke and coronary heart disease (CHD). A cohort of 75 236 male construction workers was followed from 1989-2004. Exposure to psychosocial stress was determined by a questionnaire answered in 1989-1993. Events of ischemic stroke and CHD were found by linkage to the Swedish Causes of Death and National Patient registers. Hazard ratios (HR) were obtained from Cox regression models, adjusted for age, smoking habits, body mass index and systolic blood pressure. There were 1884 cases of CHD and 739 cases of ischemic stroke. Regarding ischemic stroke, no association was found between job demands [HR 1.12, 95% confidence interval (95% CI) 0.89-1.40, highest versus lowest quintile] or job control (HR 1.04, 95% CI 0.82-1.32, lowest versus highest quintile). Regarding CHD, job demands were associated to CHD (HR 1.18, 95% CI 1.02-1.37, highest vs. lowest quintile), but no consistent trend was seen among quintiles. The results were inconsistent in relation to job control. The division of JDC into four categories showed no significant associations with either ischemic stroke or CHD. This exploratory study showed no significant associations between psychosocial work environment and ischemic stroke, and the associations between job demands and control and CHD were inconsistent and weak. The combination of job control and job demand showed no significant associations with either ischemic stroke or CHD.

Medication adherence and stroke/TIA risk in treated hypertensives: results from the REGARDS study.

PubMed

Cummings, Doyle M; Letter, Abraham J; Howard, George; Howard, Virginia J; Safford, Monika M; Prince, Valerie; Muntner, Paul

2013-01-01

The extent to which low medication adherence in hypertensive individuals contributes to disparities in stroke and transient ischemic attack (TIA) risk is poorly understood. Investigators examined the relationship between self-reported medication adherence and blood pressure (BP) control (<140/90 mm Hg), Framingham Stroke Risk Score, and physician-adjudicated stroke/TIA incidence in treated hypertensive subjects (n = 15,071; 51% black; 57% in Stroke Belt) over 4.9 years in the national population-based REGARDS cohort study. Mean systolic BP varied from 130.8 ± 16.2 mm Hg in those reporting high adherence to 137.8 ± 19.5 mm Hg in those reporting low adherence (P for trend < .0001). In logistic regression models, each level of worsening medication adherence was associated with significant and increasing odds of inadequately controlled BP (≥140/90 mm Hg; score = 1, odds ratio [95% confidence interval], 1.20 [1.09-1.30]; score = 2, 1.27 [1.08-1.49]; score = 3 or 4, 2.21 [1.75-2.78]). In hazard models using systolic BP as a mediator, those reporting low medication adherence had 1.08 (1.04-1.14) times greater risk of stroke and 1.08 (1.03-1.12) times greater risk of stroke or TIA. Low medication adherence was associated with inadequate BP control and an increased risk of incident stroke or TIA. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Patent foramen ovale is not associated with an increased risk of stroke recurrence.

PubMed

Feurer, R; Sadikovic, S; Sepp, D; Esposito, L; Schleef, M; Bockelbrink, A; Schwarze, J; Hemmer, B; Sander, D; Poppert, H

2010-11-01

Despite numerous studies suggesting a relationship between paradoxical embolism from a patent foramen ovale (PFO) and stroke, the role of PFO as a risk factor for cerebral ischaemia remains controversial. We therefore sought to determine the association between a RLS detected by contrast-enhanced transcranial Doppler ultrasonography (c-TCD) and recurrent stroke in an unselected population sample. We analyzed the records of 763 patients with diagnosis of cerebral ischaemia at our institution. All patients had undergone TCD-based detection of RLS. Embolic signals have been measured both under resting conditions and after performing a Valsalva maneuver. For follow-up, all patients were contacted by mail, which included a standardized questionnaire. Endpoints of follow-up were defined as recurrence of cerebral ischaemia, occurrence of myocardial infarction or death from any cause. Follow-up data were available in 639 patients (83.7%). At baseline, a RLS was detected in 140 (28%) men and in 114 (42%) women. Ten shunt-carriers (1.6%) and 32 patients (5.0%) without RLS had suffered a recurrent stroke. After adjustment for age, sex, and atrial fibrillation, the hazard ratio of RLS for stroke recurrence was 0.86 (95% CI 0.41-1.79). The condition of RLS at rest adjusted for age, sex, stroke subtype, and cardiovascular risk factors was not found to increase the risk of stroke substantially (HR 1.16 [95% CI 0.41-3.29]) Our data suggest that the risk of recurrent stroke in subjects with PFO is not significantly increased in comparison with subject without it. © 2010 The Author(s). Journal compilation © 2010 EFNS.

Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial).

PubMed

Washam, Jeffrey B; Hellkamp, Anne S; Lokhnygina, Yuliya; Piccini, Jonathan P; Berkowitz, Scott D; Nessel, Christopher C; Becker, Richard C; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Singer, Daniel E; Patel, Manesh R

2017-08-15

Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS 2 score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Outcomes of Temporary Interruption of Rivaroxaban Compared With Warfarin in Patients With Nonvalvular Atrial Fibrillation

PubMed Central

Sherwood, Matthew W.; Douketis, James D.; Patel, Manesh R.; Piccini, Jonathan P.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Spyropoulos, Alex C.; Hankey, Graeme J.; Singer, Daniel E.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.; Becker, Richard C.

2014-01-01

Background During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. Methods and Results In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non–central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3–30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36–1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80–2.00]; P=0.32). Conclusions TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767. PMID:24552831

The Japan Statin Treatment Against Recurrent Stroke (J-STARS): A Multicenter, Randomized, Open-label, Parallel-group Study.

PubMed

Hosomi, Naohisa; Nagai, Yoji; Kohriyama, Tatsuo; Ohtsuki, Toshiho; Aoki, Shiro; Nezu, Tomohisa; Maruyama, Hirofumi; Sunami, Norio; Yokota, Chiaki; Kitagawa, Kazuo; Terayama, Yasuo; Takagi, Makoto; Ibayashi, Setsuro; Nakamura, Masakazu; Origasa, Hideki; Fukushima, Masanori; Mori, Etsuro; Minematsu, Kazuo; Uchiyama, Shinichiro; Shinohara, Yukito; Yamaguchi, Takenori; Matsumoto, Masayasu

2015-09-01

Although statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined in Asian, in whom stroke profiles are different from Caucasian. This study examined whether treatment with low-dose pravastatin prevents stroke recurrence in ischemic stroke patients. This is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced non-cardioembolic ischemic stroke. All patients had a total cholesterol level between 4.65 and 6.21 mmol/L at enrollment, without the use of statins. The pravastatin group patients received 10 mg of pravastatin/day; the control group patients received no statins. The primary endpoint was the occurrence of stroke and transient ischemic attack (TIA), with the onset of each stroke subtype set to be one of the secondary endpoints. Although 3000 patients were targeted, 1578 patients (491 female, age 66.2 years) were recruited and randomly assigned to pravastatin group or control group. During the follow-up of 4.9 ± 1.4 years, although total stroke and TIA similarly occurred in both groups (2.56 vs. 2.65%/year), onset of atherothrombotic infarction was less frequent in pravastatin group (0.21 vs. 0.64%/year, p = 0.0047, adjusted hazard ratio 0.33 [95%CI 0.15 to 0.74]). No significant intergroup difference was found for the onset of other stroke subtypes, and for the occurrence of adverse events. Although whether low-dose pravastatin prevents recurrence of total stroke or TIA still needs to be examined in Asian, this study has generated a hypothesis that it may reduce occurrence of stroke due to larger artery atherosclerosis. This study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and Innovation.

Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation.

PubMed

Lip, G Y H; Frison, L; Grind, M

2008-07-01

To test the hypothesis that stroke and systemic embolic events (SEE) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) III and V trials are different between paroxysmal and persistent atrial fibrillation (AF). Data analysis from two cohorts of patients enrolled in the prospective SPORTIF III and V clinical trials (n = 7329); 836 subjects (11.4%) with paroxysmal AF [mean age 70.1 years (SD = 9.5)] were compared with 6493 subjects with persistent AF for this ancillary study. The annual event rates for stroke/SEE are 1.73% for persistent AF and 0.93% for paroxysmal AF. In a multivariate analysis, after adjusting for stroke risk factors, gender and aspirin usage, the differences remained statistically significant with a higher hazard ratio (HR) for stroke/SEE in persistent AF [vs. paroxysmal AF, HR 1.87, 95% confidence interval (CI) 1.04-3.36; P = 0.037]. In 'high risk' patients (with >or=2 stroke risk factors) annual event rates for stroke/SEE were 2.08% for persistent AF and 1.27% for paroxysmal AF (adjusted HR = 1.68, 95% CI 0.91-3.1, P = 0.098). Elderly patients had annual event rates for stroke/SEE of 2.38% for persistent AF and 1.13% for paroxysmal AF (adjusted HR = 2.27, 95% CI 0.92-5.59, P = 0.075). Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate, compared with 0.61% for previous VKA takers (HR = 0.33, 95% CI 0.11-1.01, P = 0.052). In this large clinical trial cohort of anticoagulated AF patients, those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF, although both groups had broadly similar stroke risk factors. Subjects with paroxysmal AF at 'high risk' had stroke/SEE rates that were not significantly different to persistent AF subjects.

Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in "real-world" clinical practice. A propensity-matched analysis of 76,940 patients.

PubMed

Li, Xiaoyan Shawn; Deitelzweig, Steve; Keshishian, Allison; Hamilton, Melissa; Horblyuk, Ruslan; Gupta, Kiran; Luo, Xuemei; Mardekian, Jack; Friend, Keith; Nadkarni, Anagha; Pan, Xianying; Lip, Gregory Y H

2017-06-02

The ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA 2 DS 2 -VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59-0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54-0.65) than warfarin initiators. Different types of stroke/SE and major bleeding - including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding - were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA 2 DS 2 -VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest "real-world" study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various high-risk subgroups and both the standard- and low-dose apixaban dose regimens.

Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis.

PubMed

van Walraven, Carl; Hart, Robert G; Singer, Daniel E; Laupacis, Andreas; Connolly, Stuart; Petersen, Palle; Koudstaal, Peter J; Chang, Yuchiao; Hellemons, Beppie

2002-11-20

Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke and other vascular events. To compare the risk of vascular and bleeding events in patients with nonvalvular AF treated with vitamin K -inhibiting oral anticoagulants or acetylsalicylic acid (aspirin). Pooled analysis of patient-level data from 6 published, randomized clinical trials. A total of 4052 patients with AF randomly assigned to receive therapeutic doses of oral anticoagulant or aspirin with or without low-dose oral anticoagulants. Ischemic and hemorrhagic stroke, other cardiovascular events, all-cause death, and major bleeding events. Person-year incidence rates were calculated to provide crude comparisons. Relative efficacy was assessed using proportional hazards modeling stratified by study. The variation of the oral anticoagulant's relative effect by pertinent patient factors was explored with interaction terms. All analyses were conducted using the intention-to-treat principle. Patients receiving oral anticoagulant and aspirin were balanced for important prognostic factors. There was no significant heterogeneity between trials in the relative efficacy of oral anticoagulant vs aspirin for any outcome. Patients receiving oral anticoagulant were significantly less likely to experience any stroke (2.4 vs 4.5 events per 100 patient-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71), ischemic stroke (HR, 0.48; 95% CI, 0.37-0.63), or cardiovascular events (HR, 0.71; 95% CI, 0.59-0.85) but were more likely to experience major bleeding (2.2 vs 1.3 events per 100 patient-years; HR, 1.71; 95% CI, 1.21-2.41). The reduction in ischemic stroke risk was similar in patients with paroxysmal AF (1.5 vs 4.7 events per 100 patient-years; HR, 0.32; 95% CI, 0.16-0.61; P<.001). Treating 1000 patients with AF for 1 year with oral anticoagulant rather than aspirin would prevent 23 ischemic strokes while causing 9 additional major bleeds. Overall all-cause survival did not differ but appeared to improve for oral anticoagulant patients 3 years after therapy was started. Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, ischemic strokes, and cardiovascular events for patients with nonvalvular chronic or paroxysmal AF but modestly increases the absolute risk of major bleeding. The balance of benefits and risks varies by patient subgroup.

Dietary patterns within educational groups and their association with CHD and stroke in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort.

PubMed

Biesbroek, Sander; Kneepkens, Mirjam C; van den Berg, Saskia W; Fransen, Heidi P; Beulens, Joline W; Peeters, Petra H M; Boer, Jolanda M A

2018-04-01

Higher-educated people often have healthier diets, but it is unclear whether specific dietary patterns exist within educational groups. We therefore aimed to derive dietary patterns in the total population and by educational level and to investigate whether these patterns differed in their composition and associations with the incidence of fatal and non-fatal CHD and stroke. Patterns were derived using principal components analysis in 36 418 participants of the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Self-reported educational level was used to create three educational groups. Dietary intake was estimated using a validated semi-quantitative FFQ. Hazard ratios were estimated using Cox Proportional Hazard analysis after a mean follow-up of 16 years. In the three educational groups, similar 'Western', 'prudent' and 'traditional' patterns were derived as in the total population. However, with higher educational level a lower population-derived score for the 'Western' and 'traditional' patterns and a higher score on the 'prudent' pattern were observed. These differences in distribution of the factor scores illustrate the association between education and food consumption. After adjustments, no differences in associations between population-derived dietary patterns and the incidence of CHD or stroke were found between the educational groups (P interaction between 0·21 and 0·98). In conclusion, although in general population and educational groups-derived dietary patterns did not differ, small differences between educational groups existed in the consumption of food groups in participants considered adherent to the population-derived patterns (Q4). This did not result in different associations with incident CHD or stroke between educational groups.

Continued Use of Warfarin in Veterans with Atrial Fibrillation After Dementia Diagnosis.

