Potential impact of single-risk-factor versus total risk management for the prevention of cardiovascular events in Seychelles.

PubMed

Ndindjock, Roger; Gedeon, Jude; Mendis, Shanthi; Paccaud, Fred; Bovet, Pascal

2011-04-01

To assess the prevalence of cardiovascular (CV) risk factors in Seychelles, a middle-income African country, and compare the cost-effectiveness of single-risk-factor management (treating individuals with arterial blood pressure ≥ 140/90 mmHg and/or total serum cholesterol ≥ 6.2 mmol/l) with that of management based on total CV risk (treating individuals with a total CV risk ≥ 10% or ≥ 20%). CV risk factor prevalence and a CV risk prediction chart for Africa were used to estimate the 10-year risk of suffering a fatal or non-fatal CV event among individuals aged 40-64 years. These figures were used to compare single-risk-factor management with total risk management in terms of the number of people requiring treatment to avert one CV event and the number of events potentially averted over 10 years. Treatment for patients with high total CV risk (≥ 20%) was assumed to consist of a fixed-dose combination of several drugs (polypill). Cost analyses were limited to medication. A total CV risk of ≥ 10% and ≥ 20% was found among 10.8% and 5.1% of individuals, respectively. With single-risk-factor management, 60% of adults would need to be treated and 157 cardiovascular events per 100000 population would be averted per year, as opposed to 5% of adults and 92 events with total CV risk management. Management based on high total CV risk optimizes the balance between the number requiring treatment and the number of CV events averted. Total CV risk management is much more cost-effective than single-risk-factor management. These findings are relevant for all countries, but especially for those economically and demographically similar to Seychelles.

Statin use and risk for type 2 diabetes: what clinicians should know.

PubMed

Maki, Kevin C; Diwadkar-Navsariwala, Veda; Kramer, Melvyn W

2018-03-01

Statins are the first line of pharmacologic treatment for the management of hypercholesterolemia in patients at risk for atherosclerotic cardiovascular (CV) disease. In recent years, several randomized, controlled trials (RCTs) and observational studies have reported increased risk for new-onset type 2 diabetes mellitus (T2D) with statin treatment, particularly with use of high-intensity statins that reduce low-density lipoprotein cholesterol (LDL-C) by 50% or more. This paper summarizes the data from RCTs and observational studies for statin-associated T2D risk, and puts into perspective this evidence, weighed against the established benefits of statin therapy for CV risk reduction. In RCTs, the increase in T2D risk with statin therapy appears to be attributable mainly to those with major T2D risk factors. The increase in incidence of T2D in those with major risk is approximately 25% for statin use, compared to placebo, and for intensive statin therapy compared to moderate-intensity statin therapy. However, in those with major T2D risk factors, the number of CV disease events prevented for each excess case of T2D is close to or greater than one, indicating that the risk-benefit ratio still strongly favors use of statin therapy, or intensive statin therapy, for patients with sufficient CV disease risk to warrant cholesterol-lowering drug therapy. Recommendations are summarized for evaluation of the T2D risk factor profile before initiation of and during statin therapy. In addition, the importance of lifestyle management and other preventive measures is emphasized for management of risks for both T2D and CV disease events in patients receiving statin therapy.

Low-density lipoprotein cholesterol levels and lipid-modifying therapy prescription patterns in the real world: An analysis of more than 33,000 high cardiovascular risk patients in Japan.

PubMed

Teramoto, Tamio; Uno, Kiyoko; Miyoshi, Izuru; Khan, Irfan; Gorcyca, Katherine; Sanchez, Robert J; Yoshida, Shigeto; Mawatari, Kazuhiro; Masaki, Tomoya; Arai, Hidenori; Yamashita, Shizuya

2016-08-01

Low-density lipoprotein cholesterol (LDL-C) is a key modifiable risk factor in the development of cardiovascular (CV) disease. In 2012, the Japan Atherosclerosis Society (JAS) issued guidelines recommending statins as first-line pharmacotherapy for lowering LDL-C in patients at high risk for CV events. This study assessed achievement of recommended LDL-C goals and lipid-modifying therapy (LMT) use in a high CV risk population in Japan. Patients from the Medical Data Vision (MDV) database, an electronic hospital-based claims database in Japan, who met the following inclusion criteria were included in this study: LDL-C measurement in 2013; ≥20 years of age; ≥2 years representation in the database; and a high CV risk condition (recent acute coronary syndrome (ACS), other coronary heart disease (CHD), ischemic stroke, peripheral arterial disease (PAD) or diabetes). LDL-C goal attainment was assessed based on LDL-C targets in the JAS guidelines. A total of 33,325 high CV risk patients met the inclusion criteria. Overall, 68% of the cohort achieved guideline recommended LDL-C targets, with only 42% receiving current treatment with statins. Attainment of LDL-C goals was 68% for ACS, 55% for CHD, and 80% each for ischemic stroke, PAD, and diabetes patients. Concomitant use of non-statin LMTs was low. In a high CV risk population in a routine care setting in Japan, guideline recommended LDL-C goal attainment and utilization of statins and other LMT was low. In addition, physicians appeared to be more likely to consider the initiation of statins in patients with higher baseline LDL-C levels. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Potential impact of single-risk-factor versus total risk management for the prevention of cardiovascular events in Seychelles

PubMed Central

Ndindjock, Roger; Gedeon, Jude; Mendis, Shanthi; Paccaud, Fred

2011-01-01

Abstract Objective To assess the prevalence of cardiovascular (CV) risk factors in Seychelles, a middle-income African country, and compare the cost-effectiveness of single-risk-factor management (treating individuals with arterial blood pressure ≥ 140/90 mmHg and/or total serum cholesterol ≥ 6.2 mmol/l) with that of management based on total CV risk (treating individuals with a total CV risk ≥ 10% or ≥ 20%). Methods CV risk factor prevalence and a CV risk prediction chart for Africa were used to estimate the 10-year risk of suffering a fatal or non-fatal CV event among individuals aged 40–64 years. These figures were used to compare single-risk-factor management with total risk management in terms of the number of people requiring treatment to avert one CV event and the number of events potentially averted over 10 years. Treatment for patients with high total CV risk (≥ 20%) was assumed to consist of a fixed-dose combination of several drugs (polypill). Cost analyses were limited to medication. Findings A total CV risk of ≥ 10% and ≥ 20% was found among 10.8% and 5.1% of individuals, respectively. With single-risk-factor management, 60% of adults would need to be treated and 157 cardiovascular events per 100 000 population would be averted per year, as opposed to 5% of adults and 92 events with total CV risk management. Management based on high total CV risk optimizes the balance between the number requiring treatment and the number of CV events averted. Conclusion Total CV risk management is much more cost-effective than single-risk-factor management. These findings are relevant for all countries, but especially for those economically and demographically similar to Seychelles. PMID:21479093

Exercise-induced hypertension, cardiovascular events, and mortality in patients undergoing exercise stress testing: a systematic review and meta-analysis.

PubMed

Schultz, Martin G; Otahal, Petr; Cleland, Verity J; Blizzard, Leigh; Marwick, Thomas H; Sharman, James E

2013-03-01

The prognostic relevance of a hypertensive response to exercise (HRE) is ill-defined in individuals undergoing exercise stress testing. The study described here was intended to provide a systematic review and meta-analysis of published literature to determine the value of exercise-related blood pressure (BP) (independent of office BP) for predicting cardiovascular (CV) events and mortality. Online databases were searched for published longitudinal studies reporting exercise-related BP and CV events and mortality rates. We identified for review 12 longitudinal studies with a total of 46,314 individuals without significant coronary artery disease, with total CV event and mortality rates recorded over a mean follow-up of 15.2±4.0 years. After adjustment for age, office BP, and CV risk factors, an HRE at moderate exercise intensity carried a 36% greater rate of CV events and mortality (95% CI, 1.02-1.83, P = 0.039) than that of subjects without an HRE. Additionally, each 10mm Hg increase in systolic BP during exercise at moderate intensity was accompanied by a 4% increase in CV events and mortality, independent of office BP, age, or CV risk factors (95% CI, 1.01-1.07, P = 0.02). Systolic BP at maximal workload was not significantly associated with the outcome of an increased rate of CV, whether analyzed as a categorical (HR=1.49, 95% CI, 0.90-2.46, P = 0.12) or a continuous (HR=1.01, 95% CI, 0.98-1.04, P = 0.53) variable. An HRE at moderate exercise intensity during exercise stress testing is an independent risk factor for CV events and mortality. This highlights the need to determine underlying pathophysiological mechanisms of exercise-induced hypertension.

Angiopoietin-2 serum levels correlate with severity, early onset and cardiovascular disease in patients with rheumatoid arthritis.

PubMed

López-Mejías, Raquel; Corrales, Alfonso; Genre, Fernanda; Hernández, José L; Ochoa, Rodrigo; Blanco, Ricardo; González-Juanatey, Carlos; Martín, Javier; Llorca, Javier; González-Gay, Miguel A

2013-01-01

Rheumatoid arthritis (RA) is an inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular (CV) disease. Angiopoietin-2 (Angpt-2), a marker of endothelial cell activation, has been proposed as a mediator of angiogenesis, which might play an important role in the regulation of endothelial integrity and inflammation. Therefore, the aim of this study was to determine whether Angpt-2 is related to severity and CV disease in RA patients. Angpt-2 serum levels were measured by enzyme linked immunosorbent assay (ELISA) in 290 patients with RA. A control group of 100 individuals frequency matched by age and sex and classic CV risk factors and CV disease was also assessed. Eighty-four patients with RA (28.9%) had experienced CV events. Also, extra-articular manifestations were present in 41 (14%) of these patients. Although there were not significant differences between patients and controls, a correlation between age at the time of disease onset and Angpt-2 was observed in RA patients (r=-0.31; p=0.02). Angpt-2 serum levels also correlated positively with extra-articular disease (mean±standard deviation in RA patients with and without extra-articular manifestations were 2476±1716 pg/ml and 1897±1228 pg/ml, respectively; p=0.01). Moreover, after adjustment for sex, age at RA diagnosis and CV risk factors, Angpt-2 levels were higher in RA patients with CV disease than in RA patients without CV complications (2472±1826 pg/ml vs. 1875±1101 pg/ml; p=0.05). Angpt-2 serum levels remained significantly higher in RA patients with CV disease compared to those without CV disease after additional adjustment for extra-articular manifestations (p=0.04). Our results show that Angpt-2 serum levels correlate with disease severity, early onset and CV disease in RA patients.

Cardiovascular Safety of Biologics and JAK Inhibitors in Patients with Rheumatoid Arthritis.

PubMed

Kang, Eun Ha; Liao, Katherine P; Kim, Seoyoung C

2018-05-30

Increased cardiovascular (CV) risk and associated mortality in rheumatoid arthritis (RA) are not fully explained by traditional CV risk factors. This review discusses the epidemiology and mechanisms of increased CV risk in RA and treatment effects on CV risk focusing on biologic disease-modifying anti-rheumatic drugs (DMARDs) and JAK inhibitors. Intermediary metabolic changes by inflammatory cytokines are observed in body composition, lipid profile, and insulin sensitivity of RA patients, leading to accelerated atherosclerosis and increased CV risk. Successful treatment with DMARDs has shown beneficial effects on these metabolic changes and ultimately CV outcomes, in proportion to the treatment efficacy in general but also with drug-specific mechanisms. Recent data provide further information on comparative CV safety between biologic DMARDs or JAK inhibitors as well as their safety signals for non-atherosclerotic CV events. CV benefits or safety signals associated with DMARD treatments can differ despite similar drug efficacy against RA, suggesting that both anti-inflammatory and drug-specific mechanisms are involved in altering CV risk.

Explaining the Cardiovascular Risk Associated with Rheumatoid Arthritis: Traditional Risk Factors Versus Markers of Rheumatoid Arthritis Severity

PubMed Central

Solomon, Daniel H.; Kremer, Joel; Curtis, Jeffrey R; Hochberg, Marc C.; Reed, George; Tsao, Peter; Farkouh, Michael E.; Setoguchi, Soko; Greenberg, Jeffrey D.

2010-01-01

Background Cardiovascular (CV) disease has a major impact on patients with rheumatoid arthritis (RA), however, the relative contributions of traditional CV risk factors and markers of RA severity are unclear. We examined the relative importance of traditional CV risk factors and RA markers in predicting CV events. Methods A prospective longitudinal cohort study was conducted in the setting of the CORRONA registry in the United States. Baseline data from subjects with RA enrolled in the CORRONA registry were examined to determine predictors of CV outcomes, including myocardial infarction (MI), stroke or transient ischemic attack (TIA). Possible predictors were of two types: traditional CV risk factors and markers of RA severity. The discriminatory value of these variables was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) in logistic regression. We then assessed the incidence rate for CV events among subjects with an increasing number of traditional CV risk factors and/or RA severity markers. Results The cohort consisted of 10,156 patients with RA followed for a median of 22 months. We observed 76 primary CV events during follow-up for a composite event rate of 3.98 (95% CI 3.08 – 4.88) per 1,000 patient-years. The c-statistic improved from 0.57 for models with only CV risk factors to 0.67 for models with CV risk factors plus age and gender. The c-statistic improved further to 0.71 when markers of RA severity were also added. The incidence rate for CV events was 0 (95% CI 0 – 5.98) for persons without any CV risk factors or markers of RA severity, while in the group with two or more CV risk factors and 3 or more markers of RA severity the incidence was 7.47 (95% CI 4.21–10.73) per 1,000 person-years. Conclusions Traditional CV risk factors and markers of RA severity both contribute to models predicting CV events. Increasing numbers of both types of factors are associated with greater risk. PMID:20444756

Ischaemic cardiovascular risk and prescription of non-steroidal anti-inflammatory drugs for musculoskeletal complaints.

PubMed

Koffeman, Aafke R; Valkhoff, Vera E; Jong, Geert W'T; Warlé-van Herwaarden, Margreet F; Bindels, Patrick J E; Sturkenboom, Miriam C J M; Luijsterburg, Pim A J; Bierma-Zeinstra, Sita M A

2014-06-01

To determine the influence of ischaemic cardiovascular (CV) risk on prescription of non-steroidal anti-inflammatory drugs (NSAIDs) by general practitioners (GPs) in patients with musculoskeletal complaints. Cohort study. A healthcare database containing the electronic GP medical records of over one million patients throughout the Netherlands. A total of 474 201 adults consulting their GP with a new musculoskeletal complaint between 2000 and 2010. Patients were considered at high CV risk if they had a history of myocardial infarction, angina pectoris, stroke, transient ischaemic attack, or peripheral arterial disease, and at low CV risk if they had no CV risk factors. Frequency of prescription of non-selective (ns)NSAIDs and selective cyclooxygenase-2 inhibitors (coxibs). Overall, 24.4% of patients were prescribed an nsNSAID and 1.4% a coxib. Of the 41,483 patients with a high CV risk, 19.9% received an nsNSAID and 2.2% a coxib. These patients were more likely to be prescribed a coxib than patients with a low CV risk (OR 1.9, 95% CI 1.8-2.0). Prescription of nsNSAIDs decreased over time in all risk groups and was lower in patients with a high CV risk than in patients with a low CV risk (OR 0.8, 95% CI 0.7-0.8). Overall, patients with a high CV risk were less likely to be prescribed an NSAID for musculoskeletal complaints than patients with a low CV risk. Nevertheless, one in five high CV risk patients received an NSAID, indicating that there is still room for improvement.

Sex hormone therapy and progression of cardiovascular disease in menopausal women.

PubMed

Alhurani, Rabe E; Chahal, C Anwar A; Ahmed, Ahmed T; Mohamed, Essa A; Miller, Virginia M

2016-07-01

One of the most controversial health decisions facing women is deciding upon the use of hormonal treatments for symptoms of menopause. This brief review focuses on the historical context of use of menopausal hormone treatments (MHT), summarizes results of major observational, primary and secondary prevention studies of MHT and cardiovascular (CV) outcomes, provides evidence for how sex steroids modulate CV function and identifies challenges for future research. As medicine enters an era of personalization of treatment options, additional research into sex differences in the aetiology of CV diseases will lead to better risk identification for CV disease in women and identify whether a woman might receive CV benefit from specific formulations and doses of MHT. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Evaluation critique of state of the art dyslipidemia management in general and with a special emphasis on the Indian population.

PubMed

Whayne, Thomas F

2007-01-01

Classically, there have been three well established major cardiovascular risk factors, hypercholesterolemia, hypertension and tobacco abuse. With accumulating clinical evidence, diabetes can now be added as a fourth major risk factor. Much interest in various other risk factors and possible causative factors has been generated, but it should be remembered that of all these, low density lipoproteins (LDL) remains the gold standard for evaluating risk. The common perception is that only caucasians in the western world have significant cardiovascular (CV) risk. However, much clinical information to the contrary has accumulated and now it is realized that many other ethnic groups also have significant CV disease, such as in India, especially in the urban population. Dyslipidemias of specific lipoproteins and their treatment is an important part of understanding and managing CV disease and risk. Various plasma factors such as homocysteine and lipoprotein (a) [(a)] have been considered to have definite associations with CV disease, but any treatment benefit remains in doubt. In addition, inflammatory risk factors are considered to be of significant clinical interest, especially high sensitivity C-Reactive protein (hsCRP). Where do these factors fit into routine clinical practice still awaits clarification. Only two of these inflammatory risk (Lp-factors can be tested commercially on a routine clinical basis and these are hsCRP and Lipoprotein-associated Phospholipase A2 Lp-PLA2). Their clinical utillity is not established and acceptance is limited: some third party health coverage organizations refuse to pay for such analyses. In the past, women have been looked upon as not having significant CV disease. More recently, evidence suggests that women may have more CV disease than men, and that physicians may have failed to realize this and act accordingly. The true situation is that women have less CV disease than men prior to menopause and then they slowly catch up. However, some women under age 50 have an especially malignant form of CV disease and in these cases, myocardial infarction mortality is twice that of men. The explanation and management is the subject of much clinical investigation. In both India and the western world, perhaps the most important medical problem is the metabolic syndrome (MS) and this combination of CV risk factors multiplies the significance of each. For the difficult patient not tolerant of or sufficiently responsive to conventional therapy, alternative diets and medications can frequently offer just enough benefit in lowering LDL to allow the patient to attain their target level. Future treatments undoubtedly will involve genetics, but for now, aggressive medication use can favorably modify risk although not eliminate it.

Utility of Saxagliptin in the Treatment of Type 2 Diabetes: Review of Efficacy and Safety.

PubMed

Jain, Rajeev

2015-11-01

Type 2 diabetes mellitus (T2DM) is a complex disease in which multiple organs and hormones contribute to the pathogenesis of disease. The intestinal hormone, glucagon-like peptide-1 (GLP-1), secreted in response to nutrient ingestion, increases insulin secretion from pancreatic β-cells and reduces glucagon secretion from pancreatic α-cells. GLP-1 is inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme. Saxagliptin is a DPP-4 inhibitor that prevents the degradation of endogenous GLP-1 and prolongs its actions on insulin and glucagon secretion. This article reviews the efficacy and safety of saxagliptin in patients with T2DM. A PubMed literature search was conducted to identify relevant, peer-reviewed saxagliptin clinical trial articles published between January 2008 and June 2015. Search terms included "saxagliptin" and "DPP-4 inhibitors". In clinical trials, saxagliptin significantly improved glycemic control when used as monotherapy or as add-on therapy to other antidiabetes agents and was associated with a low risk of hypoglycemia. In a large cardiovascular (CV) outcomes trial (SAVOR) in patients with T2DM and with established CV disease or multiple CV risk factors, saxagliptin neither increased nor decreased CV risk compared with placebo as assessed by the composite end point of death from CV causes, nonfatal myocardial infarction, or nonfatal stroke. Unexpectedly, more patients in the saxagliptin (3.5%) than in the placebo group (2.8%) were hospitalized for heart failure. Saxagliptin demonstrated statistically significant and clinically meaningful improvements in glycemic control and a low risk of hypoglycemia in patients with T2DM. However, this positive profile needs to be tempered by the observation of an increased risk of hospitalization for heart failure in the SAVOR trial. Results from ongoing CV outcome trials with other DPP-4 inhibitors may provide additional data on how best to manage patients with T2DM who are at risk for heart failure. AstraZeneca LP.

Metabolic syndrome, hepatic steatosis, and cardiovascular risk in children.

PubMed

Rutigliano, Irene; Vinci, Roberta; De Filippo, Gianpaolo; Mancini, Monica; Stoppino, Luca; d'Apolito, Maria; Giardino, Ida; Macarini, Luca; Pettoello Mantovani, Massimo; Campanozzi, Angelo

2017-04-01

Pediatric metabolic syndrome (MetS) is a well-recognized entity; however, there is no consensus on its exact value in predicting long-term cardiovascular (CV) risk. Hepatic steatosis (HS) is another emerging condition associated with pediatric obesity, and data have been reported suggesting a possible role of HS in CV risk linked to MetS. The aim of the present study was to evaluate the usefulness of HS and MetS cluster in predicting CV risk linked to pediatric obesity. We studied 803 overweight and obese children (395 girls and 408 boys, mean age 9.4 ± 2.5 y, body mass index z-score 2.2 ± 0.53) with complete clinical and biological assessment. MetS was defined using the modified criteria of the American Heart Association. The diagnosis and severity of the HS was based on ultrasound. To assess CV risk, all patients underwent ultrasonography to measure carotid intima-media thickness (cIMT)-a validated marker of subclinical vascular disease. The overall prevalence of MetS was 13.07%; HS was significantly higher in patients with MetS (40.9 versus 18.5%; P < 0.001; odds ratio, 3.059; 95% confidence interval, 1.98-4.7). Spearman's correlation between HS grade and the number of MetS criteria met by each patient was significant (r = 0.285; P < 0.001). No statistical difference was recorded in cIMT and cIMT z-scores between patients with or without MetS, until inclusion of HS as an additional criterion for the diagnosis of MetS. In this case, there was a significant difference in cIMT z-scores between the two groups. In multiple linear regression analysis, the cIMT z-score value was better predicted with HS grade and the MetS cluster (adjusted R 2  = 2.6%; P = 0.002) than when using the MetS cluster only. HS could be used as additional criterion in detecting pediatric MetS phenotype at higher risk for long-term CV morbidity. Copyright © 2016 Elsevier Inc. All rights reserved.

Mild cognitive impairment in symptomatic and asymptomatic cerebrovascular disease.

PubMed

Popović, Irena Martinić; Serić, Vesna; Demarin, Vida

2007-06-15

We tried to evaluate and to compare usefulness of two brief cognitive tests in early detection of cognitive decline in subjects with increased cerebrovascular (CV) risk. As CV risk factors are recognised as important in etiology of dementia, we also aimed to determine the possible associations of specific CV risk factors and cognitive results. Patients (PGs) with first-ever stroke or TIA (N=110) and CV symptoms-free controls (CGs) with CV risk factors present (N=45) matched for age, gender and education level were tested using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) on admission, at three- and six-month points. In all subjects, detailed CV risk factors profile was assessed. We observed the decrement in cognitive performance during the six-month study period in both groups, more evident if MoCA (p<0.001) than if MMSE was used (p=0.022). Six months after first stroke/TIA 83.6% PGs scored below normal range on MoCA. In PGs, positive associations for cognitive decrement and multiple CV risk factors (>2) were found (p=0.034 for MMSE; p=0.002 for MoCA). In CGs, positive associations were found for cognitive decrement and arterial hypertension with increased IMT values (p<0.001 for MMSE) and for multiple CV risk factors and arterial hypertension (p=0.003 for MoCA). The use of MoCA could aid to early recognition of cognitive deficits in persons with increased CV risk. Individuals with multiple CV risk factors seem to have increased risk of cognitive decline.

SMAD3 rs17228212 Gene Polymorphism Is Associated with Reduced Risk to Cerebrovascular Accidents and Subclinical Atherosclerosis in Anti-CCP Negative Spanish Rheumatoid Arthritis Patients

PubMed Central

Genre, Fernanda; Castañeda, Santos; González-Juanatey, Carlos; Llorca, Javier; Corrales, Alfonso; Miranda-Filloy, José A.; Rueda-Gotor, Javier; Gómez-Vaquero, Carmen; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Pascual-Salcedo, Dora; Balsa, Alejandro; López-Longo, Francisco J.; Carreira, Patricia; Blanco, Ricardo; González-Álvaro, Isidoro; Martín, Javier; González-Gay, Miguel A.

2013-01-01

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA. Methods One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography. Results No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP) status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA) after adjustment for demographic and classic CV risk factors (HR [95%CI]=0.36 [0.14–0.94], p=0.038) in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094) in the anti-CCP negative RA patients. Conclusions Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have importance to establish predictive models of CV disease in RA patients according to anti-CCP status. PMID:24204921

SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.

PubMed

García-Bermúdez, Mercedes; López-Mejías, Raquel; Genre, Fernanda; Castañeda, Santos; González-Juanatey, Carlos; Llorca, Javier; Corrales, Alfonso; Miranda-Filloy, José A; Rueda-Gotor, Javier; Gómez-Vaquero, Carmen; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Pascual-Salcedo, Dora; Balsa, Alejandro; López-Longo, Francisco J; Carreira, Patricia; Blanco, Ricardo; González-Álvaro, Isidoro; Martín, Javier; González-Gay, Miguel A

2013-01-01

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA. One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography. No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP) status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA) after adjustment for demographic and classic CV risk factors (HR [95%CI]=0.36 [0.14-0.94], p=0.038) in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094) in the anti-CCP negative RA patients. Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have importance to establish predictive models of CV disease in RA patients according to anti-CCP status.

Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis.

PubMed

Borow, Kenneth M; Nelson, John R; Mason, R Preston

2015-09-01

Residual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive statin therapy, underscoring the need for additional intervention. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into membrane phospholipids and atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through rupture. Specific salutary actions have been reported relating to endothelial function, oxidative stress, foam cell formation, inflammation, plaque formation/progression, platelet aggregation, thrombus formation, and plaque rupture. EPA also improves atherogenic dyslipidemia characterized by reduction of triglycerides without raising low-density lipoprotein cholesterol. Other beneficial effects of EPA include vasodilation, resulting in blood pressure reductions, as well as improved membrane fluidity. EPA's effects are at least additive to those of statins when given as adjunctive therapy. In this review, we present data supporting the biologic plausibility of EPA as an anti-atherosclerotic agent with potential clinical benefit for prevention of CV events, as well as its cellular effects and molecular mechanisms of action. REDUCE-IT is an ongoing, randomized, controlled study evaluating whether the high-purity ethyl ester of EPA (icosapent ethyl) at 4 g/day combined with statin therapy is superior to statin therapy alone for reducing CV events in high-risk patients with mixed dyslipidemia. The results from this study are expected to clarify the role of EPA as adjunctive therapy to a statin for reduction of residual CV risk. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

AMSSM Position Statement on Cardiovascular Preparticipation Screening in Athletes: Current Evidence, Knowledge Gaps, Recommendations, and Future Directions.

PubMed

Drezner, Jonathan A; OʼConnor, Francis G; Harmon, Kimberly G; Fields, Karl B; Asplund, Chad A; Asif, Irfan M; Price, David E; Dimeff, Robert J; Bernhardt, David T; Roberts, William O

2016-09-01

Cardiovascular (CV) screening in young athletes is widely recommended and routinely performed before participation in competitive sports. While there is general agreement that early detection of cardiac conditions at risk for sudden cardiac arrest and death (SCA/D) is an important objective, the optimal strategy for CV screening in athletes remains an issue of considerable debate. At the center of the controversy is the addition of a resting electrocardiogram (ECG) to the standard preparticipation evaluation using history and physical examination. The American Medical Society for Sports Medicine (AMSSM) formed a task force to address the current evidence and knowledge gaps regarding preparticipation CV screening in athletes from the perspective of a primary care sports medicine physician. The absence of definitive outcomes-based evidence at this time precludes AMSSM from endorsing any single or universal CV screening strategy for all athletes including legislative mandates. This statement presents a new paradigm to assist the individual physician in assessing the most appropriate CV screening strategy unique to their athlete population, community needs, and resources. The decision to implement a CV screening program, with or without the addition of ECG, necessitates careful consideration of the risk of SCA/D in the targeted population and the availability of cardiology resources and infrastructure. Importantly, it is the individual physician's assessment in the context of an emerging evidence base that the chosen model for early detection of cardiac disorders in the specific population provides greater benefit than harm. American Medical Society for Sports Medicine is committed to advancing evidenced-based research and educational initiatives that will validate and promote the most efficacious strategies to foster safe sport participation and reduce SCA/D in athletes.

Cardiovascular risk of patients with gout seen at rheumatology clinics following a structured assessment.

PubMed

Andrés, Mariano; Bernal, José Antonio; Sivera, Francisca; Quilis, Neus; Carmona, Loreto; Vela, Paloma; Pascual, Eliseo

2017-07-01

Gout-associated cardiovascular (CV) risk relates to comorbidities and crystal-led inflammation. The aim was to estimate the CV risk by prediction tools in new patients with gout and to assess whether ultrasonographic carotid changes are present in patients without high CV risk. Cross-sectional study. Consecutive new patients with crystal-proven gout underwent a structured CV consultation, including CV events, risk factors and two risk prediction tools-the Systematic COronary Evaluation (SCORE) and the Framingham Heart Study (FHS). CV risk was stratified according to current European guidelines. Carotid ultrasound (cUS) was performed in patients with less than very high CV risk. The presence of carotid plaques was studied depending on the SCORE and FHS by the area under the curve (AUC) of receiver operating curves. 237 new patients with gout were recruited. CV stratification by scores showed a predominance of very high (95 patients, 40.1%) and moderate (72 patients, 30.5%) risk levels. cUS was performed in 142 patients, finding atheroma plaques in 66 (46.5%, 95% CI 37.8 to 54.2). Following cUS findings, patients classified as very high risk increased from 40.1% up to 67.9% (161/237 patients). SCORE and FHS predicted moderately (AUC 0.711 and 0.683, respectively) the presence of atheroma plaques at cUS. The majority of patients presenting with gout may be at very high CV risk, indicating the need for initiating optimal prevention strategies at this stage. Risk prediction tools appear to underestimate the presence of carotid plaque in patients with gout. 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/.

High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in Individuals Without Previous Cardiovascular Conditions: The CANHEART Study.

PubMed

Ko, Dennis T; Alter, David A; Guo, Helen; Koh, Maria; Lau, Geoffrey; Austin, Peter C; Booth, Gillian L; Hogg, William; Jackevicius, Cynthia A; Lee, Douglas S; Wijeysundera, Harindra C; Wilkins, John T; Tu, Jack V

2016-11-08

The prognostic importance of high-density lipoprotein cholesterol (HDL-C) as a specific risk factor for cardiovascular (CV) disease has been challenged by recent clinical trials and genetic studies. This study sought to reappraise the association of HDL-C level with CV and non-CV mortality using a "big data" approach. An observational cohort study was conducted using the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) dataset, which was created by linking together 17 different individual-level data sources. People were included if they were between 40 and 105 years old on January 1, 2008, living in Ontario, Canada, without previous CV conditions or severe comorbidities, and had an outpatient fasting cholesterol measurement in the year prior to the inception date. The primary outcome was cause-specific mortality. A total of 631,762 individuals were included. The mean age of our cohort was 57.2 years, 55.4% were women, and mean HDL-C level was 55.2 mg/dl. There were 17,952 deaths during a mean follow-up of 4.9 ± 0.4 years. The overall all-cause mortality rate was 8.1 per 1,000 person-years for men and 6.6 per 1,000 person-years for women. Individuals with lower HDL-C levels were more likely to have low incomes, unhealthy lifestyle, higher triglycerides levels, other cardiac risk factors, and medical comorbidities. Individuals with lower HDL-C levels were independently associated with higher risk of CV, cancer, and other mortality compared with individuals in the reference ranges of HDL-C levels. In addition, individuals with higher HDL levels (>70 mg/dl in men, >90 mg/dl in women) had increased hazard of non-CV mortality. Complex associations exist between HDL-C levels and sociodemographic, lifestyle, comorbidity factors, and mortality. HDL-C level is unlikely to represent a CV-specific risk factor given similarities in its associations with non-CV outcomes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Statistical power analysis of cardiovascular safety pharmacology studies in conscious rats.

PubMed

Bhatt, Siddhartha; Li, Dingzhou; Flynn, Declan; Wisialowski, Todd; Hemkens, Michelle; Steidl-Nichols, Jill

2016-01-01

Cardiovascular (CV) toxicity and related attrition are a major challenge for novel therapeutic entities and identifying CV liability early is critical for effective derisking. CV safety pharmacology studies in rats are a valuable tool for early investigation of CV risk. Thorough understanding of data analysis techniques and statistical power of these studies is currently lacking and is imperative for enabling sound decision-making. Data from 24 crossover and 12 parallel design CV telemetry rat studies were used for statistical power calculations. Average values of telemetry parameters (heart rate, blood pressure, body temperature, and activity) were logged every 60s (from 1h predose to 24h post-dose) and reduced to 15min mean values. These data were subsequently binned into super intervals for statistical analysis. A repeated measure analysis of variance was used for statistical analysis of crossover studies and a repeated measure analysis of covariance was used for parallel studies. Statistical power analysis was performed to generate power curves and establish relationships between detectable CV (blood pressure and heart rate) changes and statistical power. Additionally, data from a crossover CV study with phentolamine at 4, 20 and 100mg/kg are reported as a representative example of data analysis methods. Phentolamine produced a CV profile characteristic of alpha adrenergic receptor antagonism, evidenced by a dose-dependent decrease in blood pressure and reflex tachycardia. Detectable blood pressure changes at 80% statistical power for crossover studies (n=8) were 4-5mmHg. For parallel studies (n=8), detectable changes at 80% power were 6-7mmHg. Detectable heart rate changes for both study designs were 20-22bpm. Based on our results, the conscious rat CV model is a sensitive tool to detect and mitigate CV risk in early safety studies. Furthermore, these results will enable informed selection of appropriate models and study design for early stage CV studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk factor management: antiatherogenic therapies.

PubMed

Gielen, Stephan; Sandri, Marcus; Schuler, Gerhard; Teupser, Daniel

2009-08-01

Despite the advances in interventional techniques, the management of stable atherosclerosis remains the domain of optimal guideline-oriented therapy. Recent studies on the effects of aggressive lipid lowering on atheroma volume changes using intravascular ultrasound indicate that it is possible to achieve atherosclerosis regression by reaching low-density lipoprotein (LDL) levels less than 75 mg/dl. The pleiotropic anti-inflammatory effects of statins contribute to the reduction of cardiovascular (CV) event observed with aggressive lipid lowering. As a second important strategy to prevent disease progression, lifestyle changes with regular physical exercise are capable of halting the atherosclerotic process and reducing angina symptoms and CV events. Optimal medical therapy, a healthy lifestyle with regular physical exercise, and coronary interventions are not mutually exclusive treatment strategies. Over the last few decades, both have proved to be effective in significantly reducing the CV mortality in the Western world. However, risk factor modification contributed to at least half the effect in the reduction of CV mortality. This figure provides an estimate of what could be achieved if we were to take risk factor modification more seriously - especially in the acute care setting. The knowledge is there: today we have a better understanding on how to stop progression and even induce regression of atherosclerosis. Much research still needs to be done and will be done. In the meantime, however, our primary focus should lie in implementing what is already known. In addition, it is essential not just to treat CV risk factors, but also to treat them to achieve the target values as set by the guidelines of European Society of Cardiology.

The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events.

PubMed

Egeberg, Alexander; Skov, Lone; Joshi, Aditya A; Mallbris, Lotus; Gislason, Gunnar H; Wu, Jashin J; Rodante, Justin; Lerman, Joseph B; Ahlman, Mark A; Gelfand, Joel M; Mehta, Nehal N

2017-10-01

Psoriasis is associated with risk of cardiovascular (CV) disease (CVD) and a major adverse CV event (MACE). Whether psoriasis duration affects risk of vascular inflammation and MACEs has not been well characterized. We utilized two resources to understand the effect of psoriasis duration on vascular disease and CV events: (1) a human imaging study and (2) a population-based study of CVD events. First, patients with psoriasis (N = 190) underwent fludeoxyglucose F 18 positron emission tomography/computed tomography (duration effect reported as a β-coefficient). Second, MACE risk was examined by using nationwide registries (adjusted hazard ratios in patients with psoriasis (n = 87,161) versus the general population (n = 4,234,793). In the human imaging study, patients were young, of low CV risk by traditional risk scores, and had a high prevalence of cardiometabolic diseases. Vascular inflammation by fludeoxyglucose F 18 positron emission tomography/computed tomography was significantly associated with disease duration (β = 0.171, P = .002). In the population-based study, psoriasis duration had strong relationship with MACE risk (1.0% per additional year of psoriasis duration [hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]). These studies utilized observational data. We found detrimental effects of psoriasis duration on vascular inflammation and MACE, suggesting that cumulative duration of exposure to low-grade chronic inflammation may accelerate vascular disease development and MACEs. Providers should consider inquiring about duration of disease to counsel for heightened CVD risk in psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. All rights reserved.

Preventing cardiovascular disease in primary care: role of a national risk factor management program.

PubMed

McGrath, Emer R; Glynn, Liam G; Murphy, Andrew W; O Conghaile, Aengus; Canavan, Michelle; Reid, Claire; Moloney, Brian; O'Donnell, Martin J

2012-04-01

Heartwatch, a structured risk factor modification program for secondary prevention of cardiovascular (CV) disease (CVD) in primary care, is associated with improvements in CV risk factors in participating patients. However, it is not known whether Heartwatch translates into reductions in clinically important CV events. The aim of the study was to determine the association between participation in Heartwatch and future risk of CV events in patients with CVD. The study consisted of a prospective cohort of 1,609 patients with CVD in primary care practices. Of these, 97.5% had data available on Heartwatch participation status, of whom 15.2% were Heartwatch participants. Cox proportional hazards models were used to determine the association between Heartwatch participation and risk of the CV composite (CV death, nonfatal myocardial infarction, heart failure, and nonfatal stroke). All-cause mortality and CV mortality were secondary outcome measures. During follow-up, the CV composite occurred in 208 patients (13.6%). Of Heartwatch participants, 8.4% experienced the CV composite compared with 14.5% of nonparticipants (P = .003). Participation in Heartwatch was associated with a significantly reduced risk of the CV composite (hazard ratio [HR] 0.52, 95% CI, 0.31-0.87), CV mortality (HR 0.31, 95% CI, 0.11-0.89), and all-cause mortality (HR 0.32, 95% CI, 0.15-0.68). Heartwatch participation was also associated with greater reductions in mean systolic blood pressure (P = .047), mean diastolic blood pressure (P < .001), and greater use of secondary preventative therapies for CVD, such as lipid-lowering agents (P < .001), β-blockers (P < .001), and angiotensin-converting enzyme inhibitors (P < .001). Heartwatch is associated with a reduced risk of major vascular events and improved risk factor modification, supporting its potential as a nationwide program for secondary prevention of CVD. Copyright © 2012 Mosby, Inc. All rights reserved.

Characterizing cardiovascular risk in women with polycystic ovary syndrome: more than the sum of its parts?

PubMed

Chang, Alice Y; Wild, Robert A

2009-07-01

Polycystic ovary syndrome (PCOS), a condition of irregular menses and androgen excess, is the most common endocrinopathy of young women. Insulin resistance is a well-established feature among many women with PCOS, even in the nonobese. Therefore, it is not surprising that PCOS is frequently associated with cardiovascular risk factors and the metabolic syndrome. However, it is not known whether PCOS is an independent risk factor for atherosclerosis and cardiovascular (CV) events or whether CV risk is attributable to associated risk factors. We review previous studies on CV risk and disease in women with PCOS, describing the pitfalls and challenges in ascribing CV risk to PCOS. Women with PCOS might be partly reassured that their relative risk approximates that of the metabolic syndrome (RR 1.5) and also strongly counseled at the individual level about the greatest potential threat to their CV health, the development of type 2 diabetes.

Association of Fibroblast Growth Factor 23 With Recurrent Cardiovascular Events in Patients After an Acute Coronary Syndrome: A Secondary Analysis of a Randomized Clinical Trial.

PubMed

Bergmark, Brian A; Udell, Jacob A; Morrow, David A; Cannon, Christopher P; Steen, Dylan L; Jarolim, Petr; Budaj, Andrzej; Hamm, Christian; Guo, Jianping; Im, KyungAh; Kuder, Julia F; Braunwald, Eugene; Sabatine, Marc S; O'Donoghue, Michelle L

2018-04-18

Elevated fibroblast growth factor 23 (FGF-23) concentrations are associated with myocardial fibrosis and renin-angiotensin system upregulation, potentially providing prognostic information distinct from standard cardiovascular (CV) biomarkers. To evaluate the association of FGF-23 with recurrent CV events in patients after an acute coronary syndrome (ACS). C-terminal FGF-23 was measured in plasma samples using an established enzyme-linked immunosorbent assay system for 4947 patients within 30 days of ACS (median, 14 days) and with 1 additional CV risk factor in the Stabilization of Plaques Using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) trial of the lipoprotein-associated phospholipase A2 inhibitor darapladib vs placebo performed from December 1, 2009, to April 24, 2014 (median follow-up, 2.5 years). Analyses were adjusted for clinical risk factors, renal function, and established cardiorenal biomarkers. This secondary analysis was performed from September 25, 2014, to October 1, 2017. The FGF-23 concentration at baseline. The primary end point for this post hoc analysis was the composite of CV death or hospitalization for heart failure. In this study, baseline FGF-23 concentrations were available for 4947 patients (median age, 64.0 years; interquartile range, 59.0-71.0 years; 1276 [25.8%] female). Patients with higher FGF-23 concentrations were older and more likely female, with a greater proportion of hypertension, diabetes, and previous myocardial infarction. After multivariable adjustment for baseline clinical characteristics and established biomarkers (high-sensitivity troponin I, brain-type natriuretic peptide, and high-sensitivity C-reactive protein), FGF-23 concentration in the top quartile was independently associated with an increased risk of CV death or heart failure hospitalization (adjusted hazard ratio [HR], 2.35; 95% CI, 1.82-3.02; P < .001) and its individual components. Elevated FGF-23 concentration was also associated with an increased risk of all-cause mortality (adjusted HR, 2.27; 95% CI, 1.73-2.97; P < .001) and CV death, myocardial infarction, or stroke (adjusted HR, 1.42; 95% CI, 1.17-1.71; P < .001). When analyses were stratified by patient sex, the association between FGF-23 and CV risk, including CV death or heart failure, appeared to be attenuated in women (adjusted HR, 1.11; 95% CI, 0.70-1.76; P = .67) compared with men (HR, 3.11; 95% CI, 2.29-4.22; P < .001; P < .001 for interaction). In patients stabilized after ACS, elevated FGF-23 concentrations may be associated with recurrent major CV events and all-cause mortality, providing information independent of established clinical risk factors and cardiorenal biomarkers. A potential sex difference in these findings deserves further study.

Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

DOE PAGES

Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; ...

2014-10-22

Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ( 1H; 0.5 Gy, 1 GeV) and iron ion ( 56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiatedmore » mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.« less

Upper Arm Central Venous Port Implantation: A 6-Year Single Institutional Retrospective Analysis and Pictorial Essay of Procedures for Insertion

PubMed Central

Shiono, Masatoshi; Takahashi, Shin; Kakudo, Yuichi; Takahashi, Masanobu; Shimodaira, Hideki; Kato, Shunsuke; Ishioka, Chikashi

2014-01-01

Background The requirement of central venous (CV) port implantation is increasing with the increase in the number of cancer patients and advancement in chemotherapy. In our division, medical oncologists have implanted all CV ports to save time and consultation costs to other departments. Recently, upper arm implantation has become the first choice as a safe and comfortable method in our unit. Here we report our experience and discuss the procedure and its potential advantages. Methods All CV port implantations (n = 599) performed in our unit from January 2006 to December 2011 were analyzed. Procedural success and complication rates between subclavian and upper arm groups were compared. Results Both groups had similar patient characteristics. Upper arm CV port and subclavian implantations were equivalently successful and safe. Although we only retrospectively analyzed data from a single center, the upper arm group had a significantly lower overall postprocedural complication rate than the subclavian group. No pneumothorax risk, less risk of arterial puncture by ultrasound, feasibility of stopping potential arterial bleeding, and prevention of accidental arterial cannulation by targeting the characteristic solitary basilic vein were the identified advantages of upper arm CV port implantation. In addition to the aforementioned advantages, there is no risk of “pinch-off syndrome,” possibly less patient fear of manipulation, no scars on the neck and chest, easier accessibility, and compatibility with the “peripherally inserted central catheter” technique. Conclusions Upper arm implantation may benefit clinicians and patients with respect to safety and comfort. We also introduce our methods for upper arm CV port implantation with the videos. PMID:24614412

Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

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

Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah

Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ( 1H; 0.5 Gy, 1 GeV) and iron ion ( 56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiatedmore » mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.« less

The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH).

PubMed

2011-03-01

The aim of this study was to test the hypothesis that patients with atherosclerotic cardiovascular (CV) disease optimally treated on a statin but with residual atherogenic dyslipidemia (low high-density lipoprotein cholesterol [HDL-C] and high triglycerides) will benefit from addition of niacin with fewer CV events compared with placebo. Statin monotherapy trials have found 25%-35% CV risk reduction relative to placebo, leaving significant residual risk. Patients with atherogenic dyslipidemia have substantially increased CV risk. Participants were men and women with established CV disease and atherogenic dyslipidemia. Lipid entry criteria varied by gender and statin dose at screening. All participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain low-density lipoprotein cholesterol (LDL-C) 40-80 mg/dL (1.03-2.07 mmol/L). Participants were randomized to extended-release niacin or matching placebo. The primary end point was time to occurrence of the first of the following: coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization. This event-driven trial will have 85% power to show a 25% reduction in primary event frequency after 850 patients have experienced a primary outcome event. AIM-HIGH completed enrollment in April 2010. Follow-up is expected to continue through 2012. AIM-HIGH was designed to determine whether treating residual dyslipidemia with niacin further reduces cardiovascular events in patients with CV disease on a statin at target levels of low-density lipoprotein cholesterol. Copyright © 2011 Mosby, Inc. All rights reserved.

Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality.

PubMed

O'Keefe, James H; Bhatti, Salman K; Patil, Harshal R; DiNicolantonio, James J; Lucan, Sean C; Lavie, Carl J

2013-09-17

Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cardiovascular risk management in rheumatoid arthritis patients still suboptimal: the Implementation of Cardiovascular Risk Management in Rheumatoid Arthritis project.

PubMed

van den Oever, Inge A M; Heslinga, Maaike; Griep, Ed N; Griep-Wentink, Hanneke R M; Schotsman, Rob; Cambach, Walter; Dijkmans, Ben A C; Smulders, Yvo M; Lems, Willem F; Boers, Maarten; Voskuyl, Alexandre E; Peters, Mike J L; van Schaardenburg, Dirkjan; Nurmohamed, Micheal T

2017-09-01

To assess the 10-year cardiovascular (CV) risk score and to identify treatment and undertreatment of CV risk factors in patients with established RA. Demographics, CV risk factors and prevalence of cardiovascular disease (CVD) were assessed by questionnaire. To calculate the 10-year CV risk score according to the Dutch CV risk management guideline, systolic blood pressure was measured and cholesterol levels were determined from fasting blood samples. Patients were categorized into four groups: indication for treatment but not treated; inadequately treated, so not meeting goals (systolic blood pressure ⩽140 mmHg and/or low-density lipoprotein ⩽2.5 mmol/l); adequately treated; or no treatment necessary. A total of 720 consecutive RA patients were included, 375 from Reade and 345 from the Antonius Hospital. The mean age of patients was 59 years (s.d. 12) and 73% were female. Seventeen per cent of the patients had a low 10-year CV risk (<10%), 21% had an intermediate risk (10-19%), 53% a high risk (⩾20%) and 9% had CVD. In total, 69% had an indication for preventive treatment (cholesterol-lowering or antihypertensive drugs). Of those, 42% received inadequate treatment and 40% received no treatment at all. Optimal CV risk management remains a major challenge and better awareness and management are urgently needed to reduce the high risk of CVD in the RA population. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A simulation model to investigate the impact of cardiovascular risk in renal transplantation.

PubMed

McLean, D R; Jardine, A G

2005-06-01

Premature cardiovascular (CV) disease is the leading cause of death following renal transplantation and, as a consequence of death with a functioning graft, it is a major cause of graft loss. Renal transplant recipients have a high prevalence of CV risk factors that influence both patient and graft survival. We used data on the relationship between CV risk factors and graft and patient survivals to develop a discrete event simulation model to study the possible impact of CV risk factor reduction on transplant outcome. The simulation was based on a renal unit in a population that has the risk factor profile of patients from the West of Scotland. We studied the dynamic between patient numbers on the waiting list compared to the transplanted list. After establishing results pertinent to the renal unit, we investigated in what way potential changes to transplant policy affected patient numbers. These perturbations included changing the number of transplants performed, changing the incidence of acute rejection, and interventional policies where patients on the waiting list were selectively transplanted taking into account their CV risk factor profiles. Overall, the model predicts that reducing CV risk in the population with end-stage renal failure awaiting kidney transplantation will have comparable benefits to foreseeable developments in immunosuppression or attainable increases in transplant numbers. Moreover, addressing CV risk has benefits for all patients regardless of whether or not they ultimately receive a kidney transplant.

Global Cardiovascular Risk Assessment by Family Physicians in Suez Canal University-Family Medicine Centers-Egypt

PubMed Central

Nour-Eldein, Hebatallah; Abdelsalam, Shimaa A.; Nasr, Gamila M.; Abdelwahed, Hassan A.

2013-01-01

Background: The close sustained contact of family physician with their patients and local community makes preventive care an integral part of their routine work. Most cardiovascular diseases (CVD) can be prevented by addressing their risk factors. There are several guidelines that recommend different CV risk assessment tools to support CV prevention strategies. Aim: This study aimed to assess awareness and attitude of global CV risk assessment and use of their tools by family physicians; aiming to improve CV prevention service. Methods: The current study is a cross-sectional descriptive analytic. Sixty-five family physicians were asked to respond to, validated anonymous questionnaire to collect data about characteristics of family physicians, their awareness, attitude, current use, barriers, and recommendations of global CV risk assessment. Statistical Package for Social Sciences (SPSS) version 18 was used for data entry and analysis. Results: Awareness of guidelines of global CV risk assessment was relatively higher regarding the American guidelines (30.8%) than that recommended by World Health Organization (WHO) for Egypt (20.2%). 50.8% of participants had favorable attitude. There was statistical significant relationship between attitude scores and physician characteristics; age (P = 0.003), qualification (P = 0.001) and number of patients seen per week (P = 0.009). Routine use of global CV risk assessment tools was reported only (23%) by family physicians. Conclusion: Relative higher attitude scores than use of global CV risk assessment tools in practice. The most frequent barriers were related to lack of resources and shortage in training/skills and the raised suggestions were towards training. PMID:26664843

Global Cardiovascular Risk Assessment by Family Physicians in Suez Canal University-Family Medicine Centers-Egypt.

PubMed

Nour-Eldein, Hebatallah; Abdelsalam, Shimaa A; Nasr, Gamila M; Abdelwahed, Hassan A

2013-01-01

The close sustained contact of family physician with their patients and local community makes preventive care an integral part of their routine work. Most cardiovascular diseases (CVD) can be prevented by addressing their risk factors. There are several guidelines that recommend different CV risk assessment tools to support CV prevention strategies. This study aimed to assess awareness and attitude of global CV risk assessment and use of their tools by family physicians; aiming to improve CV prevention service. The current study is a cross-sectional descriptive analytic. Sixty-five family physicians were asked to respond to, validated anonymous questionnaire to collect data about characteristics of family physicians, their awareness, attitude, current use, barriers, and recommendations of global CV risk assessment. Statistical Package for Social Sciences (SPSS) version 18 was used for data entry and analysis. Awareness of guidelines of global CV risk assessment was relatively higher regarding the American guidelines (30.8%) than that recommended by World Health Organization (WHO) for Egypt (20.2%). 50.8% of participants had favorable attitude. There was statistical significant relationship between attitude scores and physician characteristics; age (P = 0.003), qualification (P = 0.001) and number of patients seen per week (P = 0.009). Routine use of global CV risk assessment tools was reported only (23%) by family physicians. Relative higher attitude scores than use of global CV risk assessment tools in practice. The most frequent barriers were related to lack of resources and shortage in training/skills and the raised suggestions were towards training.

[Independent risk factors for severe cardiovascular events in male patients with gout: Results of a 7-year prospective study].

PubMed

Eliseev, M S; Denisov, I S; Markelova, E I; Glukhova, S I; Nasonov, E L

To determine risk factors for severe cardiovascular (CV) events (CVEs) in male patients with crystal-verified gout. 251 male patients with crystal-verified gout were prospectively followed up in 2003 to 2013. The mean follow-up period was 6.9±2.0 years. New severe CVE cases and deaths were recorded. Logistic regression was used to analyze the impact of traditional and other risk factors and allopurinol use on the risk for severe CVEs. 32 patients died during the follow-up period. Severe CVEs were recorded in 58 (23.1%) patients; CVE deaths were notified in 22 (8.8%) patients. The risk of all severe CVEs was high for hypertension, increased serum high-sensitivity C-reactive protein (hs-CRP) level (>5 mg/l), ≥ stage III chronic kidney disease (CKD) (glomerular filtration rate, <60 ml/min/1.73 m2), alcohol intake (>20 g/day), coronary heart disease (CHD), and a family history of premature CHD. The risk of fatal CVEs was highest for elevated serum hs-CRP level, ≥ stage III CKD, a family history of premature CHD, hypercholesterolemia, upper quartile of serum uric acid levels (>552 µmol/l), and regular intake of allopurinol. In addition to the traditional risk factors of CV catastrophes, the presence of chronic inflammation and the impact of high serum uric acid levels may explain the high frequency of CV catastrophes.

Risk of no-reflow in culprit lesion versus culprit vessel PCI in acute STEMI.

PubMed

Arslan, Uğur; Yaman, Mehmet; Kocaoğlu, İbrahim; Turan, Oğuzhan Ekrem; Yücel, Huriye; Aksakal, Aytekin; Günaydin, İlksen Atasoy; Hakan Ateş, Ahmet

2015-09-01

The present report describes patients with acute ST-elevation myocardial infarction who had at least two lesions in the culprit vessel (CV) during primary percutaneous coronary intervention (PCI). Here, we aimed to examine two different strategies, namely, PCI of only culprit lesion (CL) versus PCI of all lesions in the CV in the setting of acute ST-elevation myocardial infarction. Patients who underwent primary PCI were examined for the presence of an additional lesion in the infarct-related artery and divided into two groups according to the PCI strategy: CV versus CL groups. Coronary angiograms were examined for coronary thrombolysis in myocardial infarction (TIMI) flow and major clinical outcomes were determined. Of 637 patients, 472 (74.1%) underwent primary PCI for the CV (CV group) and 165 (25.9%) underwent primary PCI only for CL (CL group). TIMI flow before primary PCI and after stenting of the CL was similar; however, TIMI flow after completion of the procedure was significantly better in the CL group (P=0.022). The composite of death, nonfatal myocardial infarction and repeat revascularization was significantly better in the CL group (P=0.041) and early stent thrombosis was observed more commonly in the CV group [14 (3.0%) patients vs. 1 (0.6%) patient, P=0.09]. In the presence of an additional lesion in the CV during primary PCI, deferring stenting for the non-CL in the culprit artery after stenting the CL may be considered to prevent the development of no-reflow or slow-reflow, and thus major clinical adverse events may be reduced.

One-Lung Ventilation with Additional Ipsilateral Ventilation of Low Tidal Volume and High Frequency in Lung Lobectomy

PubMed Central

Feng, Yong; Wang, Jianyue; Zhang, Yang; Wang, Shiduan

2016-01-01

Background To investigate the protective effects of additional ipsilateral ventilation of low tidal volume and high frequency on lung functions in the patients receiving lobectomy. Material/Methods Sixty patients receiving lung lobectomy were randomized into the conventional one-lung ventilation (CV) group (n=30) and the ipsilateral low tidal volume high frequency ventilation (LV) group (n=30). In the CV group, patients received only contralateral OLV. In the LV group, patients received contralateral ventilation and additional ipsilateral ventilation of low tidal volume of 1–2 ml/kg and high frequency of 40 times/min. Normal lung tissues were biopsied for the analysis of lung injury. Lung injury was scored by evaluating interstitial edema, alveolar edema, neutrophil infiltration, and alveolar congestion. Results At 30 min and 60 min after the initiation of one-lung ventilation and after surgery, patients in the LV group showed significantly higher ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen than those in the CV group (P<0.001). Lung injury was significantly less severe (2.7±0.7) in the LV group than in the CV group (3.1±0.7) (P=0.006). Conclusions Additional ipsilateral ventilation of low tidal volume and high frequency can decrease the risk of hypoxemia and alleviate lung injury in patients receiving lobectomy. PMID:27166086

Influence of high cardiovascular risk in asymptomatic people on the duration and cost of sick leave: results of the ICARIA study.

PubMed

Calvo-Bonacho, Eva; Ruilope, Luis Miguel; Sánchez-Chaparro, Miguel Angel; Cerezo, Cesar; Catalina-Romero, Carlos; Martínez-Muñoz, Paloma; Banegas, José R; Waeber, Bernard; Gonzalez-Quintela, Arturo; Zanchetti, Alberto

2014-02-01

We investigated the potential influence of a moderate-to-high cardiovascular (CV) risk (CVR) (defined as a Systematic COronary Risk Evaluation model, or SCORE ≥ 4%), in the absence of an established CV disease, on the duration and cost of CV and non-CV sick leave (SL) resulting from common and occupational accidents or diseases. We conducted a prospective cohort study on 690 135 workers with a 1-year follow-up and examined CV- and non-CV-related SL episodes. To obtain baseline values, CVR factors were initially assessed at the beginning of the year during routine medical examination. The CVR was calculated with the SCORE charts for all subjects. Moderate-to-high CVR was defined as SCORE ≥ 4%. A baseline SCORE ≥ 4% was associated with a higher risk for long-term CV and non-CV SL, as revealed by follow-up assessment. This translated into an increased cost, estimated at €5 801 464.18 per year. Furthermore, pharmacological treatment for hypertension or hyperlipidaemia was significantly associated with longer SL duration. Moderate-to-high CVR in asymptomatic subjects was significantly associated with the duration and cost of CV and non-CV SL. These results constitute the first body of evidence that the SCORE charts can be used to identify people with a non-established CV disease, which might ultimately translate into more lost workdays and therefore increased cost for society.

Cardiovascular risk factor management in patients with RA compared to matched non-RA patients

PubMed Central

Cawston, Helene; Bourhis, Francois; Al, Maiwenn; Rutten-van Mölken, Maureen P. M. H.; Liao, Katherine P.; Solomon, Daniel H.

2016-01-01

Objective. RA is associated with a 50–60% increase in risk of cardiovascular (CV) death. This study aimed to compare management of CV risk factors in RA and matched non-RA patients. Methods. A retrospective cohort study was conducted using UK clinical practice data. Patients presenting with an incident RA diagnosis were matched 1:4 to non-RA patients based on a propensity score for RA, entry year, CV risk category and treatment received at index date (date of RA diagnosis). Patients tested and treated for CV risk factors as well as those attaining CV risk factor management goals were evaluated in both groups. Results. Between 1987 and 2010, 24 859 RA patients were identified and matched to 87 304 non-RA patients. At index date, groups had similar baseline characteristics. Annual blood pressure, lipids and diabetes-related testing were similar in both groups, although CRP and ESR were higher in RA patients at diagnosis and decreased over time. RA patients prescribed antihypertensives increased from 38.2% at diagnosis to 45.7% at 5 years, from 14.0 to 20.6% for lipid-lowering treatments and from 5.1 to 6.4% for antidiabetics. Similar treatment percentages were observed in non-RA patients, although slightly lower for antihypertensives. Modest (2%) but significantly lower attainment of lipid and diabetes goals at 1 year was observed in RA patients. Conclusion. There were no differences between groups in the frequency of testing and treatment of CV risk factors. Higher CV risk in RA patients seems unlikely to be driven by differences in traditional CV risk factor management. PMID:26705329

Cardiovascular risk factor management in patients with RA compared to matched non-RA patients.

PubMed

Alemao, Evo; Cawston, Helene; Bourhis, Francois; Al, Maiwenn; Rutten-van Mölken, Maureen P M H; Liao, Katherine P; Solomon, Daniel H

2016-05-01

RA is associated with a 50-60% increase in risk of cardiovascular (CV) death. This study aimed to compare management of CV risk factors in RA and matched non-RA patients. A retrospective cohort study was conducted using UK clinical practice data. Patients presenting with an incident RA diagnosis were matched 1:4 to non-RA patients based on a propensity score for RA, entry year, CV risk category and treatment received at index date (date of RA diagnosis). Patients tested and treated for CV risk factors as well as those attaining CV risk factor management goals were evaluated in both groups. Between 1987 and 2010, 24 859 RA patients were identified and matched to 87 304 non-RA patients. At index date, groups had similar baseline characteristics. Annual blood pressure, lipids and diabetes-related testing were similar in both groups, although CRP and ESR were higher in RA patients at diagnosis and decreased over time. RA patients prescribed antihypertensives increased from 38.2% at diagnosis to 45.7% at 5 years, from 14.0 to 20.6% for lipid-lowering treatments and from 5.1 to 6.4% for antidiabetics. Similar treatment percentages were observed in non-RA patients, although slightly lower for antihypertensives. Modest (2%) but significantly lower attainment of lipid and diabetes goals at 1 year was observed in RA patients. There were no differences between groups in the frequency of testing and treatment of CV risk factors. Higher CV risk in RA patients seems unlikely to be driven by differences in traditional CV risk factor management. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Propeptide big-endothelin, N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study.

PubMed

Gergei, Ingrid; Krämer, Bernhard K; Scharnagl, Hubert; Stojakovic, Tatjana; März, Winfried; Mondorf, Ulrich

The endothelin system (Big-ET-1) is a key regulator in cardiovascular (CV) disease and congestive heart failure (CHF). We have examined the incremental value of Big-ET-1 in predicting total and CV mortality next to the well-established CV risk marker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP). Big-ET-1 and NT-proBNP were determined in 2829 participants referred for coronary angiography (follow-up 9.9 years). Big-ET-1 is an independent predictor of total, CV mortality and death due to CHF. The conjunct use of Big-ET-1 and NT-proBNP improves the risk stratification of patients with intermediate to high risk of CV death and CHF. Big-ET-1improves risk stratification in patients referred for coronary angiography.

Can pleiotropic effects of eicosapentaenoic acid (EPA) impact residual cardiovascular risk?

PubMed

Nelson, John R; True, Wayne S; Le, Viet; Mason, R Preston

2017-11-01

Residual cardiovascular (CV) risk persists even in statin-treated patients with optimized low-density lipoprotein cholesterol (LDL-C) levels. Other pathways beyond cholesterol contribute to CV risk and the key to reducing residual risk may be addressing non-cholesterol risk factors through pleiotropic mechanisms. The purpose of this review is to examine the literature relating to the potential role of the omega-3 fatty acid eicosapentaenoic acid (EPA) in reducing residual CV risk. The literature shows that EPA can robustly lower plasma triglyceride (TG) levels without raising LDL-C levels and documents EPA to have a broad range of beneficial effects on the atherosclerotic pathway, including those on lipids, lipoproteins, inflammation, oxidation, phospholipid membranes, and the atherosclerotic plaque itself. Clinical imaging studies have consistently demonstrated that EPA decreases plaque vulnerability and prevents plaque progression. The evidence therefore points to a potential role for EPA to reduce residual CV risk. A large randomized study of statin-treated Japanese patients demonstrated that EPA ethyl ester reduced major coronary events by 19% (P = 0.011). However, while there has been significant benefit demonstrated in this and another Japanese CV outcomes study, the question as to whether EPA can play a role in reducing residual CV risk remains to be addressed in broader populations. The large, global, ongoing, randomized, placebo-controlled REDUCE-IT study of high-risk statin-treated patients with persistent hypertriglyceridemia is currently underway to investigate the potential of icosapent ethyl (high-purity prescription EPA ethyl ester) as an add-on therapy to reduce residual CV risk.

Food as Medicine for Secondary Prevention of Cardiovascular Events Following an Acute Coronary Syndrome.