PubMed

Orkaby, Ariela R; Ozonoff, Al; Reisman, Joel I; Miller, Donald R; Zhao, Shibei; Rose, Adam J

2017-02-01

To determine the effectiveness of warfarin in older adults with dementia. Retrospective cohort study. Department of Veterans Affairs national healthcare system. Veterans aged 65 and older (73% aged ≥75, 99% male, 91% white) who had been receiving warfarin for nonvalvular atrial fibrillation for at least 6 months, were newly diagnosed with dementia in fiscal year 2007 or 2008, and were not enrolled in Medicare Advantage (n = 2,572). The onset of dementia was defined according to International Classification of Diseases, Ninth Revision, code. Participants were followed for up to 4 years for persistence of warfarin therapy, anticoagulation control, major hemorrhage, ischemic stroke, and all-cause mortality. The average CHADS2 score was 3.3 ± 1.3. After a diagnosis of dementia, 405 individuals (16%) persisted on warfarin therapy. Unadjusted Cox proportional hazards analysis demonstrated a protective effect of warfarin in prevention of ischemic stroke (hazard ratio (HR) = 0.64, 95% confidence interval (CI) = 0.46-0.89, P = .008), major bleeding (HR = 0.72, 95% CI = 0.55-0.94, P = .02), and all-cause mortality (HR = 0.66, 95% CI = 0.55-0.79, P < .001). Using propensity score matching, the protective effect of continuing warfarin persisted in prevention of stroke (HR = 0.74, 95% CI = 0.54-0.996, P = .047) and mortality (HR = 0.72, 95% CI = 0.60-0.87, P < .001), with no statistically significant decrease in risk of major bleeding (HR = 0.78, 95% CI = 0.61-1.01, P = .06). Discontinuing warfarin after a diagnosis of dementia is associated with a significant increase in stroke and mortality. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Life Satisfaction and Risk of Chronic Diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany Study

PubMed Central

Feller, Silke; Teucher, Birgit; Kaaks, Rudolf; Boeing, Heiner; Vigl, Matthaeus

2013-01-01

Objective The aim of the study was to examine the prospective association between life satisfaction and risk of type 2 diabetes mellitus, myocardial infarction, stroke, and cancer. Previous studies suggested that psychosocial factors may affect the development of chronic diseases but the impact of positive attitudes, in particular life satisfaction, is yet to be determined. Methods The analysis included 50,358 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study in Potsdam and Heidelberg. Life satisfaction was assessed in a baseline interview and incident cases of chronic diseases were identified and verified during follow-up. Hazard ratios were calculated using Cox proportional hazards regression models that were systematically multivariable-adjusted for established risk factors and prevalent diseases. Results During an average of 8 years of follow-up 2,293 cases of cancer, 1,840 cases of type 2 diabetes mellitus, 440 cases of stroke, and 562 cases of myocardial infarction were observed. Women who were unsatisfied with life at baseline showed in all models a significantly increased risk of cancer (HR: 1.45; 95% CI: 1.18-1.78) and stroke (HR: 1.69; 95% CI: 1.05-2.73) as well as an increased risk of type 2 diabetes mellitus by trend across categories (p-trend=0.04) compared to women very satisfied with life. In men, a relationship between life satisfaction and stroke was found but did not persist after consideration of lifestyle factors and prevalent diseases. No significant association was observed between life satisfaction and risk of myocardial infarction. Conclusions The results of this study suggest that reduced life satisfaction is related to the development of chronic diseases—particularly in women and partly mediated by established risk factors. PMID:23977388

Association of Sleep Duration with Chronic Diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study

PubMed Central

von Ruesten, Anne; Weikert, Cornelia; Fietze, Ingo; Boeing, Heiner

2012-01-01

Background In view of the reduced number of hours devoted to sleep in modern western societies the question arises what effects might result from sleep duration on occurrence of chronic diseases. Methods Data from 23 620 middle-aged participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, that were recruited between 1994–1998, were analyzed by using Cox proportional hazard regression to examine the association between self-reported sleep duration at baseline and incidence of chronic diseases, such as diabetes, myocardial infarction, stroke, and cancer. Results During a mean follow-up period of 7.8 years 841 incident cases of type 2 diabetes, 197 cases of myocardial infarction, 169 incident strokes, and 846 tumor cases were observed. Compared to persons sleeping 7-<8 h/day, participants with sleep duration of <6 h had a significantly increased risk of stroke (Hazard Ratio (HR) = 2.06, 95% confidence interval (CI): 1.18–3.59), cancer (HR = 1.43, 95% CI: 1.09–1.87), and overall chronic diseases (HR = 1.31, 95% CI: 1.10–1.55) in multivariable adjusted models. Self-reported daytime sleep at baseline was not associated with incident chronic diseases in the overall study sample. However, there had been an effect modification of daytime sleep by hypertension showing that daytime sleep was inversely related to chronic disease risk among non-hypertensive participants but directly related to chronic diseases among hypertensives. Conclusion Sleep duration of less than 6 h is a risky behavior for the development of chronic diseases, particularly stroke and cancer, and should be therefore addressed in public health campaigns. PMID:22295122

Association of sleep duration with chronic diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study.

PubMed

von Ruesten, Anne; Weikert, Cornelia; Fietze, Ingo; Boeing, Heiner

2012-01-01

In view of the reduced number of hours devoted to sleep in modern western societies the question arises what effects might result from sleep duration on occurrence of chronic diseases. Data from 23 620 middle-aged participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, that were recruited between 1994-1998, were analyzed by using Cox proportional hazard regression to examine the association between self-reported sleep duration at baseline and incidence of chronic diseases, such as diabetes, myocardial infarction, stroke, and cancer. During a mean follow-up period of 7.8 years 841 incident cases of type 2 diabetes, 197 cases of myocardial infarction, 169 incident strokes, and 846 tumor cases were observed. Compared to persons sleeping 7-<8 h/day, participants with sleep duration of <6 h had a significantly increased risk of stroke (Hazard Ratio (HR) = 2.06, 95% confidence interval (CI): 1.18-3.59), cancer (HR = 1.43, 95% CI: 1.09-1.87), and overall chronic diseases (HR = 1.31, 95% CI: 1.10-1.55) in multivariable adjusted models. Self-reported daytime sleep at baseline was not associated with incident chronic diseases in the overall study sample. However, there had been an effect modification of daytime sleep by hypertension showing that daytime sleep was inversely related to chronic disease risk among non-hypertensive participants but directly related to chronic diseases among hypertensives. Sleep duration of less than 6 h is a risky behavior for the development of chronic diseases, particularly stroke and cancer, and should be therefore addressed in public health campaigns.

Transient ischemic attack: management in the emergency department and impact of an outpatient neurovascular clinic.

PubMed

Hosier, Gregory W; Phillips, Stephen J; Doucette, Steve P; Magee, Kirk D; Gubitz, Gordon J

2016-09-01

1) To evaluate whether transient ischemic attack (TIA) management in emergency departments (EDs) of the Nova Scotia Capital District Health Authority followed Canadian Best Practice Recommendations, and 2) to assess the impact of being followed up in a dedicated outpatient neurovascular clinic. Retrospective chart review of all patients discharged from EDs in our district from January 1, 2011 to December 31, 2012 with a diagnosis of TIA. Cox proportional hazards models, Kaplan-Meier survival curve, and propensity matched analyses were used to evaluate 90-day mortality and readmission. Of the 686 patients seen in the ED for TIA, 88.3% received computed tomography (CT) scanning, 86.3% received an electrocardiogram (ECG), 35% received vascular imaging within 24 hours of triage, 36% were seen in a neurovascular clinic, and 4.2% experienced stroke, myocardial infarction, or vascular death within 90 days. Rates of antithrombotic use were increased in patients seen in a neurovascular clinic compared to those who were not (94% v. 86.3%, p<0.0001). After adjustment for age, sex, vascular disease risk factors, and stroke symptoms, the risk of readmission for stroke, myocardial infarction, or vascular death was lower for those seen in a neurovascular clinic compared to those who were not (adjusted hazard ratio 0.28; 95% confidence interval 0.08-0.99, p=0.048). The majority of patients in our study were treated with antithrombotic agents in the ED and investigated with CT and ECG within 24 hours; however, vascular imaging and neurovascular clinic follow-up were underutilized. For those with neurovascular clinic follow-up, there was an association with reduced risk of subsequent stroke, myocardial infarction, or vascular death.

Coffee consumption and risk of total and cardiovascular mortality among patients with type 2 diabetes.

PubMed

Bidel, S; Hu, G; Qiao, Q; Jousilahti, P; Antikainen, R; Tuomilehto, J

2006-11-01

Higher habitual coffee drinking has been associated with a lower risk of developing type 2 diabetes. The relation between coffee consumption and risk of cardiovascular disease (CVD) has been examined in many studies, but the issue remains controversial. This study was designed to assess the association between coffee consumption and CVD mortality among patients with type 2 diabetes. We prospectively followed 3,837 randomly ascertained Finnish patients with type 2 diabetes aged 25 to 74 years. Coffee consumption and other study parameters were determined at baseline. The International Classification of Diseases was used to identify CHD, CVD and stroke cases using computerised record linkage to the national Death Registry. The associations between coffee consumption at baseline and risk of total, CVD, CHD, and stroke mortality were analysed by using Cox proportional hazards models. During the average follow-up of 20.8 years, 1,471 deaths were recorded, of which 909 were coded as CVD, 598 as CHD and 210 as stroke. The respective multivariate-adjusted hazard ratios in participants who drank 0-2, 3-4, 5-6, and > or =7 cups of coffee daily were 1.00, 0.77, 0.68 and 0.70 for total mortality (P<0.001 for trend), 1.00, 0.79, 0.70 and 0.71 for CVD mortality (P=0.006 for trend), 1.00, 0.78, 0.70 and 0.63 for CHD mortality (p=0.01 for trend), and 1.00, 0.77, 0.64 and 0.90 for stroke mortality (p=0.12 for trend). In this large prospective study we found that in type 2 diabetic patients coffee drinking is associated with reduced total, CVD and CHD mortality.

High-sensitive C-reactive protein and dual antiplatelet in intracranial arterial stenosis.

PubMed

Li, Jiejie; Wang, Anxin; Zhao, Xingquan; Liu, Liping; Meng, Xia; Lin, Jinxi; Jing, Jing; Zou, Xinying; Wang, Yilong; Wang, Yongjun

2018-02-06

To determine the relationship of high-sensitive C-reactive protein (hsCRP) and the efficacy and safety of dual antiplatelet therapy in patients with and without intracranial arterial stenosis (ICAS) in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. A subgroup of 807 patients with both magnetic resonance angiography images and hsCRP measurement was analyzed. Cox proportional hazards models were used to assess the interaction of hsCRP levels with the effects of dual and single antiplatelet therapy. A total of 358 (44.4%) patients had ICAS and 449 (55.6%) did not. The proportion of patients with elevated hsCRP levels was higher in the ICAS group than in the non-ICAS group (40.2% vs 30.1%, p = 0.003). There was significant interaction between hsCRP and the 2 antiplatelet therapy groups in their effects on recurrent stroke after adjustment for confounding factors in the patients with ICAS ( p = 0.012), but not in those without ( p = 0.256). Compared with aspirin alone, clopidogrel plus aspirin significantly reduced the risk of recurrent stroke only in the patients with ICAS and nonelevated hsCRP levels (adjusted hazard ratio 0.27; 95% confidence interval 0.11 to 0.69; p = 0.006). Similar results were observed for composite vascular events. No significant difference in bleeding was found. Presence of both ICAS and nonelevated hsCRP levels may predict better response to dual antiplatelet therapy in reducing new stroke and composite vascular events in minor stroke or high-risk TIA patients. Further large-scale randomized and controlled clinical trials are needed to confirm this finding. © 2018 American Academy of Neurology.

Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement

PubMed Central

Whincup, Peter H; Gilg, Julie A; Emberson, Jonathan R; Jarvis, Martin J; Feyerabend, Colin; Bryant, Andrew; Walker, Mary; Cook, Derek G

2004-01-01

Objective To examine the associations between a biomarker of overall passive exposure to tobacco smoke (serum cotinine concentration) and risk of coronary heart disease and stroke. Design Prospective population based study in general practice (the British regional heart study). Participants 4729 men in 18 towns who provided baseline blood samples (for cotinine assay) and a detailed smoking history in 1978-80. Main outcome measure Major coronary heart disease and stroke events (fatal and non-fatal) during 20 years of follow up. Results 2105 men who said they did not smoke and who had cotinine concentrations < 14.1 ng/ml were divided into four equal sized groups on the basis of cotinine concentrations. Relative hazards (95% confidence intervals) for coronary heart disease in the second (0.8-1.4 ng/ml), third (1.5-2.7 ng/ml), and fourth (2.8-14.0 ng/ml) quarters of cotinine concentration compared with the first (≥ 0.7 ng/ml) were 1.45 (1.01 to 2.08), 1.49 (1.03 to 2.14), and 1.57 (1.08 to 2.28), respectively, after adjustment for established risk factors for coronary heart disease. Hazard ratios (for cotinine 0.8-14.0 ν ≥ 0.7 ng/ml) were particularly increased during the first (3.73, 1.32 to 10.58) and second five year follow up periods (1.95, 1.09 to 3.48) compared with later periods. There was no consistent association between cotinine concentration and risk of stroke. Conclusion Studies based on reports of smoking in a partner alone seem to underestimate the risks of exposure to passive smoking. Further prospective studies relating biomarkers of passive smoking to risk of coronary heart disease are needed. PMID:15229131

Mortality after hemorrhagic stroke: data from general practice (The Health Improvement Network).

PubMed

González-Pérez, Antonio; Gaist, David; Wallander, Mari-Ann; McFeat, Gillian; García-Rodríguez, Luis A

2013-08-06

To investigate short-term case fatality and long-term mortality after intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) using data from The Health Improvement Network database. Thirty-day case fatality was stratified by age, sex, and calendar year after ICH and SAH using logistic regression. Cox proportional hazards regression analyses were used to estimate the risk of death during the first year of follow-up and survivors at 1 year. Case fatality after ICH was 42.0%, compared with 28.7% after SAH. It increased with age (ICH: 29.7% for 20-49 years, 54.6% for 80-89 years; SAH: 20.3% for 20-49 years, 56.7% for 80-89 years; both p-trend < 0.001), and decreased over the period 2000-2001 to 2006-2008 (ICH: from 53.1% to 35.8%, p-trend < 0.001; SAH: from 33.3% to 24.7%, p-trend = 0.02). Risk of death was significantly higher among stroke patients during the first year of follow-up compared with controls (ICH: hazard ratio [HR] 2.60, 95% confidence interval [CI] 2.09-3.24, p < 0.01; SAH: HR 2.87, 95% CI 2.07-3.97, p < 0.01) and remained elevated among survivors at 1 year (ICH: HR 2.02, 95% CI 1.75-2.32, p < 0.01; SAH: HR 1.32, 95% CI 1.02-1.69, p = 0.03). More than one-third of individuals die in the first month after hemorrhagic stroke, and patients younger than 50 years are more likely to die after ICH than SAH. Short-term case fatality has decreased over time. Patients who survive hemorrhagic stroke have a continuing elevated risk of death compared with matched individuals from the general population.

Effect of having a sense of purpose in life on the risk of death from cardiovascular diseases.

PubMed

Koizumi, Megumi; Ito, Hiroshi; Kaneko, Yoshihiro; Motohashi, Yutaka

2008-01-01

Many studies have focused on disease causality, but few of them deal with health-promoting factors. Thus, we examined the effect of having a sense of purpose in life (ikigai) on mortality from cardiovascular disease (CVD). In 1988, we conducted a prospective cohort study of 2,959 Japanese subjects, ranging in age from 40 to 74 years, and followed them till the end of 2003. The level of their sense of purpose in life was evaluated by a self-administered questionnaire. After excluding those with a history of heart disease, stroke, or malignant tumor, 1,618 subjects (832 men and 786 women) who had completed the questionnaire were used in the analyses with Cox's proportional hazards model. During the average 13.3 years of follow up, 249 deaths (172 men and 77 women) occurred as a result of all causes: 32 from heart disease, 31 from stroke, 63 from CVD, and 104 from malignant tumors. The adjusted hazard ratios for death in men with a strong sense of purpose in life, as compared with those with a low sense of purpose, were 0.28 (95% confidence interval: 0.10-0.84) for stroke, 0.56 (0.28-1.10) for CVD, and 0.62 (0.45-0.86) as a result of all causes. In women, no significant relationship was found between having a sense of purpose in life and mortality; this was possibly because the smaller number of deaths reduced the statistical significance. We found that in men, having a sense of purpose in life affected the risk of death as a result of all causes, stroke, and CVD.

Effect of Having a Sense of Purpose in Life on the Risk of Death from Cardiovascular Diseases

PubMed Central

Koizumi, Megumi; Ito, Hiroshi; Kaneko, Yoshihiro; Motohashi, Yutaka

2008-01-01

Background Many studies have focused on disease causality, but few of them deal with health-promoting factors. Thus, we examined the effect of having a sense of purpose in life (ikigai) on mortality from cardiovascular disease (CVD). Methods In 1988, we conducted a prospective cohort study of 2,959 Japanese subjects, ranging in age from 40 to 74 years, and followed them till the end of 2003. The level of their sense of purpose in life was evaluated by a self-administered questionnaire. After excluding those with a history of heart disease, stroke, or malignant tumor, 1,618 subjects (832 men and 786 women) who had completed the questionnaire were used in the analyses with Cox’s proportional hazards model. Results During the average 13.3 years of follow up, 249 deaths (172 men and 77 women) occurred as a result of all causes: 32 from heart disease, 31 from stroke, 63 from CVD, and 104 from malignant tumors. The adjusted hazard ratios for death in men with a strong sense of purpose in life, as compared with those with a low sense of purpose, were 0.28 (95% confidence interval: 0.10-0.84) for stroke, 0.56 (0.28-1.10) for CVD, and 0.62 (0.45-0.86) as a result of all causes. In women, no significant relationship was found between having a sense of purpose in life and mortality; this was possibly because the smaller number of deaths reduced the statistical significance. Conclusion We found that in men, having a sense of purpose in life affected the risk of death as a result of all causes, stroke, and CVD. PMID:18753736

Retinal microvascular changes and subsequent vascular events after ischemic stroke.

PubMed

De Silva, D A; Manzano, J J F; Liu, E Y; Woon, F-P; Wong, W-X; Chang, H-M; Chen, C; Lindley, R I; Wang, J J; Mitchell, P; Wong, T-Y; Wong, M-C

2011-08-30

Retinal microvasculature changes are associated with vascular events including stroke in healthy populations. It is not known whether retinal microvascular changes predict recurrent vascular events after ischemic stroke. We examined the relationship between retinal microvascular signs and subsequent vascular events in a prospective cohort of 652 acute ischemic stroke patients admitted to a tertiary hospital in Singapore from 2005 to 2007. Retinal photographs taken within 1 week of stroke onset were assessed in a masked manner for quantitative and qualitative measures. Follow-up data over 2-4 years were obtained by standardized telephone interview and then were verified from medical records. Predictors of recurrent vascular events (cerebrovascular, coronary, vascular death, and composite vascular events) were determined using Cox regression models. Follow-up data over a median of 29 months were obtained for 89% (652 patients) of the cohort. After adjustment for covariates including traditional risk factors and index stroke etiology, patients with severe arteriovenous nicking (AVN) were more likely to have a recurrent cerebrovascular event (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.20-4.33) compared with those without AVN. Patients with severe focal arteriolar narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR 2.75, 95% CI 1.14-6.63) or subsequent composite vascular event (HR 2.77, 95% CI 1.31-5.86) compared to those without FAN. Retinal microvascular changes predicted subsequent vascular events after ischemic stroke, independent of traditional risk factors and stroke subtype. Thus, retinal imaging has a potential role in predicting the risk of recurrent vascular events after ischemic stroke and in understanding novel vascular risk factors.

The association between nut consumption and the risk of total and ischemic stroke in a German cohort study.

PubMed

di Giuseppe, R; Fjeld, M K; Dierkes, J; Theoflylaktopoulou, D; Arregui, M; Boeing, H; Weikert, C

2015-04-01

Nuts have beneficial effects on coronary heart disease and many cardiovascular risk factors. However, their effect on stroke is less established, and no studies on the topic are available in Northern and Central European populations. Therefore, we aimed at investigating the association between nut consumption and the risk of stroke in a German population. We used data from a prospective cohort of 26,285 participants of the European Prospective Investigation into the Cancer and Nutrition Potsdam Study. During a median follow-up time of 8.3 years (interquartile range: 7.5-9.2), 288 incident cases of stroke occurred. Nut consumption (standard portion size of 50 g) was assessed at baseline with a semiquantitative food-frequency questionnaire. The median nut intake was 0.82 g per day, interquartile range: 0.41-4.11. In the multivariable model, an increased risk of stroke was observed among participants who never consumed nuts (hazard ratio (HR): 1.56, 95% confidence interval: 1.17-2.08), compared with those consuming <½ portion/week. However, there was no evidence of a dose-response relationship between nut consumption and stroke. Compared with those who consumed <½ portion/week, the multivariable HR for total stroke was 1.06 (0.75-1.52) among those who consumed ½ to 1 portion/week and 1.37 (0.92-2.05) for those who consumed >1 portion/week. Similar nonsignificant associations were observed in stratified analysis for gender, or for fatal and nonfatal stroke. We could not observe an association between nut consumption and the risk of developing stroke (fatal/nonfatal) in a population with low habitual nut consumption.

Association between gastrointestinal bleeding and 3-year mortality in patients with acute, first-ever ischemic stroke.

PubMed

Chou, Yu-Fang; Weng, Wei-Chieh; Huang, Wen-Yi

2017-10-01

The influence of gastrointestinal bleeding on clinical presentation and outcomes of patients with acute ischemic stroke remains controversial. We investigate the effect of gastrointestinal bleeding on the outcomes of patients with acute, first-ever ischemic stroke. We enrolled 934 patients with acute, first-ever ischemic stroke and followed up them for 3years. Patients were divided into 2 groups according to the presence or absence of gastrointestinal bleeding during acute stroke stage. Clinical presentation, stroke risk factors, laboratory data, co-morbidities, and outcomes were recorded. Seventy-six (8.1%) patients had gastrointestinal bleeding at admission. The prevalence of old age, atrial fibrillation, and previous transient ischemic attack was higher in patients with gastrointestinal bleeding (P<0.001, P=0.038, and P=0.018, respectively). Total anterior circulation syndrome occurred more frequently among patients with gastrointestinal bleeding (P<0.001). The mean length of acute ward stay, initial impaired consciousness, and stroke in evolution were higher in patients with gastrointestinal bleeding (P<0.001, P<0.001, and P<0.001, respectively). The occurrence of pneumonia and dependent functional outcome were higher in patients with gastrointestinal bleeding (P<0.001 and P<0.001, respectively). A multivariate Cox regression analysis revealed that gastrointestinal bleeding is a significant risk factor for 3-year all-cause mortality (hazard ratio=2.76; 95% confidence interval=1.61-4.72; P<0.001). In conclusion, gastrointestinal bleeding is associated with increased risk of 3-year mortality in patients with acute, first-ever ischemic stroke. Prophylactic therapies for gastrointestinal bleeding might improve ischemic stroke outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modern medical treatment with or without carotid endarterectomy for severe asymptomatic carotid atherosclerosis.

PubMed

Kolos, Igor; Troitskiy, Alexandr; Balakhonova, Tatiana; Shariya, Merab; Skrypnik, Denis; Tvorogova, Tatiana; Deev, Alexandr; Boytsov, Sergey

2015-10-01

This study assessed the value of modern medical treatment (MMT) with and without carotid endarterectomy (CEA) in patients with asymptomatic severe carotid artery stenosis. We conducted a randomized trial involving 55 patients with 70% to 79% carotid stenosis at three Russian centers. Between 2009 and 2013, 31 patients were randomized to undergo CEA with MMT (CEA group) and 24 to receive MMT alone. The primary end point was nonfatal ipsilateral stroke or death from any cause during a follow-up period of 5.0 years. The secondary end point was any nonfatal stroke, carotid revascularization, or death from any cause during follow-up. The trial was stopped after a median follow-up of 3.3 years (maximum, 5.0 years). There were two primary events in the CEA group and nine events in the MMT group. The 3.3-year cumulative primary event rates were 6.5% in the CEA group and 37.5% in the MMT group (hazard ratio for the MMT group, 5.06; 95% confidence interval, 1.53-16.79; P = .008). The 3.3-year cumulative secondary end point was 12.9% in the CEA group and 50.0% in the MMT group (hazard ratio for the MMT group, 4.23; 95% confidence interval, 1.55-11.53; P = .0048). CEA as an initial management strategy could reduce the risk of death and major cerebrovascular events when added to MMT. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Bleeding risk in patients with atrial fibrillation: the AMADEUS study.

PubMed

Lane, Deirdre A; Kamphuisen, Pieter W; Minini, Pascal; Büller, Harry R; Lip, Gregory Y H

2011-07-01

This study aimed to assess the impact of combination antithrombotic therapy on stroke and bleeding risk compared with anticoagulation therapy only in patients with atrial fibrillation (AF). Post hoc analysis of 4,576 patients with AF (mean ± SD age, 70.1 ± 9.1 years; men, 66.5%) enrolled in the Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation (AMADEUS) trial were randomized to receive either subcutaneous idraparinux (2.5 mg weekly) (n = 2,283) or dose-adjusted vitamin K antagonists (VKAs) (international normalized ratio, 2.0-3.0) (n = 2,293). Of these patients, 848 (18.5%) received antiplatelet therapy (aspirin, clopidogrel, ticlopidine, etc) in addition to anticoagulation treatment (combination antithrombotic therapy). A total of 572 (15.3% per year) clinically relevant bleeding and 103 (2.6% per year) major bleeding events occurred. Patients receiving combination antithrombotic therapy had a 2.3- to 2.5-fold increased risk of clinically relevant bleeding events and major bleeding events, respectively, compared with those receiving anticoagulation therapy only. Multivariate analyses (hazard ratio, 95% CI) revealed that the risk of clinically relevant bleeding was significantly increased by age 65 to 74 years (1.44, 1.14-1.82) and ≥ 75 years (1.59, 1.24-2.04, P = .001) and by combination antithrombotic therapy (2.47, 2.07-2.96, P < .0001). The same held true for major bleeding events, with analogous figures for age 65 to 74 years (2.26, 1.08-4.71) and ≥ 75 years (4.19, 1.98-8.87, P = .0004) and for combination antithrombotic therapy (2.23, 1.49-3.34, P < .0001). Combination antithrombotic therapy was not associated with a decrease in ischemic stroke risk compared with anticoagulation therapy only (11 [1.4% per year] vs 22 [0.7% per year]; adjusted hazard ratio, 2.01; 95% CI, 0.94-4.30; P = .07). Combination antithrombotic therapy increases the risk of clinically relevant bleeding and major bleeding in patients with AF and does not appear to reduce the risk of stroke.

Effectiveness and Safety of Dabigatran, Rivaroxaban, and Apixaban Versus Warfarin in Nonvalvular Atrial Fibrillation.

PubMed

Yao, Xiaoxi; Abraham, Neena S; Sangaralingham, Lindsey R; Bellolio, M Fernanda; McBane, Robert D; Shah, Nilay D; Noseworthy, Peter A

2016-06-13

The introduction of non-vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may not translate to routine practice. We aimed to evaluate the effectiveness and safety of dabigatran, rivaroxaban, and apixaban by comparing each agent with warfarin. Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15 390), dabigatran versus warfarin (n=28 614), and rivaroxaban versus warfarin (n=32 350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio [HR] 0.67, 95% CI 0.46-0.98, P=0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76-1.26, P=0.98; rivaroxaban: HR 0.93, 95% CI 0.72-1.19, P=0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban: HR 0.45, 95% CI 0.34-0.59, P<0.001; dabigatran: HR 0.79, 95% CI 0.67-0.94, P<0.01), and rivaroxaban was associated with a similar risk (HR 1.04, 95% CI 0.90-1.20], P=0.60). All non-vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding. In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated with similar risk of stroke but lower risk of major bleeding, and rivaroxaban was associated with similar risks of both stroke and major bleeding in comparison to warfarin. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

[TECOS: confirmation of the cardiovascular safety of sitaliptin].

PubMed

Scheen, A J; Paquot, N

2015-10-01

The cardiovascular safety of sitagliptin has been evaluated in TECOS ("Trial Evaluating Cardiovascular Outcomes with Sitagliptin"). TECOS recruited patients with type 2 diabetes and a history of cardiovascular disease who received, as add-on to their usual therapy, either sitagliptin (n = 7.257) or placebo (n = 7.266), with a median follow-up of 3 years. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% confidence interval, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). The cardiovascular safety of sitagliptin, which was already shown in meta-analyses of phase II-III randomised controlled trials and in observational cohort studies in real life, is now confirmed in the landmark prospective cardiovascular outcome study TECOS.

30-day mortality and readmission after hemorrhagic stroke among Medicare beneficiaries in Joint Commission primary stroke center-certified and noncertified hospitals.