PubMed

Paruchuri, Vijayapraveena; Gaztanaga, Juan; Rambhujun, Vikash; Smith, Robin; Farkouh, Michael E

2018-06-13

Cardiovascular disease is the leading cause of death in men and women in the USA. Once a patient experiences an acute coronary syndrome (ACS), they are at increased risk for hospital readmission within 30 days and 6 months after discharge and more importantly, they have worse survival. Hospital readmissions lead to poor clinical outcomes for the patient and also significantly increase healthcare costs due to repeat diagnostic evaluation, imaging, and coronary interventions. The goal after hospital discharge is to modify cardiovascular (CV) risk factors including hypertension, hyperlipidemia, and diabetes to prevent repeat coronary events; however, drug therapy is only one aspect. Several diets have been shown to decrease weight and reduce these risk factors over short durations; however, most people typically cannot sustain their diet and regain the weight. The Intelligent Quisine (IQ) diet is a prepared meal plan that was designed to meet the American Heart Association and American Diabetes Association nutritional guidelines and simplify the daily consumption of a nutritionally complete, calorie conscious meal. The IQ diet has been shown to significantly reduce blood pressure, cholesterol levels, glucose levels, and weight over a 10-week period. Additional studies have shown that patients are able to remain compliant on the diet for a year and maintain the reduction of their CV risk factors. If patients are consistent with a healthy calorie conscious and nutritionally complete diet modifying CV risk factors long term, then food could be as powerful in reducing CV events as evidence-based drug therapy. There is a need to begin conceptualizing food as medicine. To this end, it is time for a randomized control trial implementing the IQ diet versus current standard dietary recommendations in a large number of patients and measuring hard CV endpoints. Many readmissions can be avoided with proper patient education and support emphasizing lifestyle modifications such as eating healthy and smoking cessation on a foundation of optimal medical therapy.

Early Dynamic Risk Stratification with Baseline Troponin Levels and 90-minute ST Segment Resolution to Predict 30 Day Cardiovascular Mortality in STEMI: Analysis from CLARITY TIMI-28

PubMed Central

Sherwood, Matthew W.; Morrow, David A.; Scirica, Benjamin M.; Jiang, Songtao; Bode, Christoph; Rifai, Nader; Gerszten, Robert E.; Gibson, C. Michael; Cannon, Christopher P.; Braunwald, Eugene; Sabatine, Marc S.

2010-01-01

Background Troponin is the preferred biomarker for risk stratification in non-ST-elevation ACS. The incremental prognostic utility of the initial magnitude of troponin elevation and its value in conjunction with ST segment resolution (STRes) in STEMI is less well-defined. Methods Troponin T (TnT) was measured in 1250 patients at presentation undergoing fibrinolysis for STEMI in CLARITY-TIMI 28. STRes was measured at 90 minutes. Multivariable logistic regression was used to examine the independent association between TnT levels, STRes, and 30-day cardiovascular (CV) mortality. Results Patients were classified into undetectable TnT at baseline (n=594), detectable but below the median of 0.12 ng/ml (n=330), and above the median (n=326). Rates of 30-day CV death were 1.5%, 4.5%, and 9.5% respectively (P<0.0001). Compared with those with undetectable levels and adjusting for baseline factors, the odds ratios for 30-day CV death were 4.56 (1.72-12.08, P=0.002) and 5.81 (2.29-14.73, P=0.0002) for those below and above the median, respectively. When combined with STRes, there was a significant gradient of risk, and in a multivariable model both baseline TnT (P=0.004) and STRes (P=0.003) were significant predictors of 30-day CV death. The addition of TnT and STRes to clinical risk factors significantly improved the C-statistic (0.86 to 0.90, P=0.02) and the integrated discriminative improvement 7.1% (P=0.0009). Conclusions Baseline TnT and 90-minute STRes are independent predictors of 30-day CV death in patients with STEMI. Use of these two simple, readily available tools can aid clinicians in early risk stratification. PMID:20569707

Feasibility and Diagnostic Value of Cardiovascular Magnetic Resonance Imaging After Acute Ischemic Stroke of Undetermined Origin.

PubMed

Haeusler, Karl Georg; Wollboldt, Christian; Bentheim, Laura Zu; Herm, Juliane; Jäger, Sebastian; Kunze, Claudia; Eberle, Holger-Carsten; Deluigi, Claudia Christina; Bruder, Oliver; Malsch, Carolin; Heuschmann, Peter U; Endres, Matthias; Audebert, Heinrich J; Morguet, Andreas J; Jensen, Christoph; Fiebach, Jochen B

2017-05-01

Etiology of acute ischemic stroke remains undetermined (cryptogenic) in about 25% of patients after state-of-the-art diagnostic work-up. One-hundred and three patients with magnetic resonance imaging (MRI)-proven acute ischemic stroke of undetermined origin were prospectively enrolled and underwent 3-T cardiac MRI and magnetic resonance angiography of the aortic arch in addition to state-of-the-art diagnostic work-up, including transesophageal echocardiography (TEE). We analyzed the feasibility, diagnostic accuracy, and added value of cardiovascular MRI (cvMRI) compared with TEE for detecting sources of stroke. Overall, 102 (99.0%) ischemic stroke patients (median 63 years [interquartile range, 53-72], 24% female, median NIHSS (National Institutes of Health Stroke Scale) score on admission 2 [interquartile range, 1-4]) underwent cvMRI and TEE in hospital; 89 (86.4%) patients completed the cvMRI examination. In 93 cryptogenic stroke patients, a high-risk embolic source was found in 9 (8.7%) patients by cvMRI and in 11 (11.8%) patients by echocardiography, respectively. cvMRI and echocardiography findings were consistent in 80 (86.0%) patients, resulting in a degree of agreement of κ=0.24. In 82 patients with cryptogenic stroke according to routine work-up, including TEE, cvMRI identified stroke etiology in additional 5 (6.1%) patients. Late gadolinium enhancement consistent with previous myocardial infarction was found in 13 (14.6%) out of 89 stroke patients completing cvMRI. Only 2 of these 13 patients had known coronary artery disease. Our study demonstrated that cvMRI was feasible in the vast majority of included patients with acute ischemic stroke. The diagnostic information of cvMRI seems to be complementary to TEE but is not replacing echocardiography after acute ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01917955. © 2017 American Heart Association, Inc.

Causes of Death in a Contemporary Cohort of Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: Insights From the TECOS Trial.

PubMed

Sharma, Abhinav; Green, Jennifer B; Dunning, Allison; Lokhnygina, Yuliya; Al-Khatib, Sana M; Lopes, Renato D; Buse, John B; Lachin, John M; Van de Werf, Frans; Armstrong, Paul W; Kaufman, Keith D; Standl, Eberhard; Chan, Juliana C N; Distiller, Larry A; Scott, Russell; Peterson, Eric D; Holman, Rury R

2017-12-01

We evaluated the specific causes of death and their associated risk factors in a contemporary cohort of patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study ( n = 14,671), a cardiovascular (CV) safety trial adding sitagliptin versus placebo to usual care in patients with type 2 diabetes and ASCVD (median follow-up 3 years). An independent committee blinded to treatment assignment adjudicated each cause of death. Cox proportional hazards models were used to identify risk factors associated with each outcome. A total of 1,084 deaths were adjudicated as the following: 530 CV (1.2/100 patient-years [PY], 49% of deaths), 338 non-CV (0.77/100 PY, 31% of deaths), and 216 unknown (0.49/100 PY, 20% of deaths). The most common CV death was sudden death ( n = 145, 27% of CV death) followed by acute myocardial infarction (MI)/stroke ( n = 113 [MI n = 48, stroke n = 65], 21% of CV death) and heart failure (HF) ( n = 63, 12% of CV death). The most common non-CV death was malignancy ( n = 154, 46% of non-CV death). The risk of specific CV death subcategories was lower among patients with no baseline history of HF, including sudden death (hazard ratio [HR] 0.4; P = 0.0036), MI/stroke death (HR 0.47; P = 0.049), and HF death (HR 0.29; P = 0.0057). In this analysis of a contemporary cohort of patients with diabetes and ASCVD, sudden death was the most common subcategory of CV death. HF prevention may represent an avenue to reduce the risk of specific CV death subcategories. © 2017 by the American Diabetes Association.

[Smoking, vaping and cardiovascular risk : an update].

PubMed

Dalkou, Sofia; Clair, Carole

2017-06-07

It is well known that tobacco smoking increases cardiovascular (CV) mortality and morbidity, however, smoking cessation is often neglected compared to other CV risk factors. Behavioral counseling as well as smoking cessation treatments are efficient and do not increase the risk of CV events when used for a defined duration. Electronic nicotine delivery systems (ENDS) contain potentially cardiotoxic substances but in lower concentrations than in cigarettes. The CV effect of ENDS is to date difficult to assess and depends on the type of device used and its mode of consumption. For smokers with a known CV disease who have quit smoking using ENDS, it is recommended that they stop using them as soon as they have stabilized.

Testosterone and the Heart.

PubMed

Goodale, Travis; Sadhu, Archana; Petak, Steven; Robbins, Richard

2017-01-01

Testosterone (T) has a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular (CV) risk. Low T levels in men may increase their risk of developing coronary artery disease (CAD), metabolic syndrome, and type 2 diabetes. Reduced T levels in men with congestive heart failure (CHF) portends a poor prognosis and is associated with increased mortality. Studies have reported a reduced CV risk with higher endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent T replacement therapy versus untreated men. Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes. There are no large long-term, placebo-controlled, randomized clinical trials to provide definitive conclusions about TRT and CV risk. However, there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not. In fact, existing data suggests that T therapy may offer CV benefits to men.

The periconception maternal cardiovascular risk profile influences human embryonic growth trajectories in IVF/ICSI pregnancies.

PubMed

Wijnands, K P J; van Uitert, E M; Roeters van Lennep, J E; Koning, A H J; Mulders, A G M G J; Laven, J S E; Steegers, E A P; Steegers-Theunissen, R P M

2016-06-01

Is the maternal cardiovascular (CV) risk profile associated with human embryonic growth trajectories and does the mode of conception affect this association? This small study suggests that the maternal CV risk profile is inversely associated with first trimester embryonic growth trajectories in in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) pregnancies, but not in spontaneously conceived pregnancies. Maternal high-blood pressure and smoking affect placental function, accompanied by increased risk of fetal growth restriction and low-birthweight. Mothers who experience pregnancies complicated by fetal growth restriction are at increased risk of CV disease in later life. In a prospective periconception birth cohort conducted in a tertiary hospital, 111 singleton ongoing pregnancies with reliable pregnancy dating, no pre-existing maternal disease and no malformed live borns were investigated. Spontaneously conceived pregnancies with a reliable first day of the last menstrual period and a regular menstrual cycle of 25-31 days only (n = 66) and IVF/ICSI pregnancies (n = 45) were included. Women underwent weekly three-dimensional ultrasound scans (3D US) from 6- to 13-week gestational age. To estimate embryonic growth, serial crown-rump length (CRL) measurements were performed using the V-Scope software in a BARCO I-Space. Maternal characteristics and CV risk factors were collected by self-administered questionnaires. The CV risk profile was created based on a score of risk factors, including maternal age, body-mass index, CV disease in the family, diet and smoking. Quartiles of the CV risk score were calculated. Associations between the CV risk score and embryonic growth were assessed using square root transformed CRL in multivariable linear mixed model analyses. From the 111 included pregnancies, 696 3D US data sets were obtained of which 637 (91.5%) CRLs could be measured. In the total group, The CV risk score was inversely, but not significantly associated with embryonic growth (-0.03√mm; P = 0.291). Stratified by mode of conception, the CV risk score was inversely and significantly associated with embryonic growth (β = -0.04√mm; P = 0.025, adjusted for possible confounders) in the IVF/ICSI group. Compared with the first quartile, embryos in the upper quartile were 10.4% smaller at 6(+0) weeks (4.4 versus 4.9 mm) and 3.1% smaller at 12(+0) weeks (56.5 versus 58.4 mm) of gestation. Although the CV risk score was slightly, but significantly, higher in women conceiving spontaneously compared with those undergoing IVF/ICSI treatment [CV risk score = 2.06 (SD: 1.23) and 1.60 (SD: 1.15), respectively], no association was established with embryonic growth in that particular group. Participants included in the present cohort are women with a singleton ongoing pregnancy without any pre-existing disease and selected from a tertiary hospital. Hence, they represent a selected group of women. Larger and population-based periconception birth cohort studies are recommended to demonstrate external validity. Differences in embryonic growth between pregnancies conceived spontaneously and after IVF/ICSI treatment in relation with CV risk factors substantiate the importance of more investigation into differences in sensitivity of endometrial, endothelial, placental and embryonic tissues. Funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. The authors declare no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dietary flavonoid intake and cardiovascular risk: a population-based cohort study.

PubMed

Ponzo, Valentina; Goitre, Ilaria; Fadda, Maurizio; Gambino, Roberto; De Francesco, Antonella; Soldati, Laura; Gentile, Luigi; Magistroni, Paola; Cassader, Maurizio; Bo, Simona

2015-07-08

The cardio-protective effects of flavonoids are still controversial; many studies referred to the benefits of specific foods, such as soy, cocoa, tea. A population-based cohort of middle-aged adults, coming from a semi-rural area where the consumption of those foods is almost negligible, was studied. The primary objective was establishing if flavonoid intake was inversely associated with the cardiovascular (CV) risk evaluated after 12-year follow-up; the associations between flavonoid intake and CV incidence and mortality and all-cause mortality were also evaluated. In 2001-2003, a cohort of 1,658 individuals completed a validated food-frequency questionnaire. Anthropometric, laboratory measurements, medical history and the vital status were collected at baseline and during 2014. The CV risk was estimated with the Framingham risk score. Individuals with the lowest tertile of flavonoid intake showed a worse metabolic pattern and less healthy lifestyle habits. The 2014 CV risk score and the increase in the risk score from baseline were significantly higher with the lowest intake of total and all subclasses of flavonoids, but isoflavones, in a multiple regression model. During follow-up, 125 CV events and 220 deaths (84 of which due to CV causes) occurred. CV non-fatal events were less frequent in individuals with higher flavonoid intake (HR = 0.64; 95%CI 0.42-1.00 and HR = 0.46; 95%CI 0.28-0.75 for the second and third tertiles, respectively) in Cox-regression models, after multiple adjustments. All subclasses of flavonoids, but flavones and isoflavones, were inversely correlated with incident CV events, with HRs ranging from 0.42 (flavan-3-ols) to 0.56 (anthocyanidins). Being in the third tertile of flavan-3-ols (HR = 0.68; 95% CI 0.48-0.96), anthocyanidins (HR = 0.66; 95% CI 0.46-0.95) and flavanones (HR = 0.59; 95% CI 0.40-0.85) was inversely associated with all-cause mortality. Total and subclasses of flavonoids were not significantly associated with the risk of CV mortality. Flavonoid intake was inversely associated with CV risk, CV non-fatal events and all-cause mortality in a cohort with a low consumption of soy, tea and cocoa, which are typically viewed as the foods responsible for flavonoid-related benefits.

Prognostic value of aortic stiffness and calcification for cardiovascular events and mortality in dialysis patients: outcome of the calcification outcome in renal disease (CORD) study.

PubMed

Verbeke, Francis; Van Biesen, Wim; Honkanen, Eero; Wikström, Björn; Jensen, Per Bruno; Krzesinski, Jean-Marie; Rasmussen, Merete; Vanholder, Raymond; Rensma, Pieter L

2011-01-01

Radiographic calcification and arterial stiffness each individually are predictive of outcome in dialysis patients. However, it is unknown whether combined assessment of these intermediate endpoints also provides additional predictive value. Scoring of abdominal aortic calcification (AAC) using plain lateral abdominal x-ray and measurement of carotid-femoral pulse wave velocity (PWV) were performed in a cohort of 1084 prevalent dialysis patients recruited from 47 European dialysis centers. During a follow-up of 2 years, 234 deaths and 91 nonfatal cardiovascular (CV) events occurred. Compared with the lowest tertile of AAC, the risk of an event was increased by a factor 3.7 in patients with a score of 5 to 15 (middle tertile), and by a factor 8.6 in patients with scores of 16 to 24. Additionally, each 1-m/s increase in PWV was associated with a 15% higher risk. At higher AAC (scores ≥ 5), the effect of PWV was attenuated because of a negative PWV × AAC interaction (hazard ratio [HR]: 0.895 and 0.865 for middle and upper AAC tertiles). After accounting for age, diabetes, and serum albumin, AAC and PWV remained independent predictors of outcome. AAC and central arterial stiffness are independent predictors of mortality and nonfatal CV events in dialysis patients. The risk associated with an increased PWV is less pronounced at higher levels of calcification. Assessment of AAC and PWV is feasible in a clinical setting and both may be used for an accurate CV risk estimation in this heterogeneous population.

Subclinical Kidney Damage in Hypertensive Patients: A Renal Window Opened on the Cardiovascular System. Focus on Microalbuminuria.

PubMed

Mulè, Giuseppe; Castiglia, Antonella; Cusumano, Claudia; Scaduto, Emilia; Geraci, Giulio; Altieri, Dario; Di Natale, Epifanio; Cacciatore, Onofrio; Cerasola, Giovanni; Cottone, Santina

2017-01-01

The kidney is one of the major target organs of hypertension.Kidney damage represents a frequent event in the course of hypertension and arterial hypertension is one of the leading causes of end-stage renal disease (ESRD).ESRD has long been recognized as a strong predictor of cardiovascular (CV) morbidity and mortality. However, over the past 20 years a large and consistent body of evidence has been produced suggesting that CV risk progressively increases as the estimated glomerular filtration rate (eGFR) declines and is already significantly elevated even in the earliest stages of renal damage. Data was supported by the very large collaborative meta-analysis of the Chronic Kidney Disease Prognosis Consortium, which provided undisputable evidence that there is an inverse association between eGFR and CV risk. It is important to remember that in evaluating CV disease using renal parameters, GFR should be assessed simultaneously with albuminuria.Indeed, data from the same meta-analysis indicate that also increased urinary albumin levels or proteinuria carry an increased risk of all-cause and CV mortality. Thus, lower eGFR and higher urinary albumin values are not only predictors of progressive kidney failure, but also of all-cause and CV mortality, independent of each other and of traditional CV risk factors.Although subjects with ESRD are at the highest risk of CV diseases, there will likely be more events in subjects with mil-to-moderate renal dysfunction, because of its much higher prevalence.These findings are even more noteworthy when one considers that a mild reduction in renal function is very common in hypertensive patients.The current European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension recommend to sought in every patient signs of subclinical (or asymptomatic) renal damage. This was defined by the detection of eGFR between 30 mL/min/1.73 m 2 and 60 mL/min/1.73 m 2 or the presence of microalbuminuria (MAU), that is an amount of albumin in the urine of 30-300 mg/day or an albumin/creatinine ratio, preferentially on morning spot urine, of 30-300 mg/g.There is clear evidence that urinary albumin excretion levels, even below the cut-off values used to define MAU, are associated with an increased risk of CV events. The relationships of MAU with a variety of risk factors, such as blood pressure, diabetes and metabolic syndrome and with several indices of subclinical organ damage, may contribute, at least in part, to explain the enhanced CV risk conferred by MAU. Nonetheless, several studies showed that the association between MAU and CV disease remains when all these risk factors are taken into account in multivariate analyses. Therefore, the exact pathophysiological mechanisms explaining the association between MAU and CV risk remain to be elucidated. The simple search for MAU and in general of subclinical renal involvement in hypertensive patients may enable the clinician to better assess absolute CV risk, and its identification may induce physicians to encourage patients to make healthy lifestyle changes and perhaps would prompt to more aggressive modification of standard CV risk factors.

Safety and efficacy of ezetimibe: A meta-analysis.

PubMed

Savarese, Gianluigi; De Ferrari, Gaetano M; Rosano, Giuseppe M C; Perrone-Filardi, Pasquale

2015-12-15

The addition of ezetimibe to statin therapy has been widely demonstrated to significantly reduce low-density lipoprotein cholesterol levels. However, the efficacy of ezetimibe in reducing CV events and its safety has been less investigated. The aim of the current meta-analysis was to report efficacy and safety of ezetimibe from randomized clinical trials. Randomized clinical trials with a follow-up of at least 24 weeks, enrolling more than 200 patients, comparing ezetimibe versus placebo or ezetimibe plus another hypolipidemic agent versus the same hypolipidemic drug alone and reporting at least one event among all-cause and CV mortality, myocardial infarction (MI), stroke and new onset of cancer were included in the analysis. 7 trials enrolling 31,048 patients (median follow-up 34.1 ± 26.3 months; 70% women; mean age 61 ± 8 years) were included in the analysis. Compared to control therapy, ezetimibe significantly reduced the risk of MI by 13.5% (RR: 0.865, 95% CI: 0.801 to 0.934, p<0.001) and the risk of any stroke by 16.0% (RR: 0.840, 95% CI: 0.744 to 0.949, p=0.005), without any effect on all-cause and CV mortality (RR: 1.003, 95% CI: 0.954 to 1.055, p=0.908; RR: 0.958, 95% CI: 0.879 to 1.044, p=0.330; respectively) and risk of new cancer (RR: 1.040, 95% CI: 0.965 to 1.120, p=0.303). Ezetimibe significantly reduces the risk of MI and stroke without any effect on all-cause and CV mortality and risk of cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Risk perception of obesity and bariatric surgery in patients seeking treatment for obesity.

PubMed

Prasad, Chaithra; Batsis, John A; Lopez-Jimenez, Francisco; Clark, Matthew M; Somers, Virend K; Sarr, Michael G; Collazo-Clavell, Maria L

2014-06-01

Bariatric surgery (BSx) produces clinically relevant weight loss that translates into improved quality of life, decreased mortality, and reduction in medical comorbidities, including cardiovascular (CV) risk. Little is known about patients' decision-making process to undergo BSx, but risk perception is known to influence medical decision-making. This study examined CV and BSx risk perception in obese subjects undergoing BSx (n = 268) versus those managed medically (MM) (n = 273). This retrospective population-based survey of subjects evaluated for BSx had 148 (55%) and 88 (32%) responders in the BSx and MM groups, respectively. Survey questions assessed risk perceptions and habits prior to weight loss intervention. CV risk was calculated using the Framingham Risk Score (FRS). At baseline, BSx subjects had a greater body mass index and greater prevalence of diabetes and depression. Follow-up mean weight loss was greater in the BSx group. BSx subjects perceived obesity as a greater risk to their overall health than the surgical risk. FRS declined in the BSx group (10 to 5%; p < 0.001) while there was no change in the MM group (8 to 8%; p = 0.54). Those without a measurable decrease in CV risk had a greater tendency to perceive the risk of BSx as greater than that of obesity. Obese subjects undergoing BSx are more likely than MM subjects to perceive obesity as a greater risk to their health than BSx. MM subjects generally underestimate their CV risk and overestimate the risk of BSx. Active discussion of CV risk using the FRS and the perception of risk associated with bariatric surgery can enhance patients' ability to make an informed decision regarding their management. © The European Society of Cardiology 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Prevention of cardiovascular disease in rheumatoid arthritis.

PubMed

Hollan, I; Dessein, P H; Ronda, N; Wasko, M C; Svenungsson, E; Agewall, S; Cohen-Tervaert, J W; Maki-Petaja, K; Grundtvig, M; Karpouzas, G A; Meroni, P L

2015-10-01

The increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) has been recognized for many years. However, although the characteristics of CVD and its burden resemble those in diabetes, the focus on cardiovascular (CV) prevention in RA has lagged behind, both in the clinical and research settings. Similar to diabetes, the clinical picture of CVD in RA may be atypical, even asymptomatic. Therefore, a proactive screening for subclinical CVD in RA is warranted. Because of the lack of clinical trials, the ideal CVD prevention (CVP) in RA has not yet been defined. In this article, we focus on challenges and controversies in the CVP in RA (such as thresholds for statin therapy), and propose recommendations based on the current evidence. Due to the significant contribution of non-traditional, RA-related CV risk factors, the CV risk calculators developed for the general population underestimate the true risk in RA. Thus, there is an enormous need to develop adequate CV risk stratification tools and to identify the optimal CVP strategies in RA. While awaiting results from randomized controlled trials in RA, clinicians are largely dependent on the use of common sense, and extrapolation of data from studies on other patient populations. The CVP in RA should be based on an individualized evaluation of a broad spectrum of risk factors, and include: 1) reduction of inflammation, preferably with drugs decreasing CV risk, 2) management of factors associated with increased CV risk (e.g., smoking, hypertension, hyperglycemia, dyslipidemia, kidney disease, depression, periodontitis, hypothyroidism, vitamin D deficiency and sleep apnea), and promotion of healthy life style (smoking cessation, healthy diet, adjusted physical activity, stress management, weight control), 3) aspirin and influenza and pneumococcus vaccines according to current guidelines, and 4) limiting use of drugs that increase CV risk. Rheumatologists should take responsibility for the education of health care providers and RA patients regarding CVP in RA. It is immensely important to incorporate CV outcomes in testing of anti-rheumatic drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis.

PubMed

Kappus, Natalie; Weinstock-Guttman, Bianca; Hagemeier, Jesper; Kennedy, Cheryl; Melia, Rebecca; Carl, Ellen; Ramasamy, Deepa P; Cherneva, Mariya; Durfee, Jacqueline; Bergsland, Niels; Dwyer, Michael G; Kolb, Channa; Hojnacki, David; Ramanathan, Murali; Zivadinov, Robert

2016-02-01

Cardiovascular (CV) risk factors have been associated with changes in clinical outcomes in patients with multiple sclerosis (MS). To investigate the frequency of CV risks in patients with MS and their association with MRI outcomes. In a prospective study, 326 patients with relapsing-remitting MS and 163 patients with progressive MS, 61 patients with clinically isolated syndrome (CIS) and 175 healthy controls (HCs) were screened for CV risks and scanned on a 3T MRI scanner. Examined CV risks included hypertension, heart disease, smoking, overweight/obesity and type 1 diabetes. MRI measures assessed lesion volumes (LVs) and brain atrophy. Association between individual or multiple CV risks and MRI outcomes was examined adjusting for age, sex, race, disease duration and treatment status. Patients with MS showed increased frequency of smoking (51.7% vs 36.5%, p = 0.001) and hypertension (33.9% vs 24.7%, p=0.035) compared with HCs. In total, 49.9% of patients with MS and 36% of HCs showed ≥ 2 CV risks (p = 0.003), while the frequency of ≥ 3 CV risks was 18.8% in the MS group and 8.6% in the HCs group (p = 0.002). In patients with MS, hypertension and heart disease were associated with decreased grey matter (GM) and cortical volumes (p < 0.05), while overweight/obesity was associated with increased T1-LV (p < 0.39) and smoking with decreased whole brain volume (p = 0.049). Increased lateral ventricle volume was associated with heart disease (p = 0.029) in CIS. Patients with MS with one or more CV risks showed increased lesion burden and more advanced brain atrophy. 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/

Prevalence and prognostic impact of electrocardiographic abnormalities in outpatients with extracardiac artery disease.

PubMed

Hysing, Per; Jonason, Tommy; Leppert, Jerzy; Hedberg, Pär

2017-11-24

Identifying cardiac disease in patients with extracardiac artery disease (ECAD) is essential for clinical decision-making. Electrocardiography (ECG) is an easily accessible tool to unmask subclinical cardiac disease and to risk stratify patient with or without manifest cardiovascular disease (CV). We aimed to examine the prevalence and prognostic impact of ECG changes in outpatients with ECAD. Outpatients with carotid or lower extremity artery disease (n = 435) and community-based controls (n = 397) underwent resting ECG. The patients were followed during a median of 4·8 years for CV events (hospitalization or death caused by ischaemic heart disease, cardiac arrest, heart failure, or stroke). ECG abnormalities were classified according to the Minnesota Code. Major (33% versus 15%, P<0·001) but not minor ECG abnormalities (23% versus 26%, P = 0·42) were significantly more common in patients versus controls. During the follow-up, 141 patients experienced CV events. Both major ECG abnormalities [hazard ratio (HR) 1·58, 95% confidence interval (CI) 1·11-2·25, P = 0·012] and any ECG abnormalities (HR 1·57, 95% CI 1·06-2·33, P = 0·024) were significantly associated with CV events after adjustment for potential risk factors. In conclusion, ECG abnormalities were common in these outpatients with ECAD. Major and any ECG abnormalities were independent predictors of CV events. Addition of easily accessible ECG information might be useful in risk stratification for such patients. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Cardiovascular risk in rheumatoid arthritis: assessment, management and next steps

PubMed Central

Zegkos, Thomas; Kitas, George; Dimitroulas, Theodoros

2016-01-01

Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) morbidity and mortality which cannot be fully explained by traditional CV risk factors; cumulative inflammatory burden and antirheumatic medication-related cardiotoxicity seem to be important contributors. Despite the acknowledgment and appreciation of CV disease burden in RA, optimal management of individuals with RA represents a challenging task which remains suboptimal. To address this need, the European League Against Rheumatism (EULAR) published recommendations suggesting the adaptation of traditional risk scores by using a multiplication factor of 1.5 if two of three specific criteria are fulfilled. Such guidance requires proper coordination of several medical specialties, including general practitioners, rheumatologists, cardiologists, exercise physiologists and psychologists to achieve a desirable result. Tight control of disease activity, management of traditional risk factors and lifestyle modification represent, amongst others, the most important steps in improving CV disease outcomes in RA patients. Rather than enumerating studies and guidelines, this review attempts to critically appraise current literature, highlighting future perspectives of CV risk management in RA. PMID:27247635

Testosterone and the Heart

PubMed Central

Goodale, Travis; Sadhu, Archana; Petak, Steven; Robbins, Richard

2017-01-01

Testosterone (T) has a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular (CV) risk. Low T levels in men may increase their risk of developing coronary artery disease (CAD), metabolic syndrome, and type 2 diabetes. Reduced T levels in men with congestive heart failure (CHF) portends a poor prognosis and is associated with increased mortality. Studies have reported a reduced CV risk with higher endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent T replacement therapy versus untreated men. Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes. There are no large long-term, placebo-controlled, randomized clinical trials to provide definitive conclusions about TRT and CV risk. However, there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not. In fact, existing data suggests that T therapy may offer CV benefits to men. PMID:28740585

Cardiorespiratory fitness and cardiovascular risk in patients with ankylosing spondylitis: a cross-sectional comparative study.

PubMed

Halvorsen, Silje; Vøllestad, Nina Køpke; Provan, Sella Arrestad; Semb, Anne Grete; van der Heijde, Désirée; Hagen, Kåre Birger; Dagfinrud, Hanne

2013-06-01

To investigate the associations between cardiorespiratory fitness (CRF) and the level of cardiovascular (CV) risk factors in patients with ankylosing spondylitis (AS) and controls. In a cross-sectional comparative study, CRF was measured with a maximal treadmill test for estimation of peak oxygen uptake. Metabolic syndrome (MS), body composition, traditional CV risk factors, and inflammatory markers were assessed. Multivariable linear regression models were used to study the associations between CRF and CV risk factors. All models were adjusted for age, sex, and smoking, and for inflammation when C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR) were not already included as dependent variables. A total of 126 patients (mean ± SD age 47.9 ± 10.8 years) and 111 controls (mean ± SD age 52.1 ± 11.1 years) were included. There were significant inverse associations between CRF and body mass index, waist circumference, triglycerides, CRP level, and ESR (P < 0.001-0.03) for patients and controls. Also, significant associations were found between CRF and high-density lipoprotein (HDL) cholesterol (β = 0.03, P < 0.001) and blood pressure (BP; β = -0.9 for systolic and β = -0.6 for diastolic; P < 0.01) in controls, but these associations were not found in patients (β = 0, P = 0.69 for HDL cholesterol; β = -0.04, P = 0.87 for systolic pressure; and β = -0.14, P = 0.34 for diastolic pressure) (additional adjustments for medication). Higher CRF was associated with a lower risk for MS in both patients (odds ratio [OR] 0.91, P = 0.03) and controls (OR 0.89, P = 0.01). CRF was associated with favorable levels of CV risk factors and lower risk of MS in both AS patients and controls. However, established findings of an association between CRF and BP and HDL cholesterol in healthy adults were not confirmed in AS patients. Copyright © 2013 by the American College of Rheumatology.

Eicosapentaenoic Acid as a Potential Therapeutic Approach to Reduce Cardiovascular Risk in Patients with End-Stage Renal Disease on Hemodialysis: A Review

PubMed Central

Borow, Kenneth M.; Mason, R. Preston; Vijayaraghavan, Krishnaswami

2017-01-01

Background Patients with end-stage renal disease on hemodialysis have excess cardiovascular disease (CVD) burden with substantially increased CV event rates compared with the general population. Summary Traditional interventions that, according to standard clinical guidelines, reduce CV risk such as antihypertensive therapy, diet, exercise, and statins are not similarly effective in the hemodialysis population. This raises the question of whether additional risk factors, such as enhanced inflammation and oxidative stress, may drive the increased CVD burden in hemodialysis patients. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into the atherosclerotic plaque as well as membrane phospholipid bilayers and produces beneficial effects on inflammatory and oxidative mechanisms involved in atherosclerotic plaque formation and progression. EPA levels and the ratio of EPA to the omega-6 polyunsaturated fatty acid arachidonic acid (AA) are reduced in hemodialysis patients. Serum EPA levels have been inversely correlated with proinflammatory cytokines, and the EPA/AA ratio has been inversely associated with CV events in hemodialysis cohorts. Three recent studies involving over 800 hemodialysis patients and follow-up of 2–3 years suggest that EPA therapy may improve clinical outcomes in this patient population as evidenced by significant reductions in cardiovascular mortality, all-cause mortality, and/or CV events. Key Messages Further studies with high-purity EPA are warranted in patients on hemodialysis, especially given the fact that other interventions including antihypertensives, diet, exercise, and statins have not provided meaningful benefit. PMID:29344023

Interferon regulatory factor 5 genetic variants are associated with cardiovascular disease in patients with rheumatoid arthritis

PubMed Central

2014-01-01

Introduction Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased cardiovascular (CV) disease risk. Interferon regulatory factor 5 (IRF5) is a regulator of type I interferon induction. Recently, researchers have described an association between multiple single-nucleotide polymorphisms of the IRF5 gene and some rheumatic disorders. In this study, we aimed to evaluate whether three different haplotype blocks within the IRF5 locus which have been shown to alter the protein function are involved in the risk of CV events occurring in Spanish RA patients. Methods Three IRF5 polymorphisms (rs2004640, rs2070197 and rs10954213) representative of each haplotype group were genotyped by performing TaqMan assays using a 7900HT Fast Real-Time PCR System with tissue from a total of 2,137 Spanish patients diagnosed with RA. Among them, 390 (18.2%) had experienced CV events. The relationship of IRF5 genotypes and haplotypes to CV events was tested using Cox regression. Results Male sex, age at RA diagnosis and most traditional risk factors (hypertension, dyslipidemia and smoking habit) were associated with increased risk for CV events in the RA population. Interestingly, a protective effect of both IRF5 rs2004640 GG and IRF5 rs10954213 GG genotypes against the risk for CV events after adjusting the results for sex, age at RA diagnosis and traditional CV disease risk factors was observed (hazard ratio (HR) = 0.6, 95% confidence interval (CI) = 0.38 to 0.92, P = 0.02; and HR = 0.58, 95% CI = 0.36 to 0.95, P = 0.03, respectively). Moreover, we detected a protective effect of the GTG haplotype against the risk for CV events after adjusting the results for potential confounding factors (HR = 0.72, 95% CI = 0.56 to 0.93, P = 0.012). Conclusions Our results reveal that IRF5 gene variants are associated with risk of CV events in patients with RA. PMID:25011482

IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition.

PubMed

Reid, Tirissa J; Jin, Zhezhen; Shen, Wei; Reyes-Vidal, Carlos M; Fernandez, Jean Carlos; Bruce, Jeffrey N; Kostadinov, Jane; Post, Kalmon D; Freda, Pamela U

2015-12-01

Activity of acromegaly is gauged by levels of GH and IGF-1 and epidemiological studies demonstrate that their normalization reduces acromegaly's excess mortality rate. However, few data are available linking IGF-1 levels to features of the disease that may relate to cardiovascular (CV) risk. Therefore, we tested the hypothesis that serum IGF-1 levels relative to the upper normal limit relate to insulin sensitivity, serum CV risk markers and body composition in acromegaly. In this prospective, cross-sectional study conducted at a pituitary tumor referral center we studied 138 adult acromegaly patients, newly diagnosed and previously treated surgically, with fasting and post-oral glucose levels of endocrine and CV risk markers and body composition assessed by DXA. Active acromegaly is associated with lower insulin sensitivity, body fat and CRP levels than acromegaly in remission. %ULN IGF-1 strongly predicts insulin sensitivity, better than GH and this persists after adjustment for body fat and lean tissue mass. %ULN IGF-1 also relates inversely to CRP levels and fat mass, positively to lean tissue and skeletal muscle estimated (SM(E)) by DXA, but not to blood pressure, lipids, BMI or waist circumference. Gender interacts with the IGF-1-lean tissue mass relationship. Active acromegaly presents a unique combination of features associated with CV risk, reduced insulin sensitivity yet lower body fat and lower levels of some serum CV risk markers, a pattern that is reversed in remission. %ULN IGF-1 levels strongly predict these features. Given the known increased CV risk of active acromegaly, these findings suggest that of these factors insulin resistance is most strongly related to disease activity and potentially to the increased CV risk of active acromegaly.

Prescription patterns and appropriateness of NSAID therapy according to gastrointestinal risk and cardiovascular history in patients with diagnoses of osteoarthritis.

PubMed

Lanas, Angel; Garcia-Tell, Guillermo; Armada, Beatriz; Oteo-Alvaro, Angel

2011-04-14

Prescription of non-steroidal anti-inflammatory drugs (NSAIDs) should be based on the assessment of both gastrointestinal (GI) and cardiovascular (CV) risk for the individual patient. We aimed to assess the GI/CV risk profile and the pharmacological management of patients with osteoarthritis (OA) in clinical practice. We conducted a cross-sectional, multicentre, observational study of consecutive OA patients that visited 1,760 doctors throughout the Spanish National Health System (NHS) in a single day. The presence of GI risk factors, CV histories, hypertension and current pharmacological treatments was recorded. Of the 60,868 patients, 17,105 had a diagnosis of OA and were evaluable. The majority (93.4%) had more than one GI risk factor and 60.3% were defined to be at high-GI risk. Thirty-two percent had a history of CV events, 57.6% were treated with anti-hypertensive therapy and 22.6% had uncontrolled hypertension. One-fifth of patients were treated with non-NSAID therapies, whereas the remaining patients received NSAIDs. Non-selective NSAIDs (nsNSAID) plus proton pump inhibitor (PPI) or cyclooxigenase-2 (COX-2)-selective NSAIDs alone were more frequently prescribed in patients at increased GI risk. Patients with a positive CV history received nsNSAIDs or COX-2-selective NSAIDs in 41.3% and 31.7% of cases, respectively. When both the GI and CV histories were combined, 51% of the overall population was being prescribed drugs that were either not recommended or contraindicated. Over 90% of patients with OA are at increased GI and/or CV risk. In over half of these patients, the prescription of NSAIDs was not in accordance with current guidelines or recommendations made by regulatory agencies.

Cardiovascular risk factor burden in Africa and the Middle East: the Africa Middle East Cardiovascular Epidemiological (ACE) study.

PubMed

Alsheikh-Ali, Alawi A; Omar, Mohamed I; Raal, Frederick J; Rashed, Wafa; Hamoui, Omar; Kane, Abdoul; Alami, Mohamed; Abreu, Paula; Mashhoud, Walid M

2014-01-01

Increased urbanization in the developing world parallels a rising burden of chronic diseases. Developing countries account for ∼ 80% of global cardiovascular (CV) deaths, but contribute a paucity of systematic epidemiological data on CV risk factors. To estimate the prevalence of CV risk factors in rural and urban cohorts attending general practice clinics in the Africa and Middle East (AfME) region. In a cross-sectional epidemiological study, the presence of CV risk factors (hypertension, diabetes mellitus (diabetes), dyslipidemia, obesity, smoking and abdominal obesity) were evaluated in stable adult outpatients attending general practice primary care clinics. A rural population was defined as isolated (>50 km or lack of easy access to commuter transportation) from urban centers. 4,378 outpatients were systematically recruited from 94 clinics across 14 AfME countries. Mean age was 46 ± 14 years and 52% of outpatients were female. A high prevalence of dyslipidemia (70%) and abdominal obesity (68%) were observed, followed by hypertension (43%) and diabetes (25%). The vast majority of outpatients (92%) had at least one modifiable CV risk factor, many (74%) had more than one, and half (53%) had 3 or more. These findings were observed in both genders and across urban and rural centers. Among outpatients with pre-existing hypertension or dyslipidemia, many were not at their target blood pressure or LDL-cholesterol goals. Cardiovascular risk factors are highly prevalent among relatively young, stable outpatients attending general practice clinics across AfME. The findings support opportunistic screening for CV risk factors whenever outpatients visit a general practitioner and provide an opportunity for early identification and management of CV risk factors, including lifestyle interventions.

Cardiovascular Risk Factor Burden in Africa and the Middle East: The Africa Middle East Cardiovascular Epidemiological (ACE) Study

PubMed Central

Alsheikh-Ali, Alawi A.; Omar, Mohamed I.; Raal, Frederick J.; Rashed, Wafa; Hamoui, Omar; Kane, Abdoul; Alami, Mohamed; Abreu, Paula; Mashhoud, Walid M.

2014-01-01

Background Increased urbanization in the developing world parallels a rising burden of chronic diseases. Developing countries account for ∼80% of global cardiovascular (CV) deaths, but contribute a paucity of systematic epidemiological data on CV risk factors. Objective To estimate the prevalence of CV risk factors in rural and urban cohorts attending general practice clinics in the Africa and Middle East (AfME) region. Methods In a cross-sectional epidemiological study, the presence of CV risk factors (hypertension, diabetes mellitus (diabetes), dyslipidemia, obesity, smoking and abdominal obesity) were evaluated in stable adult outpatients attending general practice primary care clinics. A rural population was defined as isolated (>50 km or lack of easy access to commuter transportation) from urban centers. Results 4,378 outpatients were systematically recruited from 94 clinics across 14 AfME countries. Mean age was 46±14 years and 52% of outpatients were female. A high prevalence of dyslipidemia (70%) and abdominal obesity (68%) were observed, followed by hypertension (43%) and diabetes (25%). The vast majority of outpatients (92%) had at least one modifiable CV risk factor, many (74%) had more than one, and half (53%) had 3 or more. These findings were observed in both genders and across urban and rural centers. Among outpatients with pre-existing hypertension or dyslipidemia, many were not at their target blood pressure or LDL-cholesterol goals. Conclusion Cardiovascular risk factors are highly prevalent among relatively young, stable outpatients attending general practice clinics across AfME. The findings support opportunistic screening for CV risk factors whenever outpatients visit a general practitioner and provide an opportunity for early identification and management of CV risk factors, including lifestyle interventions. PMID:25090638

Moving standard deviation and moving sum of outliers as quality tools for monitoring analytical precision.

PubMed

Liu, Jiakai; Tan, Chin Hon; Badrick, Tony; Loh, Tze Ping

2018-02-01

An increase in analytical imprecision (expressed as CV a ) can introduce additional variability (i.e. noise) to the patient results, which poses a challenge to the optimal management of patients. Relatively little work has been done to address the need for continuous monitoring of analytical imprecision. Through numerical simulations, we describe the use of moving standard deviation (movSD) and a recently described moving sum of outlier (movSO) patient results as means for detecting increased analytical imprecision, and compare their performances against internal quality control (QC) and the average of normal (AoN) approaches. The power of detecting an increase in CV a is suboptimal under routine internal QC procedures. The AoN technique almost always had the highest average number of patient results affected before error detection (ANPed), indicating that it had generally the worst capability for detecting an increased CV a . On the other hand, the movSD and movSO approaches were able to detect an increased CV a at significantly lower ANPed, particularly for measurands that displayed a relatively small ratio of biological variation to CV a. CONCLUSION: The movSD and movSO approaches are effective in detecting an increase in CV a for high-risk measurands with small biological variation. Their performance is relatively poor when the biological variation is large. However, the clinical risks of an increase in analytical imprecision is attenuated for these measurands as an increased analytical imprecision will only add marginally to the total variation and less likely to impact on the clinical care. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Intimate Partner Violence perpetration and cardiovascular risk: A systematic review.

PubMed

O'Neil, Adrienne; Scovelle, Anna J

2018-06-01

Intimate Partner Violence (IPV) perpetration may induce cardiovascular reactivity and risk markers thereby precipitating early onset cardiovascular disease (CVD). However, this relationship has been largely under-researched in comparison to the health impacts of IPV victimisation. We therefore aimed to systematically review the current evidence investigating the relationship between IPV perpetration and CV risk. Six databases (CINAHL, Ovid MEDLINE, Pubmed, Scopus, ProQuest, Google Scholar) were searched between August 2016 and August 2017 using a predefined search strategy. Inclusion criteria were studies of cross sectional and longitudinal design published since 2010, presenting IPV status by perpetrators (as distinct from victims) and an outcome of CVD (e.g. cardiac disease, stroke), CV risk markers (e.g. blood pressure) and/or a composite CV risk score. Twenty two potentially eligible studies were identified and full texts recovered. After ineligible studies were excluded, four remained (total n = 10,665). Positive relationships were observed between IPV perpetration and (i) short term CV reactivity markers (higher heart rate, lower vagal ratios, shorter pre-ejection periods) and (ii) longer term CV risk factors and outcomes including greater systolic blood pressure, incident hypertension, elevated 30 year CV risk score and self-report cardiac disease. Despite being a neglected area of research characterised by a high degree of heterogeneity, the early evidence suggests that IPV perpetration may be associated with elevated risk of CVD. We discuss these findings in the context of CVD prevention from the individual, family and inter-generational perspectives and directions for future studies.

Smoking cessation and the risk of cardiovascular disease outcomes predicted from established risk scores: results of the Cardiovascular Risk Assessment among Smokers in Primary Care in Europe (CV-ASPIRE) study.

PubMed

Mallaina, Pablo; Lionis, Christos; Rol, Hugo; Imperiali, Renzo; Burgess, Andrew; Nixon, Mark; Malvestiti, Franco Mondello

2013-04-18

Smoking is a major risk factor for cardiovascular disease (CVD). This multicenter, cross-sectional survey was designed to estimate the cardiovascular (CV) risk attributable to smoking using risk assessment tools, to better understand patient behaviors and characteristics related to smoking, and characterize physician practice patterns. 1,439 smokers were recruited from Europe during 2011. Smokers were ≥40 years old, smoked > 10 cigarettes/day and had recent measurements on blood pressure and lipids. CV risk was calculated using the SCORE system, Framingham risk equations, and Progetto CUORE model. The CV risk attributable to smoking was evaluated using a simulated control (hypothetical non-smoker) with identical characteristics as the enrolled smoker. Risks assessed included CV mortality, coronary heart disease (CHD), CVD and hard CHD. Demographics, comorbidities, primary reasons for consultation, behavior towards previous attempts to quit, and interest in smoking cessation was assessed. Dependence on nicotine was evaluated using the Fagerström Test for Nicotine Dependence. GP practice patterns were assessed through a questionnaire. The prediction models consistently demonstrated a high CV risk attributable to smoking. For instance, the SCORE model demonstrated that this study population of smokers have a 100% increased probability of death due to cardiovascular disease in the next 10-years compared to non-smokers. A considerable amount of patients would like to hear from their GP about the different alternatives available to support their quitting attempt. The findings of this study reinforce the importance of smoking as a significant predictor of long-term cardiovascular events. One of the best gains in health could be obtained by tackling the most important modifiable risk factors; these results suggest smoking is among the most important.

Usefulness of Maintaining a Normal Electrocardiogram Over Time for Predicting Cardiovascular Health.

PubMed

Soliman, Elsayed Z; Zhang, Zhu-Ming; Chen, Lin Y; Tereshchenko, Larisa G; Arking, Dan; Alonso, Alvaro

2017-01-15

We hypothesized that maintaining a normal electrocardiogram (ECG) status over time is associated with low cardiovascular (CV) disease in a dose-response fashion and subsequently could be used to monitor programs aimed at promoting CV health. This analysis included 4,856 CV disease-free participants from the Atherosclerosis Risk in Communities study who had a normal ECG at baseline (1987 to 1989) and complete electrocardiographic data in subsequent 3 visits (1990 to 1992, 1993 to 1995, and 1996 to 1998). Participants were classified based on maintaining their normal ECG status during these 4 visits into "maintained," "not maintained," or "inconsistent" normal ECG status as defined by the Minnesota ECG classification. CV disease events (coronary heart disease, heart failure, and stroke) were adjudicated from Atherosclerosis Risk in Communities visit-4 through 2010. Over a median follow-up of 13.2 years, 885 CV disease events occurred. The incidence rate of CV disease events was lowest among study participants who maintained a normal ECG status, followed by those with an inconsistent pattern, and then those who did not maintain their normal ECG status (trend p value <0.001). Similarly, the greater the number of visits with a normal ECG status, the lower was the incidence rate of CV disease events (trend p value <0.001). Maintaining (vs not maintaining) a normal ECG status was associated with a lower risk of CV disease, which was lower than that observed in those with inconsistent normal ECG pattern (trend p value <0.01). In conclusion, maintaining a normal ECG status over time is associated with low risk of CV disease in a dose-response fashion, suggesting its potential use as a monitoring tool for programs promoting CV health. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of Chronic Kidney Disease to Enhance Prediction of Cardiovascular Risk in Those at Medium Risk.

PubMed

Chia, Yook Chin; Lim, Hooi Min; Ching, Siew Mooi

2015-01-01

Based on global cardiovascular (CV) risk assessment for example using the Framingham risk score, it is recommended that those with high risk should be treated and those with low risk should not be treated. The recommendation for those of medium risk is less clear and uncertain. We aimed to determine whether factoring in chronic kidney disease (CKD) will improve CV risk prediction in those with medium risk. This is a 10-year retrospective cohort study of 905 subjects in a primary care clinic setting. Baseline CV risk profile and serum creatinine in 1998 were captured from patients record. Framingham general cardiovascular disease risk score (FRS) for each patient was computed. All cardiovascular disease (CVD) events from 1998-2007 were captured. Overall, patients with CKD had higher FRS risk score (25.9% vs 20%, p = 0.001) and more CVD events (22.3% vs 11.9%, p = 0.002) over a 10-year period compared to patients without CKD. In patients with medium CV risk, there was no significant difference in the FRS score among those with and without CKD (14.4% vs 14.6%, p = 0.84) However, in this same medium risk group, patients with CKD had more CV events compared to those without CKD (26.7% vs 6.6%, p = 0.005). This is in contrast to patients in the low and high risk group where there was no difference in CVD events whether these patients had or did not have CKD. There were more CV events in the Framingham medium risk group when they also had CKD compared those in the same risk group without CKD. Hence factoring in CKD for those with medium risk helps to further stratify and identify those who are actually at greater risk, when treatment may be more likely to be indicated.

Use of Chronic Kidney Disease to Enhance Prediction of Cardiovascular Risk in Those at Medium Risk

PubMed Central

Chia, Yook Chin; Lim, Hooi Min; Ching, Siew Mooi

2015-01-01

Based on global cardiovascular (CV) risk assessment for example using the Framingham risk score, it is recommended that those with high risk should be treated and those with low risk should not be treated. The recommendation for those of medium risk is less clear and uncertain. We aimed to determine whether factoring in chronic kidney disease (CKD) will improve CV risk prediction in those with medium risk. This is a 10-year retrospective cohort study of 905 subjects in a primary care clinic setting. Baseline CV risk profile and serum creatinine in 1998 were captured from patients record. Framingham general cardiovascular disease risk score (FRS) for each patient was computed. All cardiovascular disease (CVD) events from 1998–2007 were captured. Overall, patients with CKD had higher FRS risk score (25.9% vs 20%, p = 0.001) and more CVD events (22.3% vs 11.9%, p = 0.002) over a 10-year period compared to patients without CKD. In patients with medium CV risk, there was no significant difference in the FRS score among those with and without CKD (14.4% vs 14.6%, p = 0.84) However, in this same medium risk group, patients with CKD had more CV events compared to those without CKD (26.7% vs 6.6%, p = 0.005). This is in contrast to patients in the low and high risk group where there was no difference in CVD events whether these patients had or did not have CKD. There were more CV events in the Framingham medium risk group when they also had CKD compared those in the same risk group without CKD. Hence factoring in CKD for those with medium risk helps to further stratify and identify those who are actually at greater risk, when treatment may be more likely to be indicated. PMID:26496190

Drug treatment of hypertension in older patients with diabetes mellitus.

PubMed

Yandrapalli, Srikanth; Pal, Suman; Nabors, Christopher; Aronow, Wilbert S

2018-05-01

Hypertension is more prevalent in the elderly (age>65 years) diabetic population than in the general population and shows an increasing prevalence with advancing age. Both diabetes mellitus (DM) and hypertension are independent risk factors for cardiovascular (CV) related morbidity and mortality. Optimal BP targets were not identified in elderly patients with DM and hypertension. Areas covered: In this review article, the authors briefly discuss the pathophysiology of hypertension in elderly diabetics, present evidence with various antihypertensive drug classes supporting the treatment of hypertension to reduce CV events in older diabetics, and then discuss the optimal target BP goals in these patients. Expert opinion: Clinicians should have a BP goal of less than 130/80 mm in all elderly patients with hypertension and DM, especially in those with high CV-risk. When medications are required for optimal BP control in addition to lifestyle measures, either thiazide diuretics, angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers should be considered as initial therapy. Combinations of medications are usually required in these patients because BP control is more difficult to achieve in diabetics than those without DM.

Risk of cardiovascular events, arrhythmia and all-cause mortality associated with clarithromycin versus alternative antibiotics prescribed for respiratory tract infections: a retrospective cohort study.

PubMed

Berni, Ellen; de Voogd, Hanka; Halcox, Julian P; Butler, Christopher C; Bannister, Christian A; Jenkins-Jones, Sara; Jones, Bethan; Ouwens, Mario; Currie, Craig J

2017-01-23

To determine whether treatment with clarithromycin for respiratory tract infections was associated with an increased risk of cardiovascular (CV) events, arrhythmias or all-cause mortality compared with other antibiotics. Retrospective cohort design comparing clarithromycin monotherapy for lower (LRTI) or upper respiratory tract infection (URTI) with other antibiotic monotherapies for the same indication. Routine primary care data from the UK Clinical Practice Research Datalink and inpatient data from the Hospital Episode Statistics (HES). Patients aged ≥35 years prescribed antibiotic monotherapy for LRTI or URTI 1998-2012 and eligible for data linkage to HES. The main outcome measures were: adjusted risk of first-ever CV event, within 37 days of initiation, in commonly prescribed antibiotics compared with clarithromycin. Secondarily, adjusted 37-day risks of first-ever arrhythmia and all-cause mortality. Of 700 689 treatments for LRTI and eligible for the CV analysis, there were 2071 CV events (unadjusted event rate: 29.6 per 10 000 treatments). Of 691 998 eligible treatments for URTI, there were 688 CV events (9.9 per 10 000 treatments). In LRTI and URTI, there were no significant differences in CV risk between clarithromycin and all other antibiotics combined: OR=1.00 (95% CI 0.82 to 1.22) and 0.82 (0.54 to 1.25), respectively. Adjusted CV risk in LRTI versus clarithromycin ranged from OR=1.42 (cefalexin; 95% CI 1.08 to 1.86) to 0.92 (doxycycline; 0.64 to 1.32); in URTI, from 1.17 (co-amoxiclav; 0.68 to 2.01) to 0.67 (erythromycin; 0.40 to 1.11). Adjusted mortality risk versus clarithromycin in LRTI ranged from 0.42 to 1.32; in URTI, from 0.75 to 1.43. For arrhythmia, adjusted risks in LRTI ranged from 0.68 to 1.05; in URTI, from 0.70 to 1.22. CV events were more likely after LRTI than after URTI. When analysed by specific indication, CV risk associated with clarithromycin was no different to other antibiotics. 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/.

A review of the evidence on reducing macrovascular risk in patients with atherogenic dyslipidaemia: A report from an expert consensus meeting on the role of fenofibrate-statin combination therapy.

PubMed

Aguiar, Carlos; Alegria, Eduardo; Bonadonna, Riccardo C; Catapano, Alberico L; Cosentino, Francesco; Elisaf, Moses; Farnier, Michel; Ferrières, Jean; Filardi, Pasquale Perrone; Hancu, Nicolae; Kayikcioglu, Meral; Mello E Silva, Alberto; Millan, Jesus; Reiner, Željko; Tokgozoglu, Lale; Valensi, Paul; Viigimaa, Margus; Vrablik, Michal; Zambon, Alberto; Zamorano, José Luis; Ferrari, Roberto

2015-09-01

A meeting of European experts in cardiovascular (CV) disease and lipids was convened in Paris, France, on 10 November 2014 to discuss lipid profile, and in particular atherogenic dyslipidaemia (AD), and associated CV risk. Key points that were raised and discussed during the meeting are summarised in this paper, which also accounts for further discussion and agreement on these points by the group of experts. Elevated levels of low-density lipoprotein cholesterol (LDL-c) are commonly associated with a greater CV risk than low LDL-c levels, and are routinely managed with statins. However, even for patients controlled on statins and achieving low LDL-c levels, abnormal lipid profiles observed in some patients (i.e. elevated triglyceride levels, with/without low levels of high-density lipoprotein cholesterol [HDL-c]) have been linked to the presence of a residual CV risk. Therefore, it is recommended that both triglyceride and HDL-c levels be measured, to allow for the overall CV residual risk to be adequately managed. Favourable safety and clinical data support the combination of statins with other lipid-lowering agents, such as fenofibrate. Patients who have elevated triglyceride levels plus low levels of HDL-c are most likely to achieve clinical benefit from fenofibrate-statin combination therapy. In these patients with AD, achieving target non-HDL-c levels should be a key focus of CV risk management, and the use of non-HDL-c was advocated to provide a better measure of CV risk than LDL-c levels. © 2015 Elsevier Ireland Ltd. All rights reserved.

Update on SGLT2 Inhibitors-New Data Released at the American Diabetes Association.

PubMed

Lee, Sara

2017-09-01

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are one of the newer classes of antiglycemic agents approved for the management of patients with type 2 diabetes mellitus. Due to their unique mechanism of action, SGLT2 inhibitors have shown to be beneficial beyond glucose control. The improvement in cardiovascular (CV) outcomes was first observed in the landmark EMPA-REG OUTCOMES study. Following these results, numerous CV outcome trials were designed to identify whether the beneficial CV and renal effects observed with empagliflozin are unique or a drug class effect. The benefit of SGLT2 inhibition was confirmed by the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, presented at the American Diabetes Association 77th Scientific Sessions. With over 10,000 patients, the CANVAS Program integrated data from two large CV outcome studies. Canagliflozin achieved a 14% reduction in the composite endpoint of CV mortality, nonfatal myocardial infarction (MI), or nonfatal stroke, and a 33% reduction in the risk of hospitalization for heart failure (HF) compared with placebo. Potential renal protective effects were also observed with canagliflozin; however, an increased risk of amputation with canagliflozin was seen in both CANVAS studies. The class effect of SGLT2 inhibitors was also confirmed in new analyses of the The Comparative Effectiveness of Cardiovascular Outcomes (CVD-REAL) study, which aimed to evaluate SGLT2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) in broader patient populations with type 2 diabetes mellitus. In patients who were new to SGLT2 inhibitors, significant reductions in rates of CV death and hospitalization for HF were observed compared with any other glucose-lowering agents. SGLT2 inhibitors were also associated with lower rates in hospitalization for HF in patients with and without CV disease. In addition, substudies of the EMPA-REG OUTCOME trial further provided insight on the efficacy of empagliflozin across categories of adjusted control of blood pressure, low-density lipoprotein cholesterol, and hemoglobin A1c (HbA1c) over time.

Cardiovascular and metabolic profiles amongst different polycystic ovary syndrome phenotypes: who is really at risk?

PubMed

Daan, Nadine M P; Louwers, Yvonne V; Koster, Maria P H; Eijkemans, Marinus J C; de Rijke, Yolanda B; Lentjes, Eef W G; Fauser, Bart C J M; Laven, Joop S E

2014-11-01

To study the cardiometabolic profile characteristics and compare the prevalence of cardiovascular (CV) risk factors between women with different polycystic ovary syndrome (PCOS) phenotypes. A cross-sectional multicenter study analyzing 2,288 well phenotyped women with PCOS. Specialized reproductive outpatient clinic. Women of reproductive age (18-45 years) diagnosed with PCOS. Women suspected of oligo- or anovulation underwent a standardized screening consisting of a systematic medical and reproductive history taking, anthropometric measurements, and transvaginal ultrasonography followed by an extensive endocrinologic/metabolic evaluation. Differences in cardiometabolic profile characteristics and CV risk factor prevalence between women with different PCOS phenotypes, i.e., obesity/overweight, hypertension, insulin resistance, dyslipidemia, and metabolic syndrome. Women with hyperandrogenic PCOS (n=1,219; 53.3% of total) presented with a worse cardiometabolic profile and a higher prevalence of CV risk factors, such as obesity and overweight, insulin resistance, and metabolic syndrome, compared with women with nonhyperandrogenic PCOS. In women with nonhyperandrogenic PCOS overweight/obesity (28.5%) and dyslipidemia (low-density lipoprotein cholesterol≥3.0 mmol/L; 52.2%) were highly prevalent. Women with hyperandrogenic PCOS have a worse cardiometabolic profile and higher prevalence of CV risk factors compared with women with nonhyperandrogenic PCOS. However, all women with PCOS should be screened for the presence of CV risk factors, since the frequently found derangements at a young age imply an elevated risk for the development of CV disease later in life. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Relation of Biochemical Parameters with Flow-mediated Dilatation in Patients with Metabolic Syndrome

PubMed Central

Sipahioglu, Nurver Turfaner; Ilerigelen, Barıs; Gungor, Zeynep B.; Ayaz, Gulsel; Ekmekci, Hakan; Gurel, Cigdem Bayram; Can, Gunay; Sonmez, Huseyin; Ulutin, Turgut; Sipahioglu, Fikret

2017-01-01

Background: Metabolic syndrome (MetS) is one of the high cardiovascular (CV) situations. Endothelial dysfunction, which is a common finding in patients with MetS, is related with increased CV risk. In patients with MetS, the effect of the major CV risk factors, not included in the MetS definition, on endothelial dysfunction is not well known. The aim of this study was to determine the effect of major CV risk factors such as gender, smoking, family history, and biochemical parameters on endothelial dysfunction in patients with MetS. Methods: The study was performed between December 2010 and August 2014. A total of 55 patients (15 females and 40 males) with MetS and 81 healthy controls (37 females and 44 males) with a body mass index <25 kg/m2 were enrolled in the study. Endothelial dysfunction was measured by flow-mediated dilatation (FMD), oxidative stress parameters; high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (ox-LDL), endothelial nitric oxide synthase (e-NOS), nitric oxide, and cell adhesion markers; von Willebrand factor, and e-selectin. Platelet aggregation (endothelial adenosine diphosphate), total platelet count, and mean platelet volume were additionally analyzed and demographic parameters were explored. Student's t-test, Mann-Whitney U-test, and Chi-square test were used to analyze the results. Results: The fasting blood glucose (z = 3.52, P = 0.001), hs-CRP (z = 3.23, P = 0.004), ox-LDL (z = 2.62, P = 0.013), and e-NOS (z = 2.22, P = 0.026) levels and cardiac risk score (z = 5.23, P < 0.001) were significantly higher in patients with MetS compared with the control group. Smoking was correlated with decreased FMD (χ2 = 9.26, P = 0.002) in MetS patients but not in the control group. Conclusions: Increased ox-LDL, hs-CRP, and e-NOS are likely to be a result of oxidative stress, a condition in which an imbalance occurs between the production and inactivation of reactive nitrogen and oxygen species. In addition, in patients with MetS, smoking is independently related to endothelial dysfunction. PMID:28639572

The effects of sacubitril/valsartan on coronary outcomes in PARADIGM-HF.

PubMed

Mogensen, Ulrik M; Køber, Lars; Kristensen, Søren L; Jhund, Pardeep S; Gong, Jianjian; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Swedberg, Karl; Zile, Michael R; Solomon, Scott D; Packer, Milton; McMurray, John J V

2017-06-01

Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF. We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization. At baseline, of 8399 patients, 3634 (43.3%) had a prior MI and 4796 (57.1%) had a history of any coronary artery disease. Among all patients, compared with enalapril, sacubitril/valsartan reduced the risk of the primary outcome (HR 0.80 [0.73-0.87], P<.001), the broader composite (HR 0.83 [0.76-0.90], P<.001) and the coronary composite (HR 0.83 [0.75-0.92], P<.001). Although each of the components of the coronary composite occurred less frequently in the sacubitril/valsartan group, compared with the enalapril group, only CV death was reduced significantly. Compared with enalapril, sacubitril/valsartan reduced the risk of both the primary endpoint and a coronary composite outcome in PARADIGM-HF. Additional studies on the effect of sacubitril/valsartan on atherothrombotic outcomes in high-risk patients are merited. Copyright © 2017 Elsevier Inc. All rights reserved.

Diabetes and cardiovascular risk: are dipeptidyl peptidase-4 inhibitors beneficial?