PubMed

Lichtman, Judith H; Jones, Sara B; Leifheit-Limson, Erica C; Wang, Yun; Goldstein, Larry B

2011-12-01

Ischemic stroke patients treated at Joint Commission Primary Stroke Center (JC-PSC)-certified hospitals have better outcomes. Data reflecting the impact of JC-PSC status on outcomes after hemorrhagic stroke are limited. We determined whether 30-day mortality and readmission rates after hemorrhagic stroke differed for patients treated at JC-PSC-certified versus noncertified hospitals. The study included all fee-for-service Medicare beneficiaries aged 65 years or older with a primary discharge diagnosis of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) in 2006. Covariate-adjusted logistic and Cox proportional hazards regression assessed the effect of care at a JC-PSC-certified hospital on 30-day mortality and readmission. There were 2305 SAH and 8708 ICH discharges from JC-PSC-certified hospitals and 3892 SAH and 22 564 ICH discharges from noncertified hospitals. Unadjusted in-hospital mortality (SAH: 27.5% versus 33.2%, P<0.0001; ICH: 27.9% versus 29.6%, P=0.003) and 30-day mortality (SAH: 35.1% versus 44.0%, P<0.0001; ICH: 39.8% versus 42.4%, P<0.0001) were lower in JC-PSC hospitals, but 30-day readmission rates were similar (SAH: 17.0% versus 17.0%, P=0.97; ICH: 16.0% versus 15.5%, P=0.29). Risk-adjusted 30-day mortality was 34% lower (odds ratio, 0.66; 95% confidence interval, 0.58-0.76) after SAH and 14% lower (odds ratio, 0.86; 95% confidence interval, 0.80-0.92) after ICH for patients discharged from JC-PSC-certified hospitals. There was no difference in 30-day risk-adjusted readmission rates for SAH or ICH based on JC-PSC status. Patients treated at JC-PSC-certified hospitals had lower risk-adjusted mortality rates for both SAH and ICH but similar 30-day readmission rates as compared with noncertified hospitals.

Cardiovascular Risks Associated with Incident and Prevalent Periodontal Disease

PubMed Central

Yu, Yau-Hua; Chasman, Daniel I; Buring, Julie E; Rose, Lynda; Ridker, Paul M

2014-01-01

Aim While prevalent periodontal disease associates with cardiovascular risk, little is known about how incident periodontal disease influences future vascular risk. We compared effects of incident versus prevalent periodontal disease in developing major cardiovascular diseases (CVD), myocardial infarction (MI), ischemic stroke and total CVD. Material and Methods In a prospective cohort of 39863 predominantly white women, age ≥ 45 years and free of cardiovascular disease at baseline were followed for an average of 15.7 years. Cox proportional hazard models with time-varying periodontal status (prevalent [18%], incident [7.3%] vs. never [74.7%]) were used to assess future cardiovascular risks. Results Incidence rates of all CVD outcomes were higher in women with prevalent or incident periodontal disease. For women with incident periodontal disease, risk factor adjusted hazard ratios (HRs) were 1.42 (95% CI, 1.14–1.77) for major CVD, 1.72 (1.25–2.38) for MI, 1.41(1.02–1.95) for ischemic stroke, and 1.27(1.06–1.52) for total CVD. For women with prevalent periodontal disease, adjusted HRs were 1.14 (1.00–1.31) for major CVD, 1.27 (1.04–1.56) for MI, 1.12(0.91–1.37) for ischemic stroke, and 1.15(1.03–1.28) for total CVD. Conclusion New cases of periodontal disease, not just those that are pre-existing, place women at significantly elevated risks for future cardiovascular events. PMID:25385537

Incidence Rate of Cardiovascular Disease End Points in the National Aeronautics and Space Administration Astronaut Corps.

PubMed

Ade, Carl J; Broxterman, Ryan M; Charvat, Jacqueline M; Barstow, Thomas J

2017-08-07

It is unknown whether the astronaut occupation or exposure to microgravity influences the risk of long-term cardiovascular disease (CVD). This study explored the effects of being a career National Aeronautics and Space Administration (NASA) astronaut on the risk for clinical CVD end points. During the Longitudinal Study of Astronaut Health, data were collected on 310 NASA astronauts and 981 nonastronaut NASA employees. The nonastronauts were matched to the astronauts on age, sex, and body mass index, to evaluate acute and chronic morbidity and mortality. The primary outcomes were composites of clinical CVD end points (myocardial infarction, congestive heart failure, stroke, and coronary artery bypass surgery) or coronary artery disease (CAD) end points (myocardial infarction and coronary artery bypass surgery). Of the astronauts, 5.2% had a clinical CVD end point and 2.9% had a CAD end point compared with the nonastronaut comparisons with 4.7% and 3.1% having CVD and CAD end points, respectively. In the multivariate models adjusted for traditional risk factors, astronauts had a similar risk of CVD compared with nonastronauts (adjusted hazard ratio, 1.08; 95% CI, 0.60-1.93; P =0.80). Risk of a CAD end point was similar between groups (hazard ratio, 0.97; CI, 0.45-2.08; P =0.93). In astronauts with early spaceflight experience, the risk of CVD (hazard ratio, 0.80; CI, 0.25-2.56; P =0.71) and CAD (hazard ratio, 1.23; CI: 0.27-5.61; P =0.79) compared with astronauts with no experience were not different. These findings suggest that being an astronaut is not associated with increased long-term risk of CVD development. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Do acute myocardial infarction and stroke mortality vary by distance to hospitals in Switzerland? Results from the Swiss National Cohort Study.

PubMed

Berlin, Claudia; Panczak, Radoslaw; Hasler, Rebecca; Zwahlen, Marcel

2016-11-01

Switzerland has mountains and valleys complicating the access to a hospital and critical care in case of emergencies. Treatment success for acute myocardial infarction (AMI) or stroke depends on timely treatment. We examined the relationship between distance to different hospital types and mortality from AMI or stroke in the Swiss National Cohort (SNC) Study. The SNC is a longitudinal mortality study of the census 2000 population of Switzerland. For 4.5 million Swiss residents not living in a nursing home and older than 30 years in the year 2000, we calculated driving time and straight-line distance from their home to the nearest acute, acute with emergency room, central and university hospital (in total 173 hospitals). On the basis of quintiles, we used multivariable Cox proportional hazard models to estimate HRs of AMI and stroke mortality for driving time distance groups compared to the closest distance group. Over 8 years, 19 301 AMI and 21 931 stroke deaths occurred. Mean driving time to the nearest acute hospital was 6.5 min (29.7 min to a university hospital). For AMI mortality, driving time to a university hospital showed the strongest association among the four types of hospitals with a hazard ratio (HR) of 1.19 (95% CI 1.10 to 1.30) and 1.10 (95% CI 1.01 to 1.20) for men and women aged 65+ years when comparing the highest quintile with the lowest quintile of driving time. For stroke mortality, the association with university hospital driving time was less pronounced than for AMI mortality and did not show a clear incremental pattern with increasing driving time. There was no association with driving time to the nearest hospital. The increasing AMI mortality with increasing driving time to the nearest university hospital but not to any nearest hospital reflects a complex interplay of many factors along the care pathway. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Blood Cadmium Levels and Incident Cardiovascular Events during Follow-up in a Population-Based Cohort of Swedish Adults: The Malmö Diet and Cancer Study

PubMed Central

Barregard, Lars; Sallsten, Gerd; Fagerberg, Björn; Borné, Yan; Persson, Margaretha; Hedblad, Bo; Engström, Gunnar

2015-01-01

Background: Cadmium exposure may increase the risk of cardiovascular disease. The only published longitudinal study on cadmium and incident cardiovascular disease was performed in American Indians with relatively high cadmium exposure. Objectives: Our aim was to examine the association between blood cadmium at baseline and incident cardiovascular events in a population-based study of Swedish men and women with cadmium levels similar to those of most European and U.S. populations. Methods: A Swedish population-based cohort (n = 6,103, age 46–67 years) was recruited between 1991 and 1994. After we excluded those with missing data on smoking, 4,819 participants remained. Acute coronary events, other major cardiac events, stroke, and cardiovascular mortality were followed until 2010. Associations with blood cadmium (estimated from cadmium in erythrocytes) were analyzed using Cox proportional hazards regression including potential confounders and important cardiovascular risk factors. Results: Hazard ratios for all cardiovascular end points were consistently increased for participants in the 4th blood cadmium quartile (median, 0.99 μg/L). In models that also included sex, smoking, waist circumference, education, physical activity, alcohol intake, serum triglycerides, HbA1c, and C-reactive protein, the hazard ratios comparing the highest and lowest quartiles of exposure were 1.8 (95% CI: 1.2, 2.7) for acute coronary events, and 1.9 (1.3, 2.9) for stroke. Hazard ratios in never-smokers were consistent with these estimates. Conclusions: Blood cadmium in the highest quartile was associated with incident cardiovascular disease and mortality in our population-based samples of Swedish adults. The consistent results among never-smokers are important because smoking is a strong confounder. Our findings suggest that measures to reduce cadmium exposures are warranted, even in populations without unusual sources of exposure. Citation: Barregard L, Sallsten G, Fagerberg B, Borné Y, Persson M, Hedblad B, Engström G. 2016. Blood cadmium levels and incident cardiovascular events during follow-up in a population-based cohort of Swedish adults: the Malmö Diet and Cancer Study. Environ Health Perspect 124:594–600; http://dx.doi.org/10.1289/ehp.1509735 PMID:26517380

Flow-gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival.

PubMed

Eleid, Mackram F; Sorajja, Paul; Michelena, Hector I; Malouf, Joseph F; Scott, Christopher G; Pellikka, Patricia A

2013-10-15

Among patients with severe aortic stenosis (AS) and preserved ejection fraction, those with low gradient (LG) and reduced stroke volume may have an adverse prognosis. We investigated the prognostic impact of stroke volume using the recently proposed flow-gradient classification. We examined 1704 consecutive patients with severe AS (aortic valve area <1.0 cm(2)) and preserved ejection fraction (≥50%) using 2-dimensional and Doppler echocardiography. Patients were stratified by stroke volume index (<35 mL/m(2) [low flow, LF] versus ≥35 mL/m(2) [normal flow, NF]) and aortic gradient (<40 mm Hg [LG] versus ≥40 mm Hg [high gradient, HG]) into 4 groups: NF/HG, NF/LG, LF/HG, and LF/LG. NF/LG (n=352, 21%), was associated with favorable survival with medical management (2-year estimate, 82% versus 67% in NF/HG; P<0.0001). LF/LG severe AS (n=53, 3%) was characterized by lower ejection fraction, more prevalent atrial fibrillation and heart failure, reduced arterial compliance, and reduced survival (2-year estimate, 60% versus 82% in NF/HG; P<0.001). In multivariable analysis, the LF/LG pattern was the strongest predictor of mortality (hazard ratio, 3.26; 95% confidence interval, 1.71-6.22; P<0.001 versus NF/LG). Aortic valve replacement was associated with a 69% mortality reduction (hazard ratio, 0.31; 95% confidence interval, 0.25-0.39; P<0.0001) in LF/LG and NF/HG, with no survival benefit associated with aortic valve replacement in NF/LG and LF/HG. NF/LG severe AS with preserved ejection fraction exhibits favorable survival with medical management, and the impact of aortic valve replacement on survival was neutral. LF/LG severe AS is characterized by a high prevalence of atrial fibrillation, heart failure, and reduced survival, and aortic valve replacement was associated with improved survival. These findings have implications for the evaluation and subsequent management of AS severity.

Coated-platelets predict stroke at 30 days following TIA.

PubMed

Kirkpatrick, Angelia C; Vincent, Andrea S; Dale, George L; Prodan, Calin I

2017-07-11

To examine the potential for coated-platelets, a subset of highly procoagulant platelets observed on dual agonist stimulation with collagen and thrombin, for predicting stroke at 30 days in patients with TIA. Consecutive patients with TIA were enrolled and followed up prospectively. ABCD2 scores were obtained for each patient. Coated-platelet levels, reported as percent of cells converted to coated-platelets, were determined at baseline. The primary endpoint was the occurrence of stroke at 30 days. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including coated-platelets to predict incident stroke at 30 days. A total of 171 patients with TIA were enrolled, and 10 strokes were observed at 30 days. A cutoff of 51.1% for coated-platelet levels yielded a sensitivity of 0.80 (95% confidence interval [CI] 0.55-1.0), specificity of 0.73 (95% CI 0.66-0.80), positive predictive value of 0.16 (95% CI 0.06-0.26), and negative predictive value of 0.98 (95% CI 0.96-1.0). The adjusted hazard ratio of incident stroke in patients with coated-platelet levels ≥51.1% was 10.72 compared to those with levels <51.1%. ROC analysis showed significant improvement in the predictive ability of the coated-platelet model compared to ABCD2 score (AUC 0.78 ± 0.07 vs 0.54 ± 0.07, p = 0.01). These findings suggest a role for coated-platelets in risk stratification for stroke at 30 days after TIA. © 2017 American Academy of Neurology.

Non-high-density lipoprotein cholesterol: an important predictor of stroke and diabetes-related mortality in Japanese elderly diabetic patients.

PubMed

Araki, Atsushi; Iimuro, Satoshi; Sakurai, Takashi; Umegaki, Hiroyuki; Iijima, Katsuya; Nakano, Hiroshi; Oba, Kenzo; Yokono, Koichi; Sone, Hirohito; Yamada, Nobuhiro; Ako, Junya; Kozaki, Koichi; Miura, Hisayuki; Kashiwagi, Atsunori; Kikkawa, Ryuichi; Yoshimura, Yukio; Nakano, Tadasumi; Ohashi, Yasuo; Ito, Hideki

2012-04-01

To evaluate the association of low-density lipoprotein, high-density lipoprotein and non-high-density lipoprotein cholesterol with the risk of stroke, diabetes-related vascular events and mortality in elderly diabetes patients. This study was carried out as a post-hoc landmark analysis of a randomized, controlled, multicenter, prospective intervention trial. We included 1173 elderly type 2 diabetes patients (aged ≥ 65 years) from 39 Japanese institutions who were enrolled in the Japanese elderly diabetes intervention trial study and who could be followed up for 1 year. A landmark survival analysis was carried out in which follow up was set to start 1 year after the initial time of entry. During 6 years of follow up, there were 38 cardiovascular events, 50 strokes, 21 diabetes-related deaths and 113 diabetes-related events. High low-density lipoprotein cholesterol was associated with incident cardiovascular events, and high glycated hemoglobin was associated with strokes. After adjustment for possible covariables, non-high-density lipoprotein cholesterol showed a significant association with increased risk of stroke, diabetes-related mortality and total events. The adjusted hazard ratios (95% confidence intervals) of non-high-density lipoprotein cholesterol were 1.010 (1.001-1.018, P = 0.029) for stroke, 1.019 (1.007-1.031, P < 0.001) for diabetes-related death and 1.008 (1.002-1.014; P < 0.001) for total diabetes-related events. Higher non-high-density lipoprotein cholesterol was associated with an increased risk of stroke, diabetes-related mortality and total events in elderly diabetes patients. © 2012 Japan Geriatrics Society.

Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

PubMed

Patel, Anushka; MacMahon, Stephen; Chalmers, John; Neal, Bruce; Billot, Laurent; Woodward, Mark; Marre, Michel; Cooper, Mark; Glasziou, Paul; Grobbee, Diederick; Hamet, Pavel; Harrap, Stephen; Heller, Simon; Liu, Lisheng; Mancia, Giuseppe; Mogensen, Carl Erik; Pan, Changyu; Poulter, Neil; Rodgers, Anthony; Williams, Bryan; Bompoint, Severine; de Galan, Bastiaan E; Joshi, Rohina; Travert, Florence

2008-06-12

In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately. After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001). A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.) 2008 Massachusetts Medical Society

Challenges in assessing hospital-level stroke mortality as a quality measure: comparison of ischemic, intracerebral hemorrhage, and total stroke mortality rates.

PubMed

Xian, Ying; Holloway, Robert G; Pan, Wenqin; Peterson, Eric D

2012-06-01

Public reporting efforts currently profile hospitals based on overall stroke mortality rates, yet the "mix" of hemorrhagic and ischemic stroke cases may impact this rate. Using the 2005 to 2006 New York state data, we examined the degree to which hospital stroke mortality rankings varied regarding ischemic versus hemorrhagic versus total stroke. Observed/expected ratio was calculated using the Agency for Healthcare Research and Quality Inpatient Quality Indicator software. The observed/expected ratio and outlier status based on stroke types across hospitals were examined using Pearson correlation coefficients (r) and weighted κ. Overall 30-day stroke mortality rates were 15.2% and varied from 11.3% for ischemic stroke and 37.3% for intracerebral hemorrhage. Hospital risk-adjusted ischemic stroke observed/expected ratio was weakly correlated with its own intracerebral hemorrhage observed/expected ratio (r=0.38). When examining hospital performance group (mortality better, worse, or no different than average), disagreement was observed in 35 of 81 hospitals (κ=0.23). Total stroke mortality observed/expected ratio and rankings were correlated with intracerebral hemorrhage (r=0.61 and κ=0.36) and ischemic stroke (r=0.94 and κ=0.71), but many hospitals still switched classification depending on mortality metrics. However, hospitals treating a higher percent of hemorrhagic stroke did not have a statistically significant higher total stroke mortality rate relative to those treating fewer hemorrhagic strokes. Hospital stroke mortality ratings varied considerably depending on whether ischemic, hemorrhagic, or total stroke mortality rates were used. Public reporting of stroke mortality measures should consider providing risk-adjusted outcome on separate stroke types.

Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis.

PubMed

Chaker, Layal; Baumgartner, Christine; den Elzen, Wendy P J; Ikram, M Arfan; Blum, Manuel R; Collet, Tinh-Hai; Bakker, Stephan J L; Dehghan, Abbas; Drechsler, Christiane; Luben, Robert N; Hofman, Albert; Portegies, Marileen L P; Medici, Marco; Iervasi, Giorgio; Stott, David J; Ford, Ian; Bremner, Alexandra; Wanner, Christoph; Ferrucci, Luigi; Newman, Anne B; Dullaart, Robin P; Sgarbi, José A; Ceresini, Graziano; Maciel, Rui M B; Westendorp, Rudi G; Jukema, J Wouter; Imaizumi, Misa; Franklyn, Jayne A; Bauer, Douglas C; Walsh, John P; Razvi, Salman; Khaw, Kay-Tee; Cappola, Anne R; Völzke, Henry; Franco, Oscar H; Gussekloo, Jacobijn; Rodondi, Nicolas; Peeters, Robin P

2015-06-01

The objective was to determine the risk of stroke associated with subclinical hypothyroidism. Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels. We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥ 80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

Differences in Characteristics and Outcomes Between Asian and Non-Asian Patients in the TIAregistry.org.

PubMed

Hoshino, Takao; Uchiyama, Shinichiro; Wong, Lawrence K S; Sissani, Leila; Albers, Gregory W; Bornstein, Natan M; Caplan, Louis R; Donnan, Geoffrey A; Ferro, José M; Hennerici, Michael G; Labreuche, Julien; Lavallée, Philippa C; Molina, Carlos; Rothwell, Peter M; Steg, Philippe Gabriel; Touboul, Pierre-Jean; Vicaut, Éric; Amarenco, Pierre

2017-07-01

This study provides the contemporary causes and prognosis of transient ischemic attack (TIA) and minor stroke in Asians and the direct comparisons with non-Asians. The TIAregistry.org enrolled 4789 patients (1149 Asians and 3640 non-Asians) with a TIA or minor ischemic stroke within 7 days of onset. Every participating facility had systems dedicated to urgent intervention of TIA/stroke patients by specialists. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome. Approximately 80% of patients were evaluated within 24 hours of symptom onset. At 1 year, there were no differences in the rates of composite cardiovascular events (6.8% versus 6.0%; P =0.38) and stroke (6.0% versus 4.8%; P =0.11) between Asians and non-Asians. Asians had a lower risk of cerebrovascular disease (stroke or TIA) than non-Asians (adjusted hazard ratio, 0.79; 95% confidence interval, 0.63-0.98; P =0.03); the difference was primarily driven by a lower rate of TIA in Asians (4.2% versus 8.3%; P <0.001). Moderately severe bleeding was more frequent in Asians (0.8% versus 0.3%; P =0.02). In multivariable analysis, multiple acute infarcts ( P =0.005) and alcohol consumption ( P =0.02) were independent predictors of stroke recurrence in Asians, whereas intracranial stenosis ( P <0.001), ABCD 2 score ( P <0.001), atrial fibrillation ( P =0.008), extracranial stenosis ( P =0.03), and previous stroke or TIA ( P =0.03) were independent predictors in non-Asians. The short-term stroke risk after a TIA or minor stroke was lower than expected when urgent evidence-based care was delivered, irrespective of race/ethnicity or region. However, the predictors of stroke were different for Asians and non-Asians. © 2017 American Heart Association, Inc.

Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration.

PubMed

Jolly, Sanjit S; James, Stefan; Džavík, Vladimír; Cairns, John A; Mahmoud, Karim D; Zijlstra, Felix; Yusuf, Salim; Olivecrona, Goran K; Renlund, Henrik; Gao, Peggy; Lagerqvist, Bo; Alazzoni, Ashraf; Kedev, Sasko; Stankovic, Goran; Meeks, Brandi; Frøbert, Ole

2017-01-10

Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment-elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment-elevation myocardial infarction. Included were large (n≥1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment-elevation myocardial infarction. Individual patient data were provided by the leadership of each trial. The prespecified primary efficacy outcome was cardiovascular mortality within 30 days, and the primary safety outcome was stroke or transient ischemic attack within 30 days. The 3 eligible randomized trials (TAPAS [Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction], TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia], and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) enrolled 19 047 patients, of whom 18 306 underwent PCI and were included in the primary analysis. Cardiovascular death at 30 days occurred in 221 of 9155 patients (2.4%) randomized to thrombus aspiration and 262 of 9151 (2.9%) randomized to PCI alone (hazard ratio, 0.84; 95% confidence interval, 0.70-1.01; P=0.06). Stroke or transient ischemic attack occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio, 1.43; 95% confidence interval, 0.98-2.10; P=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure, or target vessel revascularization. In the subgroup with high thrombus burden (TIMI [Thrombolysis in Myocardial Infarction] thrombus grade ≥3), thrombus aspiration was associated with fewer cardiovascular deaths (170 [2.5%] versus 205 [3.1%]; hazard ratio, 0.80; 95% confidence interval, 0.65-0.98; P=0.03) and with more strokes or transient ischemic attacks (55 [0.9%] versus 34 [0.5%]; odds ratio, 1.56; 95% confidence interval, 1.02-2.42, P=0.04). However, the interaction P values were 0.32 and 0.34, respectively. Routine thrombus aspiration during PCI for ST-segment-elevation myocardial infarction did not improve clinical outcomes. In the high thrombus burden group, the trends toward reduced cardiovascular death and increased stroke or transient ischemic attack provide a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup. URLs: http://www.ClinicalTrials.gov http://www.crd.york.ac.uk/prospero/. Unique identifiers: NCT02552407 and CRD42015025936. © 2016 American Heart Association, Inc.

The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis.

PubMed

Debette, Stéphanie; Markus, H S

2010-07-26

To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death. Systematic review and meta-analysis. PubMed from 1966 to 23 November 2009. Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death. Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome. 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested. White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

Increased Vascular Disease Mortality Risk in Prediabetic Korean Adults Is Mainly Attributable to Ischemic Stroke.

PubMed

Kim, Nam Hoon; Kwon, Tae Yeon; Yu, Sungwook; Kim, Nan Hee; Choi, Kyung Mook; Baik, Sei Hyun; Park, Yousung; Kim, Sin Gon

2017-04-01

Prediabetes is a known risk factor for vascular diseases; however, its differential contribution to mortality risk from various vascular disease subtypes is not known. The subjects of the National Health Insurance Service in Korea (2002-2013) nationwide cohort were stratified into normal glucose tolerance (fasting glucose <100 mg/dL), impaired fasting glucose (IFG) stage 1 (100-109 mg/dL), IFG stage 2 (110-125 mg/dL), and diabetes mellitus groups based on the fasting glucose level. A Cox regression analysis with counting process formulation was used to assess the mortality risk for vascular disease and its subtypes-ischemic heart disease, ischemic stroke, and hemorrhagic stroke. When adjusted for age, sex, and body mass index, IFG stage 2, but not stage 1, was associated with significantly higher all-cause mortality (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.18-1.34) and vascular disease mortality (HR, 1.27; 95% CI, 1.08-1.49) compared with normal glucose tolerance. Among the vascular disease subtypes, mortality from ischemic stroke was significantly higher (HR, 1.60; 95% CI, 1.18-2.18) in subjects with IFG stage 2 but not from ischemic heart disease and hemorrhagic stroke. The ischemic stroke mortality associated with IFG stage 2 remained significantly high when adjusted other modifiable vascular disease risk factors (HR, 1.51; 95% CI: 1.10-2.09) and medical treatments (HR, 1.75; 95% CI, 1.19-2.57). Higher IFG degree (fasting glucose, 110-125 mg/dL) was associated with increased all-cause and vascular disease mortality. The increased vascular disease mortality in IFG stage 2 was attributable to ischemic stroke, but not ischemic heart disease or hemorrhagic stroke in Korean adults. © 2017 American Heart Association, Inc.

Sugar- and artificially-sweetened beverages and the risks of incident stroke and dementia: A prospective cohort study

PubMed Central

Pase, Matthew P.; Himali, Jayandra J.; Beiser, Alexa S.; Aparicio, Hugo J.; Satizabal, Claudia L.; Vasan, Ramachandran S.; Seshadri, Sudha; Jacques, Paul F.

2017-01-01

Background and purpose Sugar- and artificially-sweetened beverage intake have been linked to cardiometabolic risk factors, which increase the risk of cerebrovascular disease and dementia. We examined whether sugar- or artificially-sweetened beverage consumption were associated with the prospective risks of incident stroke or dementia in the community-based Framingham Heart Study Offspring cohort. Methods We studied 2888 participants aged over 45 for incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged over 60 for incident dementia (mean age 69 [SD, 6] years; 46% men). Beverage intake was quantified using a food frequency questionnaire at cohort examinations 5 (1991–1995), 6 (1995–1998) and 7 (1998–2001). We quantified recent consumption at examination 7 and cumulative consumption by averaging across examinations. Surveillance for incident events commenced at examination 7 and continued for 10-years. We observed 97 cases of incident stroke (82 ischemic) and 81 cases of incident dementia (63 consistent with Alzheimer’s disease [AD]). Results After adjustments for age, sex, education (for analysis of dementia), caloric intake, diet quality, physical activity and smoking, higher recent and higher cumulative intake of artificially-sweetened soft drinks were associated with an increased risk of ischemic stroke, all-cause dementia, and AD dementia. When comparing daily cumulative intake to <1 per week (reference), the hazard ratios were 2.96 (95% CI, 1.26–6.97) for ischemic stroke and 2.89 (95% CI, 1.18–7.07) for AD. Sugar-sweetened beverages were not associated with stroke or dementia. Conclusions Artificially-sweetened soft drink consumption was associated with a higher risk of stroke and dementia. PMID:28428346

Increased risk of incident stroke associated with the cyclooxygenase 2 (COX-2) G-765C polymorphism in African-Americans: the Atherosclerosis Risk in Communities Study.

PubMed

Kohsaka, Shun; Volcik, Kelly A; Folsom, Aaron R; Wu, Kenneth K; Ballantyne, Christie M; Willerson, James T; Boerwinkle, Eric

2008-02-01

A hallmark feature of atherosclerosis is inflammation mediated by prostaglandins (PGs) catalyzed by the enzyme cyclooxygenase (COX). The present study explored whether the COX-2 G-765C polymorphism contributes to increased incidence of coronary heart disease (CHD) or stroke in the large prospective Atherosclerosis Risk in Communities (ARIC) Study. Incidences of CHD and stroke were identified through annual follow-up and hospital and death certificate surveillance. The study included 1488 incident CHD and 527 stroke events after an average of 14 years of follow-up. The frequency of the -765C variant allele was markedly different between African-Americans and whites, therefore all analyses were performed separately by race. Due to the small number of persons with the -765CC genotype, heterozygous and homozygous variant genotypes were combined for this analysis. The COX-2 G-765C polymorphism was not a significant predictor of CHD in either racial group, but it was a significant predictor of incident stroke in African-Americans. After adjustment for age and gender, the hazard rate ratio for developing stroke for the CG+CC genotypes relative to the GG genotype was 1.34 (95% confidence interval [CI] 1.03-1.74, P=0.03) in African-Americans. This result was essentially unchanged when established predictors such as smoking, diabetes and hypertension were added to the model (HRR 1.34, 95%CI 1.03-1.76, P=0.03). We have found the COX-2 G-765C polymorphism to be a risk factor for incident stroke in African-Americans. This study provides additional evidence for utilizing inflammation-related genetic polymorphisms for identifying individuals at increased risk for stroke.

Association of multiple infarctions and ICAS with outcomes of minor stroke and TIA.

PubMed

Pan, Yuesong; Meng, Xia; Jing, Jing; Li, Hao; Zhao, Xingquan; Liu, Liping; Wang, David; Johnston, S Claiborne; Wang, Yilong; Wang, Yongjun

2017-03-14

To estimate the association of different patterns of infarction and intracranial arterial stenosis (ICAS) with the prognosis of acute minor ischemic stroke and TIA. We derived data from the Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. A total of 1,089 patients from 45 of 114 participating sites of the trial undergoing baseline MRI/angiography were included in this subgroup analysis. Patterns of infarction and ICAS were recorded for each individual. The primary efficacy outcome was an ischemic stroke at the 90-day follow-up. We assessed the associations between imaging patterns and prognosis of patients using multivariable Cox regression models. Among the 1,089 patients included in this subgroup analysis, 93 (8.5%) patients had a recurrent ischemic stroke at 90 days. Compared with those without infarction or ICAS, patients with single infarction with ICAS (11.9% vs 1.3%, hazard ratio [HR] 6.25, 95% confidence intervals [CIs] 1.40-27.86, p = 0.02) and single infarction without ICAS (6.8% vs 1.3%, HR 4.65, 95% CI 1.05-20.64, p = 0.04) were all associated with an increased risk of ischemic stroke at 90 days. Patients with both multiple infarctions and ICAS were associated with approximately 13-fold risk of ischemic stroke at 90 days (18.0% vs 1.3%, HR 13.14, 95% CI 2.96-58.36, p < 0.001). The presence of multiple infarctions and ICAS were both associated with an increased risk of 90-day ischemic stroke in patients with minor stroke or TIA, while the presence of both imaging features had a combined effect. NCT00979589. © 2017 American Academy of Neurology.

Preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs and 30-day stroke mortality.

PubMed

Schmidt, Morten; Hováth-Puhó, Erzsébet; Christiansen, Christian Fynbo; Petersen, Karin L; Bøtker, Hans Erik; Sørensen, Henrik Toft

2014-11-25

To examine whether preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) influenced 30-day stroke mortality. We conducted a nationwide population-based cohort study. Using medical databases, we identified all first-time stroke hospitalizations in Denmark between 2004 and 2012 (n = 100,043) and subsequent mortality. We categorized NSAID use as current (prescription redemption within 60 days before hospital admission), former, and nonuse. Current use was further classified as new or long-term use. Cox regression was used to compute hazard ratios (HRs) of death within 30 days, controlling for potential confounding through multivariable adjustment and propensity score matching. The adjusted HR of death for ischemic stroke was 1.19 (95% confidence interval [CI]: 1.02-1.38) for current users of selective cyclooxygenase (COX)-2 inhibitors compared with nonusers, driven by the effect among new users (1.42, 95% CI: 1.14-1.77). Comparing the different COX-2 inhibitors, the HR was driven by new use of older traditional COX-2 inhibitors (1.42, 95% CI: 1.14-1.78) among which it was 1.53 (95% CI: 1.02-2.28) for etodolac and 1.28 (95% CI: 0.98-1.68) for diclofenac. The propensity score-matched analysis supported the association between older COX-2 inhibitors and ischemic stroke mortality. There was no association for former users. Mortality from intracerebral hemorrhage was not associated with use of nonselective NSAIDs or COX-2 inhibitors. Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke. Use of nonselective NSAIDs at time of admission was not associated with mortality from ischemic stroke or intracerebral hemorrhage. © 2014 American Academy of Neurology.

Secular trends in the incidence of and risk factors for ischemic stroke and its subtypes in Japanese population.

PubMed

Kubo, Michiaki; Hata, Jun; Doi, Yasufumi; Tanizaki, Yumihiro; Iida, Mitsuo; Kiyohara, Yutaka

2008-12-16

The study of long-term trends in the incidence of and risk factors for ischemic stroke subtypes could offer insights into primary and secondary prevention. We established 3 cohorts of residents >/=40 years of age in 1961, 1974, and 1988 in the Japanese community of Hisayama. Morphological examinations by autopsy or brain imaging were performed on most of the ischemic stroke cases developed in these cohorts. When 13-year follow-up data were compared, the age-adjusted incidence of ischemic stroke and lacunar infarction declined significantly from the first to the third cohort for both sexes, whereas the incidences of atherothrombotic and cardioembolic infarction did not change during this period. Hypertension was a powerful risk factor for the development of ischemic stroke, and improvement of hypertension control would have largely influenced this declining trend: The age- and sex-adjusted hazard ratio of hypertension decreased from 3.25 (95% CI 2.17 to 4.86) in the first cohort to 1.83 (1.29 to 2.58) in the third cohort. A rapid increase in the prevalence of metabolic disorders may have offset the impact of improvements in hypertension control and resulted in a slowdown of the decline in the incidence of ischemic stroke in the cohorts in the present study; however, hypertension still makes a large contribution to the development of ischemic stroke. These findings suggest that in the Japanese population, the incidence of ischemic stroke has declined significantly over the past 40 years, probably owing to better management of hypertension. There is a need for greater primary prevention efforts in the treatment of hypertension and metabolic disorders.

Smoking and mortality in stroke survivors: can we eliminate the paradox?

PubMed

Levine, Deborah A; Walter, James M; Karve, Sudeep J; Skolarus, Lesli E; Levine, Steven R; Mulhorn, Kristine A

2014-07-01

Many studies have suggested that smoking does not increase mortality in stroke survivors. Index event bias, a sample selection bias, potentially explains this paradoxical finding. Therefore, we compared all-cause, cardiovascular disease (CVD), and cancer mortality by cigarette smoking status among stroke survivors using methods to account for index event bias. Among 5797 stroke survivors of 45 years or older who responded to the National Health Interview Survey years 1997-2004, an annual, population-based survey of community-dwelling US adults, linked to the National Death Index, we estimated all-cause, CVD, and cancer mortality by smoking status using Cox proportional regression and propensity score analysis to account for demographic, socioeconomic, and clinical factors. Mean follow-up was 4.5 years. From 1997 to 2004, 18.7% of stroke survivors smoked. There were 1988 deaths in this stroke survivor cohort, with 50% of deaths because of CVD and 15% because of cancer. Current smokers had an increased risk of all-cause mortality (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.14-1.63) and cancer mortality (HR, 3.83; 95% CI, 2.48-5.91) compared with never smokers, after controlling for demographic, socioeconomic, and clinical factors. Current smokers had an increased risk of CVD mortality controlling for age and sex (HR, 1.29; 95% CI, 1.01-1.64), but this risk did not persist after controlling for socioeconomic and clinical factors (HR, 1.15; 95% CI, .88-1.50). Stroke survivors who smoke have an increased risk of all-cause mortality, which is largely because of cancer mortality. Socioeconomic and clinical factors explain stroke survivors' higher risk of CVD mortality associated with smoking. Published by Elsevier Inc.

Efficacy and safety of rivaroxaban compared with warfarin in patients with carotid artery disease and nonvalvular atrial fibrillation: Insights from the ROCKET AF trial.

PubMed

Kochar, Ajar; Hellkamp, Anne S; Lokhnygina, Yuliya; Jones, W Schuyler; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Singer, Daniel E; Piccini, Jonathan P; Patel, Manesh R

2018-01-01

Atrial fibrillation (AF) increases risk of stroke 5-fold. Carotid artery disease (CD) also augments the risk of stroke, yet there are limited data about the interplay of these 2 diseases and clinical outcomes in patients with comorbid AF and CD. Among patients with both AF and CD, use of rivaroxaban when compared with warfarin is associated with a lower risk of stroke. This post hoc analysis from ROCKET AF aimed to determine absolute rates of stroke/systemic embolism (SE) and bleeding, and the efficacy and safety of rivaroxaban compared with warfarin in patients with AF and CD (defined as history of carotid occlusive disease or carotid revascularization [endarterectomy and/or stenting]). A total of 593 (4.2%) patients had CD at enrollment. Patients with and without CD had similar rates of stroke or SE (adjusted hazard ratio [HR]: 0.99, 95% confidence interval [CI]: 0.66-1.48, P = 0.96), and there was no difference in major or nonmajor clinically relevant bleeding (adjusted HR: 1.04, 95% CI: 0.88-1.24, P = 0.62). The efficacy of rivaroxaban compared with warfarin for the prevention of stroke/SE was not statistically significant in patients with vs those without CD (interaction P = 0.25). The safety of rivaroxaban vs warfarin for major or nonmajor clinically relevant bleeding was similar in patients with and without CD (interaction P = 0.64). Patients with CD in ROCKET AF had similar risk of stroke/SE compared with patients without CD. Additionally, there was no interaction between CD and the treatment effect of rivaroxaban or warfarin for stroke prevention or safety endpoints. © 2018 Wiley Periodicals, Inc.

Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation.

PubMed

Ujeyl, Mariam; Köster, Ingrid; Wille, Hans; Stammschulte, Thomas; Hein, Rebecca; Harder, Sebastian; Gundert-Remy, Ursula; Bleek, Julian; Ihle, Peter; Schröder, Helmut; Schillinger, Gerhard; Zawinell, Anette; Schubert, Ingrid

2018-06-16

The pivotal trials for stroke prevention in non-valvular atrial fibrillation (NVAF) compared rivaroxaban, dabigatran, and apixaban with warfarin, as did most claims-based studies. Comparisons with phenprocoumon, the most frequently used vitamin K antagonist (VKA) in Germany, are scarce. Risk of bleeding, ischemic stroke, and all-cause mortality in patients with NVAF were analyzed using data for 2010 to 2014 from a large German claims database. New users of oral anticoagulants from January 2012 to December 2013 were included and observed over 1 year. Baseline characteristics were adjusted using propensity score matching and logistic regression. Several sensitivity analyses were carried out. Fifty-nine thousand four hundred forty-nine rivaroxaban, 23,654 dabigatran, 4894 apixaban, and 87,997 matched phenprocoumon users were included. Adjusted hazard ratios (95% confidence intervals) compared with phenprocoumon were as follows: hospitalized bleedings: rivaroxaban 1.04 (0.97; 1.11), dabigatran 0.87 (0.77; 0.98), and apixaban 0.65 (0.50; 0.86); ischemic stroke: rivaroxaban 1.05 (0.94; 1.17), dabigatran 1.14 (0.96; 1.35), and apixaban 1.84 (1.20; 2.84); all-cause mortality: rivaroxaban 1.17 (1.11; 1.22), dabigatran 1.04 (0.95; 1.13), and apixaban 1.14 (0.97; 1.34). With rivaroxaban, no significant differences were observed compared to phenprocoumon with regard to hospitalized bleedings or ischemic strokes. Dabigatran was associated with fewer bleedings and a similar risk of ischemic strokes compared to phenprocoumon. Apixaban was also associated with fewer bleedings but was unexpectedly associated with more ischemic strokes, possibly reflecting selective prescribing. The association of rivaroxaban with higher all-cause mortality unrelated to bleedings or strokes has been described previously but remains to be explained.

Intakes of magnesium, potassium, and calcium and the risk of stroke among men.

PubMed

Adebamowo, Sally N; Spiegelman, Donna; Flint, Alan J; Willett, Walter C; Rexrode, Kathryn M

2015-10-01

Intakes of magnesium, potassium, and calcium have been inversely associated with the incidence of hypertension, a known risk factor for stroke. However, only a few studies have examined intakes of these cations in relation to risk of stroke. The aim of this study was to investigate whether high intake of magnesium, potassium, and calcium is associated with reduced stroke risk among men. We prospectively examined the associations between intakes of magnesium, potassium, and calcium from diet and supplements, and the risk of incident stroke among 42 669 men in the Health Professionals Follow-up Study, aged 40 to 75 years and free of diagnosed cardiovascular disease and cancer at baseline in 1986. We calculated the hazard ratio of total, ischemic, and haemorrhagic strokes by quintiles of each cation intake, and of a combined dietary score of all three cations, using multivariate Cox proportional hazard models. During 24 years of follow-up, 1547 total stroke events were documented. In multivariate analyses, the relative risks and 95% confidence intervals of total stroke for men in the highest vs. lowest quintile were 0·87 (95% confidence interval, 0·74-1·02; P, trend = 0·04) for dietary magnesium, 0·89 (95% confidence interval, 0·76-1·05; P, trend = 0·10) for dietary potassium, and 0·89 (95% confidence interval, 0·75-1·04; P, trend = 0·25) for dietary calcium intake. The relative risk of total stroke for men in the highest vs. lowest quintile was 0·74 (95% confidence interval, 0·59-0·93; P, trend = 0·003) for supplemental magnesium, 0·66 (95% confidence interval, 0·50-0·86; P, trend = 0·002) for supplemental potassium, and 1·01 (95% confidence interval, 0·84-1·20; P, trend = 0·83) for supplemental calcium intake. For total intake (dietary and supplemental), the relative risk of total stroke for men in the highest vs. lowest quintile was 0·83 (95% confidence interval, 0·70-0·99; P, trend = 0·04) for magnesium, 0·88 (95% confidence interval, 0·75-4; P, trend = 6) for potassium, and 3 (95% confidence interval, 79-09; P, trend = 84) for calcium. Men in the highest quintile for a combined dietary score of all three cations had a multivariate relative risk of 0·79 (95% confidence interval, 0·67-0·92; P, trend = 0·008) for total stroke, compared with those in the lowest. A diet rich in magnesium, potassium, and calcium may contribute to reduced risk of stroke among men. Because of significant collinearity, the independent contribution of each cation is difficult to define. © 2015 World Stroke Organization.

Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke.