PubMed

Howard, Patricia A

2014-09-01

Cardiovascular (CV) disease is a major cause of morbidity and mortality in patients with diabetes. Whereas the link between glycemic control and reducing microvascular disease is firmly established, the evidence for macrovascular risk reduction remains unclear. Despite a host of available drugs for lowering serum glucose, none to date have been shown to substantially reduce CV risk and some have been associated with adverse effects. Recent trials have examined the CV effects of the dipeptidyl peptidase 4 (DPP-4) inhibitors or "gliptins."

Cardiovascular Events in Systemic Lupus Erythematosus: A Nationwide Study in Spain From the RELESSER Registry.

PubMed

Fernández-Nebro, Antonio; Rúa-Figueroa, Íñigo; López-Longo, Francisco J; Galindo-Izquierdo, María; Calvo-Alén, Jaime; Olivé-Marqués, Alejandro; Ordóñez-Cañizares, Carmen; Martín-Martínez, María A; Blanco, Ricardo; Melero-González, Rafael; Ibáñez-Rúan, Jesús; Bernal-Vidal, José Antonio; Tomero-Muriel, Eva; Uriarte-Isacelaya, Esther; Horcada-Rubio, Loreto; Freire-González, Mercedes; Narváez, Javier; Boteanu, Alina L; Santos-Soler, Gregorio; Andreu, José L; Pego-Reigosa, José M

2015-07-01

This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis. RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis. From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2-66.1], and SLE duration of 212.0 months [120.8-289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02-1.04]), hypertension (1.71 [1.20-2.44]), smoking (1.48 [1.06-2.07]), diabetes (2.2 [1.32-3.74]), dyslipidemia (2.18 [1.54-3.09]), neurolupus (2.42 [1.56-3.75]), valvulopathy (2.44 [1.34-4.26]), serositis (1.54 [1.09-2.18]), antiphospholipid antibodies (1.57 [1.13-2.17]), low complement (1.81 [1.12-2.93]), and azathioprine (1.47 [1.04-2.07]) as risk factors for CV events. We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows-for the first time-an association between diabetes and CV events in SLE patients.

Cardiovascular Events in Systemic Lupus Erythematosus

PubMed Central

Fernández-Nebro, Antonio; Rúa-Figueroa, Íñigo; López-Longo, Francisco J.; Galindo-Izquierdo, María; Calvo-Alén, Jaime; Olivé-Marqués, Alejandro; Ordóñez-Cañizares, Carmen; Martín-Martínez, María A.; Blanco, Ricardo; Melero-González, Rafael; Ibáñez-Rúan, Jesús; Bernal-Vidal, José Antonio; Tomero-Muriel, Eva; Uriarte-Isacelaya, Esther; Horcada-Rubio, Loreto; Freire-González, Mercedes; Narváez, Javier; Boteanu, Alina L.; Santos-Soler, Gregorio; Andreu, José L.; Pego-Reigosa, José M.

2015-01-01

Abstract This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis. RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis. From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2–66.1], and SLE duration of 212.0 months [120.8–289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02–1.04]), hypertension (1.71 [1.20–2.44]), smoking (1.48 [1.06–2.07]), diabetes (2.2 [1.32–3.74]), dyslipidemia (2.18 [1.54–3.09]), neurolupus (2.42 [1.56–3.75]), valvulopathy (2.44 [1.34–4.26]), serositis (1.54 [1.09–2.18]), antiphospholipid antibodies (1.57 [1.13–2.17]), low complement (1.81 [1.12–2.93]), and azathioprine (1.47 [1.04–2.07]) as risk factors for CV events. We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows—for the first time—an association between diabetes and CV events in SLE patients. PMID:26200625

Is Obesity Predictive of Cardiovascular Dysfunction Independent of Cardiovascular Risk Factors?

PubMed Central

DeVallance, Evan; Fournier, Sara B.; Donley, David A.; Bonner, Daniel E.; Lee, Kyuwan; Frisbee, Jefferson C.; Chantler, Paul D.

2015-01-01

Introduction Obesity is thought to exert detrimental effects on the cardiovascular (CV) system. However, this relationship is impacted by the co-occurrence of CV risk factors, type II diabetes (T2DM), and overt disease. We examined the relationships between obesity, assessed by body mass index (BMI) and waist circumference (WC), and CV function in 102 subjects without overt CV disease. We hypothesized that obesity would be independently predictive of CV remodeling and functional differences, especially at peak exercise. Methods Brachial (bSBP) and central (cSBP) systolic pressure, carotid-to-femoral pulse wave velocity (PWVcf) augmentation index (AGI) (by SphygmoCor), and carotid remodeling (B-mode ultrasound) were examined at rest. Further, peak exercise cardiac imaging (Doppler ultrasound) was performed to measure the coupling between the heart and arterial system. Results In backward elimination regression models, accounting for CV risk factors, neither BMI nor WC were predictors of carotid thickness or PWVcf; rather age, triglycerides, and hypertension were the main determinants. However, BMI and WC predicted carotid cross-sectional area and lumen diameter. When examining the relationship between body size and SBP, BMI (β=0.32) and WC (β=0.25) were predictors of bSBP (p<0.05), whereas, BMI was the only predictor of cSBP (β=0.22, p<0.05) indicating a differential relationship between cSBP, bSBP and body size. Further, BMI (β=−0.26) and WC (β=−0.27) were independent predictors of AGI (p<0.05). As for resting cardiac diastolic function, WC seemed to be a better predictor than BMI. However, both BMI and WC were inversely and independently related to arterial elastance (net arterial load) and end-systolic elastance (cardiac contractility) at rest and peak exercise. Discussion These findings illustrate that obesity, without T2DM and overt CV disease, and after accounting for CV risk factors, is susceptible to pathophysiological adaptations that may predispose individuals to an increased risk of CV events. PMID:24957486

Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an Increased Risk of Alzheimer Disease: Taiwan Diabetes Study.

PubMed

Li, Tsai-Chung; Yang, Chun-Pai; Tseng, Shih-Ting; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Hwang, Kai-Lin; Yang, Sing-Yu; Chiang, Jen-Huai; Lin, Cheng-Chieh

2017-09-01

The relationship between glycemic variability and the incidence of Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to examine visit-to-visit variations in fasting plasma glucose (FPG) and glycated hemoglobin (HbA 1c ) represented by the coefficient of variation (CV) and to determine whether they were independently associated with AD, irrespective of HbA 1c and other traditional risk factors in such patients. Patients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD ( n = 16,706) were included in the study. Potential risk factors were analyzed using extended Cox proportional hazards regression models for competing risk of mortality on AD incidence. During a median follow-up of 8.88 years, 831 incident cases of AD were identified, with a crude incidence rate of 3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle behaviors, diabetes-related variables, FPG and HbA 1c , drug-related variables, and comorbidities, both FPG CV and HbA 1c CV were found to be significant predictors of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06-1.52) for the third tertile in FPG CV and 1.32 (95% CI 1.11-1.58) for the third tertile in HbA 1c CV. FPG CV and HbA 1c CV are independently associated with AD. The associations between glycemic variability and AD demonstrated in this study suggest a linked pathophysiological mechanism, which is worthy of further investigation. Further research is required to confirm our results and to evaluate whether FPG CV and HbA 1c CV can be valuable therapeutic targets for patients with T2DM at risk. © 2017 by the American Diabetes Association.

NT-proBNP: Is It a More Significant Risk Factor for Mortality Than Troponin T in Incident Hemodialysis Patients?

PubMed Central

Oh, Hyung Jung; Lee, Mi Jung; Lee, Hye Sun; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kim, Yong-Lim; Kim, Yon Su; Yang, Chul Woo; Kim, Nam-Ho; Kang, Shin-Wook

2014-01-01

Abstract Numerous studies have demonstrated that cardiac biomarkers are significant predictors of cardiovascular (CV) and all-cause mortality in ESRD patients, but most of the studies were retrospective or included small numbers of patients, only prevalent dialysis patients, or measured 1 or 2 biomarkers. This study was to analyze the association between 3 cardiac biomarkers and mortality in incident HD patients. A prospective cohort of 864 incident HD patients was followed for 30 months. Based on the median values of baseline NT-proBNP, cTnT, and hsCRP, the patients were divided into “high” and “low” groups, and CV and all-cause mortality were compared between each group. Additionally, time-dependent ROC curves were constructed, and the NRI and IDI of the models with various biomarkers were calculated. The CV survival rates were significantly lower in the “high” NT-proBNP and cTnT groups compared to the corresponding “low” groups, while there was no significant difference in CV survival rate between the 2 hsCRP groups. However, all-cause mortality rates were significantly higher in all 3 “high” groups compared to each lower group. In multivariate analyses, only Ln NT-proBNP was found to be an independent predictor of mortality. Moreover, NT-proBNP was a more prognostic marker for mortality compared to cTnT. In conclusion, NT-proBNP is the biomarker that results in the most added prognostic value on top of traditional risk factors for CV and all-cause mortality in incident HD patients. PMID:25501091

Body fat mass and lean mass as predictors of survival in hemodialysis patients.

PubMed

Kakiya, R; Shoji, T; Tsujimoto, Y; Tatsumi, N; Hatsuda, S; Shinohara, K; Kimoto, E; Tahara, H; Koyama, H; Emoto, M; Ishimura, E; Miki, T; Tabata, T; Nishizawa, Y

2006-08-01

A higher body mass index (BMI) is a predictor of better survival in hemodialysis patients, although the relative importance of body fat and lean mass has not been examined in the dialysis population. We performed an observational cohort study in 808 patients with end-stage renal disease on maintenance hemodialysis. At baseline, fat mass was measured by dual-energy X-ray absorptiometry and expressed as fat mass index (FMI; kg/m2). Lean mass index (LMI) was defined as BMI minus FMI. During the mean follow-up period of 53 months, 147 deaths, including 62 cardiovascular (CV) and 85 non-CV fatal events, were recorded. In univariate analysis, LMI was not significantly associated with CV or non-CV death, whereas a higher FMI was predictive of lower risk for non-CV death. Analyses with multivariate Cox models, which took other confounding variables as covariates, indicated the independent associations between a higher LMI and a lower risk of CV death, as well as between a higher FMI and a lower risk of non-CV death. These results indicate that increased fat mass and lean mass were both conditions associated with better outcomes in the dialysis population.

Non-invasively measured structural and functional arterial characteristics and coronary heart disease risk in middle aged and elderly men.

PubMed

van Trijp, Marijke J C A; Bos, Willem J W; van der Schouw, Yvonne T; Muller, Majon; Grobbee, Diederick E; Bots, Michiel L

2006-07-01

In cardiovascular (CV) epidemiology, interest increases in studying etiologic and prognostic implications of early structural or functional changes of the large arteries. Examples of such measurements are pulse wave velocity (PWV), carotid intima-media thickness (CIMT) and augmentation index (AIx). PWV and CIMT are established markers of CV risk whereas the role of AIx as indicator of risk has not fully been established. Therefore, our aim was to relate AIx to CV risk and to compare the magnitude of relations of PWV, CIMT and AIx to CV risk. Two hundred and ninty-nine men free from cardiovascular disease (mean age 59.2 years), participated in this cross-sectional study. Cardiovascular risk profile was determined and 10-year coronary heart disease risk was estimated using the Framingham risk score (FRS). PWV, CIMT and AIx were measured and data were analyzed using linear regression models. PWV and CIMT were strongest related to FRS whereas AIx showed the weakest relation. Ten-year coronary heart disease risk increased 6.24%, 95% confidence interval (CI) [5.11;7.37] per standard deviation (S.D.) increase in PWV, 6.39% [5.24;7.54] per S.D. increase in CIMT and 2.50% [1.19;3.80] per S.D. increase in AIx. In middle aged and elderly men AIx is related to CV risk. However, compared with AIx, PWV and CIMT seem better markers of cardiovascular risk.

LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial.

PubMed

Masmiquel, L; Leiter, L A; Vidal, J; Bain, S; Petrie, J; Franek, E; Raz, I; Comlekci, A; Jacob, S; van Gaal, L; Baeres, F M M; Marso, S P; Eriksson, M

2016-02-10

Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). Mean BMI was 32.5 ± 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints.

Effect of rural-to-urban within-country migration on cardiovascular risk factors in low- and middle-income countries: a systematic review.

PubMed

Hernández, Adrián V; Pasupuleti, Vinay; Deshpande, Abhishek; Bernabé-Ortiz, Antonio; Miranda, J Jaime

2012-02-01

Limited information is available of effects of rural-to-urban within-country migration on cardiovascular (CV) risk factors in low- and middle- income countries (LMIC). A systematic review of studies evaluating these effects was performed with rural and/or urban control groups. Two teams of investigators searched observational studies in Medline, Web of Science and Scopus until May 2011. Studies evaluating international migration were excluded. Three investigators extracted the information stratified by gender. Information on 17 known CV risk factors was obtained. Eighteen studies (n=58,536) were included. Studies were highly heterogeneous with respect to study design, migrant sampling frame, migrant urban exposure and reported CV risk factors. In migrants, commonly reported CV risk factors-systolic and diastolic blood pressure, body mass index, obesity, total cholesterol and low-density lipoprotein-were usually higher or more common than in the rural group and usually lower or less common than in the urban group. This gradient was usually present in both genders. Anthropometric (waist-to-hip ratio, hip/waist circumference, triceps skinfolds) and metabolic (fasting glucose/insulin, insulin resistance) risk factors usually followed the same gradient, but conclusions were weak as information was insufficient. Hypertension, high-density lipoprotein, fibrinogen and C-reactive protein did not follow any pattern. In LMIC, most but not all, CV risk factors are higher or more common in migrants than in rural groups but lower or less common than in urban groups. Such gradients may or may not be associated with differential CV events and long-term evaluations are necessary.

Cardiovascular risk in peritoneal dialysis - a Portuguese multicenter study.

PubMed

Neves, Marta; Machado, Susana; Rodrigues, Luís; Borges, Andreia; Maia, Pedro; Campos, Mário

2014-01-01

Cardiovascular (CV) disease is the major cause of mortality in patients undergoing renal replacement therapy. The primary aim of the study was to evaluate the CV risk profile and prevalence of CV disease in patients on peritoneal dialysis (PD) in Portugal. The secondary goal was to establish parameters most associated with CV disease. Retrospective, multicenter study of the prevalent adult population on PD. Six hundred patients were included (56.7% male; mean age 53.5 ± 15.3 years), on PD for 25.6 ± 21.9 months. Patients were divided into two groups: group 1 (n=166) with CV disease and group 2 (n=434) without CV disease. Comparisons were made regarding traditional CV risk factors and those associated with uremia and PD itself, and a multivariate analysis was performed to determine variables independently associated with CV disease. At the end of the study, the prevalence of CV disease was 28%. At univariate analysis, group 1 presented a higher frequency of males (p<.01), older patients (p<.01), diabetics (p<.01), occurrence of left ventricular hypertrophy (LVH) (p<.01), mean C-reactive protein (CRP) (p=.04), lower mean parathormone level (p=.014), lower serum phosphorus (p=.02), lower daily urine output (p=.04), lower weekly Kt/V (p=.008), increased use of icodextrin and hypertonic glucose-based PD solutions (p<.001 and p=.006, respectively) and more were under continuous ambulatory PD (CAPD) (p=.014) and had a high peritoneal transport status (p=.02). Multivariate analysis provided a significant discriminatory influence pertaining to age >50 years, CRP>0.6 mg/dl, male gender, diabetes, LVH, CAPD and anuria, when comparing group 1 and group 2. Risk factors most related to the development of CV disease in PD in Portugal are age >50 years, CRP>0.6 mg/dL, male gender, diabetes, LVH, CAPD and anuria.

Improved arterial-ventricular coupling in metabolic syndrome after exercise training: a pilot study.

PubMed

Fournier, Sara B; Donley, David A; Bonner, Daniel E; Devallance, Evan; Olfert, I Mark; Chantler, Paul D

2015-01-01

The metabolic syndrome (MetS) is associated with threefold increased risk of cardiovascular (CV) morbidity and mortality, which is partly due to a blunted CV reserve capacity, reflected by a reduced peak exercise left ventricular (LV) contractility and aerobic capacity and a blunted peak arterial-ventricular coupling. To date, no study has examined whether aerobic exercise training in MetS can reverse peak exercise CV dysfunction. Furthermore, examining how exercise training alters CV function in a group of individuals with MetS before the development of diabetes and/or overt CV disease can provide insights into whether some of the pathophysiological CV changes can be delayed/reversed, lowering their CV risk. The objective of this study was to examine the effects of 8 wk of aerobic exercise training in individuals with MetS on resting and peak exercise CV function. Twenty participants with MetS underwent either 8 wk of aerobic exercise training (MetS-ExT, n = 10) or remained sedentary (MetS-NonT, n = 10) during this period. Resting and peak exercise CV function was characterized using Doppler echocardiography and gas exchange. Exercise training did not alter resting LV diastolic or systolic function and arterial-ventricular coupling in MetS. In contrast, at peak exercise, an increase in LV contractility (40%, P < 0.01), cardiac output (28%, P < 0.05), and aerobic capacity (20%, P < 0.01), but a reduction in vascular resistance (30%, P < 0.05) and arterial-ventricular coupling (27%, P < 0.01), were noted in the MetS-ExT but not in the MetS-NonT group. Furthermore, an improvement in lifetime risk score was also noted in the MetS-ExT group. These findings have clinical importance because they provide insight that some of the pathophysiological changes associated with MetS can be improved and can lower the risk of CV disease.

Promising cardiovascular and blood pressure effects of the SGLT2 inhibitors: a new class of antidiabetic drugs.

PubMed

Chrysant, S G

2017-03-01

Patients with type 2 diabetes mellitus (T2DM) exhibit an increased risk of cardiovascular (CV) events. Treatment of these patients with traditional as well as newer glucose-lowering drugs has not demonstrated superiority in CV outcomes compared to placebo, despite effective control of diabetes. However, the recently FDA-approved sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of T2DM have demonstrated promising CV-protecting and blood pressure-lowering effects in addition to their effectiveness in glucose lowering, making them a novel class of drugs for the treatment of T2DM. So far, there are three SGLT2 inhibitors approved by the FDA and EMA for the treatment of T2DM: canagliflozin, dapagliflozin and empagliflozin. They exert their antihyperglycemic effect through inhibition of SGLT2 in the kidney and significantly reduce glucose reabsorption from the proximal renal tubule. By blocking glucose reabsorption, they lead to loss of calories, weight, abdominal and total body fat, blood pressure and CV complications. One CV outcomes randomized trial and several short-term studies have shown reductions in CV events and blood pressure in patients with T2DM. It is the hope that large ongoing long-term outcome studies will provide further much-needed information, when they are completed. Copyright 2017 Clarivate Analytics.

Cardiovagal modulation, oxidative stress, and cardiovascular risk factors in prehypertensive subjects: cross-sectional study.

PubMed

Thiyagarajan, Ramkumar; Pal, Pravati; Pal, Gopal Krushna; Subramanian, Senthil Kumar; Bobby, Zachariah; Das, Ashok Kumar; Trakroo, Madanmohan

2013-07-01

Hypertension, one of the modifiable risk factors for cardiovascular disease (CVD), is known to be associated with increased oxidative stress and reduced cardiovagal modulation. Similar to hypertension, prehypertension is associated with increased risk of adverse cardiovascular (CV) events. We planned this study to find the association between prehypertension, cardiovagal modulation, oxidative stress, and associated CV risk factors. We recruited 178 subjects through hypertension screening camps conducted in Puducherry, India. Subjects were grouped into prehypertensive (n = 97) and normotensive (n = 81) groups. They were further subdivided, based on age, as young (20-39 years) and middle-aged (40-60 years) adults. We measured basal physiological parameters, heart rate variability, oxidative stress (thiobarbituric acid reactive substance and total antioxidant capacity (TAC)), and CV risk factors. We found significant increase in oxidative stress in prehypertensive subjects of both age groups but the cardiovagal modulation decreased significantly in young prehypertensive subjects when compared with normotensive subjects. Correlation of TAC with root mean square of the sum of successive R wave to R wave (RR) interval differences (RMSSD), a cardiovagal modulation parameter (r = 0. 437; P < 0.001), and mean arterial pressure (MAP) (r = -0.318; P < 0.001) was significant even after adjusting for CV risk factors. The correlation between MAP and RMSSD (r = 0.199; P = 0.009) was reduced after adjusting for CV risk factors. Prehypertension in young adults is associated with increased oxidative stress and altered cardiovagal modulation. The risk factors for CVDs in prehypertensive young adults were found to be equivalent to that of middle-aged adults who are in the twilight zone for developing CV dysfunctions.

Cost effectiveness of a systematic guidelines-based approach to the prevention and management of vascular disease in a primary care setting.

PubMed

Kamboj, Laveena; Oh, Paul; Levine, Mitchell; Kammila, Srinu; Casey, William; Harterre, Don; Goeree, Ron

2016-01-15

In Ontario, Canada, the Comprehensive Vascular Disease Prevention and Management Initiative (CVDPMI) was undertaken to improve the vascular health in communities. The CVDPMI significantly improved cardiovascular (CV) risk factor profiles from baseline to follow-up visits including the 10 year Framingham Risk Score (FRS). Although the CVDPMI improved CV risk, the economic value of this program had not been evaluated. We examined the cost effectiveness of the CVDPMI program compared to no CVDPMI program in adult patients identified at risk for an initial or subsequent vascular event in a primary care setting. A one year and a ten year cost effectiveness analyses were conducted. To determine the uncertainty around the cost per life year gained ratio, a non-parametric bootstrap analysis was conducted. The overall population base case analysis at one year resulted in a cost per CV event avoided of $70,423. FRS subgroup analyses showed the high risk cohort (FRS >20%) had an incremental cost effectiveness ratio (ICER) that was dominant. In the moderate risk subgroup (FRS 10%-20%) the ICER was $47,439 per CV event avoided and the low risk subgroup (FRS <10%) showed a highly cost ineffective result of greater than $5 million per CV event avoided. The ten year analysis resulted in a dominant ICER. At one year, the CVDPMI program is economically acceptable for patients at moderate to high risk for CV events. The CVDPMI results in increased life expectancy at an incremental cost saving to the healthcare system over a ten year period. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Visit-to-visit glycemic variability is a strong predictor of chronic obstructive pulmonary disease in patients with type 2 diabetes mellitus: Competing risk analysis using a national cohort from the Taiwan diabetes study.

PubMed

Chiu, Hsien-Tsai; Li, Tsai-Chung; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Lin, Cheng-Chieh

2017-01-01

This study aims to examine the association between visit-to-visit glucose variability, which was measured by coefficient of variation (CV) of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c), and risk of chronic obstructive pulmonary disease (COPD) in a large number of patients with type 2 diabetes with an average follow-up of 7.58 years. We conducted a retrospective cohort study on 27,257 patients with type 2 diabetes who participated in the National Diabetes Case Management Program in Taiwan. Visit-to-visit variability in HbA1c and FPG at baseline and the incidence of COPD were analyzed using a modified Cox proportional hazards model considering competing risks. A total of 2,346 incident cases of COPD. Patients were grouped into tertiles of FPG-CV and HbA1c-CV. The incidence rates in the first, second, and third tertiles were 9.87, 11.06, and 13.19, respectively, for FPG-CV and 10.2, 11.81, and 12.07, for HbA1c-CV per 1000 person-years. After adjusting for age, gender, diabetes duration, treatment type, smoking, hypertension, hyperlipidemia, baseline FPG and HbA1c levels, and complications, both FPG-CV and HbA1c-CV were independently associated with COPD. The hazard ratios of COPD for the third terile compared with the first tertile of FPG-CV were 1.26 (95% confidence interval [CI]: 1.13-1.40). Moreover, the hazard ratios of COPD for the third and second tertiles compared with the first tertile of HbA1c-CV were 1.13 (1.02-1.25) and 1.13 (1.02-1.26), respectively. Patients with FPG-CV higher than 34.6% or HbA1c-CV higher than 8.4% exhibited an increased risk of COPD. This finding confirmed the linear relationship of FPG-CV and HbA1c-CV to COPD. Visit-to-visit variability in FPG and HbA1c levels are strong predictors of COPD in patients with type 2 diabetes. Future studies should focus on lung dysfunction in diabetes, and adequate glucose control strategy in regular clinical practices must be established for COPD prevention.

Otitis media in children vaccinated during consecutive 7-valent or 10-valent pneumococcal conjugate vaccination schedules.

PubMed

Leach, Amanda Jane; Wigger, Christine; Andrews, Ross; Chatfield, Mark; Smith-Vaughan, Heidi; Morris, Peter Stanley

2014-08-11

In 2001 when 7-valent pneumococcal conjugate vaccine (PCV7) was introduced, almost all (90%) young Australian Indigenous children living in remote communities had some form of otitis media (OM), including 24% with tympanic membrane perforation (TMP). In late 2009, the Northern Territory childhood vaccination schedule replaced PCV7 with 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10). We conducted regular surveillance of all forms of OM in children in remote Indigenous communities between September 2008 and December 2012. This analysis compares children less than 36 months of age who received a primary course of at least two doses of PCV7 or PHiD-CV10, and not more than one dose of another pneumococcal vaccine. Mean ages of 444 PCV7- and 451 PHiD-CV10-vaccinated children were 20 and 18 months, respectively. Bilaterally normal middle ears were detected in 7% and 9% respectively. OM with effusion was diagnosed in 41% and 51% (Risk Difference 10% [95% Confidence Interval 3 to 17] p = 0.002), any suppurative OM (acute OM or any TMP) in 51% versus 39% (RD -12% [95% CI -19 to -5] p = 0.0004], and TMP in 17% versus 14% (RD -3% [95% CI -8 to 2] p = 0.2), respectively. Multivariate analyses described a similar independent negative association between suppurative OM and PHiD-CV10 compared to PCV7 (Odds Ratio = 0.6 [95% CI 0.4 to 0.8] p = 0.001). Additional children in the household were a risk factor for OM (OR = 2.4 [95% CI 2 to 4] p = 0.001 for the third additional child), and older age and male gender were associated with less disease. Other measured risk factors were non-significant. Similar clinical results were found for children who had received non-mixed PCV schedules. Otitis media remains a significant health and social issue for Australian Indigenous children despite PCV vaccination. Around 90% of young children have some form of OM. Children vaccinated in with PHiD-CV10 had less suppurative OM than children vaccinated with PCV7. Ongoing surveillance during the PCV13 era, and trials of early intervention including earlier and mixed vaccine schedules are warranted.

Impact of acculturation on cardiovascular risk factors among elderly Mexican Americans.

PubMed

López, Lenny; Peralta, Carmen A; Lee, Anne; Zeki Al Hazzouri, Adina; Haan, Mary N

2014-10-01

Higher levels of acculturation among Latinos have been shown to be associated with a higher prevalence of cardiovascular (CV) risk factors in some studies of middle-age persons. The association of acculturation and prevalence of CV risk factors in elderly Latinos is less well established. Acculturation was measured using the validated bidimensional Acculturation Rating Scale for Mexican Americans-II. We conducted a cross-sectional analysis of the association of acculturation with prevalence of CV risk factors among 1789 elderly men and women from the Sacramento Area Latino Study on Aging using multivariate linear and logistic regression. We tested for the interaction of acculturation with risk factors by nativity status. Median age was 69.8 years. Higher acculturation was associated with lower systolic blood pressure, lower low-density lipoprotein, higher high-density lipoprotein, and lower prevalence of CV disease after age and sex adjustment. Higher acculturation remained associated with lower level of low-density lipoprotein and higher level of high-density lipoprotein after full adjustment. Nativity status did not affect these results. Contrary to other reports in middle-aged persons, higher levels of acculturation were associated with better lipid profiles and no significant differences in other CV risk factors by acculturation level in elderly Latinos. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of arterial hypertension, type 2 diabetes and cardiovascular risk factors on ALS outcome: a population-based study.

PubMed

Moglia, Cristina; Calvo, Andrea; Canosa, Antonio; Bertuzzo, Davide; Cugnasco, Paolo; Solero, Luca; Grassano, Maurizio; Bersano, Enrica; Cammarosano, Stefania; Manera, Umberto; Pisano, Fabrizio; Mazzini, Letizia; Dalla Vecchia, Laura A; Mora, Gabriele; Chiò, Adriano

2017-11-01

To assess the prognostic influence of pre-morbid type 2 diabetes mellitus, arterial hypertension and cardiovascular (CV) risk profile on ALS phenotype and outcome in a population-based cohort of Italian patients. A total of 650 ALS patients from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid presence of type 2 diabetes mellitus, arterial hypertension was collected at the time of diagnosis. Patients' CV risk profile was calculated according to the Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice (JBS2). At the univariate analysis, the presence of pre-morbid arterial hypertension was associated with a higher age at onset of ALS and a shorter survival, and patients with a high CV risk profile had a worse prognosis than those with a low CV risk profile. The Cox multivariable analysis did not confirm such findings. Type 2 diabetes mellitus did not modify either the phenotype or the prognosis of ALS patients. This study performed on a large population-based cohort of ALS patients has demonstrated that arterial hypertension, type 2 diabetes and CV risk factors, calculated using the Framingham equation, do not influence ALS phenotype and prognosis.

Emerging biologic therapies for hypercholesterolaemia.

PubMed

Pucci, Giacomo; Cicero, Arrigo F; Borghi, Claudio; Schillaci, Giuseppe

2017-09-01

LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy. Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions. The discontinuation in the development of bococizumab due to efficacy and safety concerns, and the initial promising data about inclisiran, a long-acting small inhibiting RNA molecule against PCSK9 synthesis, is also discussed. Expert opinion: Initial data about cardiovascular (CV) outcomes in large scale, long-term studies suggest a possible further therapeutic pathway for LDL-C reduction, and currently support the notion that further LDL-C reduction, obtained with PCSK9 inhibition on top of best available therapy, provides increased CV protection in subjects at very high CV risk. The development and marketing of mAbs against PCSK9 could help to redefine current therapeutic strategies aimed at reducing cardiovascular (CV) morbidity and risk, through the reduction of LDL-C concentrations. The cost-effectiveness of these emerging drugs is yet to be established.

Association of objectively measured physical activity with cardiovascular risk in mobility-limited older adults

USDA-ARS?s Scientific Manuscript database

Background: Data are sparse regarding the impacts of habitual physical activity (PA) and sedentary behavior on cardiovascular (CV) risk in older adults with mobility limitations. Methods and Results: This study examined the baseline, cross-sectional association between CV risk and objectively measur...

Hypogonadism: Therapeutic Risks, Benefits, and Outcomes.

PubMed

Sigalos, John T; Pastuszak, Alexander W; Khera, Mohit

2018-03-01

Hypogonadism is a common condition defined by the presence of low serum testosterone levels and hypogonadal symptoms, and most commonly treated using testosterone therapy (TTh). The accuracy of diagnosis and appropriateness of treatment, along with proper follow-up, are increasingly important given the large increase in testosterone prescriptions and the recent concern for cardiovascular (CV) risk associated with TTh. In March of 2015, the US Food and Drug Administration required that testosterone product labels disclose a potential CV risk, despite the evidence base for this association being weak and inconclusive. However, TTh may improve CV outcomes rather than increase risks. Copyright © 2017 Elsevier Inc. All rights reserved.

Hypertension and cardiovascular risk assessment in dialysis patients.

PubMed

Locatelli, Francesco; Covic, Adrian; Chazot, Charles; Leunissen, Karel; Luño, José; Yaqoob, Mohammed

2004-05-01

Cardiovascular (CV) disease is the main cause of morbidity and mortality in dialysis patients. Hypertension in patients affected by chronic renal insufficiency (CRI) has been recognized as one of the major classical CV risk factors in CRI from the very beginning of the dialysis era. However, its treatment is still unsatisfactory. A discussion is employed to achieve a consensus on key points relating to the epidemiological, pathophysiological and clinical characteristics of hypertension in renal patients, in the light of global CV risk assessment. CV disease is accelerated by CRI, in particular by uraemia-specific risk factors. This is reflected by the fact that general population-based equations for calculating CV risk underestimate the real CV risk in CRI and dialysis patients. Hypertension in dialysis patients is clearly a major CV risk factor. Isolated systolic hypertension with increased pulse pressure is the most prevalent blood pressure (BP) anomaly in dialysis patients, due to stiffening of the arterial tree. BP should be assessed by clinical measurements on a routine basis, leaving 24 h monitoring for selected cases. The targets of BP control should be those recommended by the present guidelines, i.e. <140/90 mmHg, or the lowest possible values that are well tolerated. The pathophysiological cornerstone of hypertension in dialysis patients is extra-cellular volume expansion, which is typically sodium-sensitive, given the loss of renal function. Therefore, the principles of hypertension treatment in dialysis are an achievement of dry body weight, proper dialysis prescription with respect to dialysis time and intra-dialytic sodium balance, and dietary sodium and water restriction. Pharmacological treatment should only be the second option, after the adequate and complete application of all other means. No comparative pharmacological trials have specifically addressed the issue of hypertension control in dialysis patients. Therefore, this workshop group had to rely largely on data obtained in the general population. Drugs interfering with the renin-angiotensin system were felt to be the first choice, as they have widely been shown to interfere significantly with CV remodelling. Despite long-standing concerns, beta-blockers are being used increasingly even in patients with congestive heart failure and ischaemic cardiomyopathy. Other drug classes may be used in association or as first-line agents according to clinical requirements. Hypertension in renal patients has to be given particular and continued attention, and it should be adequately treated in light of the increased CV risk of this patient population. Research into the mechanisms of uraemic cardiomyopathy and cardiovascular remodelling should provide a precious new insight and lead to more precisely targeted and more effective therapies than in the past.

Testosterone deficiency in patients with erectile dysfunction: when should a higher cardiovascular risk be considered?

PubMed

Martínez-Jabaloyas, José M

2014-08-01

Low testosterone levels (low T) increase the cardiovascular (CV) risk of men with erectile dysfunction (ED). T levels associated with a higher CV risk are unknown. To determine the prevalence of CV risk factors associated with low T as defined by European Guidelines and their contribution to low T, overall and at different ages. Multicenter, cross-sectional, observational study conducted in Spain among men with ED aged ≥ 18 years visiting Urology/Andrology offices for sexual dysfunction. Anthropometric, clinical, and laboratory data, including total T (TT) values, were collected for 1,278 men. Risk factors were assessed in men with TT ≤ 8, 8-12, and ≥ 12 nmol/L, and two-group comparisons were made. Bivariate and multivariate logistic regression analyses were performed to calculate odds ratios for low T after adjusting for possible confounding factors. Mean age (standard deviation) was 58.0 (9.2) years. Age and prevalence of CV risk factors was similar in men with TT ≤ 8 nmol/L or 8-12 nmol/L and significantly higher than in men with TT >12 nmol/L. Low T was therefore considered as TT ≤ 12 nmol/L, with a prevalence of 33.3%. Obesity, hypertension, hyperlipidemia, and severe ED were the variables most strongly associated with low T: obesity in middle-aged men; hyperlipidemia, and hypertension in older men. Severe ED was a risk factor in both groups. Hypolipidemic therapy had the greater effect in young men. Multivariate analysis showed that severe ED and obesity were the strongest predictors of low T. T levels associated with increased CV risk could go as high as 12 nmol/L in men with ED, with distribution of risk factors showing differences according to age. Obesity and severe ED are the best predictors of low T-related CV risk. © 2014 International Society for Sexual Medicine.

Management of Hypercholesterolemia, Appropriateness of Therapeutic Approaches and New Drugs in Patients with High Cardiovascular Risk.

PubMed

Agabiti Rosei, Enrico; Salvetti, Massimo

2016-09-01

Control of lipid levels is one of the most effective strategies for cardiovascular (CV) event prevention. In fact, many clinical trials have clearly demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, primarily with statins, reduces major CV events and mortality. The evidence from these trials has been useful in designing the cholesterol treatment guidelines, which are mainly aimed at preventing and managing cardiovascular disease (CVD). However, available data indicate that a large proportion of patients fail to achieve lipid goals, and this is particularly frequent in patients at high or very high CV risk. Furthermore, owing to side effects, a significant percentage of patients cannot tolerate statin treatment. Hence, researchers have focused their attention on novel LDL-C-lowering agents that act via mechanisms distinct from that of statins. Among the new compounds under investigation, the monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) seem particularly promising, having recently been shown to be well tolerated and highly effective at lowering LDL-C, with a possible effect on the occurrence of CV events. Currently, alirocumab is approved by the US Food and Drug Administration (FDA) as an adjunct to diet and maximally tolerated statin therapy for use in adults with heterozygous familial hypercholesterolemia (FH) or those with atherosclerotic CV disease who require additional LDL-C lowering; it has also been recently approved by the European Medicines Agency (EMA) for use in patients with heterozygous FH, non-familial hypercholesterolemia or mixed dyslipidemia in whom statins are ineffective or not tolerated. Evolocumab is approved by the FDA as an adjunct to diet and maximally tolerated statins for adults with hetero- and homozygous FH and those with atherosclerotic CV disease who require additional lowering of LDL-C, and by the EMA in adults with primary hypercholesterolemia or mixed dyslipidemia, as an adjunct to diet, in combination with a statin or a statin with other lipid lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin; alone or in combination with other lipid lowering therapies in patients who are statin-intolerant, or those for whom a statin is contraindicated. Evolocumab is also indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolemia in combination with other lipid-lowering therapies.

Incremental prognostic value of kidney function decline over coronary artery disease for cardiovascular event prediction after coronary computed tomography.

PubMed

Bittencourt, Marcio S; Hulten, Edward A; Ghoshhajra, Brian; Abbara, Suhny; Murthy, Venkatesh L; Divakaran, Sanjay; Nasir, Khurram; Gowdak, Luis Henrique W; Riella, Leonardo V; Chiumiento, Marco; Hoffmann, Udo; Di Carli, Marcelo F; Blankstein, Ron

2015-07-01

It is unknown whether mild chronic kidney disease (CKD) is associated with adverse cardiovascular (CV) prognosis after accounting for coronary artery disease (CAD). Here we evaluated the interplay between CKD and CAD in predicting CV death or myocardial infarction (MI) and all-cause death. We included 1541 consecutive patients in the Partners registry (mean age 55 years, 43% female) over 18 years old with no known prior CAD who underwent coronary computed tomography angiography (CCTA). The results of CCTA were categorized as normal, nonobstructive (under half), or obstructive (half and over). Overall, 653 of the patients had no CAD, 583 had nonobstructive CAD, and 305 had obstructive CAD, while 1299 had eGFR over 60 ml/min per 1.73 m(2) and 242 had an eGFR under this value. The presence and severity of CAD was significantly associated with an increased rate of CV death or MI and all-cause death, even after adjustment for age, gender, symptoms, and risk factors. Similarly, reduced eGFR was significantly associated with CV death or MI and all-cause death after similar adjustment. The addition of reduced GFR to a model which included both clinical variables and CCTA findings resulted in significant improvement in the prediction of CV death or MI and all-cause death. Thus, among individuals referred for CCTA to evaluate CAD, renal dysfunction is associated with an increased rate of CV events, mainly driven by an increase in the rate of noncoronary CV events. In this group of patients, both eGFR and the presence and severity of CAD together improve the prediction of future CV events and death.

Mechanisms of atherosclerosis and cardiovascular disease in antiphospholipid syndrome and systemic lupus erythematosus. New therapeutic approaches.

PubMed

Lopez-Pedrera, Chary; Aguirre-Zamorano, M Ángeles; Pérez-Sánchez, Carlos

2017-08-22

Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are 2 highly related autoimmune-rheumatic diseases associated with an increased risk of developing cardiovascular (CV) diseases. Despite the great progresses made in understanding the pathological mechanisms leading to CV diseases in those pathologies, there is still the unmet need to improve long term prognosis. CV diseases in SLE and APS is thought to happen as the result of a complex interaction between traditional CV risk factors, immune deregulation and disease activity, including the synergic effect of cytokines, chemokines, adipokines, proteases, autoantibodies, adhesion receptors, oxidative stress and a plethora of intracellular signalling molecules. Genomic and epigenomic analyses have further allowed the identification of specific signatures explaining the proathero-thrombotic profiles of APS and SLE patients. This review examines the complex role of these heterogeneous factors, and analyses new therapeutic approaches under study to reduce the CV risk in these autoimmune disorders. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Saxagliptin for the treatment of type 2 diabetes mellitus: assessing cardiovascular data

PubMed Central

2012-01-01

Patients with type 2 diabetes mellitus (T2DM) are at high risk for cardiovascular (CV) disease; however, conclusive evidence that glycemic control leads to improved cardiovascular outcomes is lacking. Saxagliptin is a potent, selective dipeptidyl peptidase-4 inhibitor approved as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. Saxagliptin was evaluated in a series of phase III trials as monotherapy; add-on therapy to metformin, a sulfonylurea, or a thiazolidinedione; and as initial therapy in combination with metformin. Saxagliptin consistently improved glycemic control (as reflected by significant decreases in glycated hemoglobin, fasting plasma glucose, and postprandial glucose compared with controls) and was generally well tolerated. In these analyses, saxagliptin had clinically neutral effects on body weight, blood pressure, lipid levels, and other markers of CV risk compared with controls. A retrospective meta-analysis of 8 phase II and phase III trials found no evidence that saxagliptin increases CV risk in patients with T2DM (Cox proportional hazard ratio, 0.43; 95% CI, 0.23-0.80 for major adverse cardiovascular events retrospectively adjudicated). Instead, it raised the hypothesis that saxagliptin may reduce the risk of major adverse CV events. A long-term CV outcome trial, Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-THrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) is currently ongoing to determine whether saxagliptin reduces CV risk in T2DM. PMID:22248301

Assessing the Pathogenic Ability of Ralstonia pseudosolanacearum (Ralstonia solanacearum Phylotype I) from Ornamental Rosa spp. Plants.

PubMed

Tjou-Tam-Sin, Napoleon N A; van de Bilt, Jeroen L J; Westenberg, Marcel; Gorkink-Smits, Peggy P M A; Landman, N Marco; Bergsma-Vlami, Maria

2017-01-01

Ralstonia pseudosolanacearum ( Ralstonia solanacearum phylotype I) isolates found in stunted, yellowing, and wilted ornamental rose ( Rosa spp.) were assessed for their pathogenic ability in two rose cultivars (cv. "Armando" and cv. "Red Naomi") and in four solanaceous crops: tomato ( Solanum lycopersicum cv. "Money Maker"), tobacco ( Nicotiana tabacum cv. "White Burley"), eggplant ( Solanum melongena cv. "Black Beauty") and sweet pepper ( Capsicum annum cv. "Yolo Wonder"). Significant differences were observed in susceptibility between the two rose cultivars as well as between the two modes of inoculation performed. The cultivar "Armando" was significantly more susceptible than cultivar "Red Naomi," exhibiting higher disease severity and incidence. Similarly, stem inoculation after wounding was found to be significantly more effective than soil drenching, resulting in higher disease severity. Additionally, a temperature dependency in susceptibility was observed for both cultivars irrespective of the mode of inoculation, however, this was significantly more pronounced upon soil drenching. The solanaceous crops all showed to be susceptible to the R . pseudosolanacearum isolates originated from the Rosa spp. plants. Furthermore, both rose cultivars were able to harbor symptomless infections with other R . pseudosolanacearum and R. solanacearum isolates than those isolated from rose. Our results clearly demonstrated that latent infections in a rose cultivar such as cv. "Red Naomi" do occur even at temperatures as low as 20°C. This latency poses high risks for the entire floricultural industry as latently infected Rosa spp. plants are propagated and distributed over various continents, including areas where climatic conditions are optimal for the pathogen.

Longitudinal safety evaluation of connected vehicles' platooning on expressways.

PubMed

Rahman, Md Sharikur; Abdel-Aty, Mohamed

2018-08-01

Connected vehicles (CV) technology has recently drawn an increasing attention from governments, vehicle manufacturers, and researchers. One of the biggest issues facing CVs popularization associates it with the market penetration rate (MPR). The full market penetration of CVs might not be accomplished recently. Therefore, traffic flow will likely be composed of a mixture of conventional vehicles and CVs. In this context, the study of CV MPR is worthwhile in the CV transition period. The overarching goal of this study was to evaluate longitudinal safety of CV platoons by comparing the implementation of managed-lane CV platoons and all lanes CV platoons (with same MPR) over non-CV scenario. This study applied the CV concept on a congested expressway (SR408) in Florida to improve traffic safety. The Intelligent Driver Model (IDM) along with the platooning concept were used to regulate the driving behavior of CV platoons with an assumption that the CVs would follow this behavior in real-world. A high-level control algorithm of CVs in a managed-lane was proposed in order to form platoons with three joining strategies: rear join, front join, and cut-in joint. Five surrogate safety measures, standard deviation of speed, time exposed time-to-collision (TET), time integrated time-to-collision (TIT), time exposed rear-end crash risk index (TERCRI), and sideswipe crash risk (SSCR) were utilized as indicators for safety evaluation. The results showed that both CV approaches (i.e., managed-lane CV platoons, and all lanes CV platoons) significantly improved the longitudinal safety in the studied expressway compared to the non-CV scenario. In terms of surrogate safety measures, the managed-lane CV platoons significantly outperformed all lanes CV platoons with the same MPR. Different time-to-collision (TTC) thresholds were also tested and showed similar results on traffic safety. Results of this study provide useful insight for the management of CV MPR as managed-lane CV platoons. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic Markers of Cardiovascular Disease in Rheumatoid Arthritis

PubMed Central

Rodríguez-Rodríguez, Luis; López-Mejías, Raquel; García-Bermúdez, Mercedes; González-Juanatey, Carlos; González-Gay, Miguel A.; Martín, Javier

2012-01-01

Cardiovascular (CV) disease is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). It is the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases. Besides traditional CV risk factors and chronic inflammation, a number of studies have confirmed the role of genetic factors in the development of the atherogenesis observed in RA. In this regard, besides a strong association between the HLA-DRB1∗04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G > A, rs1800629) of the TNFA locus, the rs1801131 polymorphism (A > C; position + 1298) of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA. Despite considerable effort to decipher the genetic basis of CV disease in RA, further studies are required to better establish the genetic influence in the increased risk of CV events observed in patients with RA. PMID:22927710

Pregnancy-associated plasma protein-A is a stronger predictor for adverse cardiovascular outcomes after acute coronary syndrome in type-2 diabetes mellitus.

PubMed

Li, Wei-Ping; Neradilek, Moni B; Gu, Fu-Sheng; Isquith, Daniel A; Sun, Zhi-Jun; Wu, Xing; Li, Hong-Wei; Zhao, Xue-Qiao

2017-04-05

The risk prediction of pregnancy-associated plasma protein-A (PAPP-A) for future cardiovascular (CV) events post acute coronary syndrome (ACS) in patients with type-2 diabetes mellitus (T2DM) was investigated in comparison to other risk factors. PAPP-A was measured at hospital admission in 320 consecutive ACS patients (136 with T2DM and 184 without). All patients were followed for 2 years for occurrence of CV death, non-fatal MI or stroke. Effect of PAPP-A on the CV event risk was estimated using Cox regression models. Receiver operating characteristics (ROC) curves were generated to demonstrate the sensitivity and specificity of PAPP-A in predicting CV events. ACS patients with T2DM had higher PAPP-A (19.29 ± 16.36 vs. 13.29 ± 13.90 ng/ml, p < 0.001) and higher rate of CV events 2 years post ACS (27.2 vs. 13.6%, p = 0.002) than those without. Higher levels of PAPP-A were significantly associated with increased risk of CV events during 2-year follow-up [HR = 2.97 for 1 SD increase in log 10 (PAPP-A), 95% CI 2.11-4.18, p < 0.001] in T2DM and (HR = 3.16, 95% CI 2.27-4.39, p < 0.001) in non-T2DM. Among patients with T2DM, PAPP-A showed a larger area under the curve (AUC 0.79) that was significantly more predictive than hsCRP (AUC 0.64), eGFR (AUC 0.66) and LVEF < 50% (AUC 0.52); predictive ability did not improve significantly by including those factors into the model. Patients with T2DM had higher levels of PAPP-A and increased risk of CV events. Elevated PAPP-A compared to other risk factors was a stronger predictor for future CV events 2 years post ACS in patients with T2DM. Trial registration ISRCTN10805074. Registered on 20 January 2017, retrospectively registered.

Management and Outcomes Among Chinese Hospitalized Patients With Established Cardiovascular Disease or Multiple Risk Factors.

PubMed

Yang, Jingang; Yang, Yuejin; Gu, Hongqiu; Li, Wei; Hu, Dayi

2016-02-01

We assessed the management and outcomes among hospitalized patients with coronary artery disease (CAD), stroke, peripheral artery disease (PAD), or with multiple (≥ 2) cardiovascular (CV) risk factors (multiple risk factors [MRFs]). We retrospectively studied 3732 hospitalized patients of either CV disease or ≥ 2 risk factors for atherothrombosis from October 2004 to January 2005. Outcomes included CV death, myocardial infarction (MI), stroke, and hospitalization for atherothrombotic events. About one-third had disease involving ≥ 1 vascular bed. Medication was more intense in patients with CAD than in others. The lowest use of statins and antiplatelet treatment was in the PAD-only group. Patients with PAD experienced a higher CV mortality (5.1%) than the patients with CAD (3.73%) or stroke (4.1%), P < .001. Cardiovascular death ranged from 1.2% for patients with MRFs, 2.8% for patients with 1-bed disease, 4.7% for patients with 2-bed disease to 6.4% for patients with 3-bed disease (P for trend <.001). For hospitalized patients with established atherosclerotic arterial disease, a substantial increase in CV event rates occurs with increasing numbers of affected arterial beds. Patients with PAD were at an especially high risk. © The Author(s) 2015.

Calcium Channel Blockers in Secondary Cardiovascular Prevention and Risk of Acute Events: Real-World Evidence from Nested Case-Control Studies on Italian Hypertensive Elderly.

PubMed

Bettiol, Alessandra; Lucenteforte, Ersilia; Vannacci, Alfredo; Lombardi, Niccolò; Onder, Graziano; Agabiti, Nera; Vitale, Cristiana; Trifirò, Gianluca; Corrao, Giovanni; Roberto, Giuseppe; Mugelli, Alessandro; Chinellato, Alessandro

2017-12-01

Antihypertensive treatment with calcium channel blockers (CCBs) is consolidated in clinical practice; however, different studies observed increased risks of acute events for short-acting CCBs. This study aimed to provide real-world evidence on risks of acute cardiovascular (CV) events, hospitalizations and mortality among users of different CCB classes in secondary CV prevention. Three case-control studies were nested in a cohort of Italian elderly hypertensive CV-compromised CCBs users. Cases were subjects with CV events (n = 25,204), all-cause hospitalizations (n = 19,237), or all-cause mortality (n = 17,996) during the follow-up. Up to four controls were matched for each case. Current or past exposition to CCBs at index date was defined based on molecule, formulation and daily doses of the last CCB delivery. The odds ratio (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Compared to past users, current CCB users had significant reductions in risks of CV events [OR 0.88 (95% CI: 0.84-0.91)], hospitalization [0.90 (0.88-0.93)] and mortality [0.48 (0.47-0.49)]. Current users of long-acting dihydropyridines (DHPs) had the lowest risk [OR 0.87 (0.84-0.90), 0.86 (0.83-0.90), 0.55 (0.54-0.56) for acute CV events, hospitalizations and mortality], whereas current users of short-acting CCBs had an increased risk of acute CV events [OR 1.77 (1.13-2.78) for short-acting DHPs; 1.19 (1.07-1.31) for short-acting non-DHPs] and hospitalizations [OR 1.84 (0.96-3.51) and 1.23 (1.08-1.42)]. The already-existing warning on short-acting CCBs should be potentiated, addressing clinicians towards the choice of long-acting formulations.

Lifetime risk: childhood obesity and cardiovascular risk.

PubMed

Ayer, Julian; Charakida, Marietta; Deanfield, John E; Celermajer, David S

2015-06-07

In a recent report, the worldwide prevalence of childhood obesity was estimated to have increased by 47% between 1980 and 2013. As a result, substantial concerns have been raised about the future burden of cardiovascular (CV) disease that could ensue. The purpose of this review is to summarize and interpret (i) the evidence linking early life obesity with adverse changes in CV structure and function in childhood, (ii) the lifetime risk for CV disease resulting from obesity in childhood, and (iii) the potential effects of lifestyle interventions in childhood to ameliorate these risks. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Prevalence and covariates of electrocardiographic left ventricular hypertrophy in diabetic patients in Tanzania

PubMed Central

Lutale, JJK; Thordarson, H; Gulam-Abbas, Z; Vetvik, K; Gerdts, E

2008-01-01

Summary Background Left ventricular hypertrophy (LV H) has been demonstrated to be a powerful predictor of cardiovascular (CV) morbidity and mortality in diabetic as well as hypertensive patients. However, less is known about the prevalence of electrocardiographic LV H (ECG-LV H) and its relation to other CV risk factors in diabetic patients in sub-Saharan Africa. Therefore, the aim was to assess the prevalence of ECG-LV H in diabetic patients in Dar es Salaam, Tanzania, and its relation to other cardiovascular risk factors. Methods Two hundred and thirty-seven consecutive patients attending the Muhimbili diabetic clinic were studied. ECG-LVH was diagnosed by Sokolow-Lyon voltage and Cornell voltage-duration product criteria. Q waves, ST-segment deviation, T-wave abnormalities and intraventricular conduction defects were classified by the Minnesota codes. Blood pressure (BP), serum creatinine, cholesterol and triglyceride levels, and HbA1c and urinary albumin and creatinine concentrations were determined. Results The prevalence of LV H in patients was 16% by either ECG criteria; 12.2% by Sokolow-Lyon and 5.1% by Cornell product criteria. Patients with LV H had significantly higher systolic and mean BP and pulse pressure, and a higher prevalence of ST-segment abnormalities, T-wave inversion and albuminuria than those without LV H (all p < 0.05). In multivariate logistic regression analysis, systolic BP was the only independent predictor of ECG-LV H. The prevalence of ECG-LV H increased by 15% per 10 mmHg higher systolic BP [OR 1.151 (95% CI 1.00921.314), p < 0.05]. Clustering of cardiovascular risk factors differed significantly between type 1 and type 2 diabetes patients. On average, type 1 patients had 0.8 and type 2 had 2.2 additional CV risk factors. Conclusion ECG-LV H was present in 16% of diabetic patients in Tanzania. Systolic BP was the most important predictor of ECG-LV H. Clustering of CV risks was significantly higher in type 2 than in type 1 diabetics, demonstrating the need for systematic multiple risk-factor assessment in these patients. PMID:18320079

Protective Effects of Hydroxychloroquine against Accelerated Atherosclerosis in Systemic Lupus Erythematosus

PubMed Central

Cauli, Alberto

2018-01-01

Cardiovascular (CV) morbidity and mortality are a challenge in management of patients with systemic lupus erythematosus (SLE). Higher risk of CV disease in SLE patients is mostly related to accelerated atherosclerosis. Nevertheless, high prevalence of traditional cardiovascular risk factors in SLE patients does not fully explain the increased CV risk. Despite the pathological bases of accelerated atherosclerosis are not fully understood, it is thought that this process is driven by the complex interplay between SLE and atherosclerosis pathogenesis. Hydroxychloroquine (HCQ) is a cornerstone in treatment of SLE patients and has been thought to exert a broad spectrum of beneficial effects on disease activity, prevention of damage accrual, and mortality. Furthermore, HCQ is thought to protect against accelerated atherosclerosis targeting toll-like receptor signaling, cytokine production, T-cell and monocyte activation, oxidative stress, and endothelial dysfunction. HCQ was also described to have beneficial effects on traditional CV risk factors, such as dyslipidemia and diabetes. In conclusion, despite lacking randomized controlled trials unambiguously proving the protection of HCQ against accelerated atherosclerosis and incidence of CV events in SLE patients, evidence analyzed in this review is in favor of its beneficial effect. PMID:29670462

The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe.

PubMed

Simon, Tracey G; Corey, Kathleen E; Cannon, Christopher P; Blazing, Michael; Park, Jeong-Gun; O'Donoghue, Michelle L; Chung, Raymond T; Giugliano, Robert P

2018-05-26

The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of unique metabolic risk indicators that may accurately predict residual cardiovascular (CV) risk in patients with established coronary disease and metabolic dysfunction. We applied the NFS prospectively to 14,819 post-ACS patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), in the IMPROVE-IT trial, using validated NFS cutoffs. The primary endpoint included CV death, myocardial infarction, unstable angina, revascularization or stroke. Outcomes were compared between NFS categories and treatment arms using frequency of events, KM rates and adjusted Cox proportional hazard models. The ability of the NFS to predict recurrent CV events was independently validated in 5395 placebo-treated patients enrolled in the SOLID-TIMI 52 trial. Among 14,819 patients enrolled in IMPROVE-IT, 14.2% (N = 2106) were high-risk (NFS > 0.67). The high-risk group had a 30% increased risk of recurrent major CV events, compared to the low-risk NFS group (HR 1.30 [1.19-1.43]; p < 0.001). Among high-risk patients, ezetimibe/simvastatin conferred a 3.7% absolute reduction in risk of recurrent CV events, compared to placebo/simvastatin (HR 0.85 [0.74-0.98]), translating to a number-needed-to-treat of 27. Similar benefit was not found in the low-risk group (HR ezetimibe/simvastatin vs. placebo/simvastatin, 1.01 [0.91-1.12]; p-interaction = 0.053). The relationship between NFS category and recurrent CV events was independently validated in patients enrolled in SOLID-TIMI 52 (HR for NFS > 0.67 vs. NFS < -1.455 = 1.55 [1.32-1.81]; p < 0.001). Stratification of cardiovascular risk by NFS identifies an independent population of patients who are at highest risk of recurrent events, and most likely to benefit from dual lipid-lowering therapy. Clinical trials.gov: NCT00202878. Copyright © 2017 Elsevier B.V. All rights reserved.

Primordial Prevention of Cardiometabolic Risk in Childhood.

PubMed

Tanrikulu, Meryem A; Agirbasli, Mehmet; Berenson, Gerald

2017-01-01

Fetal life and childhood are important in the development of cardiometabolic risk and later clinical disease of atherosclerosis, hypertension and diabetes mellitus. Molecular and environmental conditions leading to cardiometabolic risk in early life bring us a challenge to develop effective prevention and intervention strategies to reduce cardiovascular (CV) risk in children and later disease. It is important that prevention strategies begin at an early age to reduce future CV morbidity and mortality. Pioneering work from longitudinal studies such as Bogalusa Heart Study (BHS), the Finnish Youth Study and other programs provide an awareness of the need for public and health services to begin primordial prevention. The impending CV risk beginning in childhood has a significant socioeconomic burden. Directions to achieve primordial prevention of cardiometabolic risk in children have been developed by prior longitudinal studies. Based on those studies that show risk factors in childhood as precursors of adult CV risk, implementation of primordial prevention will have effects at broad levels. Considering the epidemic of obesity, the high prevalence of hypertension and cardiometabolic risk, prevention early in life is valuable. Comprehensive health education, such as 'Health Ahead/Heart Smart', for all elementary school age children is one approach to begin primordial prevention and can be included in public education beginning in kindergarten along with the traditional education subject matter.

Cardiovascular mortality in Hispanics compared to non-Hispanic whites: a systematic review and meta-analysis of the Hispanic paradox.

PubMed

Cortes-Bergoderi, Mery; Goel, Kashish; Murad, Mohammad Hassan; Allison, Thomas; Somers, Virend K; Erwin, Patricia J; Sochor, Ondrej; Lopez-Jimenez, Francisco

2013-12-01

Hispanics, the largest minority in the U.S., have a higher prevalence of several cardiovascular (CV) risk factors than non-Hispanic whites (NHW). However, some studies have shown a paradoxical lower rate of CV events among Hispanics than NHW. To perform a systematic review and a meta-analysis of cohort studies comparing CV mortality and all-cause mortality between Hispanic and NHW populations in the U.S. We searched EMBASE, MEDLINE, Web of Science, and Scopus databases from 1950 through May 2013, using terms related to Hispanic ethnicity, CV diseases and cohort studies. We pooled risk estimates using the least and most adjusted models of each publication. We found 341 publications of which 17 fulfilled the inclusion criteria; data represent 22,340,554 Hispanics and 88,824,618 NHW, collected from 1950 to 2009. Twelve of the studies stratified the analysis by gender, and one study stratified people by place of birth (e.g. U.S.-born, Mexican-born, and Central/South American-born). There was a statistically significant association between Hispanic ethnicity and lower CV mortality (OR 0.67; 95% CI, 0.57-0.78; p<0.001), and lower all-cause mortality (0.72; 95% CI, 0.63-0.82; p<0.001). A subanalysis including only studies that reported prevalence of CV risk factors found similar results. OR for CV mortality among Hispanics was 0.49; 95% CI 0.30-0.80; p-value <0.01; and OR for all-cause mortality was 0.66; 95% CI 0.43-1.02; p-value 0.06. These results confirm the existence of a Hispanic paradox regarding CV mortality. Further studies are needed to identify the mechanisms mediating this protective CV effect in Hispanics. © 2013.

Disease Activity in Rheumatoid Arthritis and the Risk of Cardiovascular Events

PubMed Central

Solomon, DH; Reed, G; Kremer, JM; Curtis, JR; Farkouh, ME; Harrold, LR; Hochberg, MC; Tsao, P; Greenberg, J

2015-01-01

Background Use of several immunomodulatory agents has been associated with reduced cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown whether time-averaged disease activity in RA correlates with CV events. Methods We studied patients with RA followed in a longitudinal US-based registry. Time-averaged disease activity was assessed using the area under the curve of the Clinical Disease Activity Index, a validated measure of rheumatoid arthritis disease activity, assessed during follow-up. Age, gender, diabetes, hypertension, hyperlipidemia, body mass index, family history of myocardial infarction (MI), aspirin use, NSAID use presence of CV disease, and baseline immunomodulator use were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV endpoint that included MI, stroke, and CV death. Results 24,989 subjects followed for a median of 2.7 years were included in these analyses. During follow-up, we observed 422 confirmed CV endpoints for an incidence rate of 9.08 (95% confidence interval, CI, 7.90 – 10.26) per 1,000 person-years. In models adjusting for variables noted above, a 10-point reduction in time-averaged Clinical Disease Activity Index was associated with a 26% reduction in CV risk (95% confidence interval 17-34%). These results were robust in subgroup analyses stratified by presence of CV disease, use of corticosteroids, use of non-steroidal anti-inflammatory drugs or selective COX-2 inhibitors, change in RA treatment, and also when restricted to events adjudicated as definite or probable. Conclusions Reduced time-averaged disease activity in RA is associated with fewer CV events. PMID:25776112

Growth differentiation factor-15 level predicts major bleeding and cardiovascular events in patients with acute coronary syndromes: results from the PLATO study.

PubMed

Hagström, Emil; James, Stefan K; Bertilsson, Maria; Becker, Richard C; Himmelmann, Anders; Husted, Steen; Katus, Hugo A; Steg, Philippe Gabriel; Storey, Robert F; Siegbahn, Agneta; Wallentin, Lars

2016-04-21

Growth differentiation factor-15 (GDF-15) predicts death and composite cardiovascular (CV) events in patients with acute coronary syndrome (ACS). We investigated the independent associations between GDF-15 levels and major bleeding, the extent of coronary lesions and individual CV events in patients with ACS. Growth differentiation factor-15 was analysed at baseline ( ITALIC! n = 16 876) in patients with ACS randomized to ticagrelor or clopidogrel in the PLATO (PLATelet inhibition and patient Outcomes) trial. Growth differentiation factor-15 levels were related to extent of coronary artery disease (CAD) and to all types of non-coronary artery bypass grafting (CABG)-related major bleeding, spontaneous myocardial infarction (MI), stroke, and death during 12-month follow-up. In Cox proportional hazards models adjusting for established risk factors for CV disease and prognostic biomarkers (N-terminal pro B-type natriuretic peptide, cystatin C, high-sensitive C-reactive protein, and high-sensitive troponin T), 1 SD increase in ln GDF-15 was associated with increased risk of major bleeding with a hazard ratio (HR) 1.37 (95% confidence interval: 1.25-1.51) and with a similar increase in risk across different bleeding locations. For the same increase in ln GDF-15, the HR for the composite of CV death, spontaneous MI, and stroke was 1.29 (1.21-1.37), CV death 1.41 (1.30-1.53), all-cause death 1.41 (1.31-1.53), spontaneous MI 1.15 (1.05-1.26), and stroke 1.19 (1.01-1.42). The ITALIC! C-statistic improved for the prediction of CV death and non-CABG-related major bleeding when adding GDF-15 to established risk factors. In patients with ACS, higher levels of GDF-15 are associated with raised risks of all types of major non-CABG-related bleeding, spontaneous MI, and stroke as well as CV and total mortality and seem to improve risk stratification for CV-mortality and major bleeding beyond established risk factors. www.clinicaltrials.gov; NCT00391872. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Complete blood count risk score and its components, including RDW, are associated with mortality in the JUPITER trial.

PubMed

Horne, Benjamin D; Anderson, Jeffrey L; Muhlestein, Joseph B; Ridker, Paul M; Paynter, Nina P

2015-04-01

Previously, we showed that sex-specific complete blood count (CBC) risk scores strongly predicted risk of all-cause mortality in multiple sets of general medical patients. This study evaluated the CBC risk score in an independent, well-studied international primary risk population of lower-risk individuals initially free from cardiovascular (CV) disease. Observational secondary analysis of a randomized trial population. The previously derived and validated CBC score was evaluated for association with all-cause mortality among CV disease-free females (n = 6568) and males (n = 10,629) enrolled for up to 5 years in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Associations of the CBC score with CV mortality and with major CV disease were also tested. The CBC score predicted all-cause mortality, with univariable hazard ratio (HR) 4.83 (95% CI 3.70-6.31) for the third CBC score tertile vs. the first tertile, and HR 2.31 (CI 1.75-3.05) for the second tertile (p trend < 0.001). The CBC score retained significance after adjustment: HR 1.97 (CI 1.46-2.67) and 1.51 (CI 1.13-2.00) for tertiles 3 and 2 vs. 1, respectively (p trend < 0.001). The CBC score also predicted CV mortality (p trend = 0.025) and the primary JUPITER endpoint (p trend = 0.015). c-statistics for mortality were 0.729 among all, and 0.722 and 0.750 for females and males, respectively. The CBC risk score was strongly associated with all-cause mortality among JUPITER trial participants and had good discrimination. It also predicted CV-specific outcomes. This CBC score may be useful in identifying cardiac disease-free individuals at increased risk of mortality. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Nutraceuticals in lipid-lowering treatment: a narrative review on the role of chitosan.

PubMed

Patti, Angelo Maria; Katsiki, Niki; Nikolic, Dragana; Al-Rasadi, Khalid; Rizzo, Manfredi

2015-05-01

Lipid-lowering drugs may cause adverse effects and, although lipid targets may be achieved, a substantial residual cardiovascular (CV) risk remains. Treatment with agents mimicking proteins present in the body, such as incretin-based therapies, provided promising results. However, in order to improve lipids and CV risk, lifestyle measures remain important. Some researchers focused on nutraceuticals that may beneficially affect metabolic parameters and minimize CV risk. Chitosan, a dietary fiber, can regulate lipids with benefit on anthropometric parameters. The beneficial properties of dietary supplements (such as green tea extract, prebiotics, plant sterols, and stanols) on plasma lipids, lipoproteins, blood pressure, glucose, and insulin levels and their anti-inflammatory and anti-oxidant effects are documented. However, larger, prospective clinical trials are required to confirm such benefits. Such treatments may be recommended when lipid-lowering drugs are neither indicated nor tolerated as well as in order to achieve therapeutic targets and/or overcome residual CV risk. © The Author(s) 2014.

Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women’s Health Initiative

PubMed Central

Arce, Cristina M.; Rhee, Jinnie J.; Cheung, Katharine L.; Hedlin, Haley; Kapphahn, Kristopher; Franceschini, Nora; Kalil, Roberto S.; Martin, Lisa W.; Qi, Lihong; Shara, Nawar M.; Desai, Manisha; Stefanick, Marcia L.; Winkelmayer, Wolfgang C.

2015-01-01

Background Kidney disease disproportionately affects minority populations including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women’s Health Initiative. Study Design Prospective cohort study Setting & Participants Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50–79 years who self-identified as either non-Hispanic white (n=8921), African American (n=7436), or Hispanic (n=3054) were used to calculate estimated glomerular filtration rates (eGFRs). Predictors Categories of eGFR (exposure); race/ethnicity (effect modifier). Outcomes The primary outcome was the composite of three physician-adjudicated CV events: myocardial infarction (MI), stroke, or CV-related death. Measurements We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity. Results Over a mean follow-up of 7.6 years, 1424 CV events (653 MI, 627 strokes, 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship with lower eGFR being associated with higher CV risk and higher eGFR with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFR and very few events occurring in these categories. Limitations Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics. Conclusions In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women. PMID:26337132

78 FR 66990 - Additional Designations, Foreign Narcotics Kingpin Designation Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

...) [SDNTK] (Linked To: ARRENDADORA TURIN, S.A.; Linked To: DESARROLLOS BIO GAS, S.A. DE C.V.; Linked To: ECA...] (Linked To: BLUE POINT SALT, S.A. DE C.V.; Linked To: DESARROLLOS BIO GAS, S.A. DE C.V.; Linked To: ECA ENERGETICOS, S.A. DE C.V.; Linked To: ORGANIC SALT, S.A. DE C.V.; Linked To: PETRO BIO, S. DE R.L. DE C.V...

Home, automated office, and conventional office blood pressure as predictors of cardiovascular risk.

PubMed

Andreadis, Emmanuel A; Papademetriou, Vasilios; Geladari, Charalampia V; Kolyvas, George N; Angelopoulos, Epameinondas T; Aronis, Konstantinos N

2017-03-01

Automated office blood pressure (AOBP) has recently been shown to closely predict cardiovascular (CV) events in the elderly. Home blood pressure (HBP) has also been accepted as a valuable method in the prediction of CV disease. This study aimed to compare conventional office BP (OBP), HBP, and AOBP in order to evaluate their value in predicting CV events and deaths in hypertensives. We assessed 236 initially treatment naïve hypertensives, examined between 2009 and 2013. The end points were any CV and non-CV event including mortality, myocardial infarction, coronary heart disease, hospitalization for heart failure, severe arrhythmia, stroke, and intermittent claudication. We fitted proportional hazards models using the different modalities as predictors and evaluated their predictive performance using three metrics: time-dependent receiver operating characteristics curves, the Akaike's Information Criterion, and Harrell's C-index. After a mean follow-up of 7 years, 23 participants (39% women) had experienced ≥1 CV event. Conventional office systolic (hazard ratio [HR] per 1 mm Hg increase in BP, 1.028; 95% confidence interval [CI], 1.009-1.048), automated office systolic (HR per 1 mm Hg increase in BP, 1.031; 95% CI, 1.008-1.054), and home systolic (HR, 1.025; 95% CI, 1.003-1.047) were predictive of CV events. All systolic BP measurements were predictive after adjustment for other CV risk factors (P < .05). The predictive performance of the different modalities was similar. Conventional OBP was significantly higher than AOBP and average HBP. AOBP predicts equally well to OBP and HBP CV events. It appears to be comparable to HBP in the assessment of CV risk, and therefore, its introduction into guidelines and clinical practice as the reference method for assessing BP in the office seems reasonable after verification of these findings by randomized trials. Copyright © 2017 American Society of Hypertension. All rights reserved.

Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME).

PubMed

Maggi, Mario; Wu, Frederick C W; Jones, Thomas H; Jackson, Graham; Behre, Hermann M; Hackett, Geoffrey; Martin-Morales, Antonio; Balercia, Giancarlo; Dobs, Adrian S; Arver, Stefan T E; Maggio, Marcello; Cunningham, Glenn R; Isidori, Andrea M; Quinton, Richard; Wheaton, Olivia A; Siami, Flora S; Rosen, Raymond C

2016-10-01

The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG). The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2-3 years. Independent adjudication was performed on all mortalities and CV outcomes. Of 999 patients enrolled with clinically diagnosed HG, 750 (75%) initiated some form of TRT. Registry participants, including both treated and untreated patients, contributed 23 900 person-months (99.6% of the targeted) follow-up time. A total of 55 reported CV events occurred in 41 patients. Overall, five patients died of CV-related causes (3 on TRT, 2 untreated) and none of the deaths were adjudicated as treatment-related. The overall CV incidence rate was 1522 per 100 000 person-years. CV event rates for men receiving TRT were not statistically different from untreated men (P=.70). Regardless of treatment assignment, CV event rates were higher in older men and in those with increased CV risk factors or a prior history of CV events. Age and prior CV history, not TRT use, were predictors of new-onset CV events in this multi-national, prospective hypogonadism registry. © 2016 John Wiley & Sons Ltd.

Commentary: Using Impedance Cardiography to Detect Asymptomatic Cardiovascular Disease in Prehypertensive Adults with Risk Factors.

PubMed

DeMarzo, Arthur P

2018-06-01

New guidelines on hypertension eliminated the classification of prehypertension and divided those blood pressure (BP) levels into elevated BP and stage 1 hypertension. For elevated BP, this study showed that cardiovascular (CV) abnormalities were prevalent in adults over 40 years of age with at least 2 CV risk factors. Detecting abnormalities of the CV system moves a patient from being at high risk to having earlystage cardiovascular disease (CVD) and supports a decision to treat. By redefining stage 1 and lowering the target BP, the new guidelines have set an ambitious goal for early intervention to prevent progression of CVD. Proper drug selection and titration are critical. Hypertensive patients have diverse CV abnormalities that can be quantified by impedance cardiography. By stratifying patients with ventricular, vascular, and hemodynamic abnormalities, treatment can be customized based on the abnormal underlying mechanisms to rapidly control BP and prevent progression of CVD.

Cardiovascular Consequences of Binge Drinking: An Integrative Review with Implications for Advocacy, Policy, and Research.

PubMed

Piano, Mariann R; Mazzuco, Adriana; Kang, Minkyung; Phillips, Shane A

2017-03-01

Worldwide, binge drinking is a major public health problem. The popularized health risks associated with binge drinking include physical injury and motor vehicle crashes; less attention has been given to the negative effects on the cardiovascular (CV) system. The primary aims of this review were to provide a summary of the adverse effects of binge drinking on the risk and development of CV disease and to review potential pathophysiologic mechanisms. Using specific inclusion criteria, an integrative review was conducted that included data from human experimental, prospective cross-sectional, and cohort epidemiological studies that examined the association between binge drinking and CV conditions such as hypertension (HTN), myocardial infarction (MI), stroke, and arrhythmias. Studies were identified that examined the relationship between binge drinking and CV outcomes. Collectively, findings support that binge drinking is associated with a higher risk of pre-HTN, HTN, MI, and stroke in middle-aged and older adults. Binge drinking may also have adverse CV effects in young adults (aged 18 to 30). Mechanisms remain incompletely understood; however, available evidence suggests that binge drinking may induce oxidative stress and vascular injury and be proatherogenic. Public health messages regarding binge drinking need to include the effects of binge drinking on the CV system. Copyright © 2017 by the Research Society on Alcoholism.

Modulatory Effect of Inflammation on Blood Pressure Reduction via Therapeutic Lifestyle Change.

PubMed

Milani, Richard V; Lavie, Carl J

2009-01-01

Since inflammatory status, as determined by C-reactive protein (CRP) levels, is correlated with many cardiovascular (CV) disease risk factors and major CV events, we sought to determine if median levels of CRP can modulate blood pressure changes as well as other CV risk factors that are typically improved by therapeutic lifestyle changes with formal cardiac rehabilitation and exercise training (CRET) programs. We retrospectively evaluated CRP status and standard CV risk factors both before and after formal, phase II CRET programs (12 weeks; 36 educational and exercise sessions) in 635 consecutive patients with coronary artery disease after major CV events. The median CRP level at baseline was 3.2 mg/L (range, 0.2-80.1 mg/L; mean, 5.8±8.4 mg/L). After CRET, both the patients with high and those with low CRP concentrations exhibited statistically significant improvements in most CV risk factors when their CRP levels were divided by median levels. However, systolic, diastolic, and mean arterial blood pressure improved in patients with low CRP levels (each by -4%) but did not change significantly in patients with high CRP levels. In multiple regression models, only young age, low CRP levels, and low body mass index were significant independent predictors of improved mean arterial blood pressure after CRET. In contrast to patients with coronary artery disease and low levels of CRP, patients with high baseline CRP levels did not demonstrate significant reductions in blood pressure after therapeutic lifestyle changes via formal CRET programs.

Undernutrition and Overnutrition Burden for Diseases in Developing Countries: The Role of Oxidative Stress Biomarkers to Assess Disease Risk and Interventional Strategies

PubMed Central

Mastorci, Francesca; Vassalle, Cristina; Chatzianagnostou, Kyriazoula; Marabotti, Claudio; Siddiqui, Khawer; Eba, Ahmed Ould; Mhamed, Soueid Ahmed Sidi; Bandopadhyay, Arun; Nazzaro, Marco Stefano; Passera, Mirko; Pingitore, Alessandro

2017-01-01

The increased life expectancy, urbanization, and unhealthy lifestyle characterized by a shift towards a sedentary lifestyle and decreased energy expenditure are considered the main drivers of epidemiological transition. In particular, developing countries are facing a double burden caused by coexisting under- and over-nutrition, which causes a change in the disease profile from infectious diseases to a chronic degenerative pattern. This review discusses the under- and over-nutrition context in Mauritania and India, two countries that are experiencing a nutritional transition, and where we began a collaboration with local medical staff to integrate interventional and diagnostic guidelines. If many studies about diet and its relationship to non-communicable diseases are available for India, very few nutrition and cardiovascular risk studies have been conducted in Mauritania. Presently, with the exponential increase of nutrition-related diseases, targeted approaches are needed to provide balanced diets in parallel with the development of national preventive health systems and screening programs adapted to local needs. In this context, the measurement of oxidative stress biomarkers could be promising as an additive tool to assess cardiovascular (CV) risk in general population, and ameliorating prevention in patients at CV risk or with overt CV disease. Moreover, the possibility of improving the outcome by the direct employment of antioxidant remains plausible. Moreover, studies on the content of antioxidant in different foods may be helpful to develop a balanced diet, and achieve the maximal nutritional and functional properties of cultivars with benefits for human health. PMID:28594364

Undernutrition and Overnutrition Burden for Diseases in Developing Countries: The Role of Oxidative Stress Biomarkers to Assess Disease Risk and Interventional Strategies.

PubMed

Mastorci, Francesca; Vassalle, Cristina; Chatzianagnostou, Kyriazoula; Marabotti, Claudio; Siddiqui, Khawer; Eba, Ahmed Ould; Mhamed, Soueid Ahmed Sidi; Bandopadhyay, Arun; Nazzaro, Marco Stefano; Passera, Mirko; Pingitore, Alessandro

2017-06-08

The increased life expectancy, urbanization, and unhealthy lifestyle characterized by a shift towards a sedentary lifestyle and decreased energy expenditure are considered the main drivers of epidemiological transition. In particular, developing countries are facing a double burden caused by coexisting under- and over-nutrition, which causes a change in the disease profile from infectious diseases to a chronic degenerative pattern. This review discusses the under- and over-nutrition context in Mauritania and India, two countries that are experiencing a nutritional transition, and where we began a collaboration with local medical staff to integrate interventional and diagnostic guidelines. If many studies about diet and its relationship to non-communicable diseases are available for India, very few nutrition and cardiovascular risk studies have been conducted in Mauritania. Presently, with the exponential increase of nutrition-related diseases, targeted approaches are needed to provide balanced diets in parallel with the development of national preventive health systems and screening programs adapted to local needs. In this context, the measurement of oxidative stress biomarkers could be promising as an additive tool to assess cardiovascular (CV) risk in general population, and ameliorating prevention in patients at CV risk or with overt CV disease. Moreover, the possibility of improving the outcome by the direct employment of antioxidant remains plausible. Moreover, studies on the content of antioxidant in different foods may be helpful to develop a balanced diet, and achieve the maximal nutritional and functional properties of cultivars with benefits for human health.

Amino-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein but not cystatin C predict cardiovascular events in male patients with peripheral artery disease independently of ambulatory pulse pressure.

PubMed

Skoglund, Per H; Arpegård, Johannes; Ostergren, Jan; Svensson, Per

2014-03-01

Patients with peripheral arterial disease (PAD) are at high risk for cardiovascular (CV) events. We have previously shown that ambulatory pulse pressure (APP) predicts CV events in PAD patients. The biomarkers amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cystatin C are related to a worse outcome in patients with CV disease, but their predictive values have not been studied in relation to APP. Blood samples and 24-hour measurements of ambulatory blood pressure were examined in 98 men referred for PAD evaluation during 1998-2001. Patients were followed for a median of 71 months. The outcome variable was CV events defined as either CV mortality or any hospitalization for myocardial infarction, stroke, or coronary revascularization. The predictive values of log(NT-proBNP), log(hs-CRP), and log(cystatin C) alone and together with APP were assessed by multivariable Cox regression. Area under the curve (AUC) and net reclassification improvement (NRI) were calculated compared with a model containing other significant risk factors. During follow-up, 36 patients had at least 1 CV event. APP, log(NT-proBNP), and log(hs-CRP) all predicted CV events in univariable analysis, whereas log(cystatin C) did not. In multivariable analysis log(NT-proBNP) (hazard ratio (HR) = 1.62; 95% confidence interval (CI) = 1.05-2.51) and log(hs-CRP) (HR = 1.63; 95% CI = 1.19-2.24) predicted events independently of 24-hour PP. The combination of log(NT-proBNP), log(hs-CRP), and average day PP improved risk discrimination (AUC = 0.833 vs. 0.736; P < 0.05) and NRI (37%; P < 0.01) when added to other significant risk factors. NT-proBNP and hs-CRP predict CV events independently of APP and the combination of hs-CRP, NT-proBNP, and day PP improves risk discrimination in PAD patients.

ACE-inhibitors versus angiotensin receptor blockers for prevention of events in cardiovascular patients without heart failure - A network meta-analysis.

PubMed

Ricci, Fabrizio; Di Castelnuovo, Augusto; Savarese, Gianluigi; Perrone Filardi, Pasquale; De Caterina, Raffaele

2016-08-15

Angiotensin receptor blockers (ARBs) are a valuable option to reduce cardiovascular (CV) mortality and morbidity in cardiac patients in whom ACE-inhibitors (ACE-Is) cannot be used. However, clinical outcome data from direct comparisons between ACE-Is and ARBs are scarce, and some data have recently suggested superiority of ACE-Is over ARBs. We performed a Bayesian network-meta-analysis, with data from both direct and indirect comparisons, from 27 randomized controlled trials (RCTs), including a total population of 125,330 patients, to assess the effects of ACE-Is and ARBs on the composite endpoint of CV death, myocardial infarction (MI) and stroke, and on all-cause death, new-onset heart failure (HF) and new-onset diabetes mellitus (DM) in high CV risk patients without HF. Using placebo as a common comparator, we found no significant differences between ACE-Is and ARBs in preventing the composite endpoint of CV death, MI and stroke (RR: 0.92; 95% CI 0.78-1.08). When components of the composite outcome were analysed separately, ACEi and ARBs were associated with a similar risk of CV death (RR: 0.92; 95% CI 0.73-1.10), MI (RR: 0.91; 95% CI 0.78-1.07) and stroke (RR: 0.97; 95% CI 0.79-1.19), as well as a similar incident risk of all-cause death (RR: 0.94; 95% CI 0.85-1.05), new-onset HF (RR: 0.92; 95% CI 0.77-1.15) and new-onset DM (RR: 99; 95% CI 0.81-1.21). With the limitations of indirect comparisons, we found that in patients at high CV risk without HF, ARBs were similar to ACE-Is in preventing the composite endpoint of CV death, MI and stroke. Compared with ARBs, we found no evidence of statistical superiority for ACE-Is, as a class, in preventing incident risk of all-cause death, CV death, MI, stroke, new-onset DM and new-onset HF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Improved Arterial–Ventricular Coupling in Metabolic Syndrome after Exercise Training

PubMed Central

Fournier, Sara B.; Donley, David A.; Bonner, Daniel E.; DeVallance, Evan; Olfert, I. Mark; Chantler, Paul D.

2014-01-01

Purpose The metabolic syndrome (MetS) is associated with a three-fold increase risk of cardiovascular (CV) morbidity and mortality, which is in part, due to a blunted CV reserve capacity, reflected by a reduced peak exercise left ventricular contractility and aerobic capacity, and a blunted peak arterial-ventricular coupling. To date, no study has examined whether aerobic exercise training in MetS can reverse the peak exercise CV dysfunction. Further, examining how exercise training alters CV function in a group of individuals with MetS prior to the development of diabetes and/or overt CVD, can provide insights into whether some of the pathophysiological changes to the CV can be delayed/reversed, lowering their CV risk. The objective of this study was to examine the effects of 8 weeks of aerobic exercise training in individuals with MetS on resting and peak exercise CV function. Methods Twenty MetS underwent either 8 weeks of aerobic exercise training (MetS-ExT; n=10) or remained sedentary (MetS-NonT; n=10) during this time period. Resting and peak exercise CV function was characterized using Doppler echocardiography and gas exchange. Results Exercise training did not alter resting left ventricular diastolic or systolic function and arterial-ventricular coupling in MetS. In contrast, at peak exercise an increase in LV contractility (40%, p<0.01), cardiac output (28%, p<0.05) and aerobic capacity (20%, p<0.01), while a reduction in vascular resistance (30%, p<0.05) and arterial-ventricular coupling (27%, p<0.01), were noted in the MetS-ExT but not the MetS-NonT group. Further, an improvement in Lifetime Risk Score was also noted in the MetS-ExT group. Conclusions These findings have clinical importance as they provide insight that some of the pathophysiological changes associated with MetS can be improved and lower the risk of CVD. PMID:24870568

Short-Term Repeatability of Noninvasive Aortic Pulse Wave Velocity Assessment: Comparison Between Methods and Devices.

PubMed

Grillo, Andrea; Parati, Gianfranco; Rovina, Matteo; Moretti, Francesco; Salvi, Lucia; Gao, Lan; Baldi, Corrado; Sorropago, Giovanni; Faini, Andrea; Millasseau, Sandrine C; Scalise, Filippo; Carretta, Renzo; Salvi, Paolo

2017-12-08

Aortic pulse wave velocity (PWV) is an indirect index of arterial stiffness and an independent cardiovascular risk factor. Consistency of PWV assessment over time is thus an essential feature for its clinical application. However, studies providing a comparative estimate of the reproducibility of PWV across different noninvasive devices are lacking, especially in the elderly and in individuals at high cardiovascular risk. Aimed at filling this gap, short-term repeatability of PWV, estimated with 6 different devices (Complior Analyse, PulsePen-ETT, PulsePen-ET, SphygmoCor Px/Vx, BPLab, and Mobil-O-Graph), was evaluated in 102 high cardiovascular risk patients hospitalized for suspected coronary artery disease (72 males, 65 ± 13 years). PWV was measured in a single session twice, at 15-minute interval, and its reproducibility was assessed though coefficient of variation (CV), coefficient of repeatability, and intraclass correlation coefficient. The CV of PWV, measured with any of these devices, was <10%. Repeatability was higher with cuff-based methods (BPLab: CV = 5.5% and Mobil-O-Graph: CV = 3.4%) than with devices measuring carotid-femoral PWV (Complior: CV = 8.2%; PulsePen-TT: CV = 8.0%; PulsePen-ETT: CV = 5.8%; and SphygmoCor: CV = 9.5%). In the latter group, PWV repeatability was lower in subjects with higher carotid-femoral PWV. The differences in PWV between repeated measurements, except for the Mobil-O-Graph, did not depend on short-term variations of mean blood pressure or heart rate. Our study shows that the short-term repeatability of PWV measures is good but not homogenous across different devices and at different PWV values. These findings, obtained in patients at high cardiovascular risk, may be relevant when evaluating the prognostic importance of PWV. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Reproducibility of a peripheral quantitative computed tomography scan protocol to measure the material properties of the second metatarsal.

PubMed

Chaplais, Elodie; Greene, David; Hood, Anita; Telfer, Scott; du Toit, Verona; Singh-Grewal, Davinder; Burns, Joshua; Rome, Keith; Schiferl, Daniel J; Hendry, Gordon J

2014-07-19

Peripheral quantitative computed tomography (pQCT) is an established technology that allows for the measurement of the material properties of bone. Alterations to bone architecture are associated with an increased risk of fracture. Further pQCT research is necessary to identify regions of interest that are prone to fracture risk in people with chronic diseases. The second metatarsal is a common site for the development of insufficiency fractures, and as such the aim of this study was to assess the reproducibility of a novel scanning protocol of the second metatarsal using pQCT. Eleven embalmed cadaveric leg specimens were scanned six times; three times with and without repositioning. Each foot was positioned on a custom-designed acrylic foot plate to permit unimpeded scans of the region of interest. Sixty-six scans were obtained at 15% (distal) and 50% (mid shaft) of the second metatarsal. Voxel size and scan speed were reduced to 0.40 mm and 25 mm.sec(-1). The reference line was positioned at the most distal portion of the 2(nd) metatarsal. Repeated measurements of six key variables related to bone properties were subject to reproducibility testing. Data were log transformed and reproducibility of scans were assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV%). Reproducibility of the measurements without repositioning were estimated as: trabecular area (ICC 0.95; CV% 2.4), trabecular density (ICC 0.98; CV% 3.0), Strength Strain Index (SSI) - distal (ICC 0.99; CV% 5.6), cortical area (ICC 1.0; CV% 1.5), cortical density (ICC 0.99; CV% 0.1), SSI - mid shaft (ICC 1.0; CV% 2.4). Reproducibility of the measurements after repositioning were estimated as: trabecular area (ICC 0.96; CV% 2.4), trabecular density (ICC 0.98; CV% 2.8), SSI - distal (ICC 1.0; CV% 3.5), cortical area (ICC 0.99; CV%2.4), cortical density (ICC 0.98; CV% 0.8), SSI - mid shaft (ICC 0.99; CV% 3.2). The scanning protocol generated excellent reproducibility for key bone properties measured at the distal and mid-shaft regions of the 2(nd) metatarsal. This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures.

Reproducibility of a peripheral quantitative computed tomography scan protocol to measure the material properties of the second metatarsal

PubMed Central

2014-01-01

Background Peripheral quantitative computed tomography (pQCT) is an established technology that allows for the measurement of the material properties of bone. Alterations to bone architecture are associated with an increased risk of fracture. Further pQCT research is necessary to identify regions of interest that are prone to fracture risk in people with chronic diseases. The second metatarsal is a common site for the development of insufficiency fractures, and as such the aim of this study was to assess the reproducibility of a novel scanning protocol of the second metatarsal using pQCT. Methods Eleven embalmed cadaveric leg specimens were scanned six times; three times with and without repositioning. Each foot was positioned on a custom-designed acrylic foot plate to permit unimpeded scans of the region of interest. Sixty-six scans were obtained at 15% (distal) and 50% (mid shaft) of the second metatarsal. Voxel size and scan speed were reduced to 0.40 mm and 25 mm.sec-1. The reference line was positioned at the most distal portion of the 2nd metatarsal. Repeated measurements of six key variables related to bone properties were subject to reproducibility testing. Data were log transformed and reproducibility of scans were assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV%). Results Reproducibility of the measurements without repositioning were estimated as: trabecular area (ICC 0.95; CV% 2.4), trabecular density (ICC 0.98; CV% 3.0), Strength Strain Index (SSI) - distal (ICC 0.99; CV% 5.6), cortical area (ICC 1.0; CV% 1.5), cortical density (ICC 0.99; CV% 0.1), SSI – mid shaft (ICC 1.0; CV% 2.4). Reproducibility of the measurements after repositioning were estimated as: trabecular area (ICC 0.96; CV% 2.4), trabecular density (ICC 0.98; CV% 2.8), SSI - distal (ICC 1.0; CV% 3.5), cortical area (ICC 0.99; CV%2.4), cortical density (ICC 0.98; CV% 0.8), SSI – mid shaft (ICC 0.99; CV% 3.2). Conclusions The scanning protocol generated excellent reproducibility for key bone properties measured at the distal and mid-shaft regions of the 2nd metatarsal. This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures. PMID:25037451

Cardiovascular safety of empagliflozin in patients with type 2 diabetes: a meta-analysis of data from randomized placebo-controlled trials.

PubMed

Salsali, A; Kim, G; Woerle, H J; Broedl, U C; Hantel, S

2016-10-01

To assess the effect of empagliflozin on cardiovascular (CV) risk in patients with type 2 diabetes (T2DM) through a meta-analysis of data from eight placebo-controlled trials. Data were analysed from eight randomized placebo-controlled trials undertaken to investigate the efficacy and safety of empagliflozin 10 and 25 mg once daily in patients with T2DM, comprising patients at low/medium and high CV risk. Suspected CV events were prospectively adjudicated. The empagliflozin 10 and 25 mg groups were pooled for the primary analysis. The primary endpoint was a composite of CV death, non-fatal myocardial infarction (MI), non-fatal stroke and hospitalization for unstable angina [4-point major adverse CV events (MACE)]. The secondary endpoint was a composite of CV death, non-fatal MI and non-fatal stroke (3-point MACE). Risk estimates were calculated using Cox regression analysis. A total of 3835 patients received placebo and 7457 received empagliflozin. Total exposure was 7448.3 years for placebo and 15482.1 years for empagliflozin. Four-point MACE occurred in 365 (9.5%) patients receiving placebo and 635 (8.5%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.86 (95% CI 0.76, 0.98)]. Three-point MACE occurred in 307 (8.0%) patients receiving placebo and 522 (7.0%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.84 (95% CI 0.73, 0.96)]. In a meta-analysis of data from eight randomized trials involving 11 292 patients with T2DM at low/medium or high CV risk, empagliflozin was associated with a reduced risk of 4-point MACE and 3-point MACE compared with placebo. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2) inhibitor, in the management of pain and osteoarthritis

PubMed Central

Geusens, Piet; Lems, Willem

2008-01-01

Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than placebo on pain in osteoarthritis (OA), with similar analgesic and anti-inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor celecoxib, has a lower incidence of upper gastrointestinal (GI) side effects in patients not taking aspirin, and a similar incidence of cardiovascular (CV) side effects compared to naproxen or ibuprofen. In the context of earlier guidelines and taking into account the GI and CV safety results of the TARGET study, lumiracoxib had secured European Medicines Agency (EMEA) approval with as indication symptomatic treatment of OA as well as short-term management of acute pain associated with primary dysmenorrhea and following orthopedic or dental surgery. In the complex clinical context of efficiency and safety of selective and non-selective COX inhibitors, its prescription and use should be based on the risk and safety profile of the patient. In addition, there is further need for long-term GI and CV safety studies and general post-marketing safety on its use in daily practice. Meanwhile, at the time of submission of this manuscript, the EMEA has withdrawn lumiracoxib throughout Europe because of the risk of serious side effects affecting the liver. PMID:18728796

Standardization of laboratory lipid profile assessment: A call for action with a special focus on the 2016 ESC/EAS dyslipidemia guidelines - Executive summary: A consensus endorsed by the Cardiovascular Risk and Prevention Group of the Portuguese Internal Medicine Society, the Portuguese Atherosclerosis Society, the Portuguese Society of Cardiology, the Portuguese Society of Laboratory Medicine, and the Portuguese Association of Clinical Chemistry.

PubMed

da Silva, Pedro Marques; Sequeira Duarte, João; von Hafe, Pedro; Gil, Victor; Nunes de Oliveira, Jorge; de Sousa, Germano

2018-04-01

Even with improvements in lifestyle interventions, better control of cardiovascular (CV) risk factors, and improvements in CV outcomes, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in Portugal and Europe. Atherogenic dyslipidemias, particularly hypercholesterolemia, have a crucial causal role in the development of atherosclerotic CVD. The clinical approach to a patient with dyslipidemia requires an accurate diagnosis, based on harmonized and standardized lipid and lipoprotein laboratory assessments. Results and reports of these tests, together with assessment of total CV risk and the respective therapeutic targets, will help ensure that clinical guidelines and good clinical practices are followed, increasing the reliability of screening for lipid disorders, producing more accurate diagnoses and CV risk stratification, and improving CV prevention. To this end, this consensus aims to provide clinicians with practical guidance for the harmonization and standardization of laboratory lipid tests, focusing on the most recent dyslipidemia management guidelines. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Impact of Hyperuricemia on Long-term Outcomes of Kidney Transplantation: Analysis of the FAVORIT Study.

PubMed

Kalil, Roberto S; Carpenter, Myra A; Ivanova, Anastasia; Gravens-Mueller, Lisa; John, Alin A; Weir, Matthew R; Pesavento, Todd; Bostom, Andrew G; Pfeffer, Marc A; Hunsicker, Lawrence G

2017-12-01

Elevated uric acid concentration is associated with higher rates of cardiovascular (CV) morbidity and mortality in the general population. It is not known whether hyperuricemia increases the risk for CV death or transplant failure in kidney transplant recipients. Post hoc cohort analysis of the FAVORIT Study, a randomized controlled trial that examined the effect of homocysteine-lowering vitamins on CV disease in kidney transplantation. Adult recipients of kidney transplants in the United States, Canada, or Brazil participating in the FAVORIT Study, with hyperhomocysteinemia, stable kidney function, and no known history of CV disease. Uric acid concentration. The primary end point was a composite of CV events. Secondary end points were all-cause mortality and transplant failure. Risk factors included in statistical models were age, sex, race, country, treatment assignment, smoking history, body mass index, presence of diabetes mellitus, history of CV disease, blood pressure, estimated glomerular filtration rate (eGFR), donor type, transplant vintage, lipid concentrations, albumin-creatinine ratio, and uric acid concentration. Cox proportional hazards models were fit to examine the association of uric acid concentration with study end points after risk adjustment. 3,512 of 4,110 FAVORIT participants with baseline uric acid concentrations were studied. Median follow-up was 3.9 (IQR, 3.0-5.3) years. 503 patients had a primary CV event, 401 died, and 287 had transplant failure. In unadjusted analyses, uric acid concentration was significantly related to each outcome. Uric acid concentration was also strongly associated with eGFR. The relationship between uric acid concentration and study end points was no longer significant in fully adjusted multivariable models (P=0.5 for CV events; P=0.09 for death, and P=0.1 for transplant failure). Unknown use of uric acid-lowering agents among study participants. Following kidney transplantation, uric acid concentrations are not independently associated with CV events, mortality, or transplant failure. The strong association between uric acid concentrations with traditional risk factors and eGFR is a possible explanation. Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.

Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: an observation based on arsenic-exposed individuals.

PubMed

Wu, Meei-Maan; Chiou, Hung-Yi; Chen, Chi-Ling; Hsu, Ling-I; Lien, Li-Ming; Wang, Chih-Hao; Hsieh, Yi-Chen; Wang, Yuan-Hung; Hsueh, Yu-Mei; Lee, Te-Chang; Cheng, Wen-Fang; Chen, Chien-Jen

2011-12-01

Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding to stressful stimuli in experimental studies. A GT-repeat length polymorphism in the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we reported the association of GT-repeat polymorphism with blood pressure (BP) phenotypes, and their interaction on cardiovascular (CV) mortality risk in arsenic-exposed cohorts. Associations of GT-repeat polymorphism with BP phenotypes were investigated at baseline in a cross-sectional design. Effect of GT-repeat polymorphism on CV mortality was investigated in a longitudinal design stratified by hypertension. GT-repeat variants were grouped by S (<27 repeats) or L (≥ 27 repeats) alleles. Multivariate analyses were used to estimate the effect size after accounting for CV covariates. Totally, 894 participants were recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower diastolic BP (L/S genotypes, P = 0.014) and a lower possibility of being hypertensive (L/S genotypes, P = 0.048). After follow-up, HO-1 S allele was significantly associated with a reduced CV risk in hypertensive participants [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P = 0.007] but not in normotensive. Hypertensive participants without carrying the S allele had a 5.23-fold increased risk [RMR 5.23 (CI 1.99, 13.69), P = 0.0008] of CV mortality compared with normotensive carrying the S alleles. HO-1 short GT-repeat polymorphism may play a protective role in BP regulation and CV mortality risk in hypertensive individuals against environmental stressors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Which Biomarker is the Best for Predicting Mortality in Incident Peritoneal Dialysis Patients: NT-ProBNP, Cardiac TnT, or hsCRP?

PubMed Central

Oh, Hyung Jung; Lee, Mi Jung; Kwon, Young Eun; Park, Kyoung Sook; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kim, Yong-Lim; Kim, Yon Su; Yang, Chul Woo; Kim, Nam-Ho; Kang, Shin-Wook

2015-01-01

Abstract Although numerous previous studies have explored various biomarkers for their ability to predict mortality in end-stage renal disease (ESRD) patients, these studies have been limited by retrospective analyses, mostly prevalent dialysis patients, and the measurement of only 1 or 2 biomarkers. This prospective study was aimed to evaluate the association between 3 biomarkers and mortality in incident 335 ESRD patients starting continuous ambulatory peritoneal dialysis (CAPD) in Korea. According to the baseline NT-proBNP, cTnT, and hsCRP levels, the patients were stratified into tertiles, and cardiovascular (CV) and all-cause mortalities were compared. Additionally, time-dependent ROC curves were constructed, and the net reclassification index (NRI) and integrated discrimination improvement (IDI) of the models with various biomarkers were calculated. We found the upper tertile of NT-proBNP was significantly associated with increased risk of both CV and all-cause mortalities. However, the upper tertile of hsCRP was significantly related only to the high risk of all-cause mortality even after adjustment for age, sex, and white blood cell counts. Moreover, NT-proBNP had the highest predictive power for CV mortality, whereas hsCRP was the best prognostic marker for all-cause mortality among these biomarkers. In conclusions, NT-proBNP is a more significant prognostic factor for CV mortality than cTnT and hsCRP, whereas hsCRP is a more significant predictor than NT-proBNP and cTnT for all-cause mortality in incident peritoneal dialysis patients. PMID:26554763

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo.

PubMed

Bentley-Lewis, Rhonda; Aguilar, David; Riddle, Matthew C; Claggett, Brian; Diaz, Rafael; Dickstein, Kenneth; Gerstein, Hertzel C; Johnston, Peter; Køber, Lars V; Lawson, Francesca; Lewis, Eldrin F; Maggioni, Aldo P; McMurray, John J V; Ping, Lin; Probstfield, Jeffrey L; Solomon, Scott D; Tardif, Jean-Claude; Wu, Yujun; Pfeffer, Marc A

2015-05-01

Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk. Copyright © 2015. Published by Elsevier Inc.

Use of cardiovascular polypills for the secondary prevention of cerebrovascular disease.

PubMed

Masjuan, J; Gállego, J; Aguilera, J M; Arenillas, J F; Castellanos, M; Díaz, F; Portilla, J C; Purroy, F

2018-01-08

There is little control of cardiovascular (CV) risk factors in secondary prevention after an ischaemic stroke, in part due to a lack of adherence to treatment. The CV polypill may contribute to proper treatment adherence, which is necessary for CV disease prevention. This study aimed to establish how and in what cases the CV polypill should be administered. A group of 8 neurologists drafted consensus recommendations using structured brainstorming and based on their experience and a literature review. These recommendations are based on the opinion of the participating experts. The use of the CV polypill is beneficial for patients, healthcare professionals, and the health system. Its use is most appropriate for atherothrombotic stroke, lacunar stroke, stroke associated with cognitive impairment, cryptogenic stroke with CV risk factors, and silent cerebrovascular disease. It is the preferred treatment in cases of suspected poor adherence, polymedicated patients, elderly people, patients with polyvascular disease or severe atherothrombosis, young patients in active work, and patients who express a preference for the CV polypill. Administration options include switching from individual drugs to the CV polypill, starting treatment with the CV polypill in the acute phase in particular cases, use in patients receiving another statin or an angiotensin ii receptor antagonist, or de novo use if there is suspicion of poor adherence. Nevertheless, use of the CV polypill requires follow-up on the achievement of the therapeutic objectives to make dose adjustments. This document is the first to establish recommendations for the use of the CV polypill in cerebrovascular disease, beyond its advantages in terms of treatment adherence. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Spatio-temporal evolution of female lung cancer mortality in a region of Spain, is it worth taking migration into account?

PubMed

Zurriaga, Oscar; Vanaclocha, Hermelinda; Martinez-Beneito, Miguel A; Botella-Rocamora, Paloma

2008-01-31

The Comunitat Valenciana (CV) is a tourist region on the Mediterranean coast of Spain with a high rate of retirement migration. Lung cancer in women is the cancer mortality cause that has increased most in the CV during the period 1991 to 2000. Moreover, the geographical distribution of risk from this cause in the CV has been previously described and a non-homogenous pattern was determined. The present paper studies the spatio-temporal distribution of lung cancer mortality for women in the CV during the period 1987-2004, in order to gain some insight into the factors, such as migration, that have had an influence on these changes. A novel methodology, consisting of a Bayesian hierarchical model, is used in this paper. Such a model allows the handling of data with a very high disaggregation, while at the same time taking advantage of its spatial and temporal structure. The spatio-temporal pattern which was found points to geographical differences in the time trends of risk. In fact, the southern coastal side of the CV has had a higher increase in risk, coinciding with the settlement of a large foreign community in that area, mainly comprised of elderly people from the European Union. Migration has frequently been ignored as a risk factor in the description of the geographical risk of lung cancer and it is suggested that this factor should be considered, especially in tourist regions. The temporal component in disease mapping provides a more accurate depiction of risk factors acting on the population.

Population-Based Study of Cardiovascular Mortality Among Patients With Prostate Cancer Treated With Radical External Beam Radiation Therapy With and Without Adjuvant Androgen Deprivation Therapy at the British Columbia Cancer Agency

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

Kim, Julian; Vaid, Moninder; Tyldesley, Scott, E-mail: styldesl@bccancer.bc.ca

2011-07-01

Purpose: There are conflicting studies of the impact of androgen deprivation therapy (ADT) on cardiovascular (CV) mortality among prostate cancer patients receiving curative intent external beam radiation therapy (EBRT). We assessed the impact of ADT on CV mortality in patients treated in British Columbia. Methods and Materials: Provincial pharmacy and radiotherapy databases were linked to the provincial cancer registry, and defined a cohort of patients treated with curative intent EBRT between 1998 and 2005. We determined the duration of ADT and the cumulative incidence of CV death. We compared death from CV disease with and without ADT, and by durationmore » of ADT using competing risk analysis and Fine and Gray multivariant analysis. A total of 600 randomly selected patients were reviewed to determine baseline CV disease, CV risk factors, and Charlson Index. Results: Of 5,948 prostate cancer patients treated with radical intent EBRT, of whom 1,933 were treated without ADT, 674 received ADT for {<=}6 months and 3,341 received > 6 months of ADT. The cumulative CV mortality at 7 years was 2.6% (95% confidence interval [CI] 1.9-3.5%), 2.1% (95% CI = 1.2-3.5%), and 1.4 (95% CI = 1.0-2.0%) for patients with no ADT, {<=}6 months of ADT, and >6 months of ADT, respectively (Gray's p = 0.002). Baseline CV disease and risk factors were more prevalent in the no-ADT group compared with the >6-month ADT group. Conclusions: This study demonstrated a lower CV mortality rate among patients treated with longer durations of ADT than those treated without ADT. These differences likely relate to selection of patients for ADT rather than effect of ADT itself.« less

Rosiglitazone treatment and cardiovascular disease in the Veterans Affairs Diabetes Trial.

PubMed

Florez, H; Reaven, P D; Bahn, G; Moritz, T; Warren, S; Marks, J; Reda, D; Duckworth, W; Abraira, C; Hayward, R; Emanuele, N

2015-10-01

To evaluate the relationship between patterns of rosiglitazone use and cardiovascular (CV) outcomes in the Veterans Affairs Diabetes Trial (VADT). Time-dependent survival analyses, case-control and 1 : 1 propensity matching approaches were used to examine the relationship between patterns of rosiglitazone use and CV outcomes in the VADT, a randomized controlled study that assessed the effect of intensive glycaemic control on CV outcomes in 1791 patients with type 2 diabetes (T2D) whose mean age was 60.4 ± 9 years. Participants were recruited between 1 December 2000 and 31 May 2003, and were followed for 5-7.5 years (median 5.6) with a final visit by 31 May 2008. Rosiglitazone (4 mg and 8 mg daily) was initiated per protocol in both the intensive-therapy and standard-therapy groups. Main outcomes included a composite CV outcome, CV death and myocardial infarction (MI). Both daily doses of rosiglitazone were associated with lower risk for the primary composite CV outcome [4 mg: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.49-0.81 and 8 mg: HR 0.60, 95% CI 0.49-0.75] after adjusting for demographic and clinical covariates. A reduction in CV death was also observed (HR 0.25, p < 0.001, for both 4 and 8 mg/day rosiglitazone); however, the effect on MI was less evident for 8 mg/day and not significant for 4 mg/day. In older patients with T2D the use of rosiglitazone was associated with decreased risk of the primary CV composite outcome and CV death. Rosiglitazone use did not lead to a higher risk of MI. © 2015 This article is a U.S. Government work and is in the public domain in the USA.

Modulatory Effect of Inflammation on Blood Pressure Reduction via Therapeutic Lifestyle Change

PubMed Central

Milani, Richard V.; Lavie, Carl J.

2009-01-01

Purpose: Since inflammatory status, as determined by C-reactive protein (CRP) levels, is correlated with many cardiovascular (CV) disease risk factors and major CV events, we sought to determine if median levels of CRP can modulate blood pressure changes as well as other CV risk factors that are typically improved by therapeutic lifestyle changes with formal cardiac rehabilitation and exercise training (CRET) programs. Methods: We retrospectively evaluated CRP status and standard CV risk factors both before and after formal, phase II CRET programs (12 weeks; 36 educational and exercise sessions) in 635 consecutive patients with coronary artery disease after major CV events. Results: The median CRP level at baseline was 3.2 mg/L (range, 0.2–80.1 mg/L; mean, 5.8±8.4 mg/L). After CRET, both the patients with high and those with low CRP concentrations exhibited statistically significant improvements in most CV risk factors when their CRP levels were divided by median levels. However, systolic, diastolic, and mean arterial blood pressure improved in patients with low CRP levels (each by −4%) but did not change significantly in patients with high CRP levels. In multiple regression models, only young age, low CRP levels, and low body mass index were significant independent predictors of improved mean arterial blood pressure after CRET. Conclusions: In contrast to patients with coronary artery disease and low levels of CRP, patients with high baseline CRP levels did not demonstrate significant reductions in blood pressure after therapeutic lifestyle changes via formal CRET programs. PMID:21603441

Prevention and Control Program for Cardiovascular Diseases in Turkish Population: PRE-CONTROL Study Group.

PubMed

Kozan, Ömer; Zoghi, Mehdi; Ergene, Oktay; Arıcı, Mustafa; Derici, Ülver; Bakaç, Göksel; Güllü, Sevim; Sain Güven, Gülay

2013-06-01

Cardiovascular disease (CVD) is the leading cause of death throughout the world. Despite its high prevalence, the atherosclerotic process can be slowed and its consequences markedly reduced by preventive measures. The lack of risk factor awareness is a major barrier. We aimed to assess total CV risk, determine the knowledge and awareness regarding CVD, and evaluate the effectiveness of education program in urban population of Turkey. A 24-item questionnaire was used to detect CV risk factors and the awareness of participants about CVD. The feedback data for the education program were collected by either questionnaires or individual interviews with participants. For comparison of total CVD risk in men and women in different age groups, a sample t test was used. The level of statistical significance was set at p < 0.05. The prevalence of hyperlipidemia was established to be 41.3%. Nearly one-quarter of the women and one-third of the men were smokers (p < 0.001). One-quarter of the responders had a history of hypertension (men: 21.5%, women: 18.6%), and one-tenth were diabetic. The high CV risk rate was more pronounced among men (p < 0.01) and those with low socioeconomic level (p < 0.01). Awareness regarding CV risk factors following the educational program increased from 6.6% to 12.7% for high blood pressure, from 3.9% to 9.2% for diabetes mellitus, and from 10.2% to 15.1% for elevated cholesterol levels. All the increases were statistically significant. The educational program significantly increased the awareness of CVD and risk factors. The prevalence of CV risk factors was higher in low socioeconomic level groups. The knowledge and awareness of the risk factors for CVD before the education program was very low in our study group. The awareness of CVD and risk factors significantly increased following our education programs. Copyright © 2013 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

How to Practice Sports Cardiology: A Cardiology Perspective.

PubMed

Lawless, Christine E

2015-07-01

The rigorous cardiovascular (CV) demands of sport, combined with training-related cardiac adaptations, render the athlete a truly unique CV patient and sports cardiology a truly unique discipline. Cardiologists are advised to adopt a systematic approach to the CV evaluation of athletes, taking into consideration the individual sports culture, sports-specific CV demands, CV adaptations and their appearance on cardiac testing, any existing or potential interaction of the heart with the internal and external sports environment, short- and long-term CV risks, and potential effect of performance-enhancing agents and antidoping regulations. This article outlines the systematic approach, provides a detailed example, and outlines contemporary sports cardiology core competencies. Copyright © 2015 Elsevier Inc. All rights reserved.

Quality of Life and Outcomes in African Americans with CKD

PubMed Central

Fischer, Michael J.; Wang, Xuelei; Brooks, Deborah; Bruce, Marino; Charleston, Jeanne; Cleveland, William H.; Dowie, Donna; Faulkner, Marquetta; Gassman, Jennifer; Hiremath, Leena; Kendrick, Cindy; Kusek, John W.; Norris, Keith C.; Thornley-Brown, Denyse; Greene, Tom; Lash, James P.

2014-01-01

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD. PMID:24700865

Quality of life and outcomes in African Americans with CKD.

PubMed

Porter, Anna; Fischer, Michael J; Wang, Xuelei; Brooks, Deborah; Bruce, Marino; Charleston, Jeanne; Cleveland, William H; Dowie, Donna; Faulkner, Marquetta; Gassman, Jennifer; Hiremath, Leena; Kendrick, Cindy; Kusek, John W; Norris, Keith C; Thornley-Brown, Denyse; Greene, Tom; Lash, James P

2014-08-01

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD. Copyright © 2014 by the American Society of Nephrology.

Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an ageing population

PubMed Central

Lee, Siang Ing; Patel, Mitesh; Jones, Christopher M.; Narendran, Parth

2015-01-01

Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1D). However, evidence of its risks and management is often extrapolated from studies in type 2 diabetic (T2D) patients or the general population. This approach is unsatisfactory given that the underlying pathology, demographics and natural history of the disease differ between T1D and T2D. Furthermore, with a rising life expectancy, a greater number of T1D patients are exposed to the cardiovascular (CV) risk factors associated with an ageing population. The aim of this review is to examine the existing literature around CVD in T1D. We pay particular attention to CVD prevalence, how well we manage risk, potential biomarkers, and whether the studies included the older aged patients (defined as aged over 65). We also discuss approaches to the management of CV risk in the older aged. The available data suggest a significant CVD burden in patients with T1D and poor management of CV risk factors. This is underpinned by a poor evidence base for therapeutic management of CV risk specifically for patients with T1D, and in the most relevant population – the older aged patients. We would suggest that important areas remain to be addressed, particularly exploring the risks and benefits of therapeutic approaches to CVD management in the older aged. PMID:26568811

Improving treatment of cardiovascular risk factors in childhood cancer survivors | Division of Cancer Prevention

Cancer.gov

ABSTRACT Children and adolescents diagnosed with cancer now have on average >80% 5-year survival. However, premature cardiovascular (CV) disease has become the leading non-cancer cause of late mortality among childhood cancer survivors. Our existing work has shown that traditional CV risk factors such as hypertension, dyslipidemia, insulin resistance/diabetes remain very

Cardiovascular effects of sodium glucose cotransporter 2 inhibitors

PubMed Central

Cavaiola, Tricia Santos; Pettus, Jeremy

2018-01-01

As the first cardiovascular (CV) outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM), the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME®) trial, which investigated the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL), which compared SGLT2 inhibitors with other classes of glucose-lowering drugs. This review discusses the results of these three studies and, with a focus on EMPA-REG OUTCOME, examines the possible mechanisms by which SGLT2 inhibitors may reduce CV risk in patients with T2DM. PMID:29695924

Cardiovascular effects of sodium glucose cotransporter 2 inhibitors.

PubMed

Cavaiola, Tricia Santos; Pettus, Jeremy

2018-01-01

As the first cardiovascular (CV) outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM), the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME ® ) trial, which investigated the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL), which compared SGLT2 inhibitors with other classes of glucose-lowering drugs. This review discusses the results of these three studies and, with a focus on EMPA-REG OUTCOME, examines the possible mechanisms by which SGLT2 inhibitors may reduce CV risk in patients with T2DM.

Budget Impact Analysis of PCSK9 Inhibitors for the Management of Adult Patients with Heterozygous Familial Hypercholesterolemia or Clinical Atherosclerotic Cardiovascular Disease.

PubMed

Mallya, Usha G; Boklage, Susan H; Koren, Andrew; Delea, Thomas E; Mullins, C Daniel

2018-01-01

The aim of this study was to assess the budget impact of introducing the proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) alirocumab and evolocumab to market for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular (CV) disease requiring additional lowering of low-density lipoprotein cholesterol (LDL-C). A 3-year model estimated the costs of lipid-modifying therapy (LMT) and CV events to a hypothetical US health plan of 1 million members, comparing two scenarios-with and without the availability of PCSK9i as add-on therapy to statins. Proportions of patients with uncontrolled LDL-C despite receiving statins, and at risk of CV events, were estimated from real-world data. Total undiscounted annual LMT costs (2017 prices, including PCSK9i costs of $14,563.50), dispensing and healthcare costs, including the costs of CV events, were estimated for all prevalent patients in the target population, based on baseline risk factors. Maximum PCSK9i utilization of 1-5% over 3 years according to risk group (following the same pattern as current ezetimibe use), and 5-10% as a secondary scenario, were assumed. Total healthcare budget impacts per target patient (and per member) per month for years 1, 2 and 3 were $3.62($0.10), $7.22($0.20) and $10.79($0.30), respectively, assuming 1-5% maximum PCSK9i utilization, and $15.81($0.44), $31.52($0.88) and $47.12($1.31), respectively, assuming 5-10% utilization. Results were sensitive to changes in model timeframe, years to maximum PCSK9i utilization and PCSK9i costs. The budget impact of PCSK9i as add-on therapy to statins for patients with hypercholesterolemia is relatively low compared with published estimates for other specialty biologics. Drug cost rebates and discounts are likely to further reduce budget impact.

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context.

PubMed

Toth, Peter P; Danese, Mark; Villa, Guillermo; Qian, Yi; Beaubrun, Anne; Lira, Armando; Jansen, Jeroen P

2017-06-01

To estimate real-world cardiovascular disease (CVD) burden and value-based price range of evolocumab for a US-context, high-risk, secondary-prevention population. Burden of CVD was assessed using the UK-based Clinical Practice Research Datalink (CPRD) in order to capture complete CV burden including CV mortality. Patients on standard of care (SOC; high-intensity statins) in CPRD were selected based on eligibility criteria of FOURIER, a phase 3 CV outcomes trial of evolocumab, and categorized into four cohorts: high-risk prevalent atherosclerotic CVD (ASCVD) cohort (n = 1448), acute coronary syndrome (ACS) (n = 602), ischemic stroke (IS) (n = 151), and heart failure (HF) (n = 291) incident cohorts. The value-based price range for evolocumab was assessed using a previously published economic model. The model incorporated CPRD CV event rates and considered CV event reduction rate ratios per 1 mmol/L reduction in low-density lipoprotein-cholesterol (LDL-C) from a meta-analysis of statin trials by the Cholesterol Treatment Trialists Collaboration (CTTC), i.e. CTTC relationship. Multiple-event rates of composite CV events (ACS, IS, or coronary revascularization) per 100 patient-years were 12.3 for the high-risk prevalent ASCVD cohort, and 25.7, 13.3, and 23.3, respectively, for incident ACS, IS, and HF cohorts. Approximately one-half (42%) of the high-risk ASCVD patients with a new CV event during follow-up had a subsequent CV event. Combining these real-world event rates and the CTTC relationship in the economic model, the value-based price range (credible interval) under a willingness-to-pay threshold of $150,000/quality-adjusted life-year gained for evolocumab was $11,990 ($9,341-$14,833) to $16,856 ($12,903-$20,678) in ASCVD patients with baseline LDL-C levels ≥70 mg/dL and ≥100 mg/dL, respectively. Real-world CVD burden is substantial. Using the observed CVD burden in CPRD and the CTTC relationship, the cost-effectiveness analysis showed that, accounting for uncertainties, the expected value-based price for evolocumab is higher than its current annual cost, as long as the payer discount off list price is greater than 20%.

The importance of accurate measurement of aortic stiffness in patients with chronic kidney disease and end-stage renal disease.

PubMed

Adenwalla, Sherna F; Graham-Brown, Matthew P M; Leone, Francesca M T; Burton, James O; McCann, Gerry P

2017-08-01

Cardiovascular (CV) disease is the leading cause of death in chronic kidney disease (CKD) and end-stage renal disease (ESRD). A key driver in this pathology is increased aortic stiffness, which is a strong, independent predictor of CV mortality in this population. Aortic stiffening is a potentially modifiable biomarker of CV dysfunction and in risk stratification for patients with CKD and ESRD. Previous work has suggested that therapeutic modification of aortic stiffness may ameliorate CV mortality. Nevertheless, future clinical implementation relies on the ability to accurately and reliably quantify stiffness in renal disease. Pulse wave velocity (PWV) is an indirect measure of stiffness and is the accepted standard for non-invasive assessment of aortic stiffness. It has typically been measured using techniques such as applanation tonometry, which is easy to use but hindered by issues such as the inability to visualize the aorta. Advances in cardiac magnetic resonance imaging now allow direct measurement of stiffness, using aortic distensibility, in addition to PWV. These techniques allow measurement of aortic stiffness locally and are obtainable as part of a comprehensive, multiparametric CV assessment. The evidence cannot yet provide a definitive answer regarding which technique or parameter can be considered superior. This review discusses the advantages and limitations of non-invasive methods that have been used to assess aortic stiffness, the key studies that have assessed aortic stiffness in patients with renal disease and why these tools should be standardized for use in clinical trial work.

Switch-on fluorescent strategy based on crystal violet-functionalized CdTe quantum dots for detecting L-cysteine and glutathione in water and urine.

PubMed

Sheng, Zhen; Chen, Ligang

2017-10-01

The concentration of L-cysteine (Cys) and glutathione (GSH) is closely related to the critical risk of various diseases. In our study, a new rapid method for the determination of Cys and GSH in water and urine samples has been developed using a fluorescent probe technique, which was based on crystal violet (CV)-functionalized CdTe quantum dots (QDs). The original QDs emitted fluorescence light, which was turned off upon adding CV. This conjugation of CV and QDs could be attributed to electrostatic interaction between COO - of mercaptopropionic acid (MPA) on the surface of QDs and N + of CV in aqueous solution. In addition, Förster resonance energy transfer (FRET) also occurred between CdTe QDs and CV. After adding Cys or GSH to the solution, Cys or GSH exhibited a stronger binding preference toward Cd 2+ than Cd 2+ -MPA, which disturbed the interaction between MPA and QDs. Thus, most MPA was able to be separated from the surface of QDs because of the participation of Cys or GSH. Then, the fluorescence intensity of the CdTe QDs was enhanced. Good linear relationships were obtained in the range of 0.02-40 μg mL -1 and 0.02-50 μg mL -1 , and the detection limits were calculated as 10.5 ng mL -1 and 8.2 ng mL -1 , for Cys and GSH, respectively. In addition, the concentrations of biological thiols in water and urine samples were determined by the standard addition method using Cys as the standard; the quantitative recoveries were in the range of 97.3-105.8%, and relative standard deviations (RSDs) ranged from 2.5 to 3.7%. The method had several unique properties, such as simplicity, lower cost, high sensitivity, and environmental acceptability. Graphical abstract Crystal violet-functionalized CdTe quantum dots for detecting L-cysteine and glutathione with switch-on fluorescent strategy.

Cost effectiveness of atorvastatin in patients with type 2 diabetes mellitus: a pharmacoeconomic analysis of the collaborative atorvastatin diabetes study in the belgian population.

PubMed

Annemans, L; Marbaix, S; Webb, K; Van Gaal, L; Scheen, A

2010-01-01

Patients with type 2 diabetes mellitus have a high risk of developing cardiovascular (CV) disease. The clinical benefit of use of statins in patients with type 2 diabetes has been demonstrated in several randomized, controlled trials, including the CARDS clinical trial. Based on the clinical CARDS data, the favourable cost effectiveness of atorvastatin 10 mg in patients with type 2 diabetes has been demonstrated in countries such as the UK and France. This study aimed to estimate the cost effectiveness in the Belgian setting of atorvastatin 10 mg compared with no treatment for the primary prevention of CV events in type 2 diabetes patients without a history of CV disease. A Markov model with 1-year cycles was developed to simulate the CV event and death risk according to the therapeutic approach initiated. The transition probabilities for CV events in the 'no statin treatment' group were derived from the risk equations reported from the large UKPDS. Risk reductions from the CARDS clinical trial were used to adjust these CV event probabilities in the atorvastatin 10 mg treatment group. The characteristics of type 2 diabetes patients without a CV history were derived from the Belgian OCAPI survey. The public healthcare payers' perspective was taken into account for costing. The direct medical costs of CV events were based on the Public Health Authorities' hospital database for acute care costs and on the literature for the follow-up costs. The impact on the reimbursement system of generic entry to the market was considered in the drug cost. Costs were valued as at year 2009; costs and outcomes were discounted at 3% and 1.5%, respectively. Based on a 5-year time horizon, atorvastatin was demonstrated to be cost effective with an incremental cost/quality-adjusted life-year (QALY) of euro 16,681. Over a lifetime horizon (25 years), atorvastatin was demonstrated to be a cost-saving therapeutic intervention. At a threshold of euro 30,000/QALY, atorvastatin had a 98.8% probability of being cost effective. Compared with 'no treatment', use of atorvastatin 10 mg as a primary prevention intervention in Belgian type 2 diabetes patients not only improves CV outcomes, but also appears to be cost saving over a lifetime horizon.

Sex- and gender-related prevalence, cardiovascular risk and therapeutic approach in metabolic syndrome: A review of the literature.

PubMed

Pucci, Giacomo; Alcidi, Riccardo; Tap, Lisanne; Battista, Francesca; Mattace-Raso, Francesco; Schillaci, Giuseppe

2017-06-01

Metabolic syndrome (MS), a cluster of metabolic abnormalities linked to insulin-resistance and abdominal obesity, is associated with an increased risk of Type II diabetes mellitus (DM) and cardiovascular (CV) disease. Its prevalence is high, affecting 20%-30% of the general population, and increases with age in a sex-specific manner: in fact, while below 50 years it is slightly higher in men, it reverses after 50 years. The pronounced age-related increase in the prevalence of MS in women occurs as the result of several factors, which may be classified into sex- and gender-related factors. Sex-related factors, linked to genetical and biological pathways, are mainly driven by hyperandrogenism, insulin-resistance, and the associated increase in abdominal obesity and HDL-cholesterol reduction occurring after menopause. Gender-related factors are sensitive to social and cultural behaviors, dietary habits and psychosocial factors. Women are more prone than men to develop MS in response to work stress and low socio-economic status. Sex and gender differences in the prevalence of MS may translate in different CV risk associated. Prospective studies suggest that the CV risk in women with MS is not only equal but also superior to the CV risk of men with MS. This difference is mostly attenuated when adjusting for the presence of overt DM. Despite similar odds for CV events, the number of CV events may be higher in elderly women because of the higher prevalence of MS compared to men in this age group. Men and women may also have a differential response to treatments for MS, such as lifestyle measures and weight loss. Recent observations suggest that men are better responders than women to non-pharmaceutical therapeutic strategies aimed at reducing the prevalence of MS, although this should be confirmed in large-scale studies. The present review describes the impact of sex and gender on the prevalence, clinical presentation, prognostic significance and treatment of the MS. Attention to gender specificities should be a mandatory pre-requisite of clinical and epidemiological research on MS and CV disease, for a better knowledge and development of health strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lupus nephritis with preserved kidney function associated with poorer cardiovascular risk control: A call for more awareness.

PubMed

Todolí-Parra, J A; Tung-Chen, Y; Micó, L; Gutiérrez, J; Hernández-Jaras, J; Ruiz-Cerda, J L

2018-01-27

Despite the improvement in the prognosis of lupus nephritis (LN), the cardiovascular morbimortality remains high. The early recognition and remission of flares, while trying to avoid the metabolic adverse effects of medication, must be mandatory. The aim of our study was to assess the cardiovascular (CV) risk profile in a cohort of lupus patients with preserved kidney function after a nephritis episode, compared to patients without a nephritis flare. 130 patients diagnosed of SLE (32 with previous nephritis flare and 98 without) were studied in order to evaluate the CV risk profile, despite the preserved kidney function. The most prevalent risk factors were sedentary lifestyle (57.6%), overweight/obesity (38.3%) and dyslipidemia (36%), followed by smoking (32%) and hypertension (16%). Though more than a half (53.1%) was taking CV medication, a high percentage did not reach a therapeutic target value, especially regarding obesity (11.5%) and cholesterol levels (LDL-C of 16%). The prevalence of dyslipidemia (53.1% vs 30.6%), smoking (46.6% vs 27.5%), left ventricular hypertrophy (LVH) (21.4% vs 6.4%) and lower HDL-C (48.6mg/dL vs 55.4mg/dL) were significantly different in the group with previous nephritis flare. Moreover, young patients with lupus nephritis, received more pulses of corticosteroids and cyclophosphamide, had higher prevalence of hypertension, LVH, higher proteinuria, hospital admissions and waist circumference, constituting the subgroup of patients with greater aggregation of CV risk factors. Patients with previous nephritis flare showed a poor control of CV risk factors despite the preserved renal function, these patients would require a closer therapeutic management. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

The Effects of Colchicine on Risk of Cardiovascular Events and Mortality Among Patients with Gout: A Cohort Study Using Electronic Medical Records Linked with Medicare Claims

PubMed Central

Solomon, Daniel H.; Liu, Chih-Chin; Kuo, I-Hsin; Zak, Agnes; Kim, Seoyoung C.