PubMed

Søndergaard, Lars; Kasner, Scott E; Rhodes, John F; Andersen, Grethe; Iversen, Helle K; Nielsen-Kudsk, Jens E; Settergren, Magnus; Sjöstrand, Christina; Roine, Risto O; Hildick-Smith, David; Spence, J David; Thomassen, Lars

2017-09-14

The efficacy of closure of a patent foramen ovale (PFO) in the prevention of recurrent stroke after cryptogenic stroke is uncertain. We investigated the effect of PFO closure combined with antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infarctions. In this multinational trial involving patients with a PFO who had had a cryptogenic stroke, we randomly assigned patients, in a 2:1 ratio, to undergo PFO closure plus antiplatelet therapy (PFO closure group) or to receive antiplatelet therapy alone (antiplatelet-only group). Imaging of the brain was performed at the baseline screening and at 24 months. The coprimary end points were freedom from clinical evidence of ischemic stroke (reported here as the percentage of patients who had a recurrence of stroke) through at least 24 months after randomization and the 24-month incidence of new brain infarction, which was a composite of clinical ischemic stroke or silent brain infarction detected on imaging. We enrolled 664 patients (mean age, 45.2 years), of whom 81% had moderate or large interatrial shunts. During a median follow-up of 3.2 years, clinical ischemic stroke occurred in 6 of 441 patients (1.4%) in the PFO closure group and in 12 of 223 patients (5.4%) in the antiplatelet-only group (hazard ratio, 0.23; 95% confidence interval [CI], 0.09 to 0.62; P=0.002). The incidence of new brain infarctions was significantly lower in the PFO closure group than in the antiplatelet-only group (22 patients [5.7%] vs. 20 patients [11.3%]; relative risk, 0.51; 95% CI, 0.29 to 0.91; P=0.04), but the incidence of silent brain infarction did not differ significantly between the study groups (P=0.97). Serious adverse events occurred in 23.1% of the patients in the PFO closure group and in 27.8% of the patients in the antiplatelet-only group (P=0.22). Serious device-related adverse events occurred in 6 patients (1.4%) in the PFO closure group, and atrial fibrillation occurred in 29 patients (6.6%) after PFO closure. Among patients with a PFO who had had a cryptogenic stroke, the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone; however, PFO closure was associated with higher rates of device complications and atrial fibrillation. (Funded by W.L. Gore and Associates; Gore REDUCE ClinicalTrials.gov number, NCT00738894 .).

Effects of intensive blood-pressure control in type 2 diabetes mellitus.

PubMed

Cushman, William C; Evans, Gregory W; Byington, Robert P; Goff, David C; Grimm, Richard H; Cutler, Jeffrey A; Simons-Morton, Denise G; Basile, Jan N; Corson, Marshall A; Probstfield, Jeffrey L; Katz, Lois; Peterson, Kevin A; Friedewald, William T; Buse, John B; Bigger, J Thomas; Gerstein, Hertzel C; Ismail-Beigi, Faramarz

2010-04-29

There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events. A total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. After 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P=0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI, 0.85 to 1.35; P=0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%) (P<0.001). In patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. (ClinicalTrials.gov number, NCT00000620.) 2010 Massachusetts Medical Society

Treatment-resistant hypertension and the incidence of cardiovascular disease and end-stage renal disease: results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

PubMed

Muntner, Paul; Davis, Barry R; Cushman, William C; Bangalore, Sripal; Calhoun, David A; Pressel, Sara L; Black, Henry R; Kostis, John B; Probstfield, Jeffrey L; Whelton, Paul K; Rahman, Mahboob

2014-11-01

Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled hypertension despite the use of ≥3 antihypertensive medication classes or controlled hypertension while treated with ≥4 antihypertensive medication classes. Although a high prevalence of aTRH has been reported, few data are available on its association with cardiovascular and renal outcomes. We analyzed data on 14 684 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants to determine the association between aTRH (n=1870) with coronary heart disease, stroke, all-cause mortality, heart failure, peripheral artery disease, and end-stage renal disease. We defined aTRH as blood pressure not at goal (systolic/diastolic blood pressure ≥140/90 mm Hg) while taking ≥3 classes of antihypertensive medication or taking ≥4 classes of antihypertensive medication with blood pressure at goal during the year 2 ALLHAT study visit (1996-2000). Use of a diuretic was not required to meet the definition of aTRH. Follow-up occurred through 2002. The multivariable adjusted hazard ratios (95% confidence intervals) comparing participants with versus without aTRH were as follows: coronary heart disease (1.44 [1.18-1.76]), stroke (1.57 [1.18-2.08]), all-cause mortality (1.30 [1.11-1.52]), heart failure (1.88 [1.52-2.34]), peripheral artery disease (1.23 [0.85-1.79]), and end-stage renal disease (1.95 [1.11-3.41]). aTRH was also associated with the pooled outcomes of combined coronary heart disease (hazard ratio, 1.47; 95% confidence interval, 1.26-1.71) and combined cardiovascular disease (hazard ratio, 1.46; 95% confidence interval, 1.29-1.64). These results demonstrate that aTRH increases the risk for cardiovascular disease and end-stage renal disease. Studies are needed to identify approaches to prevent aTRH and reduce risk for adverse outcomes among individuals with aTRH. © 2014 American Heart Association, Inc.

Low-dose aspirin for preventing recurrent venous thromboembolism.

PubMed

Brighton, Timothy A; Eikelboom, John W; Mann, Kristy; Mister, Rebecca; Gallus, Alexander; Ockelford, Paul; Gibbs, Harry; Hague, Wendy; Xavier, Denis; Diaz, Rafael; Kirby, Adrienne; Simes, John

2012-11-22

Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism. We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up to 4 years. The primary outcome was a recurrence of venous thromboembolism. During a median follow-up period of 37.2 months, venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin (a rate of 6.5% per year vs. 4.8% per year; hazard ratio with aspirin, 0.74; 95% confidence interval [CI], 0.52 to 1.05; P=0.09). Aspirin reduced the rate of the two prespecified secondary composite outcomes: the rate of venous thromboembolism, myocardial infarction, stroke, or cardiovascular death was reduced by 34% (a rate of 8.0% per year with placebo vs. 5.2% per year with aspirin; hazard ratio with aspirin, 0.66; 95% CI, 0.48 to 0.92; P=0.01), and the rate of venous thromboembolism, myocardial infarction, stroke, major bleeding, or death from any cause was reduced by 33% (hazard ratio, 0.67; 95% CI, 0.49 to 0.91; P=0.01). There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year with placebo vs. 1.1% per year with aspirin, P=0.22) or serious adverse events. In this study, aspirin, as compared with placebo, did not significantly reduce the rate of recurrence of venous thromboembolism but resulted in a significant reduction in the rate of major vascular events, with improved net clinical benefit. These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism. (Funded by National Health and Medical Research Council [Australia] and others; Australian New Zealand Clinical Trials Registry number, ACTRN12605000004662.).

LB01.06: VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY AND CARDIOVASCULAR OUTCOMES IN FELODIPINE EVENT REDUCTION STUDY.

PubMed

Zhang, Y; Zhang, X; Liu, L; Zanchetti, A

2015-06-01

Many antihypertensive outcome trials have shown that visit-to-visit blood pressure variability is correlated closely with clinical outcomes in hypertensive patients. The objective of the study was to investigate the relationship between visit-to-visit blood pressure variability (BPV) and the major cardiovascular outcomes in the Chinese hypertensive patients. Felodipine Event Reduction (FEVER) study was a double-blind, randomized trial on 9711 Chinese hypertensive patients, in whom cardiovascular outcomes were significantly reduced by more intense therapy achieving a mean of 138 mmHg SBP compared with less-intense therapy achieving a mean of 142 mmHg. Visit-to-visit BPV during the follow-up period [defined as standard deviation (SD), coefficient of variation (CV), and average real variability(ARV)] was derived from casual cuff BP measures after six months follow-up until the end of the study. Hazard ratios (HRs), for the incidence of CVD associated with SD, CV, and ARV of SBP and DBP were calculated using Cox proportional hazard models. Overall predictive power [area under receiver operating characteristic (AUC ROC) curve] of the level of blood pressure, blood pressure variability and other baseline characteristics was calculated. In FEVER study, visit-to-visit variability in SBP were significant predictors of subsequent stroke [eg, hazard ratios [HR] for ARV, SD and CV was 1.071 (95% CI: 1.025-1.118), 1.373 (95% CI: 1.159-1.626) and 0.572 (95% CI: 0.451-0,726)]. Visit-to-visit variability in DBP were also showed similar trend [eg, HR for ARV, SD and CV was 1.066 (95% CI: 0.992-1.145), 1.931 (95% CI: 1.435-2.598) and 0.558 (95% CI: 0.438-0,710)]. However, using the analysis of AUC ROC analysis, the risk importance sequence of the stroke events in this cohort was level of SBP, age, level of DBP ARV, SD, sex, CV and treatment. Visit-to-visit blood pressure variability has some effects on the cardiovascular outcomes in the Chinese hypertensive patents in the cohort in FEVER Study. However, blood pressure per se is even more important for the development of stroke in this group of patients.

Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF.

PubMed

Hankey, Graeme J; Patel, Manesh R; Stevens, Susanna R; Becker, Richard C; Breithardt, Günter; Carolei, Antonio; Diener, Hans-Christoph; Donnan, Geoffrey A; Halperin, Jonathan L; Mahaffey, Kenneth W; Mas, Jean-Louis; Massaro, Ayrton; Norrving, Bo; Nessel, Christopher C; Paolini, John F; Roine, Risto O; Singer, Daniel E; Wong, Lawrence; Califf, Robert M; Fox, Keith A A; Hacke, Werner

2012-04-01

In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0-3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio [HR] 0·94, 95% CI 0·77-1·16) and those without (1·44%vs 1·88%; 0·77, 0·58-1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87-1·07) and those without (16·69%vs 15·19%; 1·10, 0·99-1·21; interaction p=0·08). There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF. Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clinical Correlates, Ethnic Differences, and Prognostic Implications of Perivascular Spaces in Transient Ischemic Attack and Ischemic Stroke.

PubMed

Lau, Kui-Kai; Li, Linxin; Lovelock, Caroline E; Zamboni, Giovanna; Chan, Tsz-Tai; Chiang, Man-Fung; Lo, Kin-Ting; Küker, Wilhelm; Mak, Henry Ka-Fung; Rothwell, Peter M

2017-06-01

Perivascular spaces (PVSs) are considered markers of small vessel disease. However, their long-term prognostic implications in transient ischemic attack/ischemic stroke patients are unknown. Ethnic differences in PVS prevalence are also unknown. Two independent prospective studies were conducted, 1 comprising predominantly whites with transient ischemic attack/ischemic stroke (OXVASC [Oxford Vascular] study) and 1 comprising predominantly Chinese with ischemic stroke (University of Hong Kong). Clinical and imaging correlates, prognostic implications for stroke and death, and ethnic differences in basal ganglia (BG) and centrum semiovale (CS) PVSs were studied with adjustment for age, sex, vascular risk factors, and scanner strength. Whites with transient ischemic attack/ischemic stroke (n=1028) had a higher prevalence of both BG and CS-PVSs compared with Chinese (n=974; >20 BG-PVSs: 22.4% versus 7.1%; >20 CS-PVSs: 45.8% versus 10.4%; P <0.0001). More than 20 BG or CS-PVSs were both associated with increasing age and white matter hyperintensity, although associations with BG-PVSs were stronger (all P <0.0001). During 6924 patient-years of follow-up, BG-PVSs were also independently associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio compared with <11 PVSs, 11-20 PVSs: HR, 1.15; 95% confidence interval, 0.78-1.68; >20 PVSs: HR, 1.82; 1.18-2.80; P =0.011) but not intracerebral hemorrhage ( P =0.10) or all-cause mortality ( P =0.16). CS-PVSs were not associated with recurrent stroke ( P =0.57) or mortality ( P =0.072). Prognostic associations were similar in both cohorts. Over and above ethnic differences in frequency of PVSs in transient ischemic attack/ischemic stroke patients, BG and CS-PVSs had similar risk factors, but although >20 BG-PVSs were associated with an increased risk of recurrent ischemic stroke, CS-PVSs were not. © 2017 The Authors.

Clinical Correlates, Ethnic Differences, and Prognostic Implications of Perivascular Spaces in Transient Ischemic Attack and Ischemic Stroke

PubMed Central

Lau, Kui-Kai; Li, Linxin; Lovelock, Caroline E.; Zamboni, Giovanna; Chan, Tsz-Tai; Chiang, Man-Fung; Lo, Kin-Ting; Küker, Wilhelm; Mak, Henry Ka-Fung

2017-01-01

Background and Purpose— Perivascular spaces (PVSs) are considered markers of small vessel disease. However, their long-term prognostic implications in transient ischemic attack/ischemic stroke patients are unknown. Ethnic differences in PVS prevalence are also unknown. Methods— Two independent prospective studies were conducted, 1 comprising predominantly whites with transient ischemic attack/ischemic stroke (OXVASC [Oxford Vascular] study) and 1 comprising predominantly Chinese with ischemic stroke (University of Hong Kong). Clinical and imaging correlates, prognostic implications for stroke and death, and ethnic differences in basal ganglia (BG) and centrum semiovale (CS) PVSs were studied with adjustment for age, sex, vascular risk factors, and scanner strength. Results— Whites with transient ischemic attack/ischemic stroke (n=1028) had a higher prevalence of both BG and CS-PVSs compared with Chinese (n=974; >20 BG-PVSs: 22.4% versus 7.1%; >20 CS-PVSs: 45.8% versus 10.4%; P<0.0001). More than 20 BG or CS-PVSs were both associated with increasing age and white matter hyperintensity, although associations with BG-PVSs were stronger (all P<0.0001). During 6924 patient-years of follow-up, BG-PVSs were also independently associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio compared with <11 PVSs, 11–20 PVSs: HR, 1.15; 95% confidence interval, 0.78–1.68; >20 PVSs: HR, 1.82; 1.18–2.80; P=0.011) but not intracerebral hemorrhage (P=0.10) or all-cause mortality (P=0.16). CS-PVSs were not associated with recurrent stroke (P=0.57) or mortality (P=0.072). Prognostic associations were similar in both cohorts. Conclusions— Over and above ethnic differences in frequency of PVSs in transient ischemic attack/ischemic stroke patients, BG and CS-PVSs had similar risk factors, but although >20 BG-PVSs were associated with an increased risk of recurrent ischemic stroke, CS-PVSs were not. PMID:28495831

25(OH)D deficiency is associated with fatal stroke among whites but not blacks: The NHANES-III linked mortality files

PubMed Central

Michos, Erin D.; Reis, Jared P.; Post, Wendy S.; Lutsey, Pamela L.; Gottesman, Rebecca F.; Mosley, Thomas H.; Sharrett, A. Richey; Melamed, Michal L.