2016-01-01

Background Colchicine may have beneficial effects on cardiovascular (CV) disease, but there are sparse data on its CV effect among patients with gout. We examined the potential association between colchicine and CV risk and all-cause mortality in gout. Methods The analyses used data from an electronic medical record (EMR) database linked with Medicare claims (2006–2011). To be eligible for the study cohort, subjects must have had a diagnosis of gout in the EMR and Medicare claims. New users of colchicine were identified and followed-up from the first colchicine dispensing date. Non-users had no evidence of colchicine prescriptions during the study period and were matched to users on the start of follow-up, age, and gender. Both groups were followed for the primary outcome, a composite of myocardial infarction (MI), stroke or transient ischemic attack (TIA). We calculated hazard ratios (HRs) in Cox regression, adjusting for potential confounders. Results We matched 501 users with an equal number of non-users with a median follow-up of 16.5 months. During follow-up, 28 primary CV events were observed among users and 82 among non-users. Incidence rates per 1,000 person-years were 35.6 for users and 81.8 for non-users. After full adjustment, colchicine use was associated with a 49% lower risk (HR 0.51, 95% CI 0.30 – 0.88) in the primary CV outcome as well as a 73% reduction in all-cause mortality (HR 0.27, 95% CI 017 – 0.43). Conclusion Colchicine use was associated with a reduced risk of a CV event among patients with gout. PMID:26582823

Predictors of Peak Troponin Level in Acute Coronary Syndromes: Prior Aspirin Use and SYNTAX Score

PubMed Central

Bhatt, Hemal A.; Sanghani, Dharmesh R.; Lee, David; Julliard, Kell N.; Fernaine, George A.

2015-01-01

The peak troponin level has been associated with cardiovascular (CV) mortality and adverse CV events. The association of peak troponin with CV risk factors and severity and complexity of coronary artery disease remains unknown. We assessed the predictors of peak troponin in patients with acute coronary syndrome (ACS). This study aims to determine the predictors of peak troponin in ACS. Cardiac catheterization (CC) reports and electronic medical records from 2010 to 2013 were retrospectively reviewed. A total of 219 patients were eligible for the study. All major CV risk factors, comorbidities, laboratory data, CC indications, and coronary lesion characteristics were included. Univariate and multivariate regression analyses were done. On multivariate linear regression analysis, ST-elevation myocardial infarction (p = 0.001, β = 65.16) and increasing synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) score (p = 0.002, β = 1.15) were associated with higher peak troponin. The Pearson correlation between SYNTAX score and peak troponin was r = 0.257, p = 0.001. History of daily aspirin use was associated with lower peak troponin (p = 0.002, β = −24.32). Prior statin use (p = 0.321, β = −8.98) and the presence of CV risk factors were not associated with peak troponin. Coronary artery disease severity and complexity, urgency of CC, and prior aspirin use are associated with peak troponin levels in ACS. Our findings may help predict patient population with ACS who would be at a greater risk for short- and long-term CV morbidity and mortality due to elevated peak troponin. PMID:26900312

Provocative issues in heart disease prevention.

PubMed

Juneau, Martin; Hayami, Douglas; Gayda, Mathieu; Lacroix, Sébastien; Nigam, Anil

2014-12-01

In this article, new areas of cardiovascular (CV) prevention and rehabilitation research are discussed: high-intensity interval training (HIIT) and new concepts in nutrition. HIIT consists of brief periods of high-intensity exercise interspersed by periods of low-intensity exercise or rest. The optimal mode according our work (15-second exercise intervals at peak power with passive recovery intervals of the same duration) is associated with longer total exercise time, similar time spent near peak oxygen uptake (VO2 peak) VO2 peak, and lesser perceived exertion relative to other protocols that use longer intervals and active recovery periods. Evidence also suggests that compared with moderate-intensity continuous exercise training, HIIT has superior effects on cardiorespiratory function and on the attenuation of multiple cardiac and peripheral abnormalities. With respect to nutrition, a growing body of evidence suggests that the gut microbiota is influenced by lifestyle choices and might play a pivotal role in modulating CV disease development. For example, recent evidence linking processed (but not unprocessed) meats to increased CV risk pointed to the gut microbial metabolite trimethylamine N-oxide as a potential culprit. In addition, altered gut microbiota could also mediate the proinflammatory and cardiometabolic abnormalities associated with excess added free sugar consumption, and in particular high-fructose corn syrup. Substantially more research is required, however, to fully understand how and which alterations in gut flora can prevent or lead to CV disease and other chronic illnesses. We conclude with thoughts about the appropriate role for HIIT in CV training and future research in the role of gut flora-directed interventions in CV prevention. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Effects of tofacitinib on cardiovascular risk factors and cardiovascular outcomes based on phase III and long-term extension data in patients with plaque psoriasis.

PubMed

Wu, Jashin J; Strober, Bruce E; Hansen, Peter R; Ahlehoff, Ole; Egeberg, Alexander; Qureshi, Abrar A; Robertson, Debbie; Valdez, Hernan; Tan, Huaming; Wolk, Robert

2016-11-01

Psoriasis is a systemic inflammatory condition that is associated with a higher risk of cardiovascular (CV) disease. Tofacitinib is being investigated as a treatment for psoriasis. We sought to evaluate the effects of tofacitinib on CV risk factors and major adverse CV events (MACEs) in patients with plaque psoriasis. Changes in select CV risk factors and the incidence rate (IR) of MACEs were evaluated in patients who were treated with tofacitinib. Tofacitinib treatment was associated with small, dose-dependent increases in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, while the total/HDL cholesterol ratio was unchanged. There were no changes in blood pressure and glycated hemoglobin levels; C-reactive protein levels decreased. The IRs of a MACE were low and similar for both tofacitinib doses. Among 3623 subjects treated with tofacitinib, the total patient-years of exposure was 5204, with a median follow-up of 527 days, and the IR of MACEs was 0.37 (95% confidence interval, 0.22-0.57) patients with events per 100 patient-years. There was relatively short follow-up time for patients who had MACEs. While treatment with tofacitinib is associated with a small increase in cholesterol levels, the total/HDL cholesterol ratio does not change, there are no unfavorable changes in several CV risk factors, and the incidence of MACEs is low. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Cardiovascular health promotion for children: a model for a Parish (County)-wide program (implementation and preliminary results).

PubMed

Berenson, Gerald S

2010-01-01

Cardiovascular (CV) risk factors in childhood result in a lifetime burden on the CV system. The Bogalusa Heart Study, a prevention program for children, addresses behaviors and lifestyles associated with CV risk. This prevention program utilizes the substructure of a Parish (County) that can be a model for other areas. All aspects in educating school children-the classroom, physical activity, cafeteria, teachers, and parents with community involvement-are included. The program requires cooperation of parents, schools, physicians, and political and business personnel. Their collaboration helps implement and sustain the program. Understanding the origin of coronary artery disease, hypertension, diabetes, and now the obesity epidemic shows the need to develop a framework for improving lifestyles and behaviors beginning in childhood. In addition to nutrition and exercise, the program addresses tobacco, alcohol, and drug use, and societal problems such as dropping out of school, violent behavior, and teenage pregnancy. An initial accomplishment is the entry into all elementary schools, representing approximately 7000 children. Early results show reduction in obesity, increased physical activity, improved decision making, and healthy attitudes. This public health model is inexpensive by utilizing prior research findings and integrating into community resources. Health education of children is an important aspect of preventive cardiology with a need for pediatric and adult cardiologists' involvement. 2009 Wiley Periodicals, Inc.

Cardiovascular Risk Assessment and Management in Prerenal Transplantation Candidates.

PubMed

Lindley, Eric M; Hall, Amanda K; Hess, Jordan; Abraham, Jo; Smith, Brigham; Hopkins, Paul N; Shihab, Fuad; Welt, Frederick; Owan, Theophilus; Fang, James C

2016-01-01

Cardiovascular (CV) assessment in prerenal transplant patients varies by center. Current guidelines recommend stress testing for candidates if ≥ 3 CV risk factors exist. We evaluated the CV assessment and management in 685 patients referred for kidney transplant over a 7-year period. All patients had CV risk factors, and the most common cause of end-stage renal disease was diabetes. Thirty-three percent (n = 229) underwent coronary angiography. The sensitivity of stress testing to detect obstructive coronary artery disease (CAD) was poor (0.26). Patients who had no CAD, nonobstructive CAD, or CAD with intervention had significantly higher event-free survival compared with patients with obstructive CAD without intervention. There were no adverse clinical events (death, myocardial infarction, stroke, revascularization, and graft failure) within 30 days post-transplant in patients who had preoperative angiography (n = 77). Of the transplanted patients who did not have an angiogram (n = 289), there were 8 clinical events (6 myocardial infarctions) in the first 30 days. In conclusion, our results indicate that stress testing and usual risk factors were poor predictors of obstructive CAD and that revascularization may prove beneficial in these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes.

PubMed

Maseroli, Elisa; Scavello, Irene; Vignozzi, Linda

2018-05-02

Erectile dysfunction is recognized as an opportunity for preventing cardiovascular (CV) events, and assessing the impairment of penile vascular flow by Doppler ultrasound is an important tool to ascertain CV risk. Conversely, the role of genital vascular impairment in the pathophysiology of female sexual dysfunction (FSD) remains contentious. To focus on the current scientific support for an association between CV risk factors and female sexual health in the 1st part of a 2-part review. A thorough literature search of peer-reviewed publications on the associations between CV risk factors and FSD and their underlying mechanisms was performed using the PubMed database. We present a summary of the evidence from clinical studies and discuss the possible mechanisms providing the pathophysiologic bases of vasculogenic FSD syndromes. The peripheral sexual response in women is a vascular-dependent event, and evidence suggests that cardiometabolic-related perturbations in endothelial function can determine vascular insufficiency in female genital tissues. Although epidemiologic and observational studies demonstrate that the prevalence of FSD is higher in women with diabetes mellitus, a cause-effect relation between these clinical conditions cannot be assumed. Evidence on the effect of obesity, metabolic syndrome, and polycystic ovary syndrome on sexual function in women is controversial. Data on the associations of dyslipidemia and hypertension with FSD are limited. Common cardiometabolic alterations could affect vascular function in the female genital tract. Based on limited data, there is an association between CV risk factors and female sexual health in women; however, this association appears milder than in men. Maseroli E, Scavello I, Vignozzi L. Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes. Sex Med Rev 2018;X:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Hormone therapy and clinical and surrogate cardiovascular endpoints in women with chronic kidney disease: a systematic review and meta-analysis.

PubMed

Ramesh, Sharanya; Mann, Michelle C; Holroyd-Leduc, Jayna M; Wilton, Stephen B; James, Matthew T; Seely, Ellen W; Ahmed, Sofia B

2016-09-01

Women with chronic kidney disease (CKD) experience kidney dysfunction-mediated premature menopause. The role of postmenopausal hormone therapy (HT) in this population is unclear. We sought to summarize current knowledge regarding use of postmenopausal HT and cardiovascular (CV) outcomes, and established surrogate measures of CV risk in women with CKD. This is a systematic review and meta-analysis of adult women with CKD. We searched electronic bibliographic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) (inception to 2014 December), relevant conference proceedings, tables of contents of journals, and review articles. Randomized controlled trials and observational studies examining postmenopausal HT compared with either placebo or untreated control groups were included. The intervention of interest was postmenopausal HT, and the outcome measures were all-cause and CV mortality, nonfatal CV event (myocardial infarction, stroke), and surrogate measures of CV risk (serum lipids, blood pressure). Of 12,482 references retrieved, four randomized controlled trials and two cohort studies (N = 1,666 participants) were identified. No studies reported on CV outcomes or mortality. Compared with placebo, postmenopausal HT was associated with decreased low-density lipoprotein cholesterol (-13.2 mg/dL [95% CI, -23.32 to -3.00 mg/dL]), and increased high-density lipoprotein (8.73 mg/dL [95% CI, 4.72-12.73 mg/dL]) and total cholesterol (7.96 mg/dL [95% CI, 0.07-15.84 mg/dL]). No associations were observed between postmenopausal HT triglyceride levels and blood pressure. Studies examining the effect of postmenopausal HT on CV outcomes in women with CKD are lacking. Further prospective study of the role of postmenopausal HT in this high-risk group is required.

Eplerenone improves prognosis in postmyocardial infarction diabetic patients with heart failure: results from EPHESUS.

PubMed

O'Keefe, J H; Abuissa, H; Pitt, B

2008-06-01

The Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial demonstrated that selective aldosterone blockade with eplerenone significantly reduced total mortality by 15%, combined cardiovascular (CV) mortality/CV hospitalization by 13%, CV mortality by 17% and sudden cardiac death by 21%, vs. placebo when added to standard care in patients with left ventricular systolic dysfunction (LVSD) and signs of congestive heart failure (CHF) following acute myocardial infarction (AMI). We retrospectively evaluated the effect of eplerenone vs. placebo in a subset of 1483 diabetic patients with LVSD and signs of CHF following AMI. Diabetic status was determined from medical histories at screening. Analyses were based on time to first occurrence of an event. Results were based on a Cox's proportional hazards regression model stratified by region with treatment, subgroup and treatment-by-subgroup interaction as factors. The 95% confidence intervals for the risk ratios were based on the Wald's test. Treatment with eplerenone in diabetic patients with CHF following AMI reduced the risk of the primary endpoint, a composite of CV mortality or CV hospitalization, by 17% (p = 0.031). The absolute risk reduction of the primary endpoint was greater in the diabetic cohort (5.1%) than in the non-diabetic cohort (3%). Hyperkalaemia occurred more often with eplerenone than with placebo (5.6 vs. 3%, p = 0.015). Among the diabetic cohorts, the prespecified endpoint of 'any CV disorder' occurred in 28% of the eplerenone group and 35% of the placebo group (p = 0.007). Eplerenone treatment may reduce adverse CV events in diabetic patients with LVSD and signs of CHF following AMI.

Cardiovascular burden and percutaneous interventions in Russian Federation: systematic epidemiological update

PubMed Central

2017-01-01

The situation with cardiovascular (CV) burden in Russian population is alerting, and becomes of interest due to high CV mortality, and shorter lifespan if compare with the Western society amid the absence of the established monitoring or screening system for major CV risk factors. The purpose of this systematic epidemiological update was to explore CV burden in Russia. The study represents pooled results with a systematic epidemiological review of the national mass screening, selected randomized clinical trials and statistical datasets of the national public health CV institutions exploring the trends of the CV burden in all 83 regions of Russia. We overviewed data from a number of the available Russian-speaking national data sources of 2001–2014, and NANOM-FIM trial (NCT01270139) as the only available real-world population study. The CV diseases in Russia accounted for 54.9% of all deaths in 2011–2014. The death rate was 13.3 per 1,000 citizens with CV mortality of 653.9 per 100,000. The life expectancy achieves 64.3 years for male and 76.1 years for female. The mean age of pts in trial was 51.6 years (77.2% males). A total of 175 Russian PCI centers implemented 205,902 angio a year, and 75,378 PCI achieving 531 PCI per 1,000,000 with placement of 101,451 stents (1.37 stents per PCI; 48,057 DES). The smoking (17.3% of screened with a 2,786 cigarettes a year; 70.6% in trial), excessive alcohol consumption (1.8% of screened with a 11.6 L per year; 50.6% in trial), unhealthy Russian diet (abundance of carbohydrates/sugar, saturated and trans fats in 24.3% of screened), psychosocial factors (20%) and physical inactivity (19.6% of screened) remain the major modifiable risk factors. They, in turn, affect such risk factors as dyslipidemia (86.7% in trial), obesity (16.7% of screened; BMI in trial was 28.4), and hypertension (40.8% suffered; 86.1% in trial). CV mortality was not directly associated with a level of poverty (r=0.26, P=0.02) or socio-economic development (P>0.05) in regions. The documented 27% 10-year decline of CV mortality was interpreted as a success of the national policy. Mortality statistics show the stark reality of a high CV burden in Russia. New national program and aggressive emerging efforts are required to tackle CV diseases in Russia. PMID:28164014

Cardiovascular burden and percutaneous interventions in Russian Federation: systematic epidemiological update.

PubMed

Kharlamov, Alexander N

2017-02-01

The situation with cardiovascular (CV) burden in Russian population is alerting, and becomes of interest due to high CV mortality, and shorter lifespan if compare with the Western society amid the absence of the established monitoring or screening system for major CV risk factors. The purpose of this systematic epidemiological update was to explore CV burden in Russia. The study represents pooled results with a systematic epidemiological review of the national mass screening, selected randomized clinical trials and statistical datasets of the national public health CV institutions exploring the trends of the CV burden in all 83 regions of Russia. We overviewed data from a number of the available Russian-speaking national data sources of 2001-2014, and NANOM-FIM trial (NCT01270139) as the only available real-world population study. The CV diseases in Russia accounted for 54.9% of all deaths in 2011-2014. The death rate was 13.3 per 1,000 citizens with CV mortality of 653.9 per 100,000. The life expectancy achieves 64.3 years for male and 76.1 years for female. The mean age of pts in trial was 51.6 years (77.2% males). A total of 175 Russian PCI centers implemented 205,902 angio a year, and 75,378 PCI achieving 531 PCI per 1,000,000 with placement of 101,451 stents (1.37 stents per PCI; 48,057 DES). The smoking (17.3% of screened with a 2,786 cigarettes a year; 70.6% in trial), excessive alcohol consumption (1.8% of screened with a 11.6 L per year; 50.6% in trial), unhealthy Russian diet (abundance of carbohydrates/sugar, saturated and trans fats in 24.3% of screened), psychosocial factors (20%) and physical inactivity (19.6% of screened) remain the major modifiable risk factors. They, in turn, affect such risk factors as dyslipidemia (86.7% in trial), obesity (16.7% of screened; BMI in trial was 28.4), and hypertension (40.8% suffered; 86.1% in trial). CV mortality was not directly associated with a level of poverty (r=0.26, P=0.02) or socio-economic development (P>0.05) in regions. The documented 27% 10-year decline of CV mortality was interpreted as a success of the national policy. Mortality statistics show the stark reality of a high CV burden in Russia. New national program and aggressive emerging efforts are required to tackle CV diseases in Russia.

Virgin Olive Oil and Hypertension.

PubMed

Lopez, Sergio; Bermudez, Beatriz; Montserrat-de la Paz, Sergio; Jaramillo, Sara; Abia, Rocio; Muriana, Francisco Jg

2016-01-01

The incidence of high blood pressure (BP) along with other cardiovascular (CV) risk factors on human health has been studied for many years. These studies have proven a link between unhealthy dietary habits and sedentary lifestyle with the onset of hypertension, which is a hallmark of CV and cerebrovascular diseases. The Mediterranean diet, declared by the UNESCO as an Intangible Cultural Heritage since 2013, is rich in vegetables, legumes, fruits and virgin olive oil. Thanks to its many beneficial effects, including those with regard to lowering BP, the Mediterranean diet may help people from modern countries to achieve a lower occurrence of CV disease. Data from human and animal studies have shown that the consumption of virgin olive oil shares most of the beneficial effects of the Mediterranean diet. Virgin olive oil is the only edible fat that can be consumed as a natural fruit product with no additives or preservatives, and contains a unique constellation of bioactive entities, namely oleic acid and minor constituents. In this review, we summarize what is known about the effects of virgin olive oil on hypertension.

Evaluation of the performance of existing non-laboratory based cardiovascular risk assessment algorithms

PubMed Central

2013-01-01

Background The high burden and rising incidence of cardiovascular disease (CVD) in resource constrained countries necessitates implementation of robust and pragmatic primary and secondary prevention strategies. Many current CVD management guidelines recommend absolute cardiovascular (CV) risk assessment as a clinically sound guide to preventive and treatment strategies. Development of non-laboratory based cardiovascular risk assessment algorithms enable absolute risk assessment in resource constrained countries. The objective of this review is to evaluate the performance of existing non-laboratory based CV risk assessment algorithms using the benchmarks for clinically useful CV risk assessment algorithms outlined by Cooney and colleagues. Methods A literature search to identify non-laboratory based risk prediction algorithms was performed in MEDLINE, CINAHL, Ovid Premier Nursing Journals Plus, and PubMed databases. The identified algorithms were evaluated using the benchmarks for clinically useful cardiovascular risk assessment algorithms outlined by Cooney and colleagues. Results Five non-laboratory based CV risk assessment algorithms were identified. The Gaziano and Framingham algorithms met the criteria for appropriateness of statistical methods used to derive the algorithms and endpoints. The Swedish Consultation, Framingham and Gaziano algorithms demonstrated good discrimination in derivation datasets. Only the Gaziano algorithm was externally validated where it had optimal discrimination. The Gaziano and WHO algorithms had chart formats which made them simple and user friendly for clinical application. Conclusion Both the Gaziano and Framingham non-laboratory based algorithms met most of the criteria outlined by Cooney and colleagues. External validation of the algorithms in diverse samples is needed to ascertain their performance and applicability to different populations and to enhance clinicians’ confidence in them. PMID:24373202

Immune-unreactive urinary albumin as a predictor of cardiovascular events: the Hortega Study.

PubMed

Martínez, Fernando; Pichler, Gernot; Ruiz, Adrian; Martín-Escudero, Juan C; Chaves, Felipe J; Gonzalez-Albert, Veronica; Tellez-Plaza, Maria; Heerspink, Hiddo J L; Zeeuw, Dick D E; Redon, Josep

2018-05-16

We aimed to determine if immune-unreactive albumin excretion (IURAE) is associated with cardiovascular (CV) events in a representative sample of a general population from Spain. We included 1297 subjects (mean age ± standard error 48.0 ± 0.2 years, 48% females), who participated in the Hortega Follow-Up Study. The primary endpoint was incidence of fatal and non-fatal CV events. Urinary albumin excretion (UAE) was measured in spot voided urine, frozen at -80°C, by immunonephelometry [immune-reactive albumin excretion (IRAE)] and by high-performance liquid chromatography (HPLC) [total albumin excretion (AE)]. IURAE was calculated as the difference between HPLC measurements and IRAE. We estimated fully adjusted hazard ratios (HRs) of CV incidence by Cox regression for IRAE, IURAE and total AE. After an average at-risk follow-up of 13 years, we observed 172 CV events. urinary albumin to creatinine ratio (UACR) of ≥30 mg/g assessed by IRAE, IURAE or total AE concentrations was observed in 74, 273 and 417 participants, respectively. Among discordant pairs, there were 49 events in those classified as micro- and macroalbuminuric by IURAE, but normoalbuminuric by IRAE. Only the IRAE was a significant independent factor for the incidence of CV events [HR (95% confidence interval) 1.15 (1.04-1.27)]. The association of UAE with CV events was mainly driven by heart failure (HF) [HR 1.33 (1.15-1.55) for IRAE; HR 1.38 (1.06-1.79) for IURAE; HR 1.62 (1.22-2.13) for total AE]. Those subjects who were micro- and macroalbuminuric by both IRAE and IURAE had a significant increase in risk for any CV event, and especially for HF. IRAE, IURAE and AE were associated with an increased risk for CV events, but IRAE offered better prognostic assessment.

CV 100--Still Going Strong

ERIC Educational Resources Information Center

Abrahams, A. L.

1976-01-01

Describes results of a study that used CV 100, a fuel additive for use in oil-fired heating systems, on a trial basis in 12 Ontario schools. The test showed an average 12 percent reduction in fuel costs in the schools using CV 100. (JG)

Empagliflozin in women with type 2 diabetes and cardiovascular disease - an analysis of EMPA-REG OUTCOME®.

PubMed

Zinman, Bernard; Inzucchi, Silvio E; Wanner, Christoph; Hehnke, Uwe; George, Jyothis T; Johansen, Odd Erik; Fitchett, David

2018-04-30

The global epidemic of type 2 diabetes affects women and men equally; however, the relative impact on the cardiovascular (CV) system appears greater for women than men when compared with peers without diabetes. Furthermore, women are often under-represented in CV outcome trials, resulting in less certainty about the impact of CV prevention therapies across the sexes. The EMPA-REG OUTCOME® trial, which included 28.5% women, found that empagliflozin, given in addition to standard of care, reduced the risk of CV death by 38%, heart failure (HF) hospitalisation by 35% and a composite endpoint for incident or worsening nephropathy by 39%. Here we report a secondary analysis of the trial to determine the relative effects of empagliflozin in women vs men. The population studied were individuals with type 2 diabetes (HbA 1c 53-86 mmol/mol [7-10%] and eGFR >30 ml min -1 [1.73 m] -2 ), with established atherosclerotic CV disease. Individuals were randomised to receive empagliflozin 10 mg or 25 mg, or placebo once daily in addition to standard of care, and followed. The trial continued until ≥691 individuals had experienced an adjudicated event included in the primary outcome. All CV outcome events, including HF hospitalisations and deaths were prospectively adjudicated by blinded clinical events committees. At baseline, the demographic profile of the 2004 women (age ± standard deviation 63.6 ± 8.8 years) compared with the 5016 men (age 63.0 ± 8.6 years) in the trial was largely similar, with the exception that LDL-cholesterol was numerically higher in women (2.5 ± 1.0 vs 2.1 ± 0.9 mmol/l), consistent with lower rates of lipid-lowering therapies (75.4% vs 83.2%). Women were also less likely to have smoked (31.5% vs 69.9%). The annualised incidence rate for women in the placebo group was numerically lower than in men for CV death (1.58% vs 2.19%), numerically higher for HF hospitalisation (1.75% vs 1.33%) and similar for renal events (7.22% vs 7.75%). We did not detect any effect modification by sex within the statistical power restrictions of the analysis for CV death, HF hospitalisation and incident or worsening nephropathy (interaction p values 0.32, 0.20 and 0.85, respectively). Compared with placebo, empagliflozin increased the rates of genital infections in both women (2.5% vs 10.0%) and men (1.5% vs 2.6%). CV death, HF hospitalisation and incident or worsening nephropathy rate reductions induced by empagliflozin were not different between women and men.

Virgin coconut oil and its potential cardioprotective effects.

PubMed

Babu, Abraham Samuel; Veluswamy, Sundar Kumar; Arena, Ross; Guazzi, Marco; Lavie, Carl J

2014-11-01

Emphasis on diet to improve the cardiovascular (CV) risk profile has been the focus of many studies. Recently, virgin coconut oil (VCO) has been growing in popularity due to its potential CV benefits. The chemical properties and the manufacturing process of VCO make this oil healthier than its copra-derived counterpart. This review highlights the mechanism through which saturated fatty acids contribute to CV disease (CVD), how oils and fats contribute to the risk of CVD, and the existing views on VCO and how its cardioprotective effects may make this a possible dietary intervention in isolation or in combination with exercise to help reduce the burden of CVDs.

Atorvastatin calcium plus amlodipine for the treatment of hypertension.

PubMed

Delgado-Montero, Antonia; Zamorano, Jose L

2012-12-01

Hypertension (HTN) and dyslipemia (DYL) are two of the major modifiable cardiovascular (CV) risk factors, determinants in the development of cerebrovascular and coronary heart disease (CHD). Many patients have both risk factors which increase their total CV risk compared with patients with only one risk factor. Treatment guideline recommendations are poorly implemented in real practice, in part due to numerous and complicated drug regimes which hamper patient´s adherence. In this article the authors describe the first combined fixed-dose pill of an antihypertensive and a lipid-lowering agent, the single-pill combination of amlodipine besylate and atorvastatin calcium (SPAA). They summarize the pharmacokinetic and pharmacodynamic properties of both compounds and the main randomized clinical studies, as well as real-world observational studies, made with the new combined formulation. The use of the single-pill amlodipine and atorvastatin is an adequate option for the clinician to treat hypertensive patients with DYL or high CV risk burden, with proven efficacy, tolerability, cost-effectiveness, and the advantage of improving patient treatment compliance.

Effect of bromocriptine-QR (a quick-release formulation of bromocriptine mesylate) on major adverse cardiovascular events in type 2 diabetes subjects.

PubMed

Gaziano, J Michael; Cincotta, Anthony H; Vinik, Aaron; Blonde, Lawrence; Bohannon, Nancy; Scranton, Richard

2012-10-01

Bromocriptine-QR (a quick-release formulation of bromocriptine mesylate), a dopamine D2 receptor agonist, is a US Food and Drug Administrration-approved treatment for type 2 diabetes mellitus (T2DM). A 3070-subject randomized trial demonstrated a significant, 40% reduction in relative risk among bromocriptine-QR-treated subjects in a prespecified composite cardiovascular (CV) end point that included ischemic-related (myocardial infarction and stroke) and nonischemic-related (hospitalization for unstable angina, congestive heart failure [CHF], or revascularization surgery) end points, but did not include cardiovascular death as a component of this composite. The present investigation was undertaken to more critically evaluate the impact of bromocriptine-QR on cardiovascular outcomes in this study subject population by (1) including CV death in the above-described original composite analysis and then stratifying this new analysis on the basis of multiple demographic subgroups and (2) analyzing the influence of this intervention on only the "hard" CV end points of myocardial infarction, stroke, and CV death (major adverse cardiovascular events [MACEs]). Three thousand seventy T2DM subjects on stable doses of ≤2 antidiabetes medications (including insulin) with HbA1c ≤10.0 (average baseline HbA1c=7.0) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 52-week treatment period. Subjects with heart failure (New York Heart Classes I and II) and precedent myocardial infarction or revascularization surgery were allowed to participate in the trial. Study outcomes included time to first event for each of the 2 CV composite end points described above. The relative risk comparing bromocriptine-QR with the control for the cardiovascular outcomes was estimated as a hazard ratio with 95% confidence interval on the basis of Cox proportional hazards regression. The statistical significance of any between-group difference in the cumulative percentage of CV events over time (derived from a Kaplan-Meier curve) was determined by a log-rank test on the intention-to-treat population. Study subjects were in reasonable metabolic control, with an average baseline HbA1c of 7.0±1.1, blood pressure of 128/76±14/9, and total and LDL cholesterol of 179±42 and 98±32, respectively, with 88%, 77%, and 69% of subjects being treated with antidiabetic, antihypertensive, and antihyperlipidemic agents, respectively. Ninety-one percent of the expected person-year outcome ascertainment was obtained in this study. Respecting the CV-inclusive composite cardiovascular end point, there were 39 events (1.9%) among 2054 bromocriptine-QR-treated subjects versus 33 events (3.2%) among 1016 placebo subjects, yielding a significant, 39% reduction in relative risk in this end point with bromocriptine-QR exposure (P=0.0346; log-rank test) that was not influenced by age, sex, race, body mass index, duration of diabetes, or preexisting cardiovascular disease. In addition, regarding the MACE end point, there were 14 events (0.7%) among 2054 bromocriptine-QR-treated subjects and 15 events (1.5%) among 1016 placebo-treated subjects, yielding a significant, 52% reduction in relative risk in this end point with bromocriptine-QR exposure (P<0.05; log-rank test). These findings reaffirm and extend the original observation of relative risk reduction in cardiovascular adverse events among type 2 diabetes subjects treated with bromocriptine-QR and suggest that further investigation into this impact of bromocriptine-QR is warranted. URL: http://clinicaltrials.gov. Unique Identifier: NCT00377676.

Lower physical activity is a strong predictor of cardiovascular events in elderly patients with type 2 diabetes mellitus beyond traditional risk factors: the Japanese Elderly Diabetes Intervention Trial.

PubMed

Iijima, Katsuya; Iimuro, Satoshi; Shinozaki, Tomohiro; Ohashi, Yasuo; Sakurai, Takashi; Umegaki, Hiroyuki; Araki, Atsushi; Ouchi, Yasuyoshi; Ito, Hideki

2012-04-01

It is well known that a decline in physical activity is associated with lifestyle-related diseases including cardiovascular (CV) events. However, little is known about the association between physical activity and CV events in elderly patients, because recent accumulating reports have mainly dealt with middle-aged populations. In this study, we investigated the correlation between physical activity and CV events in Japanese elderly patients with type 2 diabetes mellitus (T2DM). A total of 938 Japanese elderly patients with T2DM (447 men and 491 women, mean age 71.9 years) enrolled (2000-2002) in the Japanese Elderly Diabetes Intervention Trial (J-EDIT) were used in this study. Physical activity consisting of three components, work, sports and leisure-time, of their lifestyle was evaluated using the Baecke questionnaire at baseline. Total activity score (TAS) as a sum of each activity score was divided into four quartiles (Q1 to Q4). During a follow-up period of 65.2 months, 165 events and 71 deaths in total occurred. Higher TAS grade was associated with reduced risk of all events (hazard ratios: 0.82, 0.77 and 0.54 in Q2, Q3 and Q4, respectively) with statistical significance. Even after multivariate adjustment for covariates, higher TAS grade was a strong predictor of all events, and the prediction by TAS of cerebrovascular events was more effective than that of cardiac events. In contrast, all-cause mortality gradually decreased according to TAS grade; however, no statistical significance was found. Among the four grades of TAS, no significant change in several parameters, such as profiles of lipid and glucose metabolism, blood pressure, physical measurements, cognitive function and depression scale, was found throughout the follow-up period, suggesting that the higher level of physical activity itself was associated with the risk reduction of primary events. Lower physical activity is a strong and independent predictor of all CV events in the elderly with T2DM beyond traditional risk factors. In addition to strict management of each atherosclerotic risk factor, engagement with patients to augment and maintain the level of physical activity in their lifestyle is also essential in clinical practice. © 2012 Japan Geriatrics Society.

Communication Vulnerabilities in Working-age Australians with Musculoskeletal Conditions: A Cross-sectional Analysis.

PubMed

Lowe, Dianne B; Taylor, Michael J; Hill, Sophie J

2015-08-01

To estimate the prevalence of communication vulnerability (CV) and its association with various health measures among working-age Australians with musculoskeletal conditions (MSK). The various vulnerability characteristics may lead to inadequate communication between consumers and healthcare professionals. Prevalence of CV among 18-64 year olds, with or without MSK, was analyzed using the Australian Bureau of Statistics' National Health Survey 2007-08 data. Associations between CV and measures of health complexity (accumulating multimorbidity and risk factors) and health burden (poorer self-rated health, psychological distress, and pain restricting work) in the MSK population were estimated using logistic regression. Further analyses were conducted for each vulnerability characteristic to determine the degree of association (crude and adjusted) with measures of interest. CV were more prevalent in working-age Australians with MSK (65%) than those without (51%). Adjusted for age and sex among working-age Australians with at least 1 MSK, those with 1 or more CV were more likely to have multimorbidity [adjusted OR (aOR) = 1.8, 95% CI 1.5-2.2], lifestyle risk factors (aOR = 2.1, 95% CI 1.5-2.8), poorer self-rated health (aOR = 3.4, 95% CI 2.7-4.2), greater psychological distress (aOR = 2.9, 95% CI 2.3-3.7), and pain restricting employment (aOR = 1.7, 95% CI 1.4-2.1) compared with those without CV. For working-age people, there is an association between MSK and CV. For those with MSK, CV were associated with increased likelihood of health complexity and burden. These findings have policy and clinical relevance. Research is needed to determine whether interventions that address these specific CV characteristics reduce the burden of disease within these populations.

Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus and cardiovascular disease history or cardiovascular risk factors: results of a pooled analysis of phase 3 clinical trials.

PubMed

Cook, William; Bryzinski, Brian; Slater, Jill; Frederich, Robert; Allen, Elsie

2013-05-01

This post hoc analysis sought to assess the efficacy, safety, and tolerability of saxagliptin in patients with type 2 diabetes mellitus and cardiovascular (CV) risk factors or disease (CVD). Data from 5 randomized controlled trials were pooled to compare saxagliptin 5 mg with placebo: 2 studies of saxagliptin as monotherapy in drug-naïve patients and 1 each of saxagliptin as add-on therapy to metformin, glyburide, or a thiazolidinedione. Analysis was performed according to the following baseline/trial entry criteria: 1) history/no history of CVD; 2) ≥ 2 versus 0 to 1 CV risk factors; 3) statin use versus no statin use; and 4) hypertension versus no hypertension. Change from baseline glycated hemoglobin (HbA1c), fasting plasma glucose, and postprandial glucose levels; and the proportion of patients achieving an HbA1c level < 7% were analyzed (week 24). Safety was assessed by adverse events, hypoglycemia, and body weight. In total, 882 patients received saxagliptin 5 mg and 799 received placebo. Differences in adjusted mean change from baseline HbA1c (95% CI) were greater with saxagliptin compared with placebo in patients with a history of CVD (-0.64% [-0.90 to -0.38]) and no history of CVD (-0.68% [-0.78 to -0.58]); with ≥ 2 CV risk factors (-0.73% [-0.85 to -0.60]) and 0 to 1 CV risk factor (-0.62% [-0.75 to -0.48]); with statin use (-0.70% [-0.89 to -0.52]) and no statin use (-0.66% [-0.77 to -0.56]); and with hypertension (-0.69% [-0.82 to -0.57]) and no hypertension (-0.66% [-0.80 to -0.52]). Saxagliptin was well tolerated, with similar adverse event rates and types compared with placebo. There was a < 1% rate of confirmed hypoglycemia in all groups except in patients with CV history who received placebo (2.1%). Saxagliptin improved glycemic measures, resulted in low rates of confirmed hypoglycemia, and was well tolerated in patients with or without CVD and CV risk factors.

Treatment Strategy for Type 2 Diabetes with Obesity: Focus on Glucagon-like Peptide-1 Receptor Agonists.

PubMed

Ji, Qiuhe

2017-06-01

The progressive nature of type 2 diabetes mellitus (T2DM) calls for step-wise intensification of therapy for maintaining normal glycemic levels and lowering cardiovascular (CV) risk. Because obesity is a prominent risk factor and comorbidity of T2DM, it further elevates the CV risk in T2DM. Therefore, it is vital to manage weight, obesity, and glycemic parameters for effective T2DM management. Few oral antidiabetic drugs (sulfonylureas and thiazolidinediones) and insulin are not suitable for obese patients with T2DM because these drugs cause weight gain. The present review discusses the place of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of obese patients with T2DM and the significance of these drugs in the prevention of future CV risk in patients with T2DM. A literature search of PubMed and EMBASE was conducted by using the search terms T2DM, GLP-1RAs, obesity, and cardiovascular complication. Randomized controlled trials measuring the effect of GLP-1RAs versus that of placebo on CV outcomes were included in the review. GLP-1RAs have emerged as a therapeutic alternative; these drugs exert their actions by providing glycemic control, improving insulin resistance and ö̇-cell function, and reducing weight. The risk of hypoglycemia with GLP-1RAs is minimal; however, GLP-1RAs are associated with gastrointestinal adverse events and raise concerns regarding pancreatitis. Combining GLP-1RAs with insulin analogues results in higher efficacy, a lowered insulin dose, and reduced insulin-related hypoglycemia and weight gain. Longer acting GLP-1RAs are also associated with improvement in medication adherence. Improvement in CV risk factors such as blood pressure and lipid profile further increases their usability for improving CV outcomes. Overall, the properties of GLP-1RAs make them suitable for combination with oral antidiabetic drugs in the early stages of T2DM and with insulins in the later stages for optimizing comprehensive management of the disease. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Biologic variability of N-terminal pro-brain natriuretic peptide in healthy dogs and dogs with myxomatous mitral valve disease.

PubMed

Winter, Randolph L; Saunders, Ashley B; Gordon, Sonya G; Buch, Jesse S; Miller, Matthew W

2017-04-01

To determine the biologic variability of N-terminal pro-brain natriuretic peptide (NTproBNP) in healthy dogs and dogs with various stages of myxomatous mitral valve disease (MMVD). Thirty-eight privately owned dogs: 28 with MMVD and 10 healthy controls. Prospective clinical study with comprehensive evaluation used to group dogs as healthy or into three stages of MMVD based on current guidelines. NTproBNP was measured hourly, daily, and weekly. For each group, analytical (CV A ), within-subject (CV I ), and between-subject (CV G ) coefficients of variability were calculated in addition to percent critical change value (CCV) and index of individuality (IoI). For healthy dogs, calculated NTproBNP values were: CV A  = 4.2%; CV I  = 25.2%; CV G  = 49.3%; IoI = 0.52, and CCV = 70.8%. For dogs with MMVD, calculated NTproBNP values were: CV A  = 6.2%; CV I  = 20.0%; CV G  = 61.3%; IoI = 0.34, and CCV = 58.2%. Biologic variability affects NTproBNP concentrations in healthy dogs and dogs with MMVD. Monitoring serial individual changes in NTproBNP may be clinically relevant in addition to using population-based reference ranges to determine changes in disease status. Copyright © 2016 Elsevier B.V. All rights reserved.

Endothelial progenitor cells dysfunction and impaired tissue reparation: The missed link in diabetes mellitus development.

PubMed

Berezin, Alexander E

Diabetes mellitus (DM) is considered a leading cause of premature cardiovascular (CV) mortality and morbidity in general population and in individuals with known CV disease. Recent animal and clinical studies have shown that reduced number and weak function of endothelial progenitor cells (EPCs) may not only indicate to higher CV risk, but contribute to the impaired heart and vessels reparation in patients with DM. Moreover, EPCs having a protective impact on the vasculature may mediate the functioning of other organs and systems. Therefore, EPCs dysfunction is probably promising target for DM treatment strategy, while the role of restoring of EPCs number and functionality in CV risk diminish and reduce of DM-related complications is not fully clear. The aim of the review is summary of knowledge regarding EPCs dysfunction in DM patients. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Blood Pressure Gradients and Cardiovascular Risk Factors in Urban and Rural Populations in Abia State South Eastern Nigeria Using the WHO STEPwise Approach

PubMed Central

Okpechi, Ikechi Gareth; Chukwuonye, Innocent Ijezie; Tiffin, Nicki; Madukwe, Okechukwu Ojoemelam; Onyeonoro, Ugochukwu Uchenna; Umeizudike, Theophilus Ifeanyichukwu; Ogah, Okechukwu Samuel

2013-01-01

Background Developing countries of sub-Saharan Africa (SSA) face a double burden of non-communicable diseases (NCDs) and communicable diseases. As high blood pressure (BP) is a common global cardiovascular (CV) disorder associated with high morbidity and mortality, the relationship between gradients of BP and other CV risk factors was assessed in Abia State, Nigeria. Methods Using the WHO STEPwise approach to surveillance of chronic disease risk factors, we conducted a population-based cross-sectional survey in Abia state, Nigeria from August 2011 to March 2012. Data collected at various steps included: demographic and behavioral risk factors (Step 1); BP and anthropometric measurements (Step 2), and fasting blood cholesterol and glucose (Step 3). Results Of the 2983 subjects with complete data for analysis, 52.1% were females and 53.2% were rural dwellers. Overall, the distribution of selected CV disease risk factors was diabetes (3.6%), hypertension (31.4%), cigarette smoking (13.3%), use of smokeless tobacco (4.8%), physical inactivity (64.2%) and being overweight or obese (33.7%). Presence of hypertension, excessive intake of alcohol, smoking (cigarette and smokeless tobacco) and physical inactivity occurred more frequently in males than in females (p<0.05); while low income, lack of any formal education and use of smokeless tobacco were seen more frequently in rural dwellers than in those living in urban areas (p<0.05). The frequency of selected CV risk factors increased as BP was graded from optimal, normal to hypertension; and high BP correlated with age, gender, smokeless tobacco, overweight or obesity, annual income and level of education. Conclusion Given the high prevalence of hypertension in this part of Nigeria, there is an urgent need to focus on the reduction of preventable CV risk factors we have observed to be associated with hypertension, in order to effectively reduce the burden of NCDs in Africa. PMID:24039932

Blood pressure gradients and cardiovascular risk factors in urban and rural populations in Abia State South Eastern Nigeria using the WHO STEPwise approach.

PubMed

Okpechi, Ikechi Gareth; Chukwuonye, Innocent Ijezie; Tiffin, Nicki; Madukwe, Okechukwu Ojoemelam; Onyeonoro, Ugochukwu Uchenna; Umeizudike, Theophilus Ifeanyichukwu; Ogah, Okechukwu Samuel

2013-01-01

Developing countries of sub-Saharan Africa (SSA) face a double burden of non-communicable diseases (NCDs) and communicable diseases. As high blood pressure (BP) is a common global cardiovascular (CV) disorder associated with high morbidity and mortality, the relationship between gradients of BP and other CV risk factors was assessed in Abia State, Nigeria. Using the WHO STEPwise approach to surveillance of chronic disease risk factors, we conducted a population-based cross-sectional survey in Abia state, Nigeria from August 2011 to March 2012. Data collected at various steps included: demographic and behavioral risk factors (Step 1); BP and anthropometric measurements (Step 2), and fasting blood cholesterol and glucose (Step 3). Of the 2983 subjects with complete data for analysis, 52.1% were females and 53.2% were rural dwellers. Overall, the distribution of selected CV disease risk factors was diabetes (3.6%), hypertension (31.4%), cigarette smoking (13.3%), use of smokeless tobacco (4.8%), physical inactivity (64.2%) and being overweight or obese (33.7%). Presence of hypertension, excessive intake of alcohol, smoking (cigarette and smokeless tobacco) and physical inactivity occurred more frequently in males than in females (p<0.05); while low income, lack of any formal education and use of smokeless tobacco were seen more frequently in rural dwellers than in those living in urban areas (p<0.05). The frequency of selected CV risk factors increased as BP was graded from optimal, normal to hypertension; and high BP correlated with age, gender, smokeless tobacco, overweight or obesity, annual income and level of education. Given the high prevalence of hypertension in this part of Nigeria, there is an urgent need to focus on the reduction of preventable CV risk factors we have observed to be associated with hypertension, in order to effectively reduce the burden of NCDs in Africa.

Why is cardiovascular risk stratification important in hypertensive patients?

PubMed

Coll-De-Tuero, Gabriel; Saez, Marc; Rodriguez-Poncelas, Antonio; Barceló-Rado, Antonia; Vargas-Vila, Susanna; Garre-Olmo, Josep; Sala, Victoria; Sieira, Angels; Gelada, Esther; Gelado-Ferrero, Jesús

2012-06-01

The aim is to evaluate whether cardiovascular (CV) risk stratification in newly diagnosed hypertensive patients according to the European Society of Hypertension (ESH) guidelines, can predict the evolution of target organ damage (TOD) using routine examinations in clinical practice during 1 year. Prospective study of recently diagnosed untreated hypertensives. At the moment of inclusion and 1 year later, urinary albumin excretion rate (UAER), blood analysis, electrocardiogram, retinography, self-monitored blood pressure (BP) and ambulatory BP measurement were performed. TOD was defined following the ESH guidelines and evaluated as having favorable or unfavorable evolution. Four hundred and seventy-nine hypertensive patients were included (58.8 years; 43.4% women). The baseline prevalence of TOD was: high UAER (2.4%), left ventricular hypertrophy (LVH) (20.7%), advanced lesion of the fundus oculi (FO) (10.2%). After 1 year, no differences were found between the final systolic and diastolic BP neither in the high/very high nor in the low/moderate CV risk groups. Patients with low/moderate CV risk had less unfavorable TOD evolution, LVH (9.2% vs 41.7%; p <0.001), FO advanced damage (0.99% vs 14.3%; p <0.001), high UAER (0.3% vs 5.1%; p <0.005) and amount of TOD (9.2% vs 44.0%; 0<0.001) than those with high/very high CV risk. The odds ratios of favorable TOD evolution adjusted for BP change and antihypertensive drug treatment were (low/moderate vs high/very high CV risk); 5.14 (95% confidence interval, CI, 3.99-6.64) for LVH; 12.42 (6.67-23.14) FO advanced damage; 10.71 (3.67-31.22) high UAER and 13.99 (10.18-19.22) for amount of TOD. It is possible to detect variations in TOD in hypertensive patients with a 1-year follow-up using the examinations available in routine clinic practice. The risk determined by the ESH guidelines predicts the evolution of TOD at 1 year.

Addition of 24-Hour Heart Rate Variability Parameters to the Cardiovascular Health Study Stroke Risk Score and Prediction of Incident Stroke: The Cardiovascular Health Study.

PubMed

Bodapati, Rohan K; Kizer, Jorge R; Kop, Willem J; Kamel, Hooman; Stein, Phyllis K

2017-07-21

Heart rate variability (HRV) characterizes cardiac autonomic functioning. The association of HRV with stroke is uncertain. We examined whether 24-hour HRV added predictive value to the Cardiovascular Health Study clinical stroke risk score (CHS-SCORE), previously developed at the baseline examination. N=884 stroke-free CHS participants (age 75.3±4.6), with 24-hour Holters adequate for HRV analysis at the 1994-1995 examination, had 68 strokes over ≤8 year follow-up (median 7.3 [interquartile range 7.1-7.6] years). The value of adding HRV to the CHS-SCORE was assessed with stepwise Cox regression analysis. The CHS-SCORE predicted incident stroke (HR=1.06 per unit increment, P =0.005). Two HRV parameters, decreased coefficient of variance of NN intervals (CV%, P =0.031) and decreased power law slope (SLOPE, P =0.033) also entered the model, but these did not significantly improve the c-statistic ( P =0.47). In a secondary analysis, dichotomization of CV% (LOWCV% ≤12.8%) was found to maximally stratify higher-risk participants after adjustment for CHS-SCORE. Similarly, dichotomizing SLOPE (LOWSLOPE <-1.4) maximally stratified higher-risk participants. When these HRV categories were combined (eg, HIGHCV% with HIGHSLOPE), the c-statistic for the model with the CHS-SCORE and combined HRV categories was 0.68, significantly higher than 0.61 for the CHS-SCORE alone ( P =0.02). In this sample of older adults, 2 HRV parameters, CV% and power law slope, emerged as significantly associated with incident stroke when added to a validated clinical risk score. After each parameter was dichotomized based on its optimal cut point in this sample, their composite significantly improved prediction of incident stroke during ≤8-year follow-up. These findings will require validation in separate, larger cohorts. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Tumor necrosis factor-α inhibitor treatment and the risk of incident cardiovascular events in patients with early rheumatoid arthritis: a nested case-control study.

PubMed

Desai, Rishi J; Rao, Jaya K; Hansen, Richard A; Fang, Gang; Maciejewski, Matthew; Farley, Joel

2014-11-01

To compare the risk of cardiovascular (CV) events between use of tumor necrosis factor-α inhibitors (TNFi) and nonbiologic disease-modifying antirheumatic drugs (DMARD) in patients with early rheumatoid arthritis (RA). A nested case-control study was conducted using data from Truven's MarketScan commercial and Medicare claims database for patients with early RA who started treatment with either a TNFi or a nonbiologic DMARD between January 1, 2008, and December 31, 2010. Date of CV event diagnosis for cases was defined as the event date, and 12 age-matched and sex-matched controls were sampled using incidence density sampling. Drug exposure was defined into the following mutually exclusive categories hierarchically: (1) current use of TNFi (with or without nonbiologics), (2) past use of TNFi (with or without nonbiologics), (3) current use of nonbiologics only, and (4) past use of nonbiologics only. Current use was defined as any use in the period 90 days prior to the event date. Conditional logistic regression models were used to derive incidence rate ratios (IRR). From the cohort of patients with early RA, 279 cases of incident CV events and 3348 matched controls were identified. The adjusted risk of CV events was not significantly different between current TNFi users and current nonbiologic users (IRR 0.92, 95% CI 0.59-1.44). However, past users of nonbiologics showed significantly higher risk compared to current nonbiologic users (IRR 1.47, 95% CI 1.04-2.08). No differences in the CV risk were found between current TNFi and current nonbiologic DMARD treatment in patients with early RA.

Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis.

PubMed

Wolk, Robert; Armstrong, Ehrin J; Hansen, Peter R; Thiers, Bruce; Lan, Shuping; Tallman, Anna M; Kaur, Mandeep; Tatulych, Svitlana

Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at baseline, week 4, and week 16. Analyses included serum cholesterol levels, triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk markers, and high-density lipoprotein (HDL) function analyses. At week 16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total cholesterol/HDL-C ratio did not change. There was no significant change in the number of small dense LDL particles, which are considered to be more atherogenic than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity, linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity to promote cholesterol efflux from macrophages did not change. Lecithin-cholesterol acyltransferase activity, which is associated with reverse cholesterol transport, increased. Markers of systemic inflammation, serum amyloid A and C-reactive protein, decreased with tofacitinib. While small increases in lipid levels are observed with tofacitinib treatment in patients with psoriasis, effects on selected lipid-related parameters and other circulating CV risk biomarkers are not suggestive of an increased CV risk [NCT01276639]. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Perirenal fat is related to carotid intima-media thickness in children.

PubMed

Bassols, J; Martínez-Calcerrada, J-M; Prats-Puig, A; Carreras-Badosa, G; Xargay-Torrent, S; Lizarraga-Mollinedo, E; Feliu-Alsina, M; Riera-Pérez, E; Osiniri, I; de Zegher, F; Ibáñez, L; López-Bermejo, A

2018-04-01

It is well known that increased abdominal fat is associated with cardiovascular (CV) risk. Perirenal fat has been recently associated with CV risk in adults. However, studies with children are lacking. We investigated the relationship of perirenal fat and other abdominal fat depots (including preperitoneal, intra-abdominal and subcutaneous fat) with carotid intima-media thickness (cIMT-a surrogate marker of CV risk) in prepubertal children, so as to identify novel markers that can be easily assessed and used in the early prevention of cardiovascular disease. Subjects were 702 asymptomatic prepubertal Caucasian children (418 lean, 142 overweight and 142 obese) who were recruited in a primary care setting. Ultrasound measurements (perirenal, preperitoneal, intra-abdominal and subcutaneous fat and cIMT), clinical (body mass index (BMI) and systolic blood pressure) and metabolic parameters (insulin resistance (HOMA-IR), high molecular weight (HMW) adiponectin and serum lipids) were assessed. Perirenal fat was associated with diverse metabolic and CV risk factors in all the studied subjects. However, in overweight and obese children, perirenal fat was mostly associated with cIMT (P<0.001) and was the only fat depot that showed independent associations with cIMT in multivariate analyses (overweight chidren: β=0.250, P=0.003, r 2 =12.8%; obese children: β=0.254, P=0.002, r 2 =15.5%) after adjusting for BMI, gender, age and metabolic parameters. Perirenal fat was also the only fat depot that showed independent associations with HMW-adiponectin in obese children (β=-0.263, P=0.006, r 2 =22.8%). Perirenal fat is the main abdominal fat depot associated with cIMT, especially in overweight and obese children, and may thus represent a helpful parameter for assessing CV risk in the pediatric population.

Cardiovascular Risk and Disease Among Masters Endurance Athletes: Insights from the Boston MASTER (Masters Athletes Survey To Evaluate Risk) Initiative.

PubMed

Shapero, Kayle; Deluca, James; Contursi, Miranda; Wasfy, Meagan; Weiner, Rory B; Lewis, Gregory D; Hutter, Adolph; Baggish, Aaron L

2016-12-01

Masters athletes (MAs), people over the age of 35 that participate in competitive sports, are a rapidly growing population that may be uniquely at risk for cardiovascular (CV) disease. The objective of this study was to develop a comprehensive clinical CV profile of MA. An electronic Internet-based survey (survey response rate = 66 %) was used to characterize a community cohort of MAs residing in Eastern Massachusetts, USA. Clinical and lifestyle factors associated with prevalent CV disease were determined using logistic regression. Among 591 MAs (66 % men, age = 50 ± 9 years) with 21.3 ± 5.5 years of competitive endurance sport exposure, at least one CV risk factor was present in 64 % including the following: family history of premature atherosclerosis (32 %), prior/current tobacco exposure (23 %), hypertension (12.0 %), and dyslipidemia (7.4 %). There was a 9 % (54/591) prevalence of established CV disease which was accounted for largely by atrial fibrillation (AF) and coronary atherosclerosis (CAD). Prevalent AF was associated with years of exercise exposure [adjusted odds ratio, OR (95 % confidence intervals); OR = 1.10 (1.06, 1.21)] and hypertension [OR = 1.05 (1.01, 1.10)] while CAD was associated with dyslipidemia [OR = 9.09 (2.40, 34.39)] and tobacco use [OR = 1.78 (1.34, 3.10)] but was independent of exercise exposure. Among MAs, AF is associated with prior exercise exposure whereas CAD is associated with typical risk factors including dyslipidemia and prior tobacco use. These findings suggest that there are numerous opportunities to improve disease prevention and clinical care in this population.

The 2013 ACC/AHA 10-year atherosclerotic cardiovascular disease risk index is better than SCORE and QRisk II in rheumatoid arthritis: is it enough?

PubMed

Ozen, Gulsen; Sunbul, Murat; Atagunduz, Pamir; Direskeneli, Haner; Tigen, Kursat; Inanc, Nevsun

2016-03-01

To determine the ability of the new American College of Cardiology and American Heart Association (ACC/AHA) 10-year atherosclerotic cardiovascular disease (ASCVD) risk algorithm in detecting high cardiovascular (CV) risk, RA patients identified by carotid ultrasonography (US) were compared with Systematic Coronary Risk Evaluation (SCORE) and QRisk II algorithms. SCORE, QRisk II, 2013 ACC/AHA 10-year ASCVD risk and EULAR recommended modified versions were calculated in 216 RA patients. In sonographic evaluation, carotid intima-media thickness >0.90 mm and/or carotid plaques were used as the gold standard test for subclinical atherosclerosis and high CV risk (US+). Eleven (5.1%), 15 (6.9%) and 44 (20.4%) patients were defined as having high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. Fifty-two (24.1%) patients were US + and of those, 8 (15.4%), 7 (13.5%) and 23 (44.2%) patients were classified as high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. The ACC/AHA 10-year ASCVD risk index better identified US + patients than SCORE and QRisk II (P < 0.0001). With EULAR modification, reclassification from moderate to high risk occurred only in two, five and seven patients according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. The 2013 ACC/AHA 10-year ASCVD risk estimator was better than the SCORE and QRisk II indices in RA, but still failed to identify 55% of high risk patients. Furthermore adjustment of threshold and EULAR modification did not work well. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The importance of accurate measurement of aortic stiffness in patients with chronic kidney disease and end-stage renal disease

PubMed Central

Adenwalla, Sherna F.; Leone, Francesca M.T.; Burton, James O.; McCann, Gerry P.

2017-01-01

Abstract Cardiovascular (CV) disease is the leading cause of death in chronic kidney disease (CKD) and end-stage renal disease (ESRD). A key driver in this pathology is increased aortic stiffness, which is a strong, independent predictor of CV mortality in this population. Aortic stiffening is a potentially modifiable biomarker of CV dysfunction and in risk stratification for patients with CKD and ESRD. Previous work has suggested that therapeutic modification of aortic stiffness may ameliorate CV mortality. Nevertheless, future clinical implementation relies on the ability to accurately and reliably quantify stiffness in renal disease. Pulse wave velocity (PWV) is an indirect measure of stiffness and is the accepted standard for non-invasive assessment of aortic stiffness. It has typically been measured using techniques such as applanation tonometry, which is easy to use but hindered by issues such as the inability to visualize the aorta. Advances in cardiac magnetic resonance imaging now allow direct measurement of stiffness, using aortic distensibility, in addition to PWV. These techniques allow measurement of aortic stiffness locally and are obtainable as part of a comprehensive, multiparametric CV assessment. The evidence cannot yet provide a definitive answer regarding which technique or parameter can be considered superior. This review discusses the advantages and limitations of non-invasive methods that have been used to assess aortic stiffness, the key studies that have assessed aortic stiffness in patients with renal disease and why these tools should be standardized for use in clinical trial work. PMID:28852490

Impaired Fasting Glucose in Nondiabetic Range: Is It a Marker of Cardiovascular Risk Factor Clustering?

PubMed Central

Valentino, Giovanna; Kramer, Verónica; Bustamante, María José; Casasbellas, Cinthia; Adasme, Marcela; Salazar, Alejandra; Acevedo, Mónica

2015-01-01

Background. Impaired fasting glucose (IFG) through the nondiabetic range (100–125 mg/dL) is not considered in the cardiovascular (CV) risk profile. Aim. To compare the clustering of CV risk factors (RFs) in nondiabetic subjects with normal fasting glucose (NFG) and IFG. Material and Methods. Cross-sectional study in 3739 nondiabetic subjects. Demographics, medical history, and CV risk factors were collected and lipid profile, fasting glucose levels (FBG), C-reactive protein (hsCRP), blood pressure (BP), anthropometric measurements, and aerobic capacity were determined. Results. 559 (15%) subjects had IFG: they had a higher mean age, BMI, waist circumference, non-HDL cholesterol, BP, and hsCRP (p < 0.0001) and lower HDL (p < 0.001) and aerobic capacity (p < 0.001). They also had a higher prevalence of hypertension (34% versus 25%; p < 0.001), dyslipidemia (79% versus 74%; p < 0.001), and obesity (29% versus 16%; p < 0.001) and a higher Framingham risk score (8% versus 6%; p < 0.001). The probability of presenting 3 or more CV RFs adjusted by age and gender was significantly higher in the top quintile of fasting glucose (≥98 mg/dL; OR = 2.02; 1.62–2.51). Conclusions. IFG in the nondiabetic range is associated with increased cardiovascular RF clustering. PMID:26504260

Dyslipidemia in chronic kidney disease: are statins still indicated in reduction cardiovascular risk in patients on dialysis treatment?

PubMed

Scarpioni, Roberto; Ricardi, Marco; Melfa, Luigi; Cristinelli, Luciano

2010-12-01

Chronic kidney disease (CKD) is an increasingly health disease all around the world with a high burden of mortality and cardiovascular (CV) morbidity rate. Even when renal replacement therapy is reached, more than half patients die, mainly for CV causes due either to uremia-related cardiovascular risk factors (such as anemia, hyperhomocysteinemia, mineral bone disease-CKD with hyperparathyroidism, oxidative stress, hypoalbuminemia, chronic inflammation, prothrombotic factors) or to traditional ones (age, male gender, diabetes, obesity, hypertension, smoking, insulin levels, family history, dyslipidemia). Among the latter causes dyslipidemia represents one of the major, potentially correctable risk factor. Statins have demonstrated to effectively and safely reduce cholesterol levels in CKD patients. Here we will examine the effects of statins on CV risk factors in CKD patients and particularly in patients on dialysis treatment, in the light of the unfavorable results of the large trials 4D and AURORA, recently published, underlining the role of malnutrition/inflammation as confounding factor. Probably it will be that only with a real prevention, starting statins even in the early stages of CKD, as indicated by post hoc analysis of large trials, that we will reach results in reducing the mortality rate in CKD patients. In the meanwhile, all the other remediable CV risk factors have to be at the same time corrected. © 2010 Blackwell Publishing Ltd.

Non-Steroidal Anti-Inflammatory Drugs and Cardiovascular Outcomes in Women: Results from the Women’s Health Initiative

PubMed Central

Bavry, Anthony A.; Thomas, Fridtjof; Allison, Matthew; Johnson, Karen C.; Howard, Barbara V.; Hlatky, Mark; Manson, JoAnn E.; Limacher, Marian C.

2014-01-01

Background Conclusive data regarding cardiovascular (CV) toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) are sparse. We hypothesized that regular NSAID use is associated with increased risk for CV events in post-menopausal women, and that this association is stronger with greater cyclooxygenase (cox)-2 compared with cox-1 inhibition. Methods and Results Post-menopausal women enrolled in the Women’s Health Initiative (WHI) were classified as regular users or non-users of non-aspirin NSAIDs. Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total CV disease defined as CV death, nonfatal myocardial infarction, or nonfatal stroke. Secondary analyses considered the association of selective cox-2 inhibitors (e.g., celecoxib), non-selective agents with cox-2>cox-1 inhibition (e.g., naproxen), and non-selective agents with cox-1>cox-2 inhibition (e.g., ibuprofen) with the primary outcome. Overall, 160,801 participants were available for analysis (mean follow-up 11.2 years). Regular NSAID use at some point in time was reported by 53,142 participants. Regular NSAID use was associated with an increased hazard for CV events versus no NSAID use (HR=1.10[95% CI 1.06–1.15], Pitalic>0.001). Selective cox-2 inhibitors were associated with a modest increased hazard for CV events (HR=1.13[1.04–1.23], P=0.004; celecoxib only HR=1.13[1.01–1.27], P=0.031). Among aspirin users, concomitant selective cox-2 inhibitor use was no longer associated with increased hazard for CV events. There was an increased risk for agents with cox-2>cox-1 inhibition (HR=1.17[1.10–1.24], Pbold>0.001; naproxen only HR=1.22[1.12–1.34], P<0.001). This harmful association remained among concomitant aspirin users. We did not observe a risk elevation for agents with cox-1>cox-2 inhibition (HR=1.01[0.95–1.07], P=0.884; ibuprofen only HR=1.00[0.93–1.07], P=0.996). Conclusions Regular use of selective cox-2 inhibitors and non-selective NSAIDs with cox-2>cox-1 inhibition showed a modestly increased hazard for CV events. Non-selective agents with cox-1>cox-2 inhibition were not associated with increased CV risk. Clinical Trial Registration www.clinicaltrials.gov NCT00000611 PMID:25006185

Single nucleotide polymorphisms in long noncoding RNA, ANRIL, are not associated with severe periodontitis but with adverse cardiovascular events among patients with cardiovascular disease.

PubMed

Schulz, S; Seitter, L; Werdan, K; Hofmann, B; Schaller, H-G; Schlitt, A; Reichert, S

2018-05-06

Biological plausibility of an association between severe periodontitis and cardiovascular disease (CVD) has been proven. Genetic characteristics play an important role in both complex inflammatory diseases. Polymorphisms (single nucleotide polymorphisms [SNPs]) in the long noncoding RNA, antisense noncoding RNA in the INK4 locus (ANRIL), were shown to play a leading role in both diseases. The primary objectives of the study were to assess, among cardiovascular (CV angiographically proven ≥50% stenosis of a main coronary artery) patients, the impact of ANRIL SNPs rs133049 and rs3217992 on the severity of periodontitis and the previous history of coronary events, as well as on the occurrence of further adverse CV events. The prevalence of severe periodontitis was analyzed in 1002 CV patients. ANRIL SNPs rs133049 and rs3217992 were genotyped. The prognostic value of both ANRIL SNPs for combined CV endpoint (stroke/transient ischemic attack [TIA], myocardial infarction, death from a CV-related event, death from stroke) was evaluated after a 3-year follow-up period. Hazard ratios (HRs) were adjusted for established CV risk factors applying Cox regression. ANRIL SNPs rs133049 and rs3217992 were not associated with severe periodontitis or history of CVD in CV patients. In the Kaplan-Meier survival curve including the log rank-test (P = .036) and Cox regression (hazard ratio = 1.684, P = .009) the AA genotype of rs3217992 was shown to be an independent predictor for adverse CV events after 3 years of follow-up. SNPs in ANRIL are not risk modulators for severe periodontitis and history of CVD in CV patients. The AA genotype of ANRIL SNPs rs3217992 possesses prognostic power for further CV events within 3 years of follow-up. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevalence by Computed Tomographic Angiography of Coronary Plaques in South Asian and White Patients With Type 2 Diabetes Mellitus at Low and High Risk Using Four Cardiovascular Risk Scores (UKPDS, FRS, ASCVD, and JBS3).

PubMed

Gobardhan, Sanjay N; Dimitriu-Leen, Aukelien C; van Rosendael, Alexander R; van Zwet, Erik W; Roos, Cornelis J; Oemrawsingh, Pranobe V; Kharagjitsingh, Aan V; Jukema, J Wouter; Delgado, Victoria; Schalij, Martin J; Bax, Jeroen J; Scholte, Arthur J H A

2017-03-01

The aim of this study was to explore the association between various cardiovascular (CV) risk scores and coronary atherosclerotic burden on coronary computed tomography angiography (CTA) in South Asians with type 2 diabetes mellitus and matched whites. Asymptomatic type 2 diabetic South Asians and whites were matched for age, gender, body mass index, hypertension, and hypercholesterolemia. Ten-year CV risk was estimated using different risk scores (United Kingdom Prospective Diabetes Study [UKPDS], Framingham Risk Score [FRS], AtheroSclerotic CardioVascular Disease [ASCVD], and Joint British Societies for the prevention of CVD [JBS3]) and categorized into low- and high-risk groups. The presence of coronary artery calcium (CAC) and obstructive coronary artery disease (CAD; ≥50% stenosis) was assessed using coronary CTA. Finally, the relation between coronary atherosclerosis on CTA and the low- and high-risk groups was compared. UKPDS, FRS, and ASCVD showed no differences in estimated CV risk between 159 South Asians and 159 matched whites. JBS3 showed a significant greater absolute CV risk in South Asians (18.4% vs 14.2%, p <0.01). Higher presence of CAC score >0 (69% vs 55%, p <0.05) and obstructive CAD (39% vs 27%, p <0.05) was observed in South Asians. South Asians categorized as high risk, using UKPDS, FRS, and ASCVD, showed more CAC and CAD compared than whites. JBS3 showed no differences. In conclusion, asymptomatic South Asians with type 2 diabetes mellitus more frequently showed CAC and obstructive CAD than matched whites in the population categorized as high-risk patients using UKPDS, FRS, and ASCVD as risk estimators. However, JBS3 seems to correlate best to CAC and CAD in both ethnicity groups compared with the other risk scores. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship between FEV1 and Cardiovascular Risk Factors in General Population without Airflow Limitation.

PubMed

Lee, Jeong Hyeon; Kang, Yun-Seong; Jeong, Yun-Jeong; Yoon, Young-Soon; Kwack, Won Gun; Oh, Jin Young

2016-01-01

Purpose. We aimed to determine the value of lung function measurement for predicting cardiovascular (CV) disease by evaluating the association between FEV1 (%) and CV risk factors in general population. Materials and Methods. This was a cross-sectional, retrospective study of subjects above 18 years of age who underwent health examinations. The relationship between FEV1 (%) and presence of carotid plaque and thickened carotid IMT (≥0.8 mm) was analyzed by multiple logistic regression, and the relationship between FEV1 (%) and PWV (%), and serum uric acid was analyzed by multiple linear regression. Various factors were adjusted by using Model 1 and Model 2. Results. 1,003 subjects were enrolled in this study and 96.7% ( n = 970) of the subjects were men. In both models, the odds ratio of the presence of carotid plaque and thickened carotid IMT had no consistent trend and statistical significance. In the analysis of the PWV (%) and uric acid, there was no significant relationship with FEV1 (%) in both models. Conclusion. FEV1 had no significant relationship with CV risk factors. The result suggests that FEV1 may have no association with CV risk factors or may be insensitive to detecting the association in general population without airflow limitation.

Decreased baroreflex sensitivity is linked to the atherogenic index, retrograde inflammation, and oxidative stress in subclinical hypothyroidism.

PubMed

Syamsunder, Avupati Naga; Pal, Pravati; Pal, Gopal Krushna; Kamalanathan, Chandrakasan Sadishkumar; Parija, Subhash Chandra; Nanda, Nivedita; Sirisha, Allampalli

2017-02-01

Purpose/aim of the study: The present study investigated the link of hyperlipidemia, inflammation and oxidative stress (OS) to cardiovascular (CV) risks in subclinical hypothyroidism (SCH). We enrolled 81 subclinical hypothyroid patients and 80 healthy subjects as control. Their CV and autonomic functions were assessed by spectral analysis of heart rate variability (HRV), continuous blood pressure variability (BPV) measurement and conventional autonomic function testing. Thyroid profile, lipid profile, immunological, inflammatory and OS markers were estimated and correlated with the baro-reflex sensitivity (BRS), the marker of sympathovagal imbalance (SVI) & CV risk. Mean arterial pressure (MAP, P<0.0001), total peripheral resistance (TPR, P<0.0001), ratio of low-frequency to high-frequency power of HRV (LF-HF ratio) (P<0.0001) were significantly higher and BRS (P<0.0001) was significantly lower in SCH group than the control group. BRS significantly correlated with heart rate, MAP, LF-HF ratio, lipid risk factors, anti-thyroperoxidase antibody, thyroid-stimulating hormone, high-sensitive C-reactive protein (hsCRP), malondialdehyde (MDA) and SCH. It was concluded that SVI is associated with SCH. Though dyslipidemia, inflammation and OS contributed to decreased BRS, SCH per se contributed maximally to it. Decreased BRS could be a physiological basis of increased CV risks in patients with SCH.

Success and failure of cardiovascular disease prevention in Czech Republic over the past 30 years. Czech part of the EUROASPIRE I-IV surveys.

PubMed

Rosolová, H; Nussbaumerová, B; Mayer, O; Cífková, R; Bruthans, J

2017-04-05

Cardiovascular (CV) mortality was reduced more than 50 % in the Czech population at the turn of the century, due to an improvement of major CV risk factors in the general population, interventional procedures implemented into the treatment of acute coronary events, and new drugs (ACE inhibitors, statins etc.) for CV prevention (Czech MONICA and post-MONICA studies, 1985-2008). An insufficient level of preventive efforts is described in the Czech patients after acute coronary syndrome (Czech part of the EUROASPIRE studies, 1995-2013). Drug underdosing and wrong patients' compliance to life style and drug therapy recommendations represent two main reasons of this unsatisfactory situation. The residual vascular risk of patients with stable coronary heart disease (CHD) is still high due to a poor control of conventional risk factors on the one hand, and due to increasing weight and glucose metabolism abnormalities on the other hand. Patients with insulin resistance and glucose disorders have more frequently non LDL C dyslipidemia (atherogenic dyslipidemia), hypertriglyceridemic waist and high atherogenic index of plasma (AIP>0.24), i.e. markers of residual CV risk. Among others increased dose of statins and combined lipid modifying therapy should be implemented in patients with CHD, diabetes or metabolic syndrome.

Red meat intake in chronic kidney disease patients: Two sides of the coin.

PubMed

Mafra, Denise; Borges, Natalia A; Cardozo, Ludmila Ferreira Medeiros de Franca; Anjos, Juliana S; Black, Ana Paula; Moraes, Cristiane; Bergman, Peter; Lindholm, Bengt; Stenvinkel, Peter

2018-02-01

Red meat is an important dietary source of high biological value protein and micronutrients such as vitamins, iron, and zinc that exert many beneficial functions. However, high consumption of animal protein sources, especially red meat, results in an increased intake of saturated fat, cholesterol, iron, and salt, as well as an excessive acid load. Red meat intake may lead to an elevated production of uremic toxins by the gut microbiota, such as trimethylamine n-oxide (TMAO), indoxyl sulfate, and p-cresyl sulfate. These uremic toxins are associated with increased risk for cardiovascular (CV) mortality. Limiting the intake of red meat in patients with chronic kidney disease (CKD) thus may be a good strategy to reduce CV risk, and may slow the progression of kidney disease. In the present review, we discuss the role of red meat in the diet of patients with CKD. Additionally, we report on a pilot study that focused on the effect of a low-protein diet on TMAO plasma levels in nondialysis CKD patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Persistent subclinical hypothyroidism and cardiovascular risk in the elderly: the cardiovascular health study.

PubMed

Hyland, Kristen A; Arnold, Alice M; Lee, Jennifer S; Cappola, Anne R

2013-02-01

Use of a single set of thyroid function tests to define subclinical hypothyroidism may lead to misclassification over time and could influence findings from longitudinal studies. We assessed the risks of coronary heart disease (CHD), heart failure (HF), and cardiovascular (CV) death in older adults with persistent subclinical hypothyroidism. The study included 679 subclinically hypothyroid and 4184 euthyroid U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study and not taking thyroid preparations. We measured the 10-yr risk of incident CHD, HF, and CV death from persistent subclinical hypothyroidism, overall and stratified by degree of TSH elevation (4.5-6.9, 7.0-9.9, and 10.0-19.9 mU/liter). There was no association between persistent subclinical hypothyroidism and incident CHD [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.93-1.36], HF (HR, 1.05; 95% CI, 0.97-1.27), or CV death (HR, 1.07; 95% CI, 0.87-1.31) in adjusted analyses in which subclinical hypothyroidism was modeled as a time-varying exposure using up to four serial thyroid function tests. When subclinical hypothyroidism was stratified by degree of TSH elevation, no significant associations were found in any stratum. Findings were similar in fixed exposure analyses in which only participants with testing 2 yr apart were considered, with no association between persistent or transient subclinical hypothyroidism and incident CHD, HF, or CV death. Our data do not support increased risk of CHD, HF, or CV death in older adults with persistent subclinical hypothyroidism.

Relevance of weight in the management of patients with type 2 diabetes mellitus: towards an adipocentric approach to diabetes.

PubMed

Gorgojo Martínez, Juan José

2016-11-01

In recent decades, there has been a worldwide parallel increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), which is not surprising, given that increased visceral fat is the main risk factor for the development of T2DM in genetically predisposed individuals. An intervention focused on intensive blood glucose control in T2DM with classic drugs increases the risk of weight gain and the rate of hypoglycaemia. In contrast, weight loss through lifestyle changes, drugs and/or surgery simultaneously improves most cardiovascular (CV) risk factors, including hyperglycemia. Intensive intervention on lifestyle induces an overall benefit in patients with T2DM, but long-term weight loss is modest and has not been shown to reduce CV morbidity and mortality. The emergence of new therapeutic classes for T2DM and obesity, which simultaneously improve HbA1c, weight and other CV risk factors without inducing hypoglycaemia, represents a major change in the management of patients with diabesity. A sodium-glucose cotransporter-2 inhibitor and a GLP-1 receptor agonist have recently been shown to decrease CV and total mortality in type 2 diabetic patients with CV disease. Furthermore, bariatric surgery rapidly induces remission or improvement of T2DM in a large percentage of patients and reduces diabetes-related mortality. The emergence of new therapies raises the possibility of changing the current glucose-centred therapeutic strategy for a weight-centred approach. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Optimal waist circumference cut-off values for predicting cardiovascular risk factors in a multi-ethnic Malaysian population.

PubMed

Cheong, Kee C; Ghazali, Sumarni M; Hock, Lim K; Yusoff, Ahmad F; Selvarajah, Sharmini; Haniff, Jamaiyah; Zainuddin, Ahmad Ali; Ying, Chan Y; Lin, Khor G; Rahman, Jamalludin A; Shahar, Suzana; Mustafa, Amal N

2014-01-01

Previous studies have proposed the lower waist circumference (WC) cutoffs be used for defining abdominal obesity in Asian populations. To determine the optimal cut-offs of waist circumference (WC) in predicting cardiovascular (CV) risk factors in the multi-ethnic Malaysian population. We analysed data from 32,703 respondents (14,980 men and 17,723 women) aged 18 years and above who participated in the Third National Health and Morbidity Survey in 2006. Gender-specific logistic regression analyses were used to examine associations between WC and three CV risk factors (diabetes mellitus, hypertension, and hypercholesterolemia). The Receiver Operating Characteristic (ROC) curves were used to determine the cut-off values of WC with optimum sensitivity and specificity for detecting these CV risk factors. The odds ratio for having diabetes mellitus, hypertension, and hypercholesterolemia, or at least one of these risks, increased significantly as the WC cut-off point increased. Optimal WC cut-off values for predicting the presence of diabetes mellitus, hypertension, hypercholesterolemia and at least one of the three CV risk factors varied from 81.4 to 85.5 cm for men and 79.8 to 80.7 cm for women. Our findings indicate that WC cut-offs of 81 cm for men and 80 cm for women are appropriate for defining abdominal obesity and for recommendation to undergo cardiovascular risk screening and weight management in the Malaysian adult population. © 2014 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease.

PubMed

Tomaschitz, Andreas; Ritz, Eberhard; Pieske, Burkert; Fahrleitner-Pammer, Astrid; Kienreich, Katharina; Horina, Jörg H; Drechsler, Christiane; März, Winfried; Ofner, Michael; Pieber, Thomas R; Pilz, Stefan

2012-04-01

Animal and human studies support a clinically relevant interaction between aldosterone and parathyroid hormone (PTH) levels and suggest an impact of the interaction on cardiovascular (CV) health. This review focuses on mechanisms behind the bidirectional interactions between aldosterone and PTH and their potential impact on the CV system. There is evidence that PTH increases the secretion of aldosterone from the adrenals directly as well as indirectly by activating the renin-angiotensin system. Upregulation of aldosterone synthesis might contribute to the higher risk of arterial hypertension and of CV damage in patients with primary hyperparathyroidism. Furthermore, parathyroidectomy is followed by decreased blood pressure levels and reduced CV morbidity as well as lower renin and aldosterone levels. In chronic heart failure, the aldosterone activity is inappropriately elevated, causing salt retention; it has been argued that the resulting calcium wasting causes secondary hyperparathyroidism. The ensuing intracellular calcium overload and oxidative stress, caused by PTH and amplified by the relative aldosterone excess, may increase the risk of CV events. In the setting of primary aldosteronism, renal and faecal calcium loss triggers increased PTH secretion which in turn aggravates aldosterone secretion and CV damage. This sequence explains why adrenalectomy and blockade of the mineralocorticoid receptor tend to decrease PTH levels in patients with primary aldosteronism. In view of the reciprocal interaction between aldosterone and PTH and the potentially ensuing CV damage, studies are urgently needed to evaluate diagnostic and therapeutic strategies addressing the interaction between the two hormones.

Relation of female sex to left atrial diameter and cardiovascular death in atrial fibrillation: The AFFIRM Trial.

PubMed

Proietti, Marco; Raparelli, Valeria; Basili, Stefania; Olshansky, Brian; Lip, Gregory Y H

2016-03-15

Female sex is associated with thromboembolism related to atrial fibrillation (AF). Left atrial (LA) diameter independently predicted incident cardiovascular (CV) major events in the general population. In AF patients, LA enlargement is associated to AF occurrence and recurrence. No data have previously been reported on the relationship between LA enlargement, sex and CV death in AF patients. All patients enrolled in the AFFIRM Trial with available data about LA dimension were included in this post-hoc analysis. Of the 2615 eligible for the present analysis, LA enlargement was recorded in 67.0%, more commonly in women than in men (p=0.032). Patients with LA enlargement had higher body mass index (BMI), and were more frequently hypertensive, diabetic, and diagnosed with a structural heart disease, prior coronary artery disease (CAD) and heart failure (HF). BMI, left ventricular mass, female sex and mitral valve insufficiency (p<0.001) were associated with LA enlargement. AF female patients with LA enlargement had a higher risk for CV death (p=0.011). LA diameter showed a significant association with CV death (p<0.001). Cox regression analysis demonstrated that LA diameter was an independent predictor of CV death in female AF patients (p=0.003). LA diameter enlargement is associated with female sex, and carries a higher risk for CV death, particularly in females. LA diameter was an independent predictor of CV death in female AF patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Relationship between alcohol consumption and cardiovascular mortality--the Warsaw Pol-MONICA Project.

PubMed

Waśkiewicz, Anna; Sygnowska, Elzbieta; Drygas, Wojciech

2004-06-01

Cardioprotective effects of alcohol recently gained wide spread interest and have been examined in several studies. To assess the effects of alcohol consumption on mortality due to cardiovascular diseases (CV) in the population of the Eastern part of Warsaw. The study group consisted of representative, independent and randomly selected samples of the populations of two Warsaw districts (Praga Północ and Praga Południe), aged between 35 and 64 years. The studied subjects were examined in 1984 (2570 subjects), in 1988 (1397 subjects) and in 1993 (1485 subjects). Their survival rates were followed up until 1998. The annual beer, wine and vodka intake was assessed using a standardised questionnaire and calculated for a daily pure ethanol intake. The studied subjects were divided into four groups: abstinents and three groups according to the tertile distribution of the alcohol intake (mean alcohol intake in the first tertile: males 1.1 g/day, females 0.2 g/day, in the second tertile: 3.9 and 0.4 g/day, respectively, and in the third tertile: 28.2 and 2.8 g/day, respectively). The relative risk of death in the analysed groups was assessed using the proportional hazard Cox analysis. In total, 471 males and 244 females died during the follow-up period. There were 221 CV deaths among males and 85 among females. The relative risk of CV death after adjustment for other parameters (age, screening, cigarette smoking, body mass index, education level, cholesterol level, anginal symptoms, systolic blood pressure and self-assessed health status) was approximately 40% lower among males who consumed alcohol compared with the abstinents. The lowest risk of CV death was noted in the first tertile group. Females who consumed alcohol, had a 40-70% lower CV risk of death than abstinents the lowest risk was documented for the third tertile group. Alcohol consumption independently lowers the risk of death due to cardio-vascular diseases.

Improving accuracies of genomic predictions for drought tolerance in maize by joint modeling of additive and dominance effects in multi-environment trials.

PubMed

Dias, Kaio Olímpio Das Graças; Gezan, Salvador Alejandro; Guimarães, Claudia Teixeira; Nazarian, Alireza; da Costa E Silva, Luciano; Parentoni, Sidney Netto; de Oliveira Guimarães, Paulo Evaristo; de Oliveira Anoni, Carina; Pádua, José Maria Villela; de Oliveira Pinto, Marcos; Noda, Roberto Willians; Ribeiro, Carlos Alexandre Gomes; de Magalhães, Jurandir Vieira; Garcia, Antonio Augusto Franco; de Souza, João Cândido; Guimarães, Lauro José Moreira; Pastina, Maria Marta

2018-07-01

Breeding for drought tolerance is a challenging task that requires costly, extensive, and precise phenotyping. Genomic selection (GS) can be used to maximize selection efficiency and the genetic gains in maize (Zea mays L.) breeding programs for drought tolerance. Here, we evaluated the accuracy of genomic selection (GS) using additive (A) and additive + dominance (AD) models to predict the performance of untested maize single-cross hybrids for drought tolerance in multi-environment trials. Phenotypic data of five drought tolerance traits were measured in 308 hybrids along eight trials under water-stressed (WS) and well-watered (WW) conditions over two years and two locations in Brazil. Hybrids' genotypes were inferred based on their parents' genotypes (inbred lines) using single-nucleotide polymorphism markers obtained via genotyping-by-sequencing. GS analyses were performed using genomic best linear unbiased prediction by fitting a factor analytic (FA) multiplicative mixed model. Two cross-validation (CV) schemes were tested: CV1 and CV2. The FA framework allowed for investigating the stability of additive and dominance effects across environments, as well as the additive-by-environment and the dominance-by-environment interactions, with interesting applications for parental and hybrid selection. Results showed differences in the predictive accuracy between A and AD models, using both CV1 and CV2, for the five traits in both water conditions. For grain yield (GY) under WS and using CV1, the AD model doubled the predictive accuracy in comparison to the A model. Through CV2, GS models benefit from borrowing information of correlated trials, resulting in an increase of 40% and 9% in the predictive accuracy of GY under WS for A and AD models, respectively. These results highlight the importance of multi-environment trial analyses using GS models that incorporate additive and dominance effects for genomic predictions of GY under drought in maize single-cross hybrids.

Postmenopausal Women with a History of Irregular Menses and Elevated Androgen Measurements at High Risk for Worsening Cardiovascular Event-Free Survival: Results from the National Institutes of Health—National Heart, Lung, and Blood Institute Sponsored Women’s Ischemia Syndrome Evaluation

PubMed Central

Shaw, Leslee J.; Bairey Merz, C. Noel; Azziz, Ricardo; Stanczyk, Frank Z.; Sopko, George; Braunstein, Glenn D.; Kelsey, Sheryl F.; Kip, Kevin E.; Cooper-DeHoff, Rhonda M.; Johnson, B. Delia; Vaccarino, Viola; Reis, Steven E.; Bittner, Vera; Hodgson, T. Keta; Rogers, William; Pepine, Carl J.

2008-01-01

Background: Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described. Objective: The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health–National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women’s Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. Methods: A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (≥701 pg/ml), testosterone (≥30.9 ng/dl), or free testosterone (≥4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55). Results: Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates. Conclusion: Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events. PMID:18182456

Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health--National Heart, Lung, and Blood Institute sponsored Women's Ischemia Syndrome Evaluation.

PubMed

Shaw, Leslee J; Bairey Merz, C Noel; Azziz, Ricardo; Stanczyk, Frank Z; Sopko, George; Braunstein, Glenn D; Kelsey, Sheryl F; Kip, Kevin E; Cooper-Dehoff, Rhonda M; Johnson, B Delia; Vaccarino, Viola; Reis, Steven E; Bittner, Vera; Hodgson, T Keta; Rogers, William; Pepine, Carl J

2008-04-01

Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described. The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (> or = 701 pg/ml), testosterone (> or = 30.9 ng/dl), or free testosterone (> or = 4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55). Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates. Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events.

Ryegrass cv. Lema and guava cv. Paluma biomonitoring suitability for estimating nutritional contamination risks under seasonal climate in Southeastern Brazil.

PubMed

Bulbovas, Patricia; Camargo, Carla Z S; Domingos, Marisa

2015-08-01

The risks posed by nutrient deposition due to air pollution on ecosystems and their respective services to human beings can be appropriately estimated by bioindicator plants when they are well acclimated to the study region environmental conditions. This assumption encouraged us to comparatively evaluate the accumulation potential of ryegrass cv. Lema and guava cv. Paluma macro and micronutrients. We also indicated the most appropriate species for biomonitoring nutrient contamination risks in tropical areas of Southeastern Brazil, which are characterized by marked dry and wet seasons and complex mixtures of air pollutants from different sources (industries, vehicle traffic and agriculture). The study was conducted in 14 sites with different neighboring land uses, within the Metropolitan Region of Campinas, central-eastern region of São Paulo State. The exposure experiments with ryegrass and guava were consecutively repeated 40 (28 days each) and 12 (84 days each) times, respectively, from Oct/2010 to Sept/2013. Macro and micronutrients were analyzed and background concentrations and enrichment ratios (ER) were estimated to classify the contamination risk within the study region. Significantly higher ER suggested that ryegrass were the most appropriate accumulator species for N, S, Mg, Fe, Mn, Cu and Zn deposition and guava for K, Ca, P and B deposition. Based on these biomonitoring adjustments, we concluded that the nutrient deposition was spatially homogeneous in the study area, but clear seasonality in the contamination risk by nutritional inputs was evidenced. Significantly higher contamination risk by S, Fe, K and B occurred during the dry season and enhanced contamination risk by Mn, Cu and Zn were highlighted during the wet season. Distinctly high contamination risk was estimated for S, Fe and Mn in several exposure experiments. Copyright © 2015 Elsevier Inc. All rights reserved.

78 FR 36635 - Additional Designations, Foreign Narcotics Kingpin Designation Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-18

...) (individual) [SDNTK] (Linked To: RESTAURANT BAR LOS ANDARIEGOS, S.A. DE C.V.). 2. BUENROSTRO VILLA, Denisse... (Mexico) (individual) [SDNTK] (Linked To: RESTAURANT BAR LOS ANDARIEGOS, S.A. DE C.V.). 8. CORTES...]. 15. RESTAURANT BAR LOS ANDARIEGOS, S.A. DE C.V. (a.k.a. BARBARESCO RESTAURANT), [[Page 36638

Abdominal obesity and all-cause and cardiovascular mortality in end-stage renal disease.

PubMed

Postorino, Maurizio; Marino, Carmen; Tripepi, Giovanni; Zoccali, Carmine

2009-04-14

The aim of this study was to investigate the predictive value for all-cause and cardiovascular (CV) death of anthropometric measurements of abdominal obesity in patients with end-stage renal disease (ESRD). Surrogate measures of abdominal obesity and segmental fat distribution (waist circumference and waist/hip ratio [WHR]) are stronger predictors of all-cause and CV death than body mass index (BMI) in the general population, but the issue has never been investigated in patients with ESRD. We performed a prospective cohort study in 537 patients with ESRD (age 63 +/- 15 years). In BMI-adjusted Cox models, waist circumference was a direct predictor of all-cause and CV mortality (p < 0.001), whereas BMI showed an inverse relationship (p < 0.001) with these outcomes. The incidence rates of overall and CV death were maximal in patients with relatively lower BMI scores (below the median) and higher waist circumferences (at least the median) and minimal in patients with higher BMI scores (at least the median) and small waist circumferences (below the median). The prognostic power of waist circumference for all-cause (hazard ratio [HR] [10-cm increase]: 1.23; 95% confidence interval [CI]: 1.02 to 1.47; p = 0.03) and CV mortality (HR: 1.37; 95% CI: 1.09 to 1.73; p = 0.006) remained significant after adjustment for CV comorbidities and traditional and emerging risk factors. WHR was found to be related to all-cause (p = 0.009) and CV mortality (p = 0.07). Abdominal obesity underlies a high risk of all-cause and CV mortality in patients with ESRD. Redefinition of nutritional status by combining the metrics of abdominal obesity and BMI may refine prognosis in the ESRD population.

Intervention Associated Acute Kidney Injury and Long-Term Cardiovascular Outcomes.

PubMed

Saratzis, Athanasios; Harrison, Seamus; Barratt, Jonathan; Sayers, Robert D; Sarafidis, Pantelis A; Bown, Matthew J

2015-01-01

Acute kidney injury (AKI) has been associated with all-cause short- and long-term mortality. However, its association with cardiovascular (CV) events remains unclear. We sought to investigate this in patients undergoing open (OAR) or endovascular (EVAR) abdominal aortic aneurysm repair, as they are likely to develop both AKI and CV morbidity. A meta-analysis was subsequently performed to confirm this in other CV-interventions. AKI-incidence was assessed in a multicentre-cohort of 1,068 patients undergoing EVAR (947 individuals) or OAR electively using the 'Acute Kidney Injury Network' criteria. A composite-endpoint was used, consisting of non-fatal myocardial infarction (MI), stroke, vascular event, hospitalisation due to heart failure and CV death. A systematic literature review identified studies reporting AKI-incidence and CV events. Risk ratios (RRs) at 1 and 5 years were combined using meta-analysis. During a median follow-up of 62 months (range 11-121), AKI was associated with CV events on adjusted (for CV risk-factors) analyses (Incidence 36% of EVAR, 32% of OAR patients; hazard ratio 1.73, 95% CI 1.06-3.39, p=0.03) for the overall population. In the meta-analysis, 7 studies reported incidence of MI on 23,936 patients 1-year after coronary intervention (PCI) with a pooled RR of 1.76 (95% CI 1.45-2.83, p<0.001); at 2 years, 3 studies reported MI incidence on 17,773 patients after PCI with a pooled RR of 1.34 (95% CI 1.10-1.63, p=0.003). MI-incidence was reported 5 years after cardiac surgery by 3 studies (33,701 patients) with a pooled RR of 1.60 (95% CI 1.43-1.81). AKI is associated with long-term CV events after surgery or endovascular intervention. © 2015 S. Karger AG, Basel.

Seaworthy Quantum Key Distribution Design and Validation (SEAKEY)

DTIC Science & Technology

2015-11-12

polarization control and the CV state and the LO state are separated at a polarizing beam splitter . The CV state is delayed relative to the LO state, and... splitter or loss imperfections. We have identified a number of risks associated with implementing this design . The two most critical risks are: • The...Contractor Address: 10 Moulton Street, Cambridge, MA 02138 Title of the Project: Seaworthy Quantum Key Distribution Design and Validation (SEAKEY

Similarity between generic and brand-name antihypertensive drugs for primary prevention of cardiovascular disease: evidence from a large population-based study.

PubMed

Corrao, Giovanni; Soranna, Davide; Merlino, Luca; Mancia, Giuseppe

2014-10-01

Although generic and earlier brand-name counterparts are bioequivalent, their equivalence in preventing relevant clinical outcomes is of concern. To compare effectiveness of generic and brand-name antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes. A population-based, nested case-control study was carried out by including the cohort of 78 520 patients from Lombardy (Italy) aged 18 years or older who were newly treated with antihypertensive drugs during 2005. Cases were the 2206 patients who experienced a hospitalization for CV disease from initial prescription until 2011. One control for each case was randomly selected from the same cohort that generated cases. Logistic regression was used to model the CV risk associated with starting on and/or continuing with generic or brand-name agents. There was no evidence that patients who started on generics experienced different CV risk than those on brand-name product (OR 0·86; 95% CI 0·63-1·17). Patients at whom generics were main dispensed had not significantly difference in CV outcomes than those mainly on brand-name agents (OR 1·19; 95% CI 0·86-1·63). Compared with patients who kept initial brand-name therapy, those who experienced brand-to-generic or generic-to-brand switches, and those always on generics, did not show differential CV risks, being the corresponding ORs (and 95% CIs), 1·18 (0·96-1·47), 0·87 (0·63-1·21) and 1·08 (0·80-1·46). Our findings do not support the notion that brand-name antihypertensive agents are superior to generics for preventing CV outcomes in the real-world clinical practice. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

Mortality and cardiovascular events are best predicted by low central/peripheral pulse pressure amplification but not by high blood pressure levels in elderly nursing home subjects: the PARTAGE (Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population) study.

PubMed

Benetos, Athanase; Gautier, Sylvie; Labat, Carlos; Salvi, Paolo; Valbusa, Filippo; Marino, Francesca; Toulza, Olivier; Agnoletti, Davide; Zamboni, Mauro; Dubail, Delphine; Manckoundia, Patrick; Rolland, Yves; Hanon, Olivier; Perret-Guillaume, Christine; Lacolley, Patrick; Safar, Michel E; Guillemin, Francis

2012-10-16

The aim of the longitudinal PARTAGE study was to determine the predictive value of blood pressure (BP) and pulse pressure amplification, a marker of arterial function, for overall mortality (primary endpoint) and major cardiovascular (CV) events, in subjects older than 80 years of age living in a nursing home. Assessment of pulse indexes may be important in the evaluation of the CV risk in very elderly frail subjects. A total of 1,126 subjects (874 women) who were living in French and Italian nursing homes were enrolled (mean age, 88 ± 5 years). Central (carotid) to peripheral (brachial) pulse pressure amplification (PPA) was calculated with the help of an arterial tonometer. Clinical and 3-day self-measurements of BP were conducted. During the 2-year follow-up, 247 subjects died, and 228 experienced major CV events. The PPA was a predictor of total mortality and major CV events in this population. A 10% increase in PPA was associated with a 24% (p < 0.0003) decrease in total mortality and a 17% (p < 0.01) decrease in major CV events. Systolic BP, diastolic BP, or pulse pressure were either not associated or inversely correlated with total mortality and major CV events. In very elderly individuals living in nursing homes, low PPA from central to peripheral arteries strongly predicts mortality and adverse effects. Assessment of this parameter could help in risk estimation and improve diagnostic and therapeutic strategies in very old, polymedicated persons. In contrast, high BP is not associated with higher risk of mortality or major CV events in this population. (Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population [PARTAGE]; NCT00901355). Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Integrated and Translational Nonclinical In Vivo Cardiovascular Risk Assessment: Gaps and Opportunities

EPA Science Inventory

Cardiovascular (CV) safety concerns are a significant source of drug development attrition in the pharmaceutical industry today. Though current nonclinical testing paradigms have largely prevented catastrophic CV events in Phase I studies, many challenges relating to the inabil...

Comparative study on individual aromatase inhibitors on cardiovascular safety profile: a network meta-analysis

PubMed Central

Zhao, Xihe; Liu, Lei; Li, Kai; Li, Wusheng; Zhao, Li; Zou, Huawei

2015-01-01

The third-generation aromatase inhibitors (AIs: anastrozole, letrozole, and exemestane) have now become standard adjuvant endocrine treatment for postmenopausal estrogen receptor-positive breast cancer complementing chemotherapy and surgery. Because of the absence of direct head-to-head comparisons of these AIs, an indirect comparison is needed for individual treatment choice. In this network systemic assessment, the cardiovascular (CV) side effects in using anastrozole, letrozole, and exemestane based on original studies on AIs vs placebo or tamoxifen were compared. We integrated all available direct and indirect evidences. The odds ratio (OR) of severe CV events for indirect comparisons between exemestane and anastrozole was 1.41 (95% confidence interval [CI] =0.49–2.78), letrozole and anastrozole was 1.80 (95% CI =0.40–3.92), and letrozole and exemestane was 1.46 (95% CI =0.34–3.4). OR of subgroup risk for AIs and tamoxifen were all >1 except for thrombolism risk subgroup. The results showed that the total and severe CV risk ranking is letrozole, exemestane, and anastrozole in descending order. None of the AIs showed advantages in CV events than tamoxifen except for thromboembolism event incidence. PMID:26491345

Hormonal contraception among electronic cigarette users and cardiovascular risk: a systematic review.

PubMed

Riley, Halley E M; Berry-Bibee, Erin; England, Lucinda J; Jamieson, Denise J; Marchbanks, Polly A; Curtis, Kathryn M

2016-03-01

Women who use combined hormonal contraceptives and cigarettes have an increased risk for cardiovascular (CV) events. We reviewed the literature to determine whether women who use hormonal contraceptives (HC) and electronic cigarettes (e-cigarettes) also have an increased risk. Systematic review. We searched for articles reporting myocardial infarction (MI), stroke, venous thromboembolism, peripheral arterial disease or changes to CV markers in women using e-cigarettes and HC. We also searched for indirect evidence, such as CV outcomes among e-cigarette users in the general population and among HC users exposed to nicotine, propylene glycol or glycerol. No articles reported on outcomes among e-cigarette users using HC. Among the general population, 13 articles reported on heart rate or blood pressure after e-cigarette use. These markers generally remained normal, even when significant changes were observed. In three studies, changes were less pronounced after e-cigarette use than cigarette use. One MI was reported among 1012 people exposed to e-cigarettes in these studies. One article on nicotine and HC exposure found both exposures to be significantly associated with acute changes to heart rate, though mean heart rate remained normal. No articles on propylene glycol or glycerol and HC exposure were identified. We identified no evidence on CV outcomes among e-cigarette users using HC. Limited data reporting mostly acute outcomes suggested that CV events are rare among e-cigarette users in the general population and that e-cigarettes may affect heart rate and blood pressure less than conventional cigarettes. There is a need for research assessing joint HC and e-cigarette exposure on clinical CV outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Cross-sectional study of the ankle-brachial index and cardiovascular risk factors in postmenopausal women.

PubMed

Wierzchowski, Paweł; Dereziński, Tadeusz; Migdalski, Arkadiusz; Woda, Łukasz; Wąsikowska, Beata; Jakubowski, Grzegorz; Jawień, Arkadiusz

2017-01-01

The incidence of peripheral artery disease (PAD) and cardiovascular (CV) events in the female population has been on the increase. To analyse the risk factors of a CV event and PAD in women and to assess the usefulness of the ankle-brachial index (ABI). Evaluation of selected parameters in a cohort of 365 women living in the same district. The following data were prospectively recorded: weight, height, waist size, hip circumference, smoking, the intima-media complex, ABI value, and laboratory results. PAD symptoms, CV events and neurological events were noted. ABI was analysed assuming pathology for values: ≤ 0.9 or ≤ 1.0. Age, plasma glucose level, atrial fibrillation, and nicotine addiction were correlated independently with CV disease and stroke (p < 0.001). The high-density lipoprotein cholesterol level, height, and systolic blood pressure were correlated independently with ABI values (p < 0.05). There was no correlation between the occurrence of a CV event in the past and the ABI, irrespective of the cut-off point for the reference value (p = NS). There is no evidence that stricter criteria for the assessment of ABI better represent the vascular status in the female population.

Sports Cardiology: Core Curriculum for Providing Cardiovascular Care to Competitive Athletes and Highly Active People.

PubMed

Baggish, Aaron L; Battle, Robert W; Beckerman, James G; Bove, Alfred A; Lampert, Rachel J; Levine, Benjamin D; Link, Mark S; Martinez, Matthew W; Molossi, Silvana M; Salerno, Jack; Wasfy, Meagan M; Weiner, Rory B; Emery, Michael S

2017-10-10

The last few decades have seen substantial growth in the populations of competitive athletes and highly active people (CAHAP). Although vigorous physical exercise is an effective way to reduce the risk of cardiovascular (CV) disease, CAHAP remain susceptible to inherited and acquired CV disease, and may be most at risk for adverse CV outcomes during intense physical activity. Traditionally, multidisciplinary teams comprising athletic trainers, physical therapists, primary care sports medicine physicians, and orthopedic surgeons have provided clinical care for CAHAP. However, there is increasing recognition that a care team including qualified CV specialists optimizes care delivery for CAHAP. In recognition of the increasing demand for CV specialists competent in the care of CAHAP, the American College of Cardiology has recently established a Sports and Exercise Council. An important primary objective of this council is to define the essential skills necessary to practice effective sports cardiology. Copyright © 2017. Published by Elsevier Inc.

On the potential of acarbose to reduce cardiovascular disease

PubMed Central

2014-01-01

In the emerging landscape of cardiovascular (CV) outcome trials evaluating the effects of blood glucose lowering drugs in individuals with type 2 diabetes, it is becoming increasingly apparent that since the promising signals coming from the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits have been established for any single therapy thus far. There is an unmet need for introducing an effective pharmacological agent which could target both correlates of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha-glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic treatment for decades, but the overall significant impact of this class of drugs on modulating CV risk has only recently been appreciated. Accumulating evidence has shown that apart from its multiple effects on primarily postprandial glucose dysmetabolism, a key component of mechanisms linked to increased incidence of CV events, acarbose therapy also associates with a favorable impact on an array of surrogate markers of CV disease. Data stemming from in vitro testing of human cell lines as well as from preliminary trials in diabetic populations, like the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have highlighted – though not undisputed – the potential beneficial effects of the drug on CV morbidity. Large scale trials, like the ongoing Acarbose Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a positive effect in patients with coronary heart disease and impaired glucose tolerance. In view of its usually acceptable level of side effects that are, if they occur, mostly limited to transient gastrointestinal symptoms, acarbose could well be a strong future player in CV disease secondary prevention. Current discouraging results from many trials of antidiabetic medications to significantly lower CV event rates in diabetic patients, should only draw further attention on alternative glucose lowering agents, among which acarbose is indeed promising. PMID:24742256

On the potential of acarbose to reduce cardiovascular disease.

PubMed

Standl, Eberhard; Theodorakis, Michael J; Erbach, Michael; Schnell, Oliver; Tuomilehto, Jaakko

2014-04-16

In the emerging landscape of cardiovascular (CV) outcome trials evaluating the effects of blood glucose lowering drugs in individuals with type 2 diabetes, it is becoming increasingly apparent that since the promising signals coming from the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits have been established for any single therapy thus far. There is an unmet need for introducing an effective pharmacological agent which could target both correlates of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha-glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic treatment for decades, but the overall significant impact of this class of drugs on modulating CV risk has only recently been appreciated. Accumulating evidence has shown that apart from its multiple effects on primarily postprandial glucose dysmetabolism, a key component of mechanisms linked to increased incidence of CV events, acarbose therapy also associates with a favorable impact on an array of surrogate markers of CV disease. Data stemming from in vitro testing of human cell lines as well as from preliminary trials in diabetic populations, like the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have highlighted - though not undisputed - the potential beneficial effects of the drug on CV morbidity. Large scale trials, like the ongoing Acarbose Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a positive effect in patients with coronary heart disease and impaired glucose tolerance. In view of its usually acceptable level of side effects that are, if they occur, mostly limited to transient gastrointestinal symptoms, acarbose could well be a strong future player in CV disease secondary prevention. Current discouraging results from many trials of antidiabetic medications to significantly lower CV event rates in diabetic patients, should only draw further attention on alternative glucose lowering agents, among which acarbose is indeed promising.

Estimating the incremental net health benefit of requirements for cardiovascular risk evaluation for diabetes therapies

PubMed Central

Chawla, Anita J; Mytelka, Daniel S; McBride, Stephan D; Nellesen, Dave; Elkins, Benjamin R; Ball, Daniel E; Kalsekar, Anupama; Towse, Adrian; Garrison, Louis P

2014-01-01

Purpose To evaluate the advantages and disadvantages of pre-approval requirements for safety data to detect cardiovascular (CV) risk contained in the December 2008 U.S. Food and Drug Administration (FDA) guidance for developing type 2 diabetes drugs compared with the February 2008 FDA draft guidance from the perspective of diabetes population health. Methods We applied the incremental net health benefit (INHB) framework to quantify the benefits and risks of investigational diabetes drugs using a common survival metric (life-years [LYs]). We constructed a decision analytic model for clinical program development consistent with the requirements of each guidance and simulated diabetes drugs, some of which had elevated CV risk. Assuming constant research budgets, we estimate the impact of increased trial size on drugs investigated. We aggregate treatment benefit and CV risks for each approved drug over a 35-year horizon under each guidance. Results The quantitative analysis suggests that the December 2008 guidance adversely impacts diabetes population health. INHB was −1.80 million LYs, attributable to delayed access to diabetes therapies (−0.18 million LYs) and fewer drugs (−1.64 million LYs), but partially offset by reduced CV risk exposure (0.02 million LYs). Results were robust in sensitivity analyses. Conclusion The health outcomes impact of all potential benefits and risks should be evaluated in a common survival measure, including health gain from avoided adverse events, lost health benefits from delayed or forgone efficacious products, and impact of alternative policy approaches. Quantitative analysis of the December 2008 FDA guidance for diabetes therapies indicates that negative impact on patient health will result. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24892175

Estimating the incremental net health benefit of requirements for cardiovascular risk evaluation for diabetes therapies.

PubMed

Chawla, Anita J; Mytelka, Daniel S; McBride, Stephan D; Nellesen, Dave; Elkins, Benjamin R; Ball, Daniel E; Kalsekar, Anupama; Towse, Adrian; Garrison, Louis P

2014-03-01

To evaluate the advantages and disadvantages of pre-approval requirements for safety data to detect cardiovascular (CV) risk contained in the December 2008 U.S. Food and Drug Administration (FDA) guidance for developing type 2 diabetes drugs compared with the February 2008 FDA draft guidance from the perspective of diabetes population health. We applied the incremental net health benefit (INHB) framework to quantify the benefits and risks of investigational diabetes drugs using a common survival metric (life-years [LYs]). We constructed a decision analytic model for clinical program development consistent with the requirements of each guidance and simulated diabetes drugs, some of which had elevated CV risk. Assuming constant research budgets, we estimate the impact of increased trial size on drugs investigated. We aggregate treatment benefit and CV risks for each approved drug over a 35-year horizon under each guidance. The quantitative analysis suggests that the December 2008 guidance adversely impacts diabetes population health. INHB was -1.80 million LYs, attributable to delayed access to diabetes therapies (-0 .18 million LYs) and fewer drugs (-1.64 million LYs), but partially offset by reduced CV risk exposure (0.02 million LYs). Results were robust in sensitivity analyses. The health outcomes impact of all potential benefits and risks should be evaluated in a common survival measure, including health gain from avoided adverse events, lost health benefits from delayed or for gone efficacious products, and impact of alternative policy approaches. Quantitative analysis of the December 2008 FDA guidance for diabetes therapies indicates that negative impact on patient health will result. Copyright © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Normal body mass index with central obesity has increased risk of coronary artery calcification in Korean patients with chronic kidney disease.

PubMed

Lee, Mi Jung; Park, Jung Tak; Park, Kyoung Sook; Kwon, Young Eun; Han, Seung Hyeok; Kang, Shin-Wook; Choi, Kyu Hun; Oh, Kook-Hwan; Park, Sue Kyung; Chae, Dong Wan; Lee, Kyubeck; Hwang, Young-Hwan; Kim, Soo Wan; Kim, Yeong Hoon; Kang, Sun Woo; Lee, Joongyub; Ahn, Curie; Yoo, Tae-Hyun

2016-12-01

In chronic kidney disease (CKD), overweight and mild obesity have shown the lowest cardiovascular (CV) risk. However, central obesity has been directly associated with CV risk in these patients. This bidirectional relationship of body mass index (BMI) and central obesity prompted us to evaluate CV risk based on a combination of BMI and waist-to-hip ratio (WHR) in nondialysis CKD patients. We included 1078 patients with CKD stage 2 through 5 (nondialysis) enrolled in a nationwide prospective cohort of Korea. Patients were divided into 3 groups by BMI (normal BMI, 18.5-22.9; overweight, 23.0-27.4; and obese, 27.5 and over kg/m 2 ) and were dichotomized by a sex-specific median WHR (0.92 in males and 0.88 in females). Coronary artery calcification (CAC) was determined by multislice computed tomography. CAC (score above 10 Agatston units) was found in 477 patients. Multivariate logistic regression analysis indicated that BMI was not independently associated with CAC. However, WHR showed an independent linear and significant association with CAC (odds ratio, 1.036; 95% confidence interval, 1.007-1.065 per 0.01 increase). Furthermore, when patients were categorized into 6 groups according to a combination of BMI and WHR, normal BMI but higher WHR had the highest risk of CAC compared with the normal BMI with lower WHR group (2.104; 1.074-4.121). Thus, a normal BMI with central obesity was associated with the highest risk of CAC, suggesting that considering BMI and WHR, 2 surrogates of obesity, can help to discriminate CV risk in Korean nondialysis CKD patients. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

The Relationship Between Cardiac Conduction Times, Cardiovascular Risk Factors, and Inflammation in Patients with Early Arthritis.

PubMed

Turk, Samina A; Heslinga, Sjoerd C; Dekker, Jill; Britsemmer, Linda; van der Lugt, Véronique; Lems, Willem F; van Schaardenburg, Dirkjan; Nurmohamed, Michael T

2017-05-01

To investigate the prevalence of conduction disorders in patients with early arthritis and the relationship with inflammation and traditional cardiovascular (CV) risk factors. Patients with rheumatoid arthritis (RA) have a 2-fold higher risk of sudden cardiac death, possibly owing to conduction disorders. This increased risk might already be present at the clinical onset of arthritis. Therefore, we assessed electrocardiography, blood pressure, 28-joint Disease Activity Score (DAS28), lipid profile, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level in 480 patients with early arthritis at baseline and after 1 year. The prevalence of conduction disorders was 12.5%. Conduction times at baseline were not associated with DAS28, ESR, or CRP levels and did not change during antirheumatic treatment. Baseline and the improvement in DAS28 (European League Against Rheumatism response), ESR, and CRP were significantly associated with heart rate, lipid profile, and blood pressure. Elevated total cholesterol and blood pressure were associated with an increased QRS time. The change in heart rate differed 7.3 bpm between patients with the least versus largest DAS improvement. The prevalence of conduction disorders in patients with early arthritis was 12.5%, which is similar to the general population and was not associated with changes in inflammation markers. However, a high cholesterol was associated with a prolonged QRS time. Therefore, the emphasis of CV risk management in arthritis should not be only on treatment of disease activity but also on traditional CV risk factors. The relationship between the improvement in disease activity and heart rate is remarkable because this could imply a 10-year CV mortality risk difference of 24%.

Marital Status, Cardiovascular Diseases, and Cardiovascular Risk Factors: A Review of the Evidence.

PubMed

Manfredini, Roberto; De Giorgi, Alfredo; Tiseo, Ruana; Boari, Benedetta; Cappadona, Rosaria; Salmi, Raffaella; Gallerani, Massimo; Signani, Fulvia; Manfredini, Fabio; Mikhailidis, Dimitri P; Fabbian, Fabio

2017-06-01

There is evidence showing that marital status (MS) and marital disruption (i.e., separation, divorce, and being widowed) are associated with poor physical health outcomes, including for all-cause mortality. We checked for the available evidence on the association between MS and cardiovascular (CV) diseases, outcomes, and CV risk factors. A search across the PubMed database of all articles, including the term "marital status" in their title, was performed. All articles were then manually checked for the presence of the following terms or topic: CV diseases, acute myocardial infarction, acute coronary syndrome, coronary artery disease, cardiac arrest, heart failure, heart diseases, and CV mortality. Moreover, other search terms were: CV risk factors, hypertension, cholesterol, obesity, smoking, alcohol, fitness and/or physical activity, and health. Systematic reviews, meta-analyses, controlled trials, cohort studies, and case-control studies were potentially considered pertinent for inclusion. Case reports, comments, discussion letters, abstracts of scientific conferences, articles in other than English language, and conference abstracts or proceedings were excluded. In total, 817 references containing the title words "marital status" were found. After elimination of articles dealing with other topics, 70 records were considered pertinent. Twenty-two were eliminated for several reasons, such as old articles, no abstract, full text unavailable, other than English language, comments, and letters. Out of the remaining 48 articles, 13 were suitable for the discussion, and 35 (accounting for 1,245,967 subjects) were included in this study. Most studies showed better outcomes for married persons, and men who were single generally had the poorest results. Moreover, being married was associated with lower risk factors and better health status, even in the presence of many confounding effects.

Utility of high density lipoprotein particle concentration in predicting future major adverse cardiovascular events among patients undergoing angiography.

PubMed

May, Heidi T; Anderson, Jeffrey L; Winegar, Deborah A; Rollo, Jeffrey; Connelly, Margery A; Otvos, James D; Muhlestein, Joseph B

2016-10-01

HDL-C is recognized to be inversely associated with cardiovascular (CV) risk. However, attenuation of the association of HDL-C with CV risk may occur after adjustment for other lipoprotein parameters and in various disease states, especially in the setting of acute coronary syndrome (ACS). Recently, the number of HDL particles (HDL-P) has been suggested to improve CV risk prediction. Patients (n=2999) in the Intermountain Heart Collaborative Study who underwent angiography and had lipoprotein particle measurements determined by nuclear magnetic resonance (NMR) spectroscopy were studied. Multivariable Cox hazard regression was utilized to evaluate the association of HDL-C, HDL-P, and HDL-P subclasses with future major adverse CV events (MACE: death, myocardial infarction, heart failure, and stroke). Patients averaged 64±12years, 66% male, 26% diabetic, and 42% ACS. At angiography, 65% of patients were diagnosed with coronary artery disease (CAD). HDL-C and HDL-P averaged 41±13mg/dL and 28±8μmol/L, respectively. HDL-P (HR=0.903, p=0.001), but not HDL-C (HR=0.947, p=0.102) was significantly associated with MACE. In a model that included all HDL-P subclasses, both small (HR=0.862, p<0.0001) and medium (HR=0.922, p=0.020) were associated with CV risk, but not large HDL-P (HR=1.0042, p=0.185). Small HDL-P continued to be associated with all of the individual components of MACE, but not stroke. In this study of patients undergoing angiography, HDL-P was a strong, independent predictor of future MACE, with the smaller HDL-P accounting for this association. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Persistent Subclinical Hypothyroidism and Cardiovascular Risk in the Elderly: The Cardiovascular Health Study

PubMed Central

Hyland, Kristen A.; Arnold, Alice M.; Lee, Jennifer S.

2013-01-01

Context: Use of a single set of thyroid function tests to define subclinical hypothyroidism may lead to misclassification over time and could influence findings from longitudinal studies. Objective: We assessed the risks of coronary heart disease (CHD), heart failure (HF), and cardiovascular (CV) death in older adults with persistent subclinical hypothyroidism. Design, Setting, and Participants: The study included 679 subclinically hypothyroid and 4184 euthyroid U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study and not taking thyroid preparations. Main Outcome Measure: We measured the 10-yr risk of incident CHD, HF, and CV death from persistent subclinical hypothyroidism, overall and stratified by degree of TSH elevation (4.5–6.9, 7.0–9.9, and 10.0–19.9 mU/liter). Results: There was no association between persistent subclinical hypothyroidism and incident CHD [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.93–1.36], HF (HR, 1.05; 95% CI, 0.97–1.27), or CV death (HR, 1.07; 95% CI, 0.87–1.31) in adjusted analyses in which subclinical hypothyroidism was modeled as a time-varying exposure using up to four serial thyroid function tests. When subclinical hypothyroidism was stratified by degree of TSH elevation, no significant associations were found in any stratum. Findings were similar in fixed exposure analyses in which only participants with testing 2 yr apart were considered, with no association between persistent or transient subclinical hypothyroidism and incident CHD, HF, or CV death. Conclusions: Our data do not support increased risk of CHD, HF, or CV death in older adults with persistent subclinical hypothyroidism. PMID:23162099

Hemorheological parameters are related to subclinical atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis patients.

PubMed

Santos, Maria José; Pedro, Luís Mendes; Canhão, Helena; Fernandes E Fernandes, José; Canas da Silva, José; Fonseca, João Eurico; Saldanha, Carlota

2011-12-01

Rheological characteristics of blood are strongly linked to atherothrombosis in the general population, but its contribution to atherosclerosis in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) is currently unclear. This work examines the relationship between blood rheology, traditional cardiovascular (CV) risk factors, inflammation and subclinical atherosclerosis in SLE and RA. Whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte deformability (ED), aggregation (EA) and erythrocyte NO production were measured in 197 patients (96 SLE and 101 RA) and compared to 97 controls, all females without previous CV events. Clinical information was obtained and fasting lipids and acute phase reactants were measured. The relationship between hemorheological parameters, CV risk factors and inflammation was assessed in patients and the impact of these variables on carotid intima-media thickness (cIMT) was evaluated in univariate followed by multivariate regression analyses. WBV and ED are significantly lower in patients, while EA is elevated as compared with controls. Hemorheological disturbances correlate with CV risk factors and markers of inflammation and are more profound in patients with metabolic syndrome. Multivariable analysis showed that menopause (OR 34.72, 95%CI 4.44-271.77), obesity (OR 4.09, 95%CI 1.00-16.68) and WBV (OR 3.98; 95%CI 1.23-12.83) are positively associated whereas current corticosteroid dose (OR 0.87; 95%CI 0.78-0.98), and erythrocyte NO production (OR 0.16; 95%CI 0.05-0.52) are negatively associated with cIMT. Disturbed hemorheological parameters in SLE and RA women are related to the presence of CV risk factors and inflammation. WBV and erythrocyte NO are independently associated with the early stages of atherosclerosis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Cardiovascular recovery from psychological and physiological challenge and risk for adverse cardiovascular outcomes and all-cause mortality

PubMed Central

Panaite, Vanessa; Salomon, Kristen; Jin, Alvin; Rottenberg, Jonathan

2015-01-01

Objective Exaggerated cardiovascular (CV) reactivity to laboratory challenge has been shown to predict future CV morbidity and mortality. CV recovery, has been less studied, and has yielded inconsistent findings, possibly due to presence of moderators. Reviews on the relationship between CV recovery and CV outcomes have been limited to cross-sectional studies and have not considered methodological factors. We performed a comprehensive meta-analytic review of the prospective literature investigating CV recovery to physical and psychological challenge and adverse cardiovascular outcomes. Methods We searched PsycINFO and PubMed for prospective studies investigating the relationship between CV recovery and adverse CV outcomes. Studies were coded for variables of interest and for effect sizes (ES). We conducted a random effects weighted meta-analysis. Moderators were examined with ANOVA-analog and meta-regression analyses. Results Thirty seven studies met inclusion criteria (N=125386). Impaired recovery from challenge predicted adverse cardiovascular outcomes (summary effect, r = .17, p < .001). Physical challenge was associated with larger predictive effects than psychological challenge. Moderator analyses revealed that recovery measured at 1 minute post-exercise, passive recovery, use of mortality as an outcome measure, and older sample age were associated with larger effects. Conclusions Poor recovery from laboratory challenges predicts adverse CV outcomes, with recovery from exercise serving as a particularly strong predictor of CV outcomes. The overall ES for recovery and CV outcomes is similar to that observed for CV reactivity and suggests that the study of recovery may have incremental value for understanding adverse CV outcomes. PMID:25829236

Influence of influenza vaccination on recurrent hospitalization in patients with heart failure.

PubMed

Kaya, H; Beton, O; Acar, G; Temizhan, A; Cavusoğlu, Y; Guray, U; Zoghi, M; Ural, D; Ekmekci, A; Gungor, H; Sari, I; Oguz, D; Yucel, H; Zorlu, A; Yilmaz, M B

2017-05-01

The current study aimed to evaluate the influence of regular annual influenza vaccinations on cardiovascular (CV) death and heart failure-related hospitalizations (HFrH) in stable outpatients with heart failure with reduced ejection fraction. The Turkish research team-HF (TREAT-HF) is a network undertaking multicenter, observational cohort studies in HF. This study is a subgroup analysis of TREAT-HF outpatient cohorts who completed a questionnaire on influenza vaccination status and for whom follow-up data were available. A total of 656 patients with available follow-up data for CV death and HFrH including recurrent hospitalization were included in the study. Patients were classified into two groups: those who received regular influenza vaccination (40 %) and those who did not receive vaccination. During a mean follow-up of 15 ±6 months, 113 (18 %) patients had CV death and 471 (72 %) patients had at least one HFrH. The CV death rate was similar in both groups of patients (16 vs. 19 %, p = 0.37), whereas, HFrH and recurrent HFrH were significantly less frequently encountered in patients who received regular influenza vaccination than in those who did not receive vaccination (43 vs. 92 % and 16 vs. 66 %, p < 0.001, respectively). In a multivariate Cox proportional hazards model - in addition to a few clinical factors - vaccination status (HR = 0.30, 95 % CI = 0.17-0.51, p < 0.001) and graduation from university (HR = 0.35, 95 % CI = 0.17-0.72, p = 0.004) remained independently associated with the risk of recurrent HFrH. Regular influenza vaccination does not influence CV deaths; however, it decreases HFrH including recurrent episodes of HFrH in outpatients with heart failure with reduced ejection fraction.

Relationship of Kidney Injury Biomarkers with Long-Term Cardiovascular Outcomes after Cardiac Surgery.

PubMed

Parikh, Chirag R; Puthumana, Jeremy; Shlipak, Michael G; Koyner, Jay L; Thiessen-Philbrook, Heather; McArthur, Eric; Kerr, Kathleen; Kavsak, Peter; Whitlock, Richard P; Garg, Amit X; Coca, Steven G

2017-12-01

Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). The primary outcome was a composite of long-term CV events or death, which was assessed via national health care databases. During a median 3.8 years of follow-up, 219 (22.6%) patients experienced the primary outcome (136 CV events and 83 additional deaths). Compared with patients without postsurgical AKI, patients who experienced AKI Network stage 2 or 3 had an adjusted hazard ratio for the primary composite outcome of 3.52 (95% confidence interval, 2.17 to 5.71). However, none of the five urinary kidney injury biomarkers were significantly associated with the primary outcome. In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes. Copyright © 2017 by the American Society of Nephrology.

Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study.

PubMed

Tyczynski, Jerzy E; Oleske, Denise M; Klingman, David; Ferrufino, Cheryl P; Lee, Won Chan

2012-08-01

Obesity is a serious and rapidly growing health problem worldwide. Few therapies are available beyond diet, exercise and bariatric surgery. A previously approved medication, sibutramine, has been withdrawn from the market due to concerns over the potential of increased risk of cardiovascular (CV) events, based on a phase IV clinical trial that included only individuals at high risk for CV events. The aim of the study was to compare sibutramine users and matched non-users on rates of CV events, both overall and stratified by whether the patient qualified for on-label sibutramine use, using data from real-life clinical practice. A retrospective cohort was constructed from electronic medical record data from physician office practices (mostly primary care) in the UK and Germany, using the LifeLink™ database from IMS Health Incorporated. For patients with at least one physician visit in which sibutramine was prescribed between 1 April 1999 and 31 October 2008, the date of their first such prescription was their index date. Users and non-users were matched 1 : 1 on index date (within 30 days), sex, age group (six categories), Charlson Comorbidity Index and evidence of obesity (high body mass index [BMI] or, if BMI was missing, diagnosis of obesity or very high weight relative to height). The resultant total samples analysed were 6186 in Germany and 7264 in the UK. User and non-user cohorts in the samples were compared according to the ratio of their crude incidence rates of acute myocardial infarction (AMI), stroke and either AMI or stroke per 1000 patient-years of follow-up. Cox regression analysis was used to compare the risk of CV events as a hazard ratio (HR) with 95% confidence intervals (CIs) between sibutramine user and non-user cohorts, controlling for label status and/or history of prior CV disease at baseline. The risk of AMI, stroke and either AMI or stroke was not higher among sibutramine users than comparable non-users of sibutramine in both Germany and the UK [Germany: HR 0.47 (95% CI 0.17, 1.26), 0.43 (0.23, 0.81) and 0.44 (0.26, 0.75), respectively; UK: HR 0.44 (0.15, 1.31), 0.63 (0.25, 1.60) and 0.54 (0.27, 1.10), respectively]. Regardless of whether or not the model controlled for prior CV disease (CVD), the direction and statistical significance of the differences did not change. In the sensitivity analyses including only those without a history of CVD in the 365 days prior to the index date there was no increased risk of CV events in either Germany or the UK. This study offers a framework for the safety assessment of anti-obesity drugs using an observational epidemiological study design. Large electronic health databases were used to construct retrospective cohorts to examine the risk in a population using one specific anti-obesity drug. Use of sibutramine in general practice settings was not found to increase the risk of acute CV events.

Blood pressure reactivity to psychological stress is associated with clinical outcomes in patients with heart failure.