2011-01-01

Objective Deficient 25-hydroxyvitamin D [25(OH)D] levels are associated with cardiovascular disease (CVD) events and mortality. Both 25(OH)D deficiency and stroke are more prevalent among blacks. We examined whether low 25(OH)D contributes to the excess risk of fatal stroke in blacks compared to whites. Research Methods and Procedures The Third National Health and Nutrition Examination Survey, a probability sample of US civilians, measured 25(OH)D levels and CVD risk factors between 1988–1994. Vital status through December 2006 was obtained via linkage with the National Death Index. Among white and black adults without CVD reported at baseline (n=7981), Cox regression models were fit to estimate hazard ratios (HR) for fatal stroke by 25(OH)D status and race. Results During a median of 14.1 years, there were 116 and 60 fatal strokes among whites and blacks respectively. The risk of fatal stroke was greater in blacks compared to whites in models adjusted for socio-economic status and CVD risk factors, [HR 1.60 (95% CI 1.01–2.53)]. Mean baseline 25(OH)D levels were significantly lower in blacks compared to whites (19.4 vs 30.8 ng/mL, respectively). In multivariable-adjusted models, deficient 25(OH)D levels <15 ng/mL were associated with fatal stroke among whites [HR 2.13 (1.01–4.50)] but not blacks [HR 0.93 (0.49–1.80)]. Conclusions Vitamin D deficiency was associated with increased risk of stroke death in whites but not blacks. Although blacks had a higher rate of fatal stroke compared to whites, the low 25(OH)D levels in blacks were unrelated to stroke incidence and therefore 25(OH)D levels did not explain this excess risk. PMID:22261577

Assessment of Remote Heart Rhythm Sampling Using the AliveCor Heart Monitor to Screen for Atrial Fibrillation: The REHEARSE-AF Study.

PubMed

Halcox, Julian P J; Wareham, Kathie; Cardew, Antonia; Gilmore, Mark; Barry, James P; Phillips, Ceri; Gravenor, Michael B

2017-11-07

Asymptomatic atrial fibrillation (AF) is increasingly common in the aging population and implicated in many ischemic strokes. Earlier identification of AF with appropriate anticoagulation may decrease stroke morbidity and mortality. We conducted a randomized controlled trial of AF screening using an AliveCor Kardia monitor attached to a WiFi-enabled iPod to obtain ECGs (iECGs) in ambulatory patients. Patients ≥65 years of age with a CHADS-VASc score ≥2 free from AF were randomized to the iECG arm or routine care (RC). iECG participants acquired iECGs twice weekly over 12 months (plus additional iECGs if symptomatic) onto a secure study server with overread by an automated AF detection algorithm and by a cardiac physiologist and/or consultant cardiologist. Time to diagnosis of AF was the primary outcome measure. The overall cost of the devices, ECG interpretation, and patient management were captured and used to generate the cost per AF diagnosis in iECG patients. Clinical events and patient attitudes/experience were also evaluated. We studied 1001 patients (500 iECG, 501 RC) who were 72.6±5.4 years of age; 534 were female. Mean CHADS-VASc score was 3.0 (heart failure, 1.4%; hypertension, 54%; diabetes mellitus, 30%; prior stroke/transient ischemic attack, 6.5%; arterial disease, 15.9%; all CHADS-VASc risk factors were evenly distributed between groups). Nineteen patients in the iECG group were diagnosed with AF over the 12-month study period versus 5 in the RC arm (hazard ratio, 3.9; 95% confidence interval=1.4-10.4; P =0.007) at a cost per AF diagnosis of $10 780 (£8255). There was a similar number of stroke/transient ischemic attack/systemic embolic events (6 versus 10, iECG versus RC; hazard ratio=0.61; 95% confidence interval=0.22-1.69; P =0.34). The majority of iECG patients were satisfied with the device, finding it easy to use without restricting activities or causing anxiety. Screening with twice-weekly single-lead iECG with remote interpretation in ambulatory patients ≥65 years of age at increased risk of stroke is significantly more likely to identify incident AF than RC over a 12-month period. This approach is also highly acceptable to this group of patients, supporting further evaluation in an appropriately powered, event-driven clinical trial. URL: https://www.isrctn.com. Unique identifier: ISRCTN10709813. © 2017 American Heart Association, Inc.

Outcomes Associated With Resuming Warfarin Treatment After Hemorrhagic Stroke or Traumatic Intracranial Hemorrhage in Patients With Atrial Fibrillation.

PubMed

Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Lip, Gregory Y H

2017-04-01

The increase in the risk for bleeding associated with antithrombotic therapy causes a dilemma in patients with atrial fibrillation (AF) who sustain an intracranial hemorrhage (ICH). A thrombotic risk is present; however, a risk for serious harm associated with resumption of anticoagulation therapy also exists. To investigate the prognosis associated with resuming warfarin treatment stratified by the type of ICH (hemorrhagic stroke or traumatic ICH). This nationwide observational cohort study included patients with AF who sustained an incident ICH event during warfarin treatment from January 1, 1998, through February 28, 2016. Follow-up was completed April 30, 2016. Resumption of warfarin treatment was evaluated after hospital discharge. No oral anticoagulant treatment or resumption of warfarin treatment, included as a time-dependent exposure. One-year observed event rates per 100 person-years were calculated, and treatment strategies were compared using time-dependent Cox proportional hazards regression models with adjustment for age, sex, length of hospital stay, comorbidities, and concomitant medication use. A total of 2415 patients with AF in this cohort (1481 men [61.3%] and 934 women [38.7%]; mean [SD] age, 77.1 years [9.1 years]) sustained an ICH event. Of these events, 1325 were attributable to hemorrhagic stroke and 1090 were secondary to trauma. During the first year, 305 patients with a hemorrhagic stroke (23.0%) died, whereas 210 in the traumatic ICH group (19.3%) died. Among patients with hemorrhagic stroke, resuming warfarin therapy was associated with a lower rate of ischemic stroke or systemic embolism (SE) (adjusted hazard ratio [AHR], 0.49; 95% CI, 0.24-1.02) and an increased rate of recurrent ICH (AHR, 1.31; 95% CI, 0.68-2.50) compared with not resuming warfarin therapy, but these differences did not reach statistical significance. For patients with traumatic ICH, resuming warfarin therapy also was associated with a lower rate of ischemic stroke or SE (AHR, 0.40; 95% CI, 0.15-1.11); however, in contrast to patients with hemorrhagic stroke, therapy resumption was associated with a significantly lower rate of recurrent ICH (AHR, 0.45; 95% CI, 0.26-0.76). A reduction in mortality was associated with resuming warfarin therapy among patients with hemorrhagic stroke (AHR, 0.51; 95% CI, 0.37-0.71) and those with traumatic ICH (AHR, 0.35; 95% CI, 0.23-0.52). Resumption of warfarin therapy after spontaneous hemorrhagic stroke in patients with AF was associated with a lower rate of ischemic events and a higher rate of recurrent ICH. Among patients with a traumatic ICH, a similar lower rate of ischemic events was found; however, a lower relative risk for recurrent ICH despite resuming warfarin treatment was also revealed.

Childhood hospitalisation with infection and cardiovascular disease in early-mid adulthood: a longitudinal population-based study.

PubMed

Burgner, David P; Cooper, Matthew N; Moore, Hannah C; Stanley, Fiona J; Thompson, Peter L; de Klerk, Nicholas H; Carter, Kim W

2015-01-01

Pathogen-specific and overall infection burden may contribute to atherosclerosis and cardiovascular disease (CVD), but the effect of infection severity and timing is unknown. We investigated whether childhood infection-related hospitalisation (IRH, a marker of severity) was associated with subsequent adult CVD hospitalisation. Using longitudinal population-based statutorily-collected administrative health data from Western Australia (1970-2009), we identified adults hospitalised with CVD (ischaemic heart disease, ischaemic stroke, and peripheral vascular disease) and matched them (10:1) to population controls. We used Cox regression to assess relationships between number and type of childhood IRH and adulthood CVD hospitalisation, adjusting for sex, age, Indigenous status, socioeconomic status, and birth weight. 631 subjects with CVD-related hospitalisation in adulthood (≥ 18 years) were matched with 6310 controls. One or more childhood (< 18 years) IRH was predictive of adult CVD-related hospitalisation (adjusted hazard ratio, 1.3; 95% CI 1.1-1.6; P < 0.001). The association showed a dose-response; ≥ 3 childhood IRH was associated with a 2.2 times increased risk of CVD-related hospitalisation in adulthood (adjusted hazard ratio, 2.2; 95% CI 1.7-2.9; P < 0.001). The association was observed across all clinical diagnostic groups of infection (upper respiratory tract infection, lower respiratory tract infection, infectious gastroenteritis, urinary tract infection, skin and soft tissue infection, and other viral infection), and individually with CVD diagnostic categories (ischaemic heart disease, ischaemic stroke and peripheral vascular disease). Severe childhood infection is associated with CVD hospitalisations in adulthood in a dose-dependent manner, independent of population-level risk factors.

Frequency of cancer in patients operated on for acute peripheral arterial thrombosis and the impact on prognosis.

PubMed

Nicolajsen, Chalotte Winther; Dickenson, Maja Holch; Budtz-Lilly, Jacob; Eldrup, Nikolaj

2015-12-01

Little is known about acute peripheral arterial thrombosis in patients with concomitant cancer. Small studies suggest that revascularization in this patient group is associated with thrombosis and increased risk of amputation and death. We investigated the frequency of cancer in patients operated on for acute peripheral arterial thrombosis and the long-term risk of amputation, mortality, myocardial infarction, and stroke in a national cohort. This was a prospective case/noncase study comprising all Danish citizens undergoing vascular surgery for acute arterial thrombosis from 1986 to 2012 with up to 26 years of follow-up. A total of 7840 patients were treated surgically for acute arterial thrombosis; 2384 (30.4%) were previously diagnosed with cancer or developed cancer during the observation period. Risk of amputation was not significantly different in patients with or without cancer, except in patients with cancer diagnosed <24 months before acute limb ischemia (hazard ratio, 2.0). Mortality was significantly greater in all patients having or developing cancer within 24 months after surgery (hazard ratio, 1.2-2.2). The frequencies of myocardial infarction and stroke were similar to those among patients without cancer. One of five patients operated on for acute limb ischemia has a diagnosis of cancer, and a further 3.4% will develop cancer within 24 months. The data further show that patients with acute limb ischemia and concomitant cancer can be successfully revascularized and that the majority of these patients preserve their limb. Cancer should therefore not contravene interventional treatment. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Childhood body weight in relation to morbidity from cardiovascular disease and cancer in older adulthood: 67-year follow-up of participants in the 1947 Scottish Mental Survey.

PubMed

Batty, G David; Calvin, Catherine M; Brett, Caroline E; Čukić, Iva; Deary, Ian J

2015-11-01

Although it has been well documented that elevated body weight in middle- and older-aged populations is associated with multiple morbidities, the influence of childhood body weight on health endpoints other than coronary heart disease is not well understood. Accordingly, using a subsample of 4,620 participants (2,288 women) from the Scottish Mental Survey of 1947, we examined the association between body mass index measured at 11 years of age and future risk of 9 independent health endpoints as ascertained from national hospital admissions and cancer registers until 2014 (up to age 77 years). Although there was some evidence of a relationship between elevated childhood body mass index and higher rates of peripheral vascular disease (per each 1-standard deviation increase in body mass index, hazard ratio = 1.21, 95% confidence interval: 1.07, 1.37) and smoking-related cancers (per each 1-standard deviation increase in body mass index, hazard ratio = 1.09, 95% confidence interval: 1.01, 1.17), there was no apparent association with coronary heart disease, stroke (including ischemic stroke), heart failure, or carcinomas of the colorectum, stomach, lung, prostate, or breast. In conclusion, a relationship between childhood body weight and later morbidity was largely lacking in the present study. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Changes in Depressive Symptoms and Subsequent Risk of Stroke in the Cardiovascular Health Study

PubMed Central

Gilsanz, Paola; Kubzansky, Laura D.; Tchetgen Tchetgen, Eric J.; Wang, Qianyi; Kawachi, Ichiro; Patton, Kristen K.; Fitzpatrick, Annette L.; Kop, Willem J.; Longstreth, W.T.; Glymour, M. Maria

2016-01-01

Background and Purpose Depression is associated with stroke, but the effects of changes in depressive symptoms on stroke risk are not well understood. This study examined whether depressive symptom changes across two successive annual assessments were associated with incident stroke the following year. Methods We used visit data from 4,319 participants of the Cardiovascular Health Study who were stroke-free at baseline to examine whether changes in depressive symptoms classified across two consecutive annual assessments predicted incident first stroke during the subsequent year. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression scale (CES-D; high vs. low at ≥10). Survival models were inverse probability weighted to adjust for demographics, health behaviors, medical conditions, past depressive symptoms, censoring, and survival. Results During follow-up, 334 strokes occurred. Relative to stable low scores of depressive symptoms, improved depression symptoms were associated with almost no excess risk of stroke (aHR=1.02; 95% CI: 0.66–1.58). New-onset symptoms were non-significantly associated with elevated stroke risk (aHR=1.44; 95% CI: 0.97–2.14) while persistently high depressive symptoms were associated with elevated adjusted hazard of all-cause stroke (aHR=1.65; 95% CI: 1.06–2.56). No evidence for effect modification by race, age, or sex was found. Conclusions Persistently high symptoms of depression predicted elevated hazard of stroke. Participants with improved depressive symptoms had no elevation in stroke risk. Such findings suggest that strategies to reduce depressive symptoms may ameliorate stroke risk. PMID:27924053

Vitamin D and the risk of dementia and Alzheimer disease.

PubMed

Littlejohns, Thomas J; Henley, William E; Lang, Iain A; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H M; Fried, Linda; Kestenbaum, Bryan R; Kuller, Lewis H; Langa, Kenneth M; Lopez, Oscar L; Kos, Katarina; Soni, Maya; Llewellyn, David J

2014-09-02

To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23-4.13) and 1.53 (95% CI: 1.06-2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02-4.83) and 1.69 (95% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L. Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions. © 2014 American Academy of Neurology.