PubMed

Sherwood, Andrew; Hill, LaBarron K; Blumenthal, James A; Adams, Kirkwood F; Paine, Nicola J; Koch, Gary G; O'Connor, Christopher M; Johnson, Kristy S; Hinderliter, Alan L

2017-09-01

Cardiovascular (CV) reactivity to psychological stress has been implicated in the development and exacerbation of cardiovascular disease (CVD). Although high CV reactivity traditionally is thought to convey greater risk of CVD, the relationship between reactivity and clinical outcomes is inconsistent and may depend on the patient population under investigation. The present study examined CV reactivity in patients with heart failure (HF) and its potential association with long-term clinical outcomes. One hundred ninety-nine outpatients diagnosed with HF, with ejection fraction ≤40%, underwent an evaluation of blood pressure (BP) and heart rate reactivity to a laboratory-based simulated public-speaking stressor. Cox proportional hazards regression models were used to examine the prospective association between BP and heart rate reactivity on a combined end point of death or CV hospitalization over a 5-year median follow-up period. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) reactivity, quantified as continuous variables, were inversely related to risk of death or CV hospitalization (Ps < .01) after controlling for established risk factors, including HF disease severity and etiology. In similar models, heart rate reactivity was unrelated to outcome (P = .12). In models with tertiles of reactivity, high SBP reactivity, compared with intermediate SBP reactivity, was associated with lower risk (hazard ratio [HR] = .498, 95% CI .335-.742, P =.001), whereas low SBP reactivity did not differ from intermediate reactivity. For DBP, high reactivity was marginally associated with lower risk compared with intermediate DBP reactivity (HR = .767, 95% CI .515-1.14, P =.193), whereas low DBP reactivity was associated with greater risk (HR = 1.49, 95% CI 1.027-2.155, P =.0359). No relationship of heart rate reactivity to outcome was identified. For HF patients with reduced ejection fraction, a robust increase in BP evoked by a laboratory-based psychological challenge was associated with lower risk for adverse CVD events and may be a novel and unique marker of left ventricular systolic reserve that is accompanied by a more favorable long-term prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Two unconventional risk factors for major adverse cardiovascular events in subjects with sexual dysfunction: low education and reported partner's hypoactive sexual desire in comparison with conventional risk factors.

PubMed

Rastrelli, Giulia; Corona, Giovanni; Fisher, Alessandra D; Silverii, Antonio; Mannucci, Edoardo; Maggi, Mario

2012-12-01

The classification of subjects as low or high cardiovascular (CV) risk is usually performed by risk engines, based upon multivariate prediction algorithms. However, their accuracy in predicting major adverse CV events (MACEs) is lower in high-risk populations as they take into account only conventional risk factors. To evaluate the accuracy of Progetto Cuore risk engine in predicting MACE in subjects with erectile dysfunction (ED) and to test the role of unconventional CV risk factors, specifically identified for ED. A consecutive series of 1,233 men (mean age 53.33 ± 9.08 years) attending our outpatient clinic for sexual dysfunction was longitudinally studied for a mean period of 4.4 ± 2.6 years. Several clinical, biochemical, and instrumental parameters were evaluated. Subjects were classified as high or low risk, according to previously reported ED-specific risk factors. In the overall population, Progetto Cuore-predicted population survival was not significantly different from the observed one (P = 0.545). Accordingly, receiver operating characteristic (ROC) analysis shows that Progetto Cuore has an accuracy of 0.697 ± 0.037 (P < 0.001) in predicting MACE. Considering subjects at high risk according to ED-specific risk factors, the observed incidence of MACE was significantly higher than the expected for both low educated and patients reporting partner's hypoactive sexual desire (HSD, both <0.05), but not for other described factors. The area under ROC curves of Progetto Cuore for MACE in subjects with low education and reported partner's HSD were 0.659 ± 0.053 (P = 0.008) and 0.550 ± 0.076 (P = 0.570), respectively. Overall, Progetto Cuore is a proper instrument for evaluating CV risk in ED subjects. However, in ED, other factors such as low education and partner's HSD concur to risk profile. At variance with low education, Progetto Cuore is not accurate enough to predict MACE in subjects with partner's HSD, suggesting that the latter effect is not mediated by conventional risk factors included in the algorithm. © 2012 International Society for Sexual Medicine.

Acute coronary syndromes in deployed military personnel.

PubMed

McGraw, Leigh K; Turner, Barbara S; Stotts, Nancy A; Dracup, Kathleen A

2011-08-01

The purpose of this study was to describe the cardiovascular (CV) risk profile of deployed military men who experience acute coronary syndrome (ACS). A retrospective record review of deployed military men who experienced ACS while deployed and were treated at an overseas military medical center between 2001 and 2007 was conducted to obtain the information for this descriptive study (N= 100). Acute myocardial infarction was diagnosed in 82% of the sample, and 18% experienced unstable angina. Subjects' mean age was 44.7 years (SD± 7.6; range 29-60) and most were enlisted and reservists. Risk factors included a family history of premature coronary artery disease (41%) and smoking (47%) as well as a history of hyperlipidemia (48%), hypertension (28%), and glucose abnormalities (6%). The group was overweight (BMI 27.77 kg/m(2) ± 3.2) and low risk for CV events (Framingham risk score 7.8%[± 4.4]). Young military men are regarded as the epitome of health and fitness; however, findings from this study suggest that this generally low-risk group do indeed have multiple CV risk factors and experience ACS. Early risk factor assessment and modification, including smoking cessation, weight management, and improving dyslipidemia, is essential. ©2011 The Author(s) Journal compilation ©2011 American Academy of Nurse Practitioners.

Low Triiodothyronine Syndrome and Long-Term Cardiovascular Outcome in Incident Peritoneal Dialysis Patients.

PubMed

Chang, Tae Ik; Nam, Joo Young; Shin, Sug Kyun; Kang, Ea Wha

2015-06-05

A direct association between low triiodothyronine (T3) syndrome and cardiovascular (CV) mortality has been reported in hemodialysis patients. However, the implications of this syndrome in peritoneal dialysis (PD) patients have not been properly investigated. This study examined the association between low T3 syndrome and CV mortality including sudden death in a large cohort of incident PD patients. This prospective observational study included 447 euthyroid patients who started PD between January 2000 and December 2009. Measurement of thyroid hormones was performed at baseline. All-cause and cause-specific deaths were registered during the median 46 months of follow-up. The survival rate was compared among three groups based on tertile of T3 levels. In Kaplan-Meyer analysis, patients with the lowest tertile were significantly associated with higher risk of all-cause and CV mortality including sudden death (P<0.001 for trend). In Cox analyses, T3 level was a significant predictor of all-cause mortality (per 10-unit increase, adjusted hazard ratio [HR], 0.86; 95% confidence interval [95% CI], 0.78 to 0.94; P=0.002), CV death (per 10-unit increase, adjusted HR, 0.84; 95% CI, 0.75 to 0.98; P=0.01), and sudden death (per 10-unit increase, adjusted HR, 0.69; 95% CI, 0.56 to 0.86; P=0.001) after adjusting for well known risk factors including inflammation and malnutrition. The higher T3 level was also independently associated with lower risk for sudden death (per 10-unit increase, adjusted HR, 0.71; 95% CI, 0.56 to 0.90; P=0.01) even when accounting for competing risks of death from other causes. T3 level at the initiation of PD was a strong independent predictor of long-term CV mortality, particularly sudden death, even after adjusting well known risk factors. Low T3 syndrome might represent a factor directly implicated in cardiac complications in PD patients. Copyright © 2015 by the American Society of Nephrology.

Determinants and prognostic implications of Cardiac Troponin T measured by a sensitive assay in Type 2 Diabetes Mellitus

PubMed Central

2010-01-01

Background The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM. Methods cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if availabe (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk). Results One-hundred thirteen (90 %) had detectable cTnT at baseline and of those, 22 (18 % of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r = 0.92, p > 0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p = 0.058). Conclusions Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found. PMID:20843304

Determinants and prognostic implications of cardiac troponin T measured by a sensitive assay in type 2 diabetes mellitus.

PubMed

Hallén, Jonas; Johansen, Odd Erik; Birkeland, Kåre I; Gullestad, Lars; Aakhus, Svend; Endresen, Knut; Tjora, Solve; Jaffe, Allan S; Atar, Dan

2010-09-15

The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM. cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if available (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk). One-hundred thirteen (90%) had detectable cTnT at baseline and of those, 22 (18% of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r=0.92, p>0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p=0.058). Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found.

Alcohol's Effects on the Cardiovascular System.

PubMed

Piano, Mariann R

2017-01-01

Alcohol use has complex effects on cardiovascular (CV) health. The associations between drinking and CV diseases such as hypertension, coronary heart disease, stroke, peripheral arterial disease, and cardiomyopathy have been studied extensively and are outlined in this review. Although many behavioral, genetic, and biologic variants influence the interconnection between alcohol use and CV disease, dose and pattern of alcohol consumption seem to modulate this most. Low-to-moderate alcohol use may mitigate certain mechanisms such as risk and hemostatic factors affecting atherosclerosis and inflammation, pathophysiologic processes integral to most CV disease. But any positive aspects of drinking must be weighed against serious physiological effects, including mitochondrial dysfunction and changes in circulation, inflammatory response, oxidative stress, and programmed cell death, as well as anatomical damage to the CV system, especially the heart itself. Both the negative and positive effects of alcohol use on particular CV conditions are presented here. The review concludes by suggesting several promising avenues for future research related to alcohol use and CV disease. These include using direct biomarkers of alcohol to confirm self-report of alcohol consumption levels; studying potential mediation of various genetic, socioeconomic, and racial and ethnic factors that may affect alcohol use and CV disease; reviewing alcohol-medication interactions in cardiac patients; and examining CV effects of alcohol use in young adults and in older adults.

Alcohol’s Effects on the Cardiovascular System

PubMed Central

Piano, Mariann R.

2017-01-01

Alcohol use has complex effects on cardiovascular (CV) health. The associations between drinking and CV diseases such as hypertension, coronary heart disease, stroke, peripheral arterial disease, and cardiomyopathy have been studied extensively and are outlined in this review. Although many behavioral, genetic, and biologic variants influence the interconnection between alcohol use and CV disease, dose and pattern of alcohol consumption seem to modulate this most. Low-to-moderate alcohol use may mitigate certain mechanisms such as risk and hemostatic factors affecting atherosclerosis and inflammation, pathophysiologic processes integral to most CV disease. But any positive aspects of drinking must be weighed against serious physiological effects, including mitochondrial dysfunction and changes in circulation, inflammatory response, oxidative stress, and programmed cell death, as well as anatomical damage to the CV system, especially the heart itself. Both the negative and positive effects of alcohol use on particular CV conditions are presented here. The review concludes by suggesting several promising avenues for future research related to alcohol use and CV disease. These include using direct biomarkers of alcohol to confirm self-report of alcohol consumption levels; studying potential mediation of various genetic, socioeconomic, and racial and ethnic factors that may affect alcohol use and CV disease; reviewing alcohol–medication interactions in cardiac patients; and examining CV effects of alcohol use in young adults and in older adults. PMID:28988575

Prevalence of cavum vergae in psychosis and mood spectrum disorders.

PubMed

Landin-Romero, Ramón; Sarró, Salvador; Fernández-Corcuera, Paloma; Moro, Noemí; Manuel Goikolea, Jose; Isabel Carrión, María; Pomarol-Clotet, Edith; Amann, Benedikt L; Radua, Joaquim

2015-11-01

Midline brain abnormalities might increase susceptibility to both first-episode and chronic mental disorder. Evidence of cavum vergae (CV) abnormality in mental disorders is scarce. The presence of CV was assessed by a researcher blind to clinical information in a cross-disorder sample of 639 patients with mood and psychotic disorders and in 223 healthy controls. Homogeneous magnetic resonance imaging methods of acquisition and assessment were applied. Seven out of 639 patients with mood or psychotic disorders were detected with CV which corresponds to a prevalence of 1.1%. There were no concurrent cases of CV in the healthy control group. Identified cases which are briefly described were diagnosed from bipolar I disorder (n=2), delusional disorder (n=1), brief psychotic disorder (n=1) and schizoaffective disorder (n=3). Patients with CV had descriptively lower current IQ, executive functioning and memory scores in relation to patients without CV but this was not statistically significant. Effects of medication and lack of statistical power of the CV patient group. Midline brain abnormalities, such as CV, might represent an unspecific risk factor for the development of severe mental disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Inducing unconscious stress: Cardiovascular activity in response to subliminal presentation of threatening and neutral words.

PubMed

van der Ploeg, Melanie M; Brosschot, Jos F; Verkuil, Bart; Gillie, Brandon L; Williams, DeWayne P; Koenig, Julian; Vasey, Michael W; Thayer, Julian F

2017-10-01

Stress-related cognitive processes may occur outside of awareness, here referred to as unconscious stress, and affect one's physiological state. Evidence supporting this idea would provide necessary clarification of the relationship between psychological stress and cardiovascular (CV) health problems. We tested the hypothesis that increases in mean arterial pressure (MAP) and total peripheral resistance (TPR) and decreases in heart rate variability (HRV) would be larger when threatening stimuli are presented outside of awareness, or subliminally, compared with neutral stimuli. Additionally, it was expected that trait worry and resting HRV, as common risk factors for CV disease, would moderate the effect. We presented a subliminal semantic priming paradigm to college students that were randomly assigned to the threat (n = 56) or neutral condition (n = 60) and assessed changes from baseline of MAP, TPR, and HRV. Level of trait worry was assessed with the Penn State Worry Questionnaire. The findings indicate that CV activity changed according to the hypothesized pattern: A higher MAP and TPR and a lower HRV in the threat condition compared with the neutral condition were found with practically meaningful effect sizes. However, these findings were only statistically significant for TPR. Furthermore, changes in CV activity were not moderated by trait worry or resting HRV. This is the first study to explicitly address the role of subliminally presented threat words on health-relevant outcome measures and suggests that unconscious stress can influence peripheral vascular resistance. © 2017 Society for Psychophysiological Research.

Interaction between acyl-ghrelin and BMI predicts clinical outcomes in hemodialysis patients.

PubMed

Beberashvili, Ilia; Sinuani, Inna; Azar, Ada; Shapiro, Gregory; Feldman, Leonid; Doenyas-Barak, Keren; Stav, Kobi; Efrati, Shai

2017-01-18

Ghrelin, a gastric orexigenic peptide, and body mass index (BMI) are known as inversely associated to each other and are both linked to cardiovascular (CV) risk and mortality in maintenance hemodialysis (MHD) patients. However, it is unclear whether the interaction between ghrelin and BMI is associated with a risk of all-cause and CV death in this population. A prospective observational study was performed on 261 MHD outpatients (39% women, mean age 68.6 ± 13.6 years) recruited from October 2010 through April 2012, and were followed until November 2014 (median follow-up-28 months, interquartile range-19-34 months). We measured acyl-ghrelin (AG) levels, appetite, nutritional and inflammatory markers, prospective all-cause and cardiovascular (CV) mortality. During follow-up, 109 patients died, 51 due to CV causes. A significant interaction effect of high BMI and high AG (defined as levels higher than median) on all-cause mortality was found. Crude Cox HR for the product termed BMI x AG was 0.52, with a 95% confidence interval (CI): 0.29 to 0.95 (P = 0.03). Evaluating the interaction on an additive scale revealed that the combined predictive value of BMI and AG is larger than the sum of their individual predictive values (synergy index was 1.1). Across the four BMI-AG categories, the group with high BMI and high AG exhibited better all-cause and cardiovascular mortality irrespective of appetite and nutritional status (multivariable adjusted hazard ratios were 0.31, 95% CI 0.16 to 0.62, P = 0.001, and 0.35, 95% CI 0.13 to 0.91, P = 0.03, respectively). Data analyses made by dividing patients according to fat mass-AG, but not to lean body mass-AG categories, provided similar results. Higher AG levels enhance the favourable association between high BMI and survival in MHD patients irrespective of appetite, nutritional status and inflammation.

High Prevalence of Insecure Attachment in Patients with Primary Hypertension

PubMed Central

Balint, Elisabeth M.; Gander, Manuela; Pokorny, Dan; Funk, Alexandra; Waller, Christiane; Buchheim, Anna

2016-01-01

Hypertension is a major cardiovascular (CV) risk factor and is predicted by heightened CV reactivity to stress in healthy individuals. Patients with hypertension also show an altered stress response, while insecure attachment is linked to a heightened stress reactivity as well. This is the first study aiming to assess attachment representations in patients with primary hypertension and to investigate their CV responses when their attachment system is activated. We studied 50 patients (38 men, 12 women) with primary hypertension. The Adult Attachment Projective Picture System (AAP), a widely used and validated interview, was performed to measure the patients' attachment representations, and to activate their attachment system. Blood pressure and heart rate were measured after 10 min at rest prior to and directly after the AAP interview. Mood and state anxiety were assessed using the Multidimensional Mood State Questionnaire (MDBF) and the State Trait Anxiety Inventory-State (STAI-S) before and after the experiment. The prevalence of insecure attachment (dismissing, preoccupied, unresolved) in hypertensive patients was predominant (88%), while in non-clinical populations, only about 50% of individuals had insecure attachment patterns. Blood pressure (p < 0.001), heart rate (p = 0.016), and rate pressure product (p < 0.001) significantly increased in response to the attachment interview. Secure attached patients showed the highest rise in systolic blood pressure (p = 0.020) and the lowest heart rate compared to the other attachment groups (p = 0.043). However, attachment representation showed no significant group or interaction effects on diastolic blood pressure (DBP) and rate pressure product. Insecure attachment was highly over-represented in our sample of patients with primary hypertension. Additionally, a robust CV response to the attachment-activating stimulus was observed. Our data suggest that insecure attachment is significantly linked to primary hypertension, which implies the need for further investigations to evaluate attachment insecurity as a possible risk factor for hypertension. PMID:27536255

75 FR 64782 - Additional Designations, Foreign Narcotics Kingpin Designation Act

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-20

... Panama, Panama; R.F.C. AIN-000713-GR7 (Mexico); (ENTITY) [SDNTK]. 7. GRUPO CRISTAL CORONA S.A. DE C.V..., Juan Carlos); c/ o GRUPO CRISTAL CORONA S.A. DE C.V., Mexico City, Distrito Federal, Mexico; Calle de...); c/o GRUPO CRISTAL CORONA S.A. DE C.V., Mexico City, Distrito Federal, Mexico; c/o COMERCIALIZADORA...

Dobutamine cardiac "stress" test reveals increased arrhythmia risk in conscious rats after a single exposure to acrolein

EPA Science Inventory

Mild-to-moderate exercise is often used to stress the cardiovascular (CV) system of patients while monitoring them for electrocardiogram (ECG) abnormalities that may indicate underlying CV disease. We previously demonstrated that dobutamine, which increases heart rate (HR) and co...

Prognostic Value of Electrocardiographic Left Ventricular Hypertrophy on Cardiovascular Risk in a Non-hypertensive Community-based Population.

PubMed

Tanaka, Kentaro; Tanaka, Fumitaka; Onoda, Toshiyuki; Tanno, Kozo; Ohsawa, Masaki; Sakata, Kiyomi; Omama, Shinichi; Ogasawara, Kuniaki; Ishibashi, Yasuhiro; Itai, Kazuyoshi; Kuribayashi, Toru; Okayama, Akira; Nakamura, Motoyuki

2018-04-06

The appearance of left ventricular hypertrophy on 12-lead electrocardiography (ECG-LVH) has been clarified to be associated with the risk of incidence of cardiovascular events (CVEs) in hypertensive individuals and the general population, but not enough in non-hypertensive individuals. A total of 4,927 non-hypertensive individuals ≥ 40 years of age who were free of CVE in the general population were followed for the incidence of CVE. ECG-LVH was defined according to criteria of the Sokolow-Lyon (SL) voltage, Cornell voltage (CV), or Cornell voltage product (CP). During the average 9.8 ± 2.0 years of follow-up, 267 individuals (5.4%) had their first CVE. The hazard ratio (HR) for the incidence of CVE after full adjustment by potential confounders significantly increased in the individuals with ECG-LVH by any criteria of the SL voltage, CV, and CP (HR = 1.77, p < 0.001) compared to those with no ECG-LVH. This association was significant also in individuals without any of obesity, dyslipidemia, and diabetes mellitus or those with systolic BP <120 mmHg and diastolic BP < 80mmHg. Furthermore, ECG-LVH by each criteria provided the reclassification improvement for the CVE risk prediction model by the Framingham 10-year risk score (the net reclassification improvement = 0.17 to 0.22, each p value < 0.010). In the absence of hypertension, ECG-LVH parameters are associated with the increased risk of developed CVEs independent of the established risk factors and provide the additional prognostic value in an assessment of the CVE risk using the traditional risk factors.

Timing effects in health valuations.

PubMed

Leiter, Andrea M; Pruckner, Gerald J

2014-06-01

This paper analyzes the impact of external sources of information, conveyed by the frequency of risky events that vary across time, on the individual willingness to pay (WTP) for a reduction of mortality risk. We collected data from a contingent valuation (CV) exercise conducted in two waves (fall and winter) to examine whether individual WTP varied across periods that differed in the predominance of fatal accidents. Risk valuations were based on fatal snow avalanche accidents, that is, a type of risk with seasonal differences in occurrence. We found slightly lower but statistically significant mean WTP figures in the winter than in the fall sample because of time-varying individual risk attitudes and, therefore, recommend controlling for these factors in risk assessment CV surveys. Copyright © 2013 John Wiley & Sons, Ltd.

Physical and chemical properties, antioxidant activity, total phenol and mineral profile of seeds of seven different date fruit (Phoenix dactylifera L.) varieties.

PubMed

Juhaimi, Fahad Al; Ghafoor, Kashif; Özcan, Mehmet Musa

2012-02-01

The physical and chemical properties of the date (Phoenix dactylifera L.) fruit seeds from seven date samples (Soukari, Soulag, Barhi, Khulas, Rozaiz, Soughi and Monaif) were evaluated. Energy values of dried and ground seeds were found between 4340 kcal/kg (Barhi cv) and 4795 kcal/kg (Rozaiz cv). Also, while crude oil content of seeds were established between 4.68% (Khulas cv) and 7.96% (Monaif cv), crude protein contents were found at the levels between 3.71% (Soulag cv) and 5.47% (Barhi cv). The antioxidant activity of seeds obtained from different date fruits changed between 78.03 (mg/ml) (Monaif cv) and 79.94 (mg/ml) (Barhi cv). In addition, the total phenol contents of seeds were found between 1.98 mg gallic acid equivalents (GAE)/100 g (Barhi cv) and 4.65 mg GAE/100 g (Soughi cv). The most abundant fatty acids of the date seed oils were oleic, lauric, myristic, palmitic and stearic acids. Ca, Mg, K and P contents of date seeds were found at the high concentrations.

Reduced high-density lipoprotein cholesterol: A valuable, independent prognostic marker in peripheral arterial disease.

PubMed

Martinez-Aguilar, Esther; Orbe, Josune; Fernández-Montero, Alejandro; Fernández-Alonso, Sebastián; Rodríguez, Jose A; Fernández-Alonso, Leopoldo; Páramo, Jose A; Roncal, Carmen

2017-11-01

The prognosis of patients with peripheral arterial disease (PAD) is characterized by an exceptionally high risk for myocardial infarction, ischemic stroke, and death; however, studies in search of new prognostic biomarkers in PAD are scarce. Even though low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with higher risk of cardiovascular (CV) complications and death in different atherosclerotic diseases, recent epidemiologic studies have challenged its prognostic utility. The aim of this study was to test the predictive value of HDL-C as a risk factor for ischemic events or death in symptomatic PAD patients. Clinical and demographic parameters of 254 symptomatic PAD patients were recorded. Amputation, ischemic coronary disease, cerebrovascular disease, and all-cause mortality were recorded during a mean follow-up of 2.7 years. Multivariate analyses showed that disease severity (critical limb ischemia) was significantly reduced in patients with normal HDL-C levels compared with the group with low HDL-C levels (multivariate analysis odds ratio, 0.09; 95% confidence interval [CI], 0.03-0.24). A decreased risk for mortality (hazard ratio, 0.46; 95% CI, 0.21-0.99) and major adverse CV events (hazard ratio, 0.38; 95% CI, 0.16-0.86) was also found in patients with normal vs reduced levels of HDL-C in both Cox proportional hazards models and Kaplan-Meier estimates, after adjustment for confounding factors. Reduced HDL-C levels were significantly associated with higher risk for development of CV complications as well as with mortality in PAD patients. These findings highlight the usefulness of this simple test for early identification of PAD patients at high risk for development of major CV events. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Skin autofluorescence and the association with renal and cardiovascular risk factors in chronic kidney disease stage 3.

PubMed

McIntyre, Natasha J; Fluck, Richard J; McIntyre, Christopher W; Taal, Maarten W

2011-10-01

Tissue advanced glycation end products (AGE) accumulation is a measure of cumulative metabolic stress. Assessment of tissue AGE by skin autofluorescence (SAF) correlates well with cardiovascular (CV) outcomes in diabetic, transplant, and dialysis patients, and may be a useful marker of CV risk in earlier stages of chronic kidney disease (CKD). 1707 patients with estimated GFR 59 to 30 ml/min per 1.73 m(2) were recruited from primary care practices for the Renal Risk In Derby (RRID) study. Detailed medical history was obtained, and each participant underwent clinical assessment as well as urine and serum biochemistry tests. SAF was assessed (mean of three readings) as a measure of skin AGE deposition using a cutaneous AF device (AGE Reader™, DiagnOptics, Groningen, The Netherlands). Univariate analysis revealed significant correlations between AF readings and several potential risk factors for cardiovascular disease (CVD) and progression of CKD. SAF readings (arbitrary units) were also significantly higher among males (2.8 ± 0.7 versus 2.7 ± 0.6), diabetics (3.0 ± 0.7 versus 2.7 ± 0.6), patients with evidence of self-reported CVD (2.9 ± 0.7 versus 2.7 ± 0.6), and those with no formal educational qualifications (2.8 ± 0.6 versus 2.6 ± 0.6; P < 0.01 for all). Multivariable linear regression analysis identified hemoglobin, diabetes, age, and eGFR as the most significant independent determinants of higher SAF (standardized coefficients -0.16, 0.13, 0.12, and -0.10, respectively; R(2) = 0.17 for equation). Increased SAF is independently associated with multiple CV and renal risk factors in CKD 3. Long-term follow-up will assess the value of SAF as a predictor of CV and renal risk in this population.

Exercise and physical activity in systemic lupus erythematosus: A systematic review with meta-analyses.

PubMed

O'Dwyer, Tom; Durcan, Laura; Wilson, Fiona

2017-10-01

Systemic lupus erythematosus (SLE) associates with enhanced cardiovascular (CV) risk frequently unexplained by traditional risk factors. Physical inactivity, common in SLE, likely contributes to the burden of CV risk and may also be a factor in co-morbid chronic fatigue. This systematic review evaluates whether exercise has a deleterious effect on disease activity in SLE, and explores effects on CV function and risk factors, physical fitness and function and health-related measures. A systematic review, with meta-analyses, was conducted; quasi-randomised and randomised controlled trials in SLE comparing at least one exercise group to controls were included. MEDLINE/PubMed, EMBASE, PEDro, AMED, CINAHL, The Cochrane Central Register of Controlled Trials, and relevant conference abstracts were searched. Random-effects meta-analyses were used to pool extracted data as mean differences. Heterogeneity was evaluated with χ 2 test and I 2 , with p < 0.05 considered significant. The search identified 3068 records, and 31 full-texts were assessed for eligibility. Eleven studies, including 469 participants, were included. Overall risk of bias of these studies was unclear. Exercise interventions were reported to be safe, while adverse effects were rare. Meta-analyses suggest that exercise does not adversely affect disease activity, positively influences depression, improves cardiorespiratory capacity and reduces fatigue, compared to controls. Exercise programmes had no significant effects on CV risk factors compared to controls. Therapeutic exercise programmes appear safe, and do not adversely affect disease activity. Fatigue, depression and physical fitness were improved following exercise-based interventions. A multimodal approach may be suggested, however the optimal exercise protocol remains unclear. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of canine circovirus in dogs with acute haemorrhagic diarrhoea.

PubMed

Anderson, A; Hartmann, K; Leutenegger, C M; Proksch, A L; Mueller, R S; Unterer, S

2017-06-03

Canine circovirus (CanineCV) has been detected in some dogs with severe haemorrhagic diarrhoea, but its pathogenic role is unclear. This study evaluated a suspected association between the presence of CanineCV and acute haemorrhagic diarrhoea syndrome (AHDS) in dogs. The prevalence of CanineCV in dogs with AHDS was compared with that in healthy dogs and those infected with canine parvovirus (CPV). Additionally, time to recovery and mortality rate were compared between CanineCV-positive and CanineCV-negative dogs. Faecal samples of dogs with AHDS (n=55), healthy dogs (n=66) and dogs infected with CPV (n=54) were examined by two real-time TaqMan PCR assays targeting the replicase and capsid genes of CanineCV. CanineCV was detected in faecal samples of two dogs with AHDS, three healthy controls and seven dogs infected with CPV. Among the three groups, there was no significant difference in prevalence of CanineCV. CPV-infected animals that were coinfected with CanineCV had a significantly higher mortality rate compared with those negative for CanineCV. CanineCV does not appear to be the primary causative agent of AHDS in dogs, but might play a role as a negative co-factor in disease outcome in dogs with CPV infection. British Veterinary Association.

Erectile dysfunction in fit and healthy young men: psychological or pathological?

PubMed Central

Rastrelli, Giulia

2017-01-01

Epidemiological studies consistently show that prevalence of erectile dysfunction (ED) increases with ageing. Nonetheless, complaints of ED even in younger men are becoming more and more frequent. Healthcare professionals working in Sexual Medicine but even those operating in different clinical contexts might be adequately prepared to answer this increasing requirement. ED in younger men is likely to be overlooked and dismissed without performing any medical assessment, even the most basic ones, such as collection of medical history and physical exam. This is due to the widespread assumption that ED in younger individuals is a self-limiting condition, which does not deserve any clinical evaluation or therapy and can be managed only with patient reassurance. However, evidence shows that, in younger subjects, organic, psychological and relational conditions can contribute to the pathogenesis of ED and all these conditions might be evaluated and treated, whenever necessary. Among the organic conditions contributing to the onset of ED, metabolic and cardiovascular (CV) risk factors are surprisingly of particular relevance in this age group. In fact, in younger men with ED, even more than in older ones, recognizing CV risk factors or conditions suggestive of cardio-metabolic derangements can help identifying men who, although at low absolute risk due to young age, carry a high relative risk for development of CV events. In this view, the assessment of a possible organic component of ED even in younger individuals acquires a pivotal importance, because it offers the unique opportunity to unearth the presence of CV risk factors, thus allowing effective and high quality preventive interventions. PMID:28217453

PTH, vitamin D, and the FGF-23-klotho axis and heart: Going beyond the confines of nephrology.

PubMed

Navarro-García, José Alberto; Fernández-Velasco, María; Delgado, Carmen; Delgado, Juan F; Kuro-O, Makoto; Ruilope, Luis M; Ruiz-Hurtado, Gema

2018-04-01

Profound disturbances in mineral metabolism are closely linked to the progression of chronic kidney disease. However, increasing clinical and experimental evidence indicates that alterations in phosphate homoeostasis could have an even stronger impact on the heart. The aim of this review is to provide the reader with an update of how alterations in mineral metabolism are related to direct and indirect cardiotoxic effects beyond the nephrology setting. Evidence exists that alterations in mineral metabolism that are related to changes in parathyroid hormone (PTH), vitamin D, and the FGF-23-klotho axis have direct pathological consequences for the heart. Alterations in plasma PTH levels are associated with cardiac dysfunction and detrimental cardiac remodelling. Several clinical studies have associated vitamin D deficiency with the prevalence of cardiovascular disease (CV) and its risk factors. Recent evidences support deleterious direct and nonphosphaturic effects of FGF-23 on the heart as hypertrophy development. In contrast, reduced systemic klotho levels are related to CV damage, at least when advanced age is present. In addition, we discuss how these mineral metabolism molecules can counteract each other in some situations, in the context of failed clinical trials on cardiac protection as is the case of vitamin D supplementation. Among all mineral components, an increase in systemic FGF-23 levels is considered to have the greatest CV impact and risk. However, it is quite possible that many intracellular mechanisms mediated by FGF-23, especially those related to cardiomyocyte function, remain to be discovered. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Association between lipid levels and major adverse cardiovascular events in rheumatoid arthritis compared to non-rheumatoid arthritis patients.

PubMed

Liao, Katherine P; Liu, Jun; Lu, Bing; Solomon, Daniel H; Kim, Seoyoung C

2015-05-01

Lower levels of low-density lipoprotein (LDL) cholesterol may be associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). This study was undertaken to determine whether the complex relationship between levels of LDL and high-density lipoprotein (HDL) cholesterol and CV risk is different in RA patients as compared to non-RA controls. Using data from a US health insurance plan (2003-2012), we conducted a cohort study that included patients with RA and non-RA control subjects matched with regard to age, sex, and index date. The nonlinearity of associations between lipid levels and incidence of major adverse CV events (MACE) was tested. We used multivariable Cox proportional hazards regression models to examine for an interaction between lipid levels and RA status in relation to the risk of MACE, after adjustment for CV risk factors. In total, 16,085 RA patients and 48,499 non-RA controls were studied. The mean age was 52.6 years and 78.6% were women. The relationship between LDL cholesterol levels and incidence of MACE was nonlinear and similar between RA patients and non-RA controls (P for interaction = 0.72). No significant increase in CV risk was observed between the lowest quintile of LDL cholesterol levels (≤91.0 mg/dl) and the second, third, or fourth quintiles, whereas the highest quintile (>190.0 mg/dl) conveyed a 40% increase in risk of MACE (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.17-1.68). The relationship between HDL cholesterol levels and incidence of MACE was also nonlinear and similar between RA patients and non-RA controls (P for interaction = 0.39). Compared to the lowest quintile of HDL cholesterol levels, each successive quintile was associated with a reduced risk of MACE (HR 0.45, 95% CI 0.48-0.72 for lowest quintile [≤43.0 mg/dl] versus highest quintile [>71.0 mg/dl]). The complex relationship between LDL cholesterol levels, HDL cholesterol levels, and risk of MACE was nonlinear in RA patients and also not statistically significantly different from that in an age- and sex-matched non-RA cohort. © 2015, American College of Rheumatology.

Cardiovascular Disease Outcomes Related to Early Stage Renal Impairment Following Liver Transplantation.

PubMed

VanWagner, Lisa B; Montag, Samantha; Zhao, Lihui; Allen, Norrina B; Lloyd-Jones, Donald M; Das, Arighno; Skaro, Anton I; Hohmann, Samuel; Friedewald, John J; Levitsky, Josh

2018-03-20

In the general population, even mild renal disease is associated with increased cardiovascular (CV) complications. Whether this is true in liver transplant recipients (LTR) is unknown. This was a retrospective cohort study of 671 LTR (2002-2012) from a large urban tertiary care center and 37,322 LTR using Vizient hospitalization data linked to the United Network for Organ Sharing. The MDRD4 equation estimated GFR (eGFR). Outcomes were 1-year CV complications (death/hospitalization from myocardial infarction, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism or stroke) and mortality. Latent mixture modeling identified trajectories in eGFR in the first LT year in the 671 patients. Mean(SD) eGFR was 72.1(45.7) ml/min/1.73m. Six distinct eGFR trajectories were identified in the local cohort (n=671): qualitatively Normal-Slow Decrease (4% of cohort), Normal-Rapid Decrease (4%), Mild-Stable (18%), Mild-Slow Decrease (35%), Moderate-Stable (30%), and Severe-Stable (9%). In multivariable analyses adjusted for confounders and baseline eGFR, the greatest odds of 1-year CV complications were in the Normal-Rapid Decrease group (OR, 95% CI: 10.6, 3.0-36.9). Among the national cohort, each 5-unit lower eGFR at LT was associated with a 2% and 5% higher hazard of all-cause and CV-mortality, respectively (p<0.0001) independent of multiple confounders. Even mild renal disease at the time of LT is a risk factor for posttransplant all-cause and CV mortality. More rapid declines in eGFR soon after LT correlate with risk of adverse CV outcomes, highlighting the need to study whether early renal preservation interventions also reduce CV complications.

Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme.

PubMed

Johansen, Odd Erik; Neubacher, Dietmar; von Eynatten, Maximilian; Patel, Sanjay; Woerle, Hans-Juergen

2012-01-10

This study investigated the cardiovascular (CV) safety profile of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin versus comparator treatments. This was a pre-specified meta-analysis of CV events in linagliptin or comparator-treated patients with type 2 diabetes mellitus (T2DM) from eight Phase 3 studies. All suspected CV events were prospectively adjudicated by a blinded independent expert committee. The primary endpoint was a composite of CV death, stroke, myocardial infarction, and hospitalization for unstable angina. Three secondary composite endpoints derived from the adjudicated CV events were also pre-specified. Risk estimates were calculated using several statistical methods including Cox regression analysis. Of 5239 treated patients (mean ± SD HbA1c 65 ± 10 mmol/mol [8.0 ± 0.9%], age 58 ± 10 years, BMI 29 ± 5 kg/m2), 3319 received linagliptin once daily (5 mg, 3159; 10 mg, 160) and 1920 received comparators (placebo, 977; glimepiride 1-4 mg, 781; voglibose 0.6 mg, 162). Cumulative exposure (patient-years) was 2060 for linagliptin and 1372 for comparators. Primary CV events occurred in 11 (0.3%) patients receiving linagliptin and 23 (1.2%) receiving comparators. The hazard ratio (HR) for the primary endpoint showed significantly lower risk with linagliptin than comparators (HR 0.34 [95% confidence interval (CI) 0.16-0.70]) as did estimates for all secondary endpoints (HR ranging from 0.34 to 0.55 [all upper 95% CIs < 1.0]). These results from a large Phase 3 programme support the hypothesis that linagliptin may have CV benefits in patients with T2DM. © 2012 Johansen et al; licensee BioMed Central Ltd.

Antihyperglycemic Medications and Impact on Cardiovascular Outcomes: A Review of Current Evidence.

PubMed

Gale, Stormi E; Poon, Jeannie L; Watson, Kristin

2018-05-25

Patients with type 2 diabetes mellitus (DM) are known to be at an increased risk for macrovascular complications, and cardiovascular disease (CVD) is one of the greatest drivers of morbidity and mortality in this patient population. Over the past decade, the number of treatment options for type 2 DM has increased. In 2008, the United States Food and Drug Administration mandated an evaluation of cardiovascular (CV) outcomes associated with antihyperglycemic agents. Since that time, the CV risk-benefit profile of many antihyperglycemic treatment modalities have been evaluated; however, results have remained inconsistent. This article will review the literature on the use of pharmacologic therapies in patients with type 2 DM and associated CVD risk, as well as provide recommendations for appropriate treatment selection in this population. Current evidence has demonstrated CV benefits with metformin, select glucagon-like peptide-1 receptor agonists (liraglutide), and sodium-glucose co-transporter-2 inhibitors (canagliflozin and empagliflozin). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The relationship between work ability and oxidative stress in Japanese workers.

PubMed

Ohta, Masanori; Kumashiro, Masaharu; Eguchi, Yasumasa; Morita, Yusaku; Konno, Yoshimasa; Yamato, Hiroshi

2014-01-01

Work ability is based on the balance between personal resources and work demand. This study focused on the personal resources component of work ability. The aims of this study were to elucidate the association between work ability and cardiovascular (CV) risk factors, particularly oxidative stress, and to estimate the effect of a community-implemented lifestyle modification programme on work ability and CV risk factors. Urinary 8-iso-prostaglandin F2α (PGF2α), a biomarker of oxidative stress, was negatively correlated with psychological resources, as measured by the Work Ability Index (WAI). Overall WAI score was unchanged following the programme, while CV risk factors and antioxidative activity improved. A reduction in PGF2α levels was correlated with an improvement in subjective work ability relative to job demands, as assessed by a WAI item. Taken together, the results suggest that lifestyle modification programmes enhance the personal resources component of work ability and are associated with a reduction in oxidative stress.

Cardiovascular risk in chronic kidney disease: what is new in the pathogenesis and treatment?

PubMed

Bazyluk, Angelika; Malyszko, Jolanta; Zbroch, Edyta

2018-06-12

The prevalence of chronic kidney disease (CKD) has increased markedly over past decades due to the aging of the worldwide population. Despite the progress in the prevention and treatment, the cardiovascular (CV) morbidity and mortality remain high among patients with CKD. Although CKD is a progressive and irreversible condition, it is possible to slow decreasing kidney function, as well as the development and progression of associated with kidney disease comorbidities. Diabetes mellitus has become major cause of CKD worldwide. It is estimated that the prevalence of diabetes will increase from 425 million worldwide in 2017 to 629 million by 2045, substantially the percentage of diabetic nephropathy among CKD patients is set to rise markedly. The results of multicenter trials concerning novel antidiabetic drugs suggest that efficacy in reducing CV risk is independent of the improvement in glycemic control. This review discusses underlying causes of high CV risk and strategies reducing individual burden among CKD patients.

[Problems of cardiovascular toxicity of coxibs and non-selective NSA].

PubMed

Forejtová, S

2006-01-01

Non-steroidal antirheumatics (NSA) belong to the most often prescribed drugs. Certain observation studies indicate that they are used by 20 to 30% of population of developed countries. The most common NSA's adverse effects are gastrointestinal complications. Coxibs have been developed as an alternative to conventional non-selective NSA; with similar efficacy, they should reduce the risk of development of gastrointestinal complications. In the few last years, possible toxicity of coxibs and other non-steroidal antirheumatics has been widely discussed. The VIGOR study, which was performed 6 years ago, showed five times higher incidence of nonfatal myocardial infarction in patients with rofecoxib therapy as compared with naproxen. Afterwards, there was much debate about rofecoxib, and coxibs in general, whose cardiotoxicity was supported and confuted at the same time. Possible cardioprotective effect of naproxen was discussed too. Later on, results of the APPROVE study (Adenoma Polyp Prevention on Vioxx) made Merck & Co., Inc. withdraw rofecoxib from all markets voluntarily. In the end of 2004, three controversial studies on celecoxib were published. Although the first study (Adenoma Prevention with Celecoxib study, APC) showed higher cardiovascular risk of celecoxib, the second study (Prevention of Adenomatosus Polyps, PreSAP) did not verify these results. Surprisingly, the third study (Alzheimer Disease and Prevention Trial, ADAPT) proved 50% increase of the risk of cardiovascular (CV) toxicity of naproxen. In the last year, researchers have tried to decide whether CV toxicity is a class effect of coxib group or a class effect of all NSA. Many observation studies proved higher CV risk both of coxibs (particularly rofecoxib) and non-selective NSA including naproxen. These new findings moved the American FDA (Food and Drug Administration) to publish guidance concerning higher CV risk of all coxibs and NSA. For the time being, the EMEA (European Agency for Evaluation of Medicinal Products) does not change its attitude to NSA; coxibs are contraindicated in patients with ischemic heart disease, cerebrovascular disease and peripheral artery disease; they should be used with caution in high-risk patients. Final assessment of the problems of CV toxicity of NSA and coxibs will be a case of a long-term randomized study focused on the incidence of cardiovascular adverse effects.

Effects of physical activity and exercise training on cardiovascular risk in coronary artery disease patients with and without type 2 diabetes.

PubMed

Karjalainen, Jaana J; Kiviniemi, Antti M; Hautala, Arto J; Piira, Olli-Pekka; Lepojärvi, E Samuli; Perkiömäki, Juha S; Junttila, M Juhani; Huikuri, Heikki V; Tulppo, Mikko P

2015-04-01

Leisure-time physical activity (LTPA) and exercise training are essential parts of current guidelines for patients with coronary artery disease (CAD). However, the contributions of LTPA and exercise training to cardiovascular (CV) risk in CAD patients with type 2 diabetes (T2D) are not well established. We examined the effects of LTPA (n = 539 and n = 507; with and without T2D, respectively) and 2-year controlled, home-based exercise training (n = 63 plus 64 control subjects with T2D and n = 72 plus 68 control subjects without T2D) on the CV risk profile and composite end point among CAD patients. During the 2-year follow-up, patients with reduced LTPA at baseline had an increased risk of CV events (adjusted hazard ratio 2.3 [95% CI 1.1-5.1; P = 0.033], 2.1 [1.1-4.2; P = 0.027], and 2.0 [1.0-3.9; P = 0.044] for no LTPA, LTPA irregularly, and LTPA two to three times weekly, respectively) compared with those with LTPA more than three times weekly. Among patients who completed the 2-year exercise intervention, exercise training resulted in favorable changes in exercise capacity both in CAD patients with T2D (+0.2 ± 0.8 vs. -0.1 ± 0.8 MET, P = 0.030) and without T2D (+0.3 ± 0.7 vs. -0.1 ± 0.5 MET, P = 0.002) as compared with the control group but did not have any significant effects on major metabolic or autonomic nervous system risk factors in CAD patients with or without T2D. There is an inverse association between habitual LTPA and short-term CV outcome, but controlled, home-based exercise training has only minor effects on the CV risk profile in CAD patients with T2D. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor.

PubMed

Tenenbaum, Alexander; Klempfner, Robert; Fisman, Enrique Z

2014-12-04

The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG. Initial experience with en ezetimibe/fibrates combination seems promising. The recently released IMPROVE-IT Trial is the first to prove that adding a non-statin drug (ezetimibe) to a statin lowers the risk of future CV events. In conclusion, the classical clinical paradigm of lipids-modifying treatment should be changed and high TG should be recognized as an important target for therapy in their own right. Hypertriglyceridemia should be treated.

Risk of Cardiovascular Hospitalizations from Exposure to Coarse Particulate Matter (PM10) Below the European Union Safety Threshold.

PubMed

Vaduganathan, Muthiah; De Palma, Giuseppe; Manerba, Alessandra; Goldoni, Matteo; Triggiani, Marco; Apostoli, Pietro; Dei Cas, Livio; Nodari, Savina

2016-04-15

The association between exposure to air pollution and acute cardiovascular (CV) events is well documented; however, limited data are available evaluating the public health safety of various "doses" of particular matter (PM) below currently accepted safety thresholds. We explored the cross-sectional association between PM with aerodynamic diameter <10 μm (PM10) and daily CV hospitalizations in Brescia, Italy, using Poisson regression models adjusted for age, gender, and meteorologic indices. Average daily exposure to PM10 obtained from arithmetic means of air pollution data were captured by 4 selected monitoring stations. PM10 data were expressed as daily means (lag 0-day) or 3-day moving averages (lag 3-day) and categorized according to the European Union daily limit value of 50 μg/m(3). From September 2004 to September 2007, data from 6,000 acute CV admissions to a tertiary referral center were collected. An increase of 1 μg/m(3) PM10 at lag 0-day was independently associated with higher rates of acute hospitalizations for composite CV-related events (relative risk [RR] 1.004, 95% confidence interval [CI] 1.002 to 1.006), acute heart failure (RR 1.004, 95% CI 1.001 to 1.008), acute coronary syndromes (RR 1.002, 95% CI 0.999 to 1.005), malignant ventricular arrhythmias (RR 1.004, 95% CI 0.999 to 1.010), and atrial fibrillation (RR 1.008, 95% CI 1.003 to 1.012). Similar results were obtained using PM10 lag 3-day data. The excess PM10 CV hospitalization risk (by lag 0-day and lag 3-day) did not vary significantly above and below the 50 μg/m(3) safety threshold or by age and gender. In conclusion, increased levels of PM10, even below the current limits set by the European Union, were associated with excess risk for admissions for acute CV events. Copyright © 2016 Elsevier Inc. All rights reserved.

Strategies and methods to study female-specific cardiovascular health and disease: a guide for clinical scientists.

PubMed

Ouyang, Pamela; Wenger, Nanette K; Taylor, Doris; Rich-Edwards, Janet W; Steiner, Meir; Shaw, Leslee J; Berga, Sarah L; Miller, Virginia M; Merz, Noel Bairey

2016-01-01

In 2001, the Institute of Medicine's (IOM) report, "Exploring the Biological Contributions to Human Health: Does Sex Matter?" advocated for better understanding of the differences in human diseases between the sexes, with translation of these differences into clinical practice. Sex differences are well documented in the prevalence of cardiovascular (CV) risk factors, the clinical manifestation and incidence of cardiovascular disease (CVD), and the impact of risk factors on outcomes. There are also physiologic and psychosocial factors unique to women that may affect CVD risk, such as issues related to reproduction. The Society for Women's Health Research (SWHR) CV Network compiled an inventory of sex-specific strategies and methods for the study of women and CV health and disease across the lifespan. References for methods and strategy details are provided to gather and evaluate this information. Some items comprise robust measures; others are in development. To address female-specific CV health and disease in population, physiology, and clinical trial research, data should be collected on reproductive history, psychosocial variables, and other factors that disproportionately affect CVD in women. Variables related to reproductive health include the following: age of menarche, menstrual cycle regularity, hormone levels, oral contraceptive use, pregnancy history/complications, polycystic ovary syndrome (PCOS) components, menopause age, and use and type of menopausal hormone therapy. Other factors that differentially affect women's CV risk include diabetes mellitus, autoimmune inflammatory disease, and autonomic vasomotor control. Sex differences in aging as well as psychosocial variables such as depression and stress should also be considered. Women are frequently not included/enrolled in mixed-sex CVD studies; when they are included, information on these variables is generally not collected. These omissions limit the ability to determine the role of sex-specific contributors to CV health and disease. Lack of sex-specific knowledge contributes to the CVD health disparities that women face. The purpose of this review is to encourage investigators to consider ways to increase the usefulness of physiological and psychosocial data obtained from clinical populations, in an effort to improve the understanding of sex differences in clinical CVD research and health-care delivery for women and men.

Association of Serum Triglyceride to HDL Cholesterol Ratio with All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients.

PubMed

Chang, Tae Ik; Streja, Elani; Soohoo, Melissa; Kim, Tae Woo; Rhee, Connie M; Kovesdy, Csaba P; Kashyap, Moti L; Vaziri, Nosratola D; Kalantar-Zadeh, Kamyar; Moradi, Hamid

2017-04-03

Elevated serum triglyceride/HDL cholesterol (TG/HDL-C) ratio has been identified as a risk factor for cardiovascular (CV) disease and mortality in the general population. However, the association of this important clinical index with mortality has not been fully evaluated in patients with ESRD on maintenance hemodialysis (MHD). We hypothesized that the association of serum TG/HDL-C ratio with all-cause and CV mortality in patients with ESRD on MHD is different from the general population. We studied the association of serum TG/HDL-C ratio with all-cause and CV mortality in a nationally representative cohort of 50,673 patients on incident hemodialysis between January 1, 2007 and December 31, 2011. Association of baseline and time-varying TG/HDL-C ratios with mortality was assessed using Cox proportional hazard regression models, with adjustment for multiple variables, including statin therapy. During the median follow-up of 19 months (interquartile range, 11-32 months), 12,778 all-cause deaths and 4541 CV deaths occurred, respectively. We found that the 10th decile group (reference: sixth deciles of TG/HDL-C ratios) had significantly lower risk of all-cause mortality (hazard ratio, 0.91 [95% confidence interval, 0.83 to 0.99] in baseline and 0.86 [95% confidence interval, 0.79 to 0.94] in time-varying models) and CV mortality (hazard ratio, 0.83 [95% confidence interval, 0.72 to 0.96] in baseline and 0.77 [95% confidence interval, 0.66 to 0.90] in time-varying models). These associations remained consistent and significant across various subgroups. Contrary to the general population, elevated TG/HDL-C ratio was associated with better CV and overall survival in patients on hemodialysis. Our findings provide further support that the nature of CV disease and mortality in patients with ESRD is unique and distinct from other patient populations. Hence, it is vital that future studies focus on identifying risk factors unique to patients on MHD and decipher the underlying mechanisms responsible for poor outcomes in patients with ESRD. Copyright © 2017 by the American Society of Nephrology.

Association of Serum Triglyceride to HDL Cholesterol Ratio with All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients

PubMed Central

Chang, Tae Ik; Streja, Elani; Soohoo, Melissa; Kim, Tae Woo; Rhee, Connie M.; Kovesdy, Csaba P.; Kashyap, Moti L.; Vaziri, Nosratola D.; Kalantar-Zadeh, Kamyar

2017-01-01

Background and objectives Elevated serum triglyceride/HDL cholesterol (TG/HDL-C) ratio has been identified as a risk factor for cardiovascular (CV) disease and mortality in the general population. However, the association of this important clinical index with mortality has not been fully evaluated in patients with ESRD on maintenance hemodialysis (MHD). We hypothesized that the association of serum TG/HDL-C ratio with all-cause and CV mortality in patients with ESRD on MHD is different from the general population. Design, setting, participants, & measurements We studied the association of serum TG/HDL-C ratio with all-cause and CV mortality in a nationally representative cohort of 50,673 patients on incident hemodialysis between January 1, 2007 and December 31, 2011. Association of baseline and time-varying TG/HDL-C ratios with mortality was assessed using Cox proportional hazard regression models, with adjustment for multiple variables, including statin therapy. Results During the median follow-up of 19 months (interquartile range, 11–32 months), 12,778 all-cause deaths and 4541 CV deaths occurred, respectively. We found that the 10th decile group (reference: sixth deciles of TG/HDL-C ratios) had significantly lower risk of all-cause mortality (hazard ratio, 0.91 [95% confidence interval, 0.83 to 0.99] in baseline and 0.86 [95% confidence interval, 0.79 to 0.94] in time-varying models) and CV mortality (hazard ratio, 0.83 [95% confidence interval, 0.72 to 0.96] in baseline and 0.77 [95% confidence interval, 0.66 to 0.90] in time-varying models). These associations remained consistent and significant across various subgroups. Conclusions Contrary to the general population, elevated TG/HDL-C ratio was associated with better CV and overall survival in patients on hemodialysis. Our findings provide further support that the nature of CV disease and mortality in patients with ESRD is unique and distinct from other patient populations. Hence, it is vital that future studies focus on identifying risk factors unique to patients on MHD and decipher the underlying mechanisms responsible for poor outcomes in patients with ESRD. PMID:28193609

Effect of Bromocriptine-QR (a Quick-Release Formulation of Bromocriptine Mesylate) on Major Adverse Cardiovascular Events in Type 2 Diabetes Subjects

PubMed Central

Gaziano, J. Michael; Cincotta, Anthony H.; Vinik, Aaron; Blonde, Lawrence; Bohannon, Nancy; Scranton, Richard

2012-01-01

Background Bromocriptine-QR (a quick-release formulation of bromocriptine mesylate), a dopamine D2 receptor agonist, is a US Food and Drug Administrration–approved treatment for type 2 diabetes mellitus (T2DM). A 3070-subject randomized trial demonstrated a significant, 40% reduction in relative risk among bromocriptine-QR-treated subjects in a prespecified composite cardiovascular (CV) end point that included ischemic-related (myocardial infarction and stroke) and nonischemic-related (hospitalization for unstable angina, congestive heart failure [CHF], or revascularization surgery) end points, but did not include cardiovascular death as a component of this composite. The present investigation was undertaken to more critically evaluate the impact of bromocriptine-QR on cardiovascular outcomes in this study subject population by (1) including CV death in the above-described original composite analysis and then stratifying this new analysis on the basis of multiple demographic subgroups and (2) analyzing the influence of this intervention on only the “hard” CV end points of myocardial infarction, stroke, and CV death (major adverse cardiovascular events [MACEs]). Methods and Results Three thousand seventy T2DM subjects on stable doses of ≤2 antidiabetes medications (including insulin) with HbA1c ≤10.0 (average baseline HbA1c=7.0) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 52-week treatment period. Subjects with heart failure (New York Heart Classes I and II) and precedent myocardial infarction or revascularization surgery were allowed to participate in the trial. Study outcomes included time to first event for each of the 2 CV composite end points described above. The relative risk comparing bromocriptine-QR with the control for the cardiovascular outcomes was estimated as a hazard ratio with 95% confidence interval on the basis of Cox proportional hazards regression. The statistical significance of any between-group difference in the cumulative percentage of CV events over time (derived from a Kaplan–Meier curve) was determined by a log-rank test on the intention-to-treat population. Study subjects were in reasonable metabolic control, with an average baseline HbA1c of 7.0±1.1, blood pressure of 128/76±14/9, and total and LDL cholesterol of 179±42 and 98±32, respectively, with 88%, 77%, and 69% of subjects being treated with antidiabetic, antihypertensive, and antihyperlipidemic agents, respectively. Ninety-one percent of the expected person-year outcome ascertainment was obtained in this study. Respecting the CV-inclusive composite cardiovascular end point, there were 39 events (1.9%) among 2054 bromocriptine-QR-treated subjects versus 33 events (3.2%) among 1016 placebo subjects, yielding a significant, 39% reduction in relative risk in this end point with bromocriptine-QR exposure (P=0.0346; log-rank test) that was not influenced by age, sex, race, body mass index, duration of diabetes, or preexisting cardiovascular disease. In addition, regarding the MACE end point, there were 14 events (0.7%) among 2054 bromocriptine-QR-treated subjects and 15 events (1.5%) among 1016 placebo-treated subjects, yielding a significant, 52% reduction in relative risk in this end point with bromocriptine-QR exposure (P<0.05; log-rank test). Conclusions These findings reaffirm and extend the original observation of relative risk reduction in cardiovascular adverse events among type 2 diabetes subjects treated with bromocriptine-QR and suggest that further investigation into this impact of bromocriptine-QR is warranted. Clinical Trial Registration URL: http://clinicaltrials.gov. Unique Identifier: NCT00377676 PMID:23316290

Metabolic syndrome, insulin resistance, and chronic allograft dysfunction.

PubMed

Porrini, Esteban; Delgado, Patricia; Torres, Armando

2010-12-01

Metabolic syndrome (MS) is a cluster of cardiovascular (CV) risk factors (hypertension, dyslipidemia, obesity, and glucose homeostasis alterations), and insulin resistance (IR) is suggested to be a common pathogenic background. In the general population, MS and IR have been proven to be risk factors for diabetes, CV disease, and chronic kidney disease. In the renal transplant setting, few studies have analyzed the relevance of MS and IR. According to the few data available, the prevalence of MS in renal transplant patients has been described as 22.6% at 12 months, 37.7% at 36 months, and 64% at 6 years after transplantation. Importantly, MS has been shown to be an independent risk factor for chronic allograft dysfunction (CAD), graft failure, new-onset diabetes, and CV disease. Also, persistent hyperinsulinemia during the first posttransplant year has been related to an increase in glomerular filtration rate, probably reflecting glomerular hyperfiltration as observed in prediabetes and early type 2 diabetes. Importantly, prediabetes (impaired fasting glucose and impaired glucose tolerance), a state hallmarked by IR, proved to be highly frequent among stable renal transplant recipients (30%), which is nearly three times its incidence in the general population. Posttransplant IR has been associated with subclinical atheromatosis as assessed by carotid intima-media thickness, and with chronic subclinical inflammation. In conclusion, MS and IR are important modifiable risk factors in renal transplant recipients, and prompt interventions to avoid its deleterious effects at the metabolic, CV, and graft function levels are needed.

Advances in the management of cardiovascular risk for patients with type 2 diabetes: perspectives from the Academy for Cardiovascular Risk, Outcomes and Safety Studies in Type 2 Diabetes

PubMed Central

Schernthaner, Guntram; Jarvis, Sarah; Lotan, Chaim; Prázný, Martin; Wanner, Christoph; Wascher, Thomas C

2017-01-01

Diabetes is a global health emergency projected to affect 642 million people by 2040. Type 2 diabetes (T2D) represents 90% of diabetes cases and is associated with a range of cardiovascular (CV) risk factors that are more than double the incidence of CV disease and significantly increase mortality rates. Diabetes treatments have typically focused on improving glycemic control but their effect on CV outcomes has remained uncertain. In 2008, the US Food and Drug Administration (FDA) looked to address this knowledge gap and mandated CV outcome trials (CVOTs) for all new antidiabetic therapies. In 2015, EMPA-REG OUTCOME® became the first CVOT to present results for a sodium/glucose cotransporter 2 (SGLT2; also known as SLC5A2) inhibitor, empagliflozin. Subsequently, a regional meeting of the Academy for Cardiovascular Risk, Outcomes and Safety Studies in Type 2 Diabetes (ACROSS T2D) brought together a respected faculty of international experts and 150 physicians from 14 countries to discuss the current unmet medical needs of patients with T2D, the results from the EMPA-REG OUTCOME study and the implications of these results for clinical practice. This article summarizes the current scientific evidence and the discussions that took place at the ACROSS T2D regional meeting, which was held in Vienna, Austria, on May 30, 2016. PMID:28144148

A single exposure to diesel exhaust increases the risk of triggered cardiac arrhythmias in conscious rats during dobutamine cardiac "stress" test.

EPA Science Inventory

Mild-to-moderate exercise is often used to stress the cardiovascular (CV) system of patients while monitoring them for electrocardiogram (ECG) abnormalities that may indicate underlying CV disease. We previously used dobutamine, which increases heart rate (HR) and contractility, ...

The role of noninvasive cardiovascular testing, applied clinical nutrition and nutritional supplements in the prevention and treatment of coronary heart disease.

PubMed

Houston, Mark

2018-03-01

Numerous clinical trials suggest that we have reached a limit in our ability to decrease the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) utilizing the traditional diagnostic evaluation, prevention and treatment strategies for the top five cardiovascular risk factors of hypertension, diabetes mellitus, dyslipidemia, obesity and smoking. About 80% of heart disease (heart attacks, angina, coronary heart disease and congestive heart failure) can be prevented by optimal nutrition, optimal exercise, optimal weight and body composition, mild alcohol intake and avoiding smoking. Statistics show that approximately 50% of patients continue to have CHD or myocardial infarction (MI) despite presently defined 'normal' levels of the five risk factors listed above. This is often referred to as the 'CHD gap'. Novel and more accurate definitions and evaluations of these top five risk factors are required, such as 24 h ambulatory blood pressure (ABM) results, advanced lipid profiles, redefined fasting and 2 h dysglycemia parameters, a focus on visceral obesity and body composition and the effects of adipokines on cardiovascular risk. There are numerous traumatic insults from the environment that damage the cardiovascular system but there are only three finite vascular endothelial responses, which are inflammation, oxidative stress and immune vascular dysfunction. In addition, the concept of translational cardiovascular medicine is mandatory in order to correlate the myriad of CHD risk factors to the presence or absence of functional or structural damage to the vascular system, preclinical and clinical CHD. This can be accomplished by utilizing advanced and updated CV risk scoring systems, new and redefined CV risk factors and biomarkers, micronutrient testing, cardiovascular genetics, nutrigenomics, metabolomics, genetic expression testing and noninvasive cardiovascular testing.

The role of noninvasive cardiovascular testing, applied clinical nutrition and nutritional supplements in the prevention and treatment of coronary heart disease

PubMed Central

Houston, Mark

2018-01-01

Numerous clinical trials suggest that we have reached a limit in our ability to decrease the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) utilizing the traditional diagnostic evaluation, prevention and treatment strategies for the top five cardiovascular risk factors of hypertension, diabetes mellitus, dyslipidemia, obesity and smoking. About 80% of heart disease (heart attacks, angina, coronary heart disease and congestive heart failure) can be prevented by optimal nutrition, optimal exercise, optimal weight and body composition, mild alcohol intake and avoiding smoking. Statistics show that approximately 50% of patients continue to have CHD or myocardial infarction (MI) despite presently defined ‘normal’ levels of the five risk factors listed above. This is often referred to as the ‘CHD gap’. Novel and more accurate definitions and evaluations of these top five risk factors are required, such as 24 h ambulatory blood pressure (ABM) results, advanced lipid profiles, redefined fasting and 2 h dysglycemia parameters, a focus on visceral obesity and body composition and the effects of adipokines on cardiovascular risk. There are numerous traumatic insults from the environment that damage the cardiovascular system but there are only three finite vascular endothelial responses, which are inflammation, oxidative stress and immune vascular dysfunction. In addition, the concept of translational cardiovascular medicine is mandatory in order to correlate the myriad of CHD risk factors to the presence or absence of functional or structural damage to the vascular system, preclinical and clinical CHD. This can be accomplished by utilizing advanced and updated CV risk scoring systems, new and redefined CV risk factors and biomarkers, micronutrient testing, cardiovascular genetics, nutrigenomics, metabolomics, genetic expression testing and noninvasive cardiovascular testing. PMID:29316855

The Effect of Mirthful Laughter on the Human Cardiovascular System

PubMed Central

Miller, Michael; Fry, William F.

2009-01-01

It has become increasingly recognized and more widely acknowledged during the past several decades, that a complex relationship exists between behavior associated with emotion and the human cardiovascular (CV) system. Early studies focused on the interplay between negative emotions and elevated CV risk, an effect that has in large part been attributed to increased adrenergic activity. Thus, a variety of adverse CV effects ranging from sudden cardiac death triggered by natural disasters such as earthquakes to transient myocardial stunning resulting from heightened sympathetic overload have been identified in response to acute emotional distress. In fact, the biologic interplay between emotion and CV health has been greatly enhanced through studies of the vascular endothelium. As the largest organ in humans, the inner blood vessel lining serves as a conduit for the transfer of blood cells, lipids and various nutrients across the lumen to neighboring tissues. Healthy endothelial cells secrete vasoactive chemicals, most notably endothelial-derived relaxing factor or nitric oxide (NO), that effects smooth muscle relaxation and vessel dilation via a cyclic guanosine monophosphate (cGMP) dependent protein kinase signaling pathway. In addition, endothelial derived NO may reduce vascular inflammation by attenuating or inhibiting leukocyte adhesion and subendothelial transmigration as well as decreasing platelet activation via cGMP mediated pathways. Taken together, studying the endothelium provides an exceptional opportunity to advance our understanding of the potentially important interrelationship between emotions and the vasculature. Premised on the identification of physiological and biochemical correlates, the former was demonstrated after intracoronary administration of acetylcholine yielded paradoxical endothelial vasoconstriction in response to mental stress exercises. More recently, the brachial artery reactivity test (BART) has permitted endothelial function to be assessed in a non-invasive manner. In addition to traditional CV risk factors, exposure to negative emotions including mental stress and depression have been associated with reduced endothelial vasoreactivity as measured by BART. Whether mirthful laughter has the opposite effect garnered consideration following the discovery that μ3 opiate receptors were expressed in the vascular endothelium. Because mirthful laughter induces the release of β-endorphins which in turn have high affinity for μ3 opiate receptors, we hypothesize that such positive emotions lead to the direct release of NO and associated biological consequences. Indeed, our studies have demonstrated opposing effects on endothelial vasoreactivity between those previously established (e.g., mental stress induced by negative visual and/ or auditory stimuli) and those induced after mirthful laughter, thereby providing a potential mechanistic link between positive emotions and beneficial effects on the vasculature. This article reviews the relevant physiology and comments on the potentially wider clinical implications in the integration of this process to improve vascular health. PMID:19477604

Vitamin E in the prevention of cardiovascular disease: the importance of proper patient selection

PubMed Central

Vardi, Moshe; Levy, Nina S.; Levy, Andrew P.

2013-01-01

Vitamin E is a naturally occurring fat-soluble antioxidant which has been proposed as a treatment for both primary and secondary protection against cardiovascular (CV) events. Promising data from observational epidemiological studies associating higher vitamin E dietary intake with lower risk of CV events have not been validated in randomized controlled clinical trials assessing the effect of vitamin E on CV outcomes. While the pendulum of medical opinion has swung to suggest that high dose vitamin E supplements have no place in the treatment and prevention of CV disease, new data is emerging that allows identification of a specific target population for this treatment, namely patients with diabetes mellitus and the haptoglobin genotype 2-2. This review details the scientific basis and clinical evidence related to the effect of vitamin E on CV outcomes, and the importance of proper patient selection in gaining therapeutic benefit from this intervention. PMID:23505320

Relationship of glycaemic control and hypoglycaemic episodes to 4-year cardiovascular outcomes in people with type 2 diabetes starting insulin.

PubMed

Freemantle, N; Danchin, N; Calvi-Gries, F; Vincent, M; Home, P D

2016-02-01

To examine the relationships between glycated haemoglobin (HbA1c) and cardiovascular (CV) events in people beginning insulin in routine clinical practice in Europe, North America and Asia in a non-interventional study, the Cardiovascular Risk Evaluation in people with Type 2 Diabetes on Insulin Therapy (CREDIT) study. Data on 2999 people were collected prospectively over 4 years from physician reports. The primary outcome was the composite of stroke or myocardial infarction (MI) or CV-specific death. Events were blindly adjudicated. The relative hazards of CV events were described from Cox proportional hazards models incorporating patient risk factors, with updated average HbA1c as a time-dependent covariate. The relationship of severe and symptomatic hypoglycaemia (collected during the 6 months before yearly ascertainment) with CV and all-cause mortality was examined. A total of 147 primary events were accrued during up to 54 months of follow-up. In all, 60 CV-specific deaths, 44 non-fatal MIs and 57 non-fatal strokes occurred, totalling 161 events. There was a significant positive relationship between updated mean HbA1c and primary outcome: hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.12-1.40; p < 0.0001]. CV death [HR 1.31 (95% CI 1.10-1.57); p = 0.0027] and stroke [HR 1.36 (95% CI 1.17-1.59); p < 0.0001] were both strongly associated with HbA1c, while MI was not [HR 1.05 (95% CI 0.83-1.32)]. One or more severe hypoglycaemic episodes affected 175 participants, while 1508 participants experienced one or more symptomatic hypoglycaemic events. We found no relationship between severe/symptomatic hypoglycaemic events and CV-specific/all-cause death. Ongoing poorer glucose control was associated with CV events; hypoglycaemia was not associated with CV-specific/all-cause death. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Underestimation of Risk of Carotid Subclinical Atherosclerosis by Cardiovascular Risk Scores in Patients with Psoriatic Arthritis.

PubMed

Shen, Jiayun; Lam, Steven H; Shang, Qing; Wong, Chun-Kwok; Li, Edmund K; Wong, Priscilla; Kun, Emily W; Cheng, Isaac T; Li, Martin; Li, Tena K; Zhu, Tracy Y; Lee, Jack Jock-Wai; Chang, Mimi; Lee, Alex Pui-Wai; Tam, Lai-Shan

2018-02-01

To test the performances of established cardiovascular (CV) risk scores in discriminating subclinical atherosclerosis (SCA) in patients with psoriatic arthritis. These scores were calculated: Framingham risk score (FRS), QRISK2, Systematic COronary Risk Evaluation (SCORE), 10-year atherosclerotic cardiovascular disease risk algorithm (ASCVD) from the American College of Cardiology and the American Heart Association, and the European League Against Rheumatism (EULAR)-recommended modified versions (by 1.5 multiplication factor, m-). Carotid intima-media thickness > 0.9 mm and/or the presence of plaque determined by ultrasound were classified as SCA+. We recruited 146 patients [49.4 ± 10.2 yrs, male: 90 (61.6%)], of whom 142/137/128/118 patients were eligible to calculate FRS/QRISK2/SCORE/ASCVD. Further, 62 (42.5%) patients were SCA+ and were significantly older, with higher systolic blood pressure and higher low-density lipoprotein cholesterol (all p < 0.05). All CV risk scores were significantly higher in patients with SCA+ [FRS: 7.8 (3.9-16.5) vs 2.7 (1.1-7.8), p < 0.001; QRISK2: 5.5 (3.1-10.2) vs 2.9 (1.2-6.3), p < 0.001; SCORE: 1 (0-2) vs 0 (0-1), p < 0.001; ASCVD: 5.6 (2.6-12.4) vs 3.4 (1.4-6.1), p = 0.001]. The Hosmer-Lemeshow test revealed moderate goodness of fit for the 4 CV scores (p ranged from 0.087 to 0.686). However, of the patients with SCA+, those identified as high risk were only 44.1% (by FRS > 10%), 1.8% (QRISK2 > 20%), 10.9% (SCORE > 5%), and 43.6% (ASCVD > 7.5%). By applying the EULAR multiplication factor, 50.8%/14.3%/14.5%/54.5% of the patients with SCA+ were identified as high risk by m-FRS/m-QRISK2/m-SCORE/m-ASCVD, respectively. EULAR modification increased the sensitivity of FRS and ASCVD in discriminating SCA+ from 44% to 51%, and 44% to 55%, respectively. All CV risk scores underestimated the SCA+ risk. EULAR-recommended modification improved the sensitivity of FRS and ASCVD only to a moderate level.

76 FR 58562 - Additional Designations, Foreign Narcotics Kingpin Designation Act

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-21

... RESTAURANTES, S.A. DE C.V., Martin L. Guzman 259-3, Colonia Villa de Cortes, Delegacion Benito Juarez, Mexico...); (ENTITY) [SDNTK]. 3. FLORBEL OPERADORA DE RESTAURANTES, S.A. DE C.V., Mexico City, Distrito Federal...

Pediatric Blood Pressure and Adult Preclinical Markers of Cardiovascular Disease

PubMed Central

Magnussen, Costan G.; Smith, Kylie J.

2016-01-01

A high blood pressure level in adults is considered the single most important modifiable risk factor for global disease burden, especially those of cardiovascular (CV) origin such as stroke and ischemic heart disease. Because blood pressure levels have been shown to persist from childhood to adulthood, elevations in pediatric levels have been hypothesized to lead to increased CV burden in adulthood and, as such, might provide a window in the life course where primordial and primary prevention could be focused. In the absence of substantive data directly linking childhood blood pressure levels to overt adult CV disease, this review outlines the available literature that examines the association between pediatric blood pressure and adult preclinical markers of CV disease. PMID:27168729

Testosterone Replacement Therapy: Long-Term Safety and Efficacy

PubMed Central

Corona, Giovanni; Sforza, Alessandra

2017-01-01

Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH). The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T) therapy (TTh). In addition, concerns related to cardiovascular (CV) safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented. PMID:28497912

Potential Adverse Cardiovascular Effects From Excessive Endurance Exercise

PubMed Central

O'Keefe, James H.; Patil, Harshal R.; Lavie, Carl J.; Magalski, Anthony; Vogel, Robert A.; McCullough, Peter A.

2012-01-01

A routine of regular exercise is highly effective for prevention and treatment of many common chronic diseases and improves cardiovascular (CV) health and longevity. However, long-term excessive endurance exercise may induce pathologic structural remodeling of the heart and large arteries. Emerging data suggest that chronic training for and competing in extreme endurance events such as marathons, ultramarathons, ironman distance triathlons, and very long distance bicycle races, can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which return to normal within 1 week. Over months to years of repetitive injury, this process, in some individuals, may lead to patchy myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, creating a substrate for atrial and ventricular arrhythmias. Additionally, long-term excessive sustained exercise may be associated with coronary artery calcification, diastolic dysfunction, and large-artery wall stiffening. However, this concept is still hypothetical and there is some inconsistency in the reported findings. Furthermore, lifelong vigorous exercisers generally have low mortality rates and excellent functional capacity. Notwithstanding, the hypothesis that long-term excessive endurance exercise may induce adverse CV remodeling warrants further investigation to identify at-risk individuals and formulate physical fitness regimens for conferring optimal CV health and longevity. PMID:22677079

Nonclinical and clinical pharmacology evidence for cardiovascular safety of saxagliptin.

PubMed

Pollack, Pia S; Chadwick, Kristina D; Smith, David M; Billger, Martin; Hirshberg, Boaz; Iqbal, Nayyar; Boulton, David W

2017-09-13

In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial in patients with type 2 diabetes mellitus (T2D) at high risk of cardiovascular (CV) disease, saxagliptin did not increase the risk for major CV adverse events. However, there was an unexpected imbalance in events of hospitalization for heart failure (hHF), one of six components of the secondary CV composite endpoint, with a greater number of events observed with saxagliptin. Here, we examined findings from nonclinical safety and clinical pharmacology studies of saxagliptin with the aim of identifying any potential signals of myocardial injury. In vitro and in vivo (rat, dog, monkey) safety pharmacology and toxicology studies evaluating the potential effects of saxagliptin and its major active metabolite, 5-hydroxy saxagliptin, on the CV system are reviewed. In addition, results from saxagliptin clinical studies are discussed: one randomized, 2-period, double-blind, placebo-controlled single-ascending-dose study (up to 100 mg); one randomized, double-blind, placebo-controlled, sequential, multiple-ascending-high-dose study (up to 400 mg/day for 14 days); and one randomized, double-blind, 4-period, 4-treatment, cross-over thorough QTc study (up to 40 mg/day for 4 days) in healthy volunteers; as well as one randomized, placebo-controlled, sequential multiple-ascending-dose study in patients with T2D (up to 50 mg/day for 14 days). Neither saxagliptin nor 5-hydroxy saxagliptin affected ligand binding to receptors and ion channels (e.g. potassium channels) or action potential duration in in vitro studies. In animal toxicology studies, no changes in the cardiac conduction system, blood pressure, heart rate, contractility, heart weight, or heart histopathology were observed. In healthy participants and patients with T2D, there were no findings suggestive of myocyte injury or fluid overload. Serum chemistry abnormalities indicative of cardiac injury, nonspecific muscle damage, or fluid homeostasis changes were infrequent and balanced across treatment groups. There were no QTc changes associated with saxagliptin. No treatment-emergent adverse events suggestive of heart failure or myocardial damage were reported. The saxagliptin nonclinical and clinical pharmacology programs did not identify evidence of myocardial injury and/or CV harm that may have predicted or may explain the unexpected imbalance in the rate of hHF observed in SAVOR.

Treatment of hypertension and metabolic syndrome: lowering blood pressure is not enough for organ protection, new approach-arterial destiffening.

PubMed

Zimlichman, Reuven

2014-10-01

Cardiovascular risk factors (CVRFs) have been shown to induce end organ damage. Until now, the main approach to reduce CVRF-induced end organ damage was by normalization of CVRFs; this approach was found effective to reduce damage and cardiovascular (CV) events. However, a residual risk always remained even when CVRFs were optimally balanced. An additional risk factor which has an immense effect on the progression of end organ damage is aging. Aging is accompanied by gradual stiffening of the arteries which finally leads to CV events. Until recently, the process of arterial aging was considered as unmodifiable, but this has changed. Arterial stiffening caused by the aging process is similar to the changes seen as a result of CVRF-induced arterial damage. Actually, the presence of CVRFs causes faster arterial stiffening, and the extent of damage is proportional to the severity of the CVRF, the length of its existence, the patient's genetic factors, etc. Conventional treatments of osteoporosis and of hormonal decline at menopause are potential additional approaches to positively affect progression of arterial stiffening. The new approach to further decrease progression of arteriosclerosis, thus preventing events, is the prevention of age-associated arterial structural changes. This approach should further decrease age-associated arterial stiffening. A totally new promising approach is to study the possibility of affecting collagen, elastin, and other components of connective tissue that participate in the process of arterial stiffening. Reduction of pulse pressure by intervention in arterial stiffening process by novel methods as breaking collagen cross-links or preventing their formation is an example of future directions in treatment. This field is of enormous potential that might be revolutionary in inducing further significant reduction of cardiovascular events.

Empagliflozin and Cardiovascular Outcomes in Asian Patients With Type 2 Diabetes and Established Cardiovascular Disease　- Results From EMPA-REG OUTCOME®.

PubMed

Kaku, Kohei; Lee, Jisoo; Mattheus, Michaela; Kaspers, Stefan; George, Jyothis; Woerle, Hans-Juergen

2017-01-25

In the EMPA-REG OUTCOME ® trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular (CV) events (3-point MACE: composite of CV death, non-fatal myocardial infarction, or non-fatal stroke) by 14%, CV death by 38%, hospitalization for heart failure by 35%, and all-cause mortality by 32% in patients with type 2 diabetes (T2DM) and established CV disease. We investigated the effects of empagliflozin in patients of Asian race.Methods and Results:Patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Of 7,020 patients treated, 1,517 (21.6%) were of Asian race. The reduction in 3-point MACE in Asian patients was consistent with the overall population: 3-point MACE occurred in 79/1,006 patients (7.9%) in the pooled empagliflozin group vs. 58/511 patients (11.4%) in the placebo group (hazard ratio: 0.68 [95% confidence interval: 0.48-0.95], P-value for treatment by race interaction (Asian, White, Black/African-American): 0.0872). The effects of empagliflozin on the components of MACE, all-cause mortality, and heart failure outcomes in Asian patients were consistent with the overall population (P-values for interaction by race >0.05). The adverse event profile of empagliflozin in Asian patients was similar to the overall trial population. Reductions in the risk of CV outcomes and mortality with empagliflozin in Asian patients with T2DM and established CV disease were consistent with the overall trial population.

Use of oseltamivir after influenza infection is associated with reduced incidence of recurrent adverse cardiovascular outcomes among military health system beneficiaries with prior cardiovascular diseases.

PubMed

Casscells, S Ward; Granger, Elder; Kress, Amii M; Linton, Andrea; Madjid, Mohammad; Cottrell, Linda

2009-03-01

Influenza infection has been associated with increased risk of adverse cardiac and cerebral vascular outcomes. Oseltamivir, a treatment for influenza, has been shown to decrease the severity of an influenza episode, but few data exist regarding its potentially protective effect against recurrent vascular outcomes among influenza patients with a history of vascular disease. Electronic healthcare service and pharmacy records for 37,482 TRICARE beneficiaries, aged 18 and older, with a coded history of cardiovascular (CV) disease and a subsequent diagnosis of influenza from October 1, 2003, through September 30, 2007, were examined. Subjects were grouped according to whether they had filled a prescription for oseltamivir within 2 days of their influenza diagnosis. The incidence of recurrent CV events within 30 days after the influenza diagnosis among oseltavmivir-treated and untreated subjects was 8.5% and 21.2%, respectively (P<0.005). Subject age was a persistent and significant contributor to the likelihood of recurrent CV outcomes. After controlling for the differences in demographics among treated and untreated cohorts using a propensity-scored logistic regression model, a statistically significant protective effect was associated with oseltamivir treatment (odds ratio, 0.417; 95% CI, 0.349 to 0.498). Our findings suggests that oseltamivir treatment for influenza is associated with significant decrease in the risk of recurrent CV events in subjects with a history of CV disease. These findings merit confirmation in further prospective and controlled studies. Meanwhile, in patients with CV disease, strict adherence with current practice guidelines for prevention and treatment of influenza is recommended.

Abnormal muscle membrane function in fibromyalgia patients and its relationship to the number of tender points.

PubMed

Klaver-Król, Ewa G; Zwarts, Machiel J; Ten Klooster, Peter M; Rasker, Johannes J

2012-01-01

Fibromyalgia (FM) is a disorder characterised by chronic widespread pain in soft tissues, especially in muscles. Previous research has demonstrated a higher muscle fibre conduction velocity (CV) in painful muscles of FM patients. The primary goal of this study was to investigate whether there is also a difference in CV in non-painful, non-tender point (TP) related muscles between FM patients and controls. The secondary goal was to explore associations between the CV, the number of TPs and the complaints in FM. Surface electromyography (sEMG) was performed on the biceps brachii muscle of female FM patients (13) and matched healthy controls (13). Short static contractions were applied with the arm unloaded and loaded at 5% and 10% of maximum voluntary force. The CV was derived by cross-correlation method (CV-cc) and inter-peak latency method (CV-ipl). TP score and Fibromyalgia Impact Questionnaire (FIQ) were performed in all participants. Correlations were calculated between the CVs, TP score and items of the FIQ. In FM patients, the CV was higher than in the controls (CV-cc p=0.005; CV-ipl p=0.022). The CV was correlated with the number of TPs in FM patients (r=0.642 and 0.672 for CV-cc and CV-ipl, respectively). No correlations were found between the CV and any aspect of health status on the FIQ. The results demonstrate abnormally high muscle membrane conduction velocity in FM, even in non-TP muscles. In addition, a relationship has been found between the high membrane velocity and the number of TPs.

Utilization of lipid-modifying therapy and low-density lipoprotein cholesterol goal attainment in patients at high and very-high cardiovascular risk: Real-world evidence from Germany.

PubMed

März, Winfried; Dippel, Franz-Werner; Theobald, Karlheinz; Gorcyca, Katherine; Iorga, Şerban R; Ansell, David

2018-01-01

Elevated low-density lipoprotein cholesterol (LDL-C) is a causal risk factor for cardiovascular (CV) events. European guidelines recommend reducing LDL-C as the primary lipid target to reduce CV risk, using lifestyle modifications and lipid-lowering therapy (LLT). Many European patients do not achieve guideline-recommended LDL-C levels. The present database analysis aimed to assess LLT treatment patterns and LDL-C threshold attainment in Germany in a large, real-world cohort of patients. Patients from the Cegedim Longitudinal Practice Database in Germany who met selection criteria were included: (a) LDL-C measurement in 2013; (b) ≥20 years of age; (c) high or very-high CV risk conditions: recent acute coronary syndrome (ACS), other coronary heart disease (CHD), ischemic stroke, peripheral arterial disease (PAD) (atherosclerotic cardiovascular disease [ASCVD]) or diabetes mellitus (DM) (non-ASCVD). LDL-C threshold attainment was assessed based on LDL-C targets from 2011 European guidelines. 42,767 patients met the inclusion criteria; 35% received current statin treatment, and 30% achieved guideline-recommended LDL-C targets. Attainment of LDL-C goals among ASCVD hierarchical categories was 46.7% for recent ACS, 35.8% for ischemic stroke, 34.9% for other CHD, and 26.9% for PAD. Among patients in the non-ASCVD group with DM, 23.6% achieved LDL-C goals. Similar results were observed when patients were grouped by prevalence (patients assigned to every risk group for which they qualified). In this high/very-high CV risk population in Germany, statin utilization was low; suggesting that LLTs are not prescribed as per European guidelines. These results highlight the need to increase LLT use among high-risk patients. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Laparoscopic Roux-En-Y Gastric Bypass Improves Lipid Profile and Decreases Cardiovascular Risk: a 5-Year Longitudinal Cohort Study of 1048 Patients.

PubMed

Gero, Daniel; Favre, Lucie; Allemann, Pierre; Fournier, Pierre; Demartines, Nicolas; Suter, Michel

2018-03-01

Dyslipidemia is a known risk factor for cardiovascular (CV) events. The aim of the study was to assess lipid profiles and their impact on CV risk changes in a large patient cohort 5 years after Roux-en-Y gastric bypass (RYGB). All patients who underwent primary RYGB for severe obesity in our two hospitals between January 1999 and December 2009 were included. The Framingham risk score was used. One thousand and forty-eight patients were included, 791 women and 257 men. Five-year complete lipid profile was available for 77% of patients. At 5 years, mean body mass index (BMI) decreased from 45.7 ± 6 to 31 ± 5.8 kg/m 2 (p < 0.001), excess BMI loss (EBMIL) was 72.35 ± 22%, and total body weight loss (TWL) 31.5 ± 9%. Lipid values improved significantly. Total- and LDL-cholesterol levels dropped at 1 year from 5.4 to 4.48 mmol/L and 3.2 to 2.41 mmol/L, respectively, and slightly increased thereafter. Triglyceride levels dropped from 2 to 1.17 mmol/L at 1 year and remained unchanged. HDL levels rose continuously from 1.27 to 1.77 mmol/L at 5 years. Lipid profile improved more in patients with greater weight loss (%EBMIL ≥ 50 or %TWL ≥ 25%). Assuming that all patients were non-smokers and other baseline risk factors (hypertension, diabetes) remained unchanged at 5 years, the amelioration of the lipid profile itself yielded to a 27% reduction of CV risk (p < 0.001). RYGB results in sustained excess weight loss and in amelioration of the lipid profile from the first to fifth postoperative year. This improvement translates into significantly lower CV risk from the first year after surgery.

Decreased baroreflex sensitivity is linked to sympathovagal imbalance, low-grade inflammation, and oxidative stress in pregnancy-induced hypertension.

PubMed

Subha, M; Pal, Pravati; Pal, G K; Habeebullah, S; Adithan, C; Sridhar, M G

Pregnancy-induced hypertension (PIH) has been reported as a cardiovascular (CV) risk. We assessed the sympathovagal imbalance (SVI) and the association of inflammation and oxidative stress (OS) with CV risks in PIH. A total of 125 pregnant women having a risk factor for PIH were followed till term and the incidence of PIH was observed. Retrospectively, they were divided into two groups: Group I (those who did not develop PIH, n = 82) and Group II (those who developed PIH, n = 43). Blood pressure variability (BPV) parameters including baroreflex sensitivity (BRS), spectral heart rate variability (HRV), autonomic function tests (AFTs), inflammatory markers (interleukin-6, TNF-α, interferon-γ), and OS markers were measured in both the groups. Alterations in parasympathetic and sympathetic components of AFTs were analyzed. Link of various parameters to BRS was assessed by correlation and multiple regression analysis. Parasympathetic components of AFTs were decreased from the early part of pregnancy and sympathetic components were increased toward the later part of pregnancy. Decreased BRS, the marker of CV risk, was more prominent in Group II subjects. Independent contribution of interleukin-6 (β = 0.276, P = 0.020), TNF-α (β = 0.408, P = 0.002), interferon-γ (β = 0.355, P = 0.008), and thiobarbituric-acid reactive substance (β = 0.287, P = 0.015) to BRS was found to be significant. It was concluded that sympathetic overactivity that develops more in the later part (third trimester) of pregnancy contributes to SVI and genesis of PIH. In PIH women, CV risks are present from the beginning of pregnancy that intensifies in the later part of pregnancy. Retrograde inflammation and oxidative stress contribute to the decreased BRS in PIH.

Moderate wine consumption is associated with lower hemostatic and inflammatory risk factors over 8 years: The study of women’s health across the nation (SWAN)

PubMed Central

Janssen, Imke; Landay, Alan L.; Ruppert, Kristine; Powell, Lynda H.

2015-01-01

Moderate wine consumption has been associated with reduced cardiovascular (CV) risk, but most investigations have been conducted in Caucasian populations. To investigate the relationship of wine consumption to CV risk markers, we studied a multi-ethnic sample of middle-aged, healthy women (N = 2900; 48% white, 28% black, 7% Hispanic, 8% Chinese, 9% Japanese) participating in SWAN over 7 years with repeated assessments of CV risk factors. Consumption of wine was stable and common with 20% reporting none, 69% light (<1/day), 7% moderate ( = 1/day), and 4% heavy (>1/day). To guard against underreporting, we took the maximum reported wine consumption over 7 years as the predictor. We used mixed models with a random intercept and random time to assess the relationship between wine consumption and CV risk factors with moderate consumption as the reference. Outcome variables were log-transformed where necessary. Longitudinal models were adjusted for ethnicity, age, and time-varying menopausal status, hormone therapy use, overall alcohol consumption, high density lipoprotein (HDL), statin use, and a healthy lifestyle score based on physical activity, not smoking, and weight maintenance. Interactions of wine consumption with time were not significant. Moderate wine consumers had significantly lower levels of C-reactive protein (CRP, p < .001), fibrinogen (p < .001), factor VII (p < .01), and plasminogen activator inhibitor (PAI-1, p < .05) than women who drank no or little wine. These associations were independent of significant effects of healthy lifestyle and overall alcohol consumption and similar across ethnic groups. Moderate wine consumption may protect against CVD via inflammatory and clotting pathways. PMID:25705320

Three-Dimensional Rotational Angiography of the Inferior Vena Cava as an Adjunct to Inferior Vena Cava Filter Retrieval

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

Bozlar, Ugur; Edmunds, J. Stewart; Turba, Ulku C.

The objective of this study was to explore the role of three-dimensional (3-D) rotational angiography (RA) of the inferior vena cava (IVC; 3-D CV) before filter retrieval and its impact on treatment planning compared with standard anteroposterior cavography (sCV). Thirty patients underwent sCV and 3-D CV before IVC filter retrieval. Parameters assessed were: projection of filter arms or legs beyond the caval lumen, thrombus burden within the filter and IVC, and orientation of the filter within IVC. Skin and effective radiation doses were calculated. Statistical analysis was performed using paired Student t test and nonparametric McNemar's test. Standard anteroposterior cavographymore » detected 49 filter arms or legs projecting beyond the caval lumen in 25 patients. Three-dimensional CV demonstrated 89 filter arms or legs projecting beyond the caval lumen in 28 patients. Twenty-two patients had additional filter arms or legs projecting beyond the caval lumen detected on 3-D CV that were not detected on sCV (p < 0.001). Filter apex tilt detection differed significantly (p < 0.001) between sCV and 3-D CV, with 3-D CV being more accurate. The filter apex abutted the IVC wall in 10 patients (33%) on 3-D CV, but this was diagnosed in only 3 patients (10%) with sCV. Thrombus was detected in 8 patients (27%), 1 thrombus of which was seen only on 3-D CV, and treatment was changed in this patient because of thrombus size. Mean effective radiation doses for 3-D CV were approximately two times higher than for sCV (1.68 vs. 0.86 mSv), whereas skin doses were three times lower (12.87 vs. 35.86 mGy). Compared with sCV, performing 3-D CV before optional IVC filter retrieval has the potential to improve assessment of filter arms or legs projecting beyond the caval lumen, filter orientation, and thrombus burden.« less

A safety assessment of Coriolus versicolor biomass as a food supplement.

PubMed

Barros, Ana B; Ferrão, Jorge; Fernandes, Tito

2016-01-01

Coriolus versicolor (CV) is a common mushroom with antitumor, anti-inflammatory, antioxidant, antiviral, antibacterial, and immunomodulatory properties. The existence of these properties has been extensively proven mainly using CV extract; research on the biomass form is scarce. The aim of this study was to investigate the safety of the CV biomass form, as it is commonly used as a food supplement. CV biomass powder was dissolved in distilled water and administered daily (2.5, 5.0, and 7.5 g/kg live weight) in single doses by gavage to both female and male Charles River albino rats. No adverse or lethal effects were observed as a consequence of the daily administration of CV biomass. In addition, compared with the control group, no abnormal findings were observed at necropsy and histopathological examination. A safe profile of CV biomass for human consumption can be inferred from the absence of any remarkable adverse effects in rats.

Urine Albumin-Creatinine Ratio Versus Albumin Excretion for Albuminuria Staging: A Prospective Longitudinal Cohort Study.

PubMed

Vart, Priya; Scheven, Lieneke; Lambers Heerspink, Hiddo J; de Jong, Paul E; de Zeeuw, Dick; Gansevoort, Ron T

2016-01-01

New guidelines advocate the use of albumin-creatinine ratio (ACR) in a urine sample instead of 24-hour urinary albumin excretion (UAE) for staging albuminuria. Concern has been expressed that this may result in misclassification for reasons including interindividual differences in urinary creatinine excretion. Prospective longitudinal cohort study. We examined 7,623 participants of the PREVEND and RENAAL studies for reclassified when using ACR instead of 24-hour UAE, the characteristics of reclassified participants, and their outcomes. Albuminuria was categorized into 3 ACR and UAE categories: <30, 30 to 300, and >300mg/g or mg/24 h, respectively. Baseline ACR and 24-hour UAE. Cardiovascular (CV) morbidity and mortality and all-cause mortality. When using ACR in the early morning void instead of 24-hour UAE, 88% of participants were classified in corresponding albuminuria categories. 307 (4.0%) participants were reclassified to a higher, and 603 (7.9%), to a lower category. Participants who were reclassified to a higher ACR category in general had a worse CV risk profile compared with nonreclassified participants, whereas the reverse was true for participants reclassified to a lower ACR category. Similarly, Cox proportional hazards regression analyses showed that reclassification to a higher ACR category was associated with a tendency for increased risk for CV morbidity and mortality and all-cause mortality, whereas reclassification to a lower ACR category was associated with a tendency for lower risk. Net reclassification improvement, adjusted for age, sex, and duration of follow-up, was 0.107 (P=0.002) for CV events and 0.089 (P<0.001) for all-cause mortality. Early morning void urine collection instead of spot urine collection. Our results indicate that there is high agreement between early morning void ACR and 24-hour UAE categories. Reclassification is therefore limited, but when present, is generally indicative of the presence of CV risk factors and prognosis. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Microbiota metabolites: Pivotal players of cardiovascular damage in chronic kidney disease.

PubMed

Cosola, Carmela; Rocchetti, Maria Teresa; Cupisti, Adamasco; Gesualdo, Loreto

2018-04-01

In chronic kidney disease (CKD), cardiovascular (CV) damage is present in parallel which leads to an increased risk of CV disease. Both traditional and non-traditional risk factors contribute to CV damage in CKD. The systemic role of the microbiota as a central player in the pathophysiology of many organs is progressively emerging in the literature: the microbiota is indeed involved in a complex, bi-directional network between many organs, including the kidney and heart connection, although many of these relationships still need to be elucidated through in-depth mechanistic studies. The aim of this review is to provide evidence that microbiota metabolites influence non-traditional risk factors, such as inflammation and endothelial dysfunction in CKD-associated CV damage. Here, we report our current understanding and hypotheses on the gut-kidney and gut-heart axes and provide details on the potential mechanisms mediated by microbial metabolites. More specifically, we summarize some novel hypotheses linking the microbiota to blood pressure regulation and hypertension. We also emphasise the idea that the nutritional management of CKD should be redesigned and include the new findings from research on the intrinsic plasticity of the microbiota and its metabolites in response to food intake. The need is felt to integrate the classical salt and protein restriction approach for CKD patients with foods that enhance intestinal wellness. Finally, we discuss the new perspectives, especially the importance of taking care of the microbiota in order to prevent the risk of developing CKD and hypertension, as well as the still not tested but very promising CKD innovative treatments, such as postbiotic supplementation and bacteriotherapy. This interesting area of research offers potential complementary approaches to the management of CKD and CV damage assuming that the causal mechanisms underlying the gut-kidney and gut-heart axes are clarified. This will pave the way to the design of new personalized therapies targeting gut microbiota. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Omega-3 polyunsaturated fatty acids for cardiovascular diseases: present, past and future.

PubMed

Watanabe, Yasuhiro; Tatsuno, Ichiro

2017-08-01

Large-scale epidemiological studies on Greenlandic, Canadian and Alaskan Eskimos have examined the health benefits of omega-3 fatty acids consumed as part of the diet, and found statistically significant relative reduction in cardiovascular risk in people consuming omega-3 fatty acids. Areas covered: This article reviews studies on omega-3 fatty acids during the last 50 years, and identifies issues relevant to future studies on cardiovascular (CV) risk. Expert commentary: Although a meta-analysis of large-scale prospective cohort studies and randomized studies reported that fish and fish oil consumption reduced coronary heart disease-related mortality and sudden cardiac death, omega-3 fatty acids have not yet been shown to be effective in secondary prevention trials on patients with multiple cardiovascular disease (CVD) risk factors. The ongoing long-term CV interventional outcome studies investigate high-dose, prescription-strength omega-3 fatty acids. The results are expected to clarify the potential role of omega-3 fatty acids in reducing CV risk. The anti-inflammatory properties of omega-3 fatty acids are also important. Future clinical trials should also focus on the role of these anti-inflammatory mediators in human arteriosclerotic diseases as well as inflammatory diseases.

Exercise reveals impairments in left ventricular systolic function in patients with metabolic syndrome

PubMed Central

Fournier, Sara B.; Reger, Brian L.; Donley, David A.; Bonner, Daniel E.; Warden, Bradford E.; Gharib, Wissam; Failinger, Conard F.; Olfert, Melissa D.; Frisbee, Jefferson C.; Olfert, I. Mark; Chantler, Paul D.

2013-01-01

MetS is the manifestation of a cluster of cardiovascular (CV) risk factors and is associated with a three-fold increase risk of CV morbidity and mortality, which is suggested to be mediated, in part, by resting left ventricular (LV) systolic dysfunction. However, to what extent resting LV systolic function is impaired in MetS is controversial, and there are no data indicating whether LV systolic function is impaired during exercise. Accordingly, the objective of this study was to comprehensively examine LV and arterial responses to exercise in MetS individuals without diabetes and/or overt CVD compared to a healthy control population. CV function was characterized using Doppler echocardiography and gas exchange in MetS (n=27) vs. healthy controls (n=20) at rest and during peak exercise. At rest, MetS individuals displayed normal LV systolic function but reduced LV diastolic function vs. healthy controls. During peak exercise, individuals with MetS had impaired contractility; pump performance, and vasodilator reserve capacity vs. controls. A blunted contractile reserve response resulted in diminished arterial-ventricular coupling reserve and limited aerobic capacity in MetS vs. controls. These findings possess clinical importance as they provide insight to the pathophysiological changes in MetS that may predispose this population of individuals to an increased risk of CV morbidity and mortality. PMID:24036595

Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials.

PubMed

Iqbal, Nayyar; Parker, Artist; Frederich, Robert; Donovan, Mark; Hirshberg, Boaz

2014-02-04

It is important to establish the cardiovascular (CV) safety profile of novel antidiabetic drugs. Pooled analyses were performed of 20 randomized controlled studies (N = 9156) of saxagliptin as monotherapy or add-on therapy in patients with type 2 diabetes mellitus (T2DM) as well as a subset of 11 saxagliptin + metformin studies. Adjudicated major adverse CV events (MACE; CV death, myocardial infarction [MI], and stroke) and investigator-reported heart failure were assessed, and incidence rates (IRs; events/100 patient-years) and IR ratios (IRRs; saxagliptin/control) were calculated (Mantel-Haenszel method). In pooled datasets, the IR point estimates for MACE and individual components of CV death, MI, and stroke favored saxagliptin, but the 95% CI included 1. IRR (95% CI) for MACE in the 20-study pool was 0.74 (0.45, 1.25). The Cox proportional hazard ratio (95% CI) was 0.75 (0.46, 1.21), suggesting no increased risk of MACE in the 20-study pool. In the 11-study saxagliptin + metformin pool, the IRR for MACE was 0.93 (0.44, 1.99). In the 20-study pool, the IRR for heart failure was 0.55 (0.27, 1.12). Analysis of pooled data from 20 clinical trials in patients with T2DM suggests that saxagliptin is not associated with an increased CV risk.

Comparative Effectiveness of Renin-Angiotensin System Antagonists in Maintenance Dialysis Patients

PubMed Central

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

2017-01-01

Background/Aims Whether angiotensin converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) are differentially associated with reductions in cardiovascular events and mortality in patients receiving maintenance dialysis is uncertain. We compared outcomes between ACE and ARB users among hypertensive, maintenance dialysis patients. Methods National retrospective cohort study of hypertensive, Medicare-Medicaid eligible patients initiating chronic dialysis between 1/1/2000 to 12/31/2005. The exposure of interest was new use of either an ACEI or ARB. Outcomes were all-cause mortality (ACM) and combined cardiovascular hospitalization or death (CV-endpoint). Cox proportion hazards models were used to compare the effect of ACEI vs ARB use on ACM and, separately, CV-endpoint. Results ACM models were based on 3,555 ACEI and 1,442 ARB new users, while CV-endpoint models included 3,289 ACEI and 1,346 ARB new users. After statistical adjustments, ACEI users had higher hazard ratios for ACM (AHR = 1.22, 99% CI 1.05–1.42) and CV-endpoint (AHR = 1.12, 99% CI 0.99–1.27). Conclusions Patients initiating maintenance dialysis who received an ACEI faced an increased risk for mortality and a trend towards an increased risk for CV-endpoints when compared to patients who received an ARB. Validation of these results in a rigorous clinical trial is warranted. PMID:27871075

Comparative Effectiveness of Renin-Angiotensin System Antagonists in Maintenance Dialysis Patients.

PubMed

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

2016-01-01

Whether angiotensin converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) are differentially associated with reductions in cardiovascular events and mortality in patients receiving maintenance dialysis is uncertain. We compared outcomes between ACE and ARB users among hypertensive, maintenance dialysis patients. National retrospective cohort study of hypertensive, Medicare-Medicaid eligible patients initiating chronic dialysis between 1/1/2000 to 12/31/2005. The exposure of interest was new use of either an ACEI or ARB. Outcomes were all-cause mortality (ACM) and combined cardiovascular hospitalization or death (CV-endpoint). Cox proportion hazards models were used to compare the effect of ACEI vs ARB use on ACM and, separately, CV-endpoint. ACM models were based on 3,555 ACEI and 1,442 ARB new users, while CV-endpoint models included 3,289 ACEI and 1,346 ARB new users. After statistical adjustments, ACEI users had higher hazard ratios for ACM (AHR = 1.22, 99% CI 1.05-1.42) and CV-endpoint (AHR = 1.12, 99% CI 0.99-1.27). Patients initiating maintenance dialysis who received an ACEI faced an increased risk for mortality and a trend towards an increased risk for CV-endpoints when compared to patients who received an ARB. Validation of these results in a rigorous clinical trial is warranted. © 2016 The Author(s) Published by S. Karger AG, Basel.

Global burden of CVD: focus on secondary prevention of cardiovascular disease.

PubMed

Bansilal, Sameer; Castellano, José M; Fuster, Valentín

2015-12-01

Despite encouraging advances in prevention and treatment of atherothrombosis, cardiovascular disease (CVD) remains a major cause of deaths and disability worldwide and will continue to grow mainly due to the increase in incidence in low and middle income countries (LMIC). In Europe and the United States of America (USA), coronary heart disease (CHD) mortality rates have decreased since the mid-1990s due to improvements in acute care, however the prevalence of CHD is increasing largely in part due to the overall aging of the population, increased prevalence of cardiovascular (CV) risk factors, and improved survival of patients after a CV event. Data from clinical trials has consistently proven the efficacy of pharmacologic interventions with aspirin, statins, and blood pressure (BP)-lowering agents in reducing the risk of CV events and total mortality in the ever growing pool of patients in secondary prevention. However, large gaps between indicated therapy and prescribed medication can be observed worldwide, with very low rates of use of effective therapies in LMIC countries. Adherence to medication is very poor in chronic patients, especially those treated with multiple pharmacologic agents, and has been directly correlated to a greater incidence of recurrent CV events and increase in direct and indirect healthcare costs. In this article, we review the global burden of CV disease, status of secondary prevention therapy and major barriers for treatment adherence. Copyright © 2015 Elsevier B.V. All rights reserved.

Colesevelam, Ezetimibe, and Patients With Type 2 Diabetes Mellitus: Characteristics and Clinical Outcomes From a Health Care Database.

PubMed

Swindle, Jason P; Ye, Xin; Mallick, Rajiv; Song, Rui; Horstman, Thomas; Bays, Harold E

2014-07-01

Despite the prevalence of therapies available to patients at highest coronary heart disease risk, only a minority of type 2 diabetes mellitus (T2DM) patients reach desired cholesterol treatment levels, with limited data regarding their outcomes. To examine "real-world" effectiveness of initiating treatment with either colesevelam or ezetimibe among individuals with evidence of T2DM and hypercholesterolemia (HCh). Key outcomes included treatment patterns and cardiovascular (CV) events. This retrospective administrative claims-based study utilized medical, pharmacy, and enrollment data linked to laboratory results information from a large United States health plan (January 1, 2006, to March 31, 2011) and included individuals with recorded evidence of T2DM and HCh. The index date was the date of first pharmacy claim for colesevelam or ezetimibe, with cohort assignment based on index medication. Assessments included baseline characteristics, follow-up treatment patterns, and composite CV event, with propensity score matching to correct for sample selection bias. In total, 4231 individuals were identified with evidence of HCh and T2DM (ezetimibe n = 3384; colesevelam n = 847). After matching, the baseline characteristics between cohorts were rendered to be similar. Mean days of persistent medication use was lower with colesevelam compared with ezetimibe (P < 0.001). Compared with ezetimibe, a smaller percentage of individuals in the colesevelam cohort experienced a follow-up composite CV event, and adjusted Cox model results suggested decreased risk (hazard ratio = 0.58; P = 0.004) of a follow-up composite CV event. In this health care database analysis among patients with HCh and T2DM, colesevelam was associated with decreased risk of a composite CV event compared with ezetimibe, despite lower persistence. © The Author(s) 2014.

Intake of Marine-Derived Omega-3 Polyunsaturated Fatty Acids and Mortality in Renal Transplant Recipients

PubMed Central

Gomes Neto, António W.; Sotomayor Campos, Camilo G.; Pranger, Ilse G.; van den Berg, Else; Gans, Rijk O. B.; Soedamah-Muthu, Sabita S.; Navis, Gerjan J.; Bakker, Stephan J. L.

2017-01-01

The effect of marine-derived omega-3 polyunsaturated fatty acids (n-3 PUFA) on long-term outcome in renal transplant recipients (RTR) remains unclear. We investigated whether marine-derived n-3 PUFA intake is associated with all-cause and cardiovascular (CV) mortality in RTR. Intake of eicosapentaenoic acid plus docosahexaenoic acid (EPA-DHA) was assessed using a validated Food Frequency Questionnaire. Cox regression analyses were performed to evaluate the associations of EPA-DHA intake with all-cause and CV mortality. We included 627 RTR (age 53 ± 13 years). EPA-DHA intake was 102 (42–215) mg/day. During median follow-up of 5.4 years, 130 (21%) RTR died, with 52 (8.3%) due to CV causes. EPA-DHA intake was associated with lower risk of all-cause mortality (Hazard Ratio (HR) 0.85; 95% confidence interval (95% CI) 0.75–0.97). Age (p = 0.03) and smoking status (p = 0.01) significantly modified this association, with lower risk of all-cause and CV mortality particularly in older (HR 0.75, 95% CI 0.61–0.92; HR 0.68, 95% CI 0.48–0.95) and non-smoking RTR (HR 0.80, 95% CI 0.68–0.93; HR 0.74, 95% CI 0.56–0.98). In conclusion, marine-derived n-3 PUFA intake is inversely associated with risk of all-cause and CV mortality in RTR. The strongest associations were present in subgroups of patients, which adds further evidence to the plea for EPA-DHA supplementation, particularly in elderly and non-smoking RTR. PMID:28379169

Acute effects of beer on endothelial function and hemodynamics: a single-blind, crossover study in healthy volunteers.

PubMed

Karatzi, Kalliopi; Rontoyanni, Victoria G; Protogerou, Athanase D; Georgoulia, Aggeliki; Xenos, Konstantinos; Chrysou, John; Sfikakis, Petros P; Sidossis, Labros S

2013-09-01

Moderate consumption of beer is associated with lower cardiovascular (CV) risk. The goal of this study was to determine the effect of beer consumption on CV risk. To explore the underlying mechanisms, we studied the acute effects of the constituents of beer (alcohol and antioxidants), on established predictors of CV risk: endothelial function, aortic stiffness, pressure wave reflections and aortic pressure. In a randomized, single-blind, crossover study, 17 healthy, non-smoking, men (ages 28.5 ± 5.2 y with body mass index 24.4 ± 2.5 kg/m(2)) consumed on three separate occasions, at least 1 wk apart: 1. 400 mL of beer and 400 mL water, 2. 800 mL of dealcoholized beer (same amount of polyphenols as in the 400 mL of beer), and 3. 67 mL of vodka and 733 mL water (same amount of alcohol as in the 400 mL of beer). Each time aortic stiffness (pulse wave velocity), pressure wave reflections (AΙx), aortic and brachial pressure (Sphygmocor device), and endothelial function (brachial flow mediated dilatation) were assessed at fast and 1 and 2 h postprandial. Aortic stiffness was significantly and similarly reduced by all three interventions. However, endothelial function was significantly improved only after beer consumption (average 1.33%, 95% confidence interval [CI] 0.15-2.53). Although wave reflections were significantly reduced by all three interventions (average of beer: 9.1%, dealcoholized beer: 2.8%, vodka 8.5%, all CI within limits of significance), the reduction was higher after beer consumption compared with dealcoholized beer (P = 0.018). Pulse pressure amplification (i.e., brachial/aortic) was increased by all three test drinks. Beer acutely improves parameters of arterial function and structure, in healthy non-smokers. This benefit seems to be mediated by the additive or synergistic effects of alcohol and antioxidants and merits further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of combined vitamin D--calcium supplements on the cardiovascular system: should we be cautious?

PubMed

Challoumas, Dimitrios; Stavrou, Antonio; Pericleous, Agamemnon; Dimitrakakis, Georgios

2015-02-01

Despite the growing body of evidence on the potential effects of calcium and vitamin D as monotherapies on different cardiovascular (CV) parameters, the combined supplementation with calcium and vitamin D (CaD), which is most frequently encountered in clinical practice, has not received the attention it deserves. A literature search was conducted via EMBASE and Medline and identified 14 randomised controlled trials (RCTs) and 2 meta-analyses reporting on effects of combined supplementation with CaD on CV events, CV death, blood pressure, lipids, glucose metabolism and weight. Overall, the existing evidence does not support beneficial properties of supplementation with CaD on the CV system, nor does it suggest that a re-appraisal of the use of CaD is necessary due to adverse effects, although increased risk of CV events has been reported by some authors. The guidelines for the use of CaD supplementation need not change until well-conducted RCTs that have CV effects as primary outcomes and adjust for major confounders indicate otherwise. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Association of Ideal Cardiovascular Health and Long-term Healthcare Costs.

PubMed

Willis, Benjamin L; DeFina, Laura F; Bachmann, Justin M; Franzini, Luisa; Shay, Christina M; Gao, Ang; Leonard, David; Berry, Jarett D

2015-11-01

The American Heart Association's (AHA's) 2020 Strategic Impact Goals introduced the concept of ideal cardiovascular (CV) health based on seven health factors and behaviors associated with lower CV disease (CVD) risk. The association between CV health and healthcare costs has not been reported; therefore, we evaluated the association between CV health profile and later-life healthcare costs. Cooper Center Longitudinal Study participants (N=4,906; mean age, 56 years) receiving Medicare coverage from 1999 to 2009 were included. CV health behaviors (diet, physical activity, BMI, smoking) and CV health factors (blood pressure, total cholesterol, blood glucose) were categorized as unfavorable (zero to two ideal components); intermediate (two to four); and favorable (five to seven). Healthcare costs were cumulated from Medicare claims data, adjusted for inflation. Associations between midlife CV health status and non-CVD and CVD-related costs were estimated using multivariable quantile regression. Analyses were conducted in 2013 and 2014. Favorable CV health was prevalent in 14.8% of men and 30.1% of women, with <1% having ideal levels of all health metrics. After 31,945 person-years of Medicare follow-up, individuals with favorable CV health exhibited 24.9% (95% CI=11.7%, 36.0%) lower median annual non-CVD costs and 74.5% (57.5%, 84.7%) lower median CVD costs than those with unfavorable CV health. Annualized differences were greater for non-CVD costs than for CVD costs ($1,175 vs $566). Having more ideal CV health components in middle age, as outlined by the AHA 2020 Goals, is associated with lower non-CVD and CVD healthcare costs in later life. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Low Triiodothyronine Syndrome and Long-Term Cardiovascular Outcome in Incident Peritoneal Dialysis Patients

PubMed Central

Chang, Tae Ik; Nam, Joo Young; Shin, Sug Kyun

2015-01-01

Background and objectives A direct association between low triiodothyronine (T3) syndrome and cardiovascular (CV) mortality has been reported in hemodialysis patients. However, the implications of this syndrome in peritoneal dialysis (PD) patients have not been properly investigated. This study examined the association between low T3 syndrome and CV mortality including sudden death in a large cohort of incident PD patients. Design, setting, participants, & measurements This prospective observational study included 447 euthyroid patients who started PD between January 2000 and December 2009. Measurement of thyroid hormones was performed at baseline. All-cause and cause-specific deaths were registered during the median 46 months of follow-up. The survival rate was compared among three groups based on tertile of T3 levels. Results In Kaplan–Meyer analysis, patients with the lowest tertile were significantly associated with higher risk of all-cause and CV mortality including sudden death (P<0.001 for trend). In Cox analyses, T3 level was a significant predictor of all-cause mortality (per 10-unit increase, adjusted hazard ratio [HR], 0.86; 95% confidence interval [95% CI], 0.78 to 0.94; P=0.002), CV death (per 10-unit increase, adjusted HR, 0.84; 95% CI, 0.75 to 0.98; P=0.01), and sudden death (per 10-unit increase, adjusted HR, 0.69; 95% CI, 0.56 to 0.86; P=0.001) after adjusting for well known risk factors including inflammation and malnutrition. The higher T3 level was also independently associated with lower risk for sudden death (per 10-unit increase, adjusted HR, 0.71; 95% CI, 0.56 to 0.90; P=0.01) even when accounting for competing risks of death from other causes. Conclusions T3 level at the initiation of PD was a strong independent predictor of long-term CV mortality, particularly sudden death, even after adjusting well known risk factors. Low T3 syndrome might represent a factor directly implicated in cardiac complications in PD patients. PMID:25979970

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications.

PubMed

Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Comparing health outcomes and costs of general vaccination with pneumococcal conjugate vaccines in Sweden: a Markov model.

PubMed

By, Asa; Sobocki, Patrik; Forsgren, Arne; Silfverdal, Sven-Arne

2012-01-01

Two new pneumococcal conjugate vaccines were licensed to immunize infants and young children against pneumococcal disease. The objective of this study was to estimate the expected health benefits, costs, and incremental cost-effectiveness of routine vaccination with the 10-valent pneumococcal nontypeable hemophilus influenza protein-D conjugate vaccine (PHiD-CV) compared with the 13-valent pneumococcal conjugate vaccine (PCV13) in Sweden. A Markov cohort model was used to estimate the effect of vaccination at vaccine steady state, taking a societal perspective and using a 2+1 vaccination schedule. Price parity was assumed between the vaccines. Outcomes were measured by reduction in disease burden, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio. The results predicted that PCV13 would prevent 3 additional cases of invasive pneumococcal disease and 34 additional cases of pneumonia, whereas PHiD-CV would avoid 3 additional cases of mastoiditis, 1010 tube insertions, and 10,420 cases of ambulatory acute otitis media compared with PCV13. By combining morbidity and mortality benefits of all clinical outcomes, PHiD-CV would generate 45.3 additional QALYs compared with PCV13 and generate savings of an estimated 62 million Swedish kronors. The present study predicted lower costs and better health outcome (QALYs) gained by introducing PHiD-CV compared with PCV13 in routine vaccination. Our results indicated that PHiD-CV is cost-effective compared with PCV13 in Sweden. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

High Intrapatient Variability of Tacrolimus Exposure in the Early Period After Liver Transplantation Is Associated With Poorer Outcomes.

PubMed

Rayar, Michel; Tron, Camille; Jézéquel, Caroline; Beaurepaire, Jean Marie; Petitcollin, Antoine; Houssel-Debry, Pauline; Camus, Christophe; Verdier, Marie Clémence; Dehlawi, Ammar; Lakéhal, Mohamed; Desfourneaux, Véronique; Meunier, Bernard; Sulpice, Laurent; Bellissant, Eric; Boudjema, Karim; Lemaitre, Florian

2018-03-01

Tacrolimus (TAC) is the cornerstone of immunosuppressive regimen in liver transplantation (LT). Its pharmacokinetics is characterized by a high interpatient and intrapatient variability (IPV) leading to an unpredictable dose-response relationship. The aim of our study was to evaluate the impact of TAC IPV (IPV) on graft and patient outcomes after LT. We retrospectively analyzed 812 LT recipients treated with TAC. The IPV of TAC concentrations was estimated by calculating the coefficient of variation (CV) of whole blood trough concentrations. Patients were categorized in 2 groups: low IPV (CV < 40%) and high IPV (CV ≥ 40%). There were significantly more neurologic complications (31.2% vs 16.6%, P < 0.001), cardiovascular complications (19.7% vs 9.7%, P < 0.001), and acute renal failure requiring dialysis (8.5% vs 2.2%, P < 0.001) in the high CV group than in the low CV group. Moreover, graft survival was significantly poorer in the high CV group (hazard ratio, 1.42; 95% confidence interval, 1.04-1.95; P = 0.03). A pretransplantation elevated Model for End-Stage Liver Disease score (P < 0.001) and Child-Pugh grade (P < 0.001) were identified as risk factors for presenting a high CV. A high CV of TAC concentrations was found to be predictive of TAC-related toxicity and poorer survival.

Chlorella vulgaris Attenuates Dermatophagoides Farinae-Induced Atopic Dermatitis-Like Symptoms in NC/Nga Mice

PubMed Central

Kang, Heerim; Lee, Chang Hyung; Kim, Jong Rhan; Kwon, Jung Yeon; Seo, Sang Gwon; Han, Jae Gab; Kim, Byung Gon; Kim, Jong-Eun; Lee, Ki Won

2015-01-01

Atopic dermatitis (AD) is a chronic and inflammatory skin disease that can place a significant burden on quality of life for patients. AD most frequently appears under the age of six and although its prevalence is increasing worldwide, therapeutic treatment options are limited. Chlorella vulgaris (CV) is a species of the freshwater green algae genus chlorella, and has been reported to modulate allergy-inducible factors when ingested. Here, we examined the effect of CV supplementation on AD-like symptoms in NC/Nga mice. CV was orally administrated for six weeks while AD-like symptoms were induced via topical application of Dermatophagoides farinae extract (DFE). CV treatment reduced dermatitis scores, epidermal thickness, and skin hydration. Histological analysis also revealed that CV treatment reduced DFE-induced eosinophil and mast cell infiltration into the skin, while analysis of serum chemokine levels indicated that CV treatment downregulated thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) levels. In addition, CV treatment downregulated mRNA expression levels of IL-4 and IFN-γ. Taken together, these results suggest that CV extract may have potential as a nutraceutical ingredient for the prevention of AD. PMID:26404252

77 FR 23807 - Additional Designations, Foreign Narcotics Kingpin Designation Act

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-20

.... DE C.V.; c/o TECNOLOGIA OPTIMA CORPORATIVA S. DE R.L. DE C.V.; Paseo de los Heroes 108-104, Tijuana...; Folio Mercantil No. 13537 (Mexico); R.F.C. SFO011205UJ8 (Mexico) [SDNTK] TECNOLOGIA OPTIMA CORPORATIVA S...

Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL 2 Study.

PubMed

Kosiborod, Mikhail; Lam, Carolyn S P; Kohsaka, Shun; Kim, Dae Jung; Karasik, Avraham; Shaw, Jonathan; Tangri, Navdeep; Goh, Su-Yen; Thuresson, Marcus; Chen, Hungta; Surmont, Filip; Hammar, Niklas; Fenici, Peter

2018-06-12

Randomized trials demonstrated a lower risk of cardiovascular (CV) events with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2D) at high CV risk. Prior real-world data suggested similar SGLT-2i effects in T2D patients with a broader risk profile, but these studies focused on heart failure and death and were limited to the United States and Europe. The purpose of this study was to examine a broad range of CV outcomes in patients initiated on SGLT-2i versus other glucose-lowering drugs (oGLDs) across 6 countries in the Asia Pacific, the Middle East, and North American regions. New users of SGLT-2i and oGLDs were identified via claims, medical records, and national registries in South Korea, Japan, Singapore, Israel, Australia, and Canada. Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching. Hazard ratios (HRs) for death, hospitalization for heart failure (HHF), death or HHF, MI, and stroke were assessed by country and pooled using weighted meta-analysis. After propensity-matching, there were 235,064 episodes of treatment initiation in each group; ∼27% had established CV disease. Patient characteristics were well-balanced between groups. Dapagliflozin, empagliflozin, ipragliflozin, canagliflozin, tofogliflozin, and luseogliflozin accounted for 75%, 9%, 8%, 4%, 3%, and 1% of exposure time in the SGLT-2i group, respectively. Use of SGLT-2i versus oGLDs was associated with a lower risk of death (HR: 0.51; 95% confidence interval [CI]: 0.37 to 0.70; p < 0.001), HHF (HR: 0.64; 95% CI: 0.50 to 0.82; p = 0.001), death or HHF (HR: 0.60; 95% CI: 0.47 to 0.76; p < 0.001), MI (HR: 0.81; 95% CI: 0.74 to 0.88; p < 0.001), and stroke (HR: 0.68; 95% CI: 0.55 to 0.84; p < 0.001). Results were directionally consistent across both countries and patient subgroups, including those with and without CV disease. In this large, international study of patients with T2D from the Asia Pacific, the Middle East, and North America, initiation of SGLT-2i was associated with a lower risk of CV events across a broad range of outcomes and patient characteristics. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614). Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

2017 Taiwan lipid guidelines for high risk patients.

PubMed

Li, Yi-Heng; Ueng, Kwo-Chang; Jeng, Jiann-Shing; Charng, Min-Ji; Lin, Tsung-Hsien; Chien, Kuo-Liong; Wang, Chih-Yuan; Chao, Ting-Hsing; Liu, Ping-Yen; Su, Cheng-Huang; Chien, Shih-Chieh; Liou, Chia-Wei; Tang, Sung-Chun; Lee, Chun-Chuan; Yu, Tse-Ya; Chen, Jaw-Wen; Wu, Chau-Chung; Yeh, Hung-I

2017-04-01

In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients. Lifestyle modification is the first step to control lipid. Weight reduction, regular physical exercise and limitation of alcohol intake all reduce triglyceride (TG) levels. Lipid-lowering drugs include HMG-CoA reductase inhibitors (statins), cholesterol absorption inhibitors (ezetimibe), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, nicotinic acids (niacin), fibric acids derivatives (fibrates), and long-chain omega-3 fatty acids. Statin is usually the first line therapy. Combination therapy with statin and other lipid-lowering agents may be considered in some clinical settings. For patients with acute coronary syndrome (ACS) and stable CAD, LDL-C < 70 mg/dL is the major target. A lower target of LDL-C <55 mg/dL can be considered in ACS patients with DM. After treating LDL-C to target, non-HDL-C can be considered as a secondary target for patients with TG ≥ 200 mg/dL. The suggested non-HDL-C target is < 100 mg/dL in ACS and CAD patients. For patients with ischemic stroke or transient ischemic attack presumed to be of atherosclerotic origin, statin therapy is beneficial and LDL-C < 100 mg/dL is the suggested target. For patients with symptomatic carotid stenosis or intracranial arterial stenosis, in addition to antiplatelets and blood pressure control, LDL-C should be lowered to < 100 mg/dL. Statin is necessary for DM patients with CV disease and the LDL-C target is < 70 mg/dL. For diabetic patients who are ≥ 40 years of age, or who are < 40 years of age but have additional CV risk factors, the LDL-C target should be < 100 mg/dL. After achieving LDL-C target, combination of other lipid-lowering agents with statin is reasonable to attain TG < 150 mg/dL and HDL-C >40 in men and >50 mg/dL in women in DM. LDL-C increased CV risk in patients with CKD. In adults with glomerular filtration rate (GFR) < 60 mL/min/1.73m 2 without chronic dialysis (CKD stage 3-5), statin therapy should be initiated if LDL-C ≥ 100 mg/dL. Ezetimibe can be added to statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia. Copyright © 2016. Published by Elsevier B.V.

Characterizing new users of NSAIDs before and after rofecoxib withdrawal

PubMed Central

Usher, Cara; Bennett, Kathleen; Teeling, Mary; Feely, John

2007-01-01

What is already known about this subject • Public concern regarding the cardiovascular safety of the COX-2 inhibitors began with the withdrawal of rofecoxib from the market in September 2004. • Since then, a myriad of evidence has pointed towards an adverse cardiovascular effect of other COX-2 inhibitors in persons with cardiovascular risk. • This study examines the impact of the clinical trial publicity and drug regulatory advice on nonsteroidal anti-inflammatory drug (NSAID) prescribing in patients in general practice with known cardiovascular risk both before and after the rofecoxib withdrawal. What this study adds • Results from this study indicate that the profile of new users of NSAIDs and COX-2 inhibitors did not change despite new information becoming available. • This may highlight the uncertainty experienced by prescribers of treatment alternatives available and the lack of unbiased information at this time for at-risk groups. Aims To characterize patients initiated on nonsteroidal anti-inflammatory drugs (NSAIDs), pre and postrofecoxib withdrawal, by age, gender and concomitant cardiovascular (CV) therapy. Methods A national primary care prescription database was used to identify patients who initiated NSAID therapy pre and postrofecoxib withdrawal. Patients receiving CV therapy were identified in the same periods also. Adjusted odds ratios (OR) and 95% confidence intervals are presented. Results Female patients [OR = 1.15 (1.11, 1.19)], those over 65 years [OR = 2.76 (2.65, 2.86)] and those at CV risk [OR = 1.72 (1.67, 1.79)] were more likely to start on celecoxib (over a nonselective NSAID) than male patients, those under 65 years and those not at CV risk. Similar results were found for rofecoxib and nimesulide. Postwithdrawal analysis showed results comparable to the prewithdrawal period. Conclusion The results highlight a possible uncertainty experienced by prescribers of treatment alternatives available and a lack of unbiased information at this time for at-risk groups. PMID:17054665

Cardiovascular risk in advanced naïve HIV-infected patients starting antiretroviral therapy: Comparison of three different regimens - PREVALEAT II cohort.

PubMed

Maggi, Paolo; Bellacosa, Chiara; Leone, Armando; Volpe, Anna; Ricci, Elena Delfina; Ladisa, Nicoletta; Cicalini, Stefania; Grilli, Elisabetta; Viglietti, Rosaria; Chirianni, Antonio; Bellazzi, Lara Ines; Maserati, Renato; Martinelli, Canio; Corsi, Paola; Celesia, Benedetto Maurizio; Sozio, Federica; Angarano, Gioacchino

2017-08-01

PREVALEAT (PREmature VAscular LEsions and Antiretroviral Therapy) II is a multicenter, longitudinal cohort study aimed at the evaluation of cardiovascular risk among advanced HIV-positive, treatment-naïve patients starting their first therapy. We hypothesized that these patients, present a higher cardiovascular (CV) risk. The study included all consecutive naïve patients with less than 200 CD4 cells/ml starting antiretroviral therapy. Our primary objective was to evaluate changes in carotid intima- media thickness (IMT). Secondary endpoints included changes in flow mediated vasodilation (FMD), inflammatory markers, triglycerides and cholesterol. Patients were evaluated at time 0, and after 3, 6 and 12 months. We enrolled 119 patients, stratified into three different groups: patients receiving atazanavir/ritonavir boosted (ATV/r) based regimens, efavirenz (EFV) based regimens and darunavir/ritonavir boosted (DRV/r) based regimens. At baseline, advanced naïve patients showed a relevant deterioration of CV conditions in terms of traditional CV risk factors, endothelial dysfunction and serum biomarkers. During the 12-month follow up period, mean blood lipids significantly increased: total cholesterol from 159 to 190 mg/dL, HDL-C from 31 to 41 mg/dL, and LDL-C from 99 to 117 mg/dL. D-dimers steadily decreased (median level 624 at baseline and 214 at T3), whereas ICAM and VCAM consistently raised. DRV/r and ATV/r determined a more marked decrease of D-dimers as compared to EFV. Regarding the epi-aortic changes (IMT >1 mm or presence of atherosclerotic plaques), patients in the DRV/r group were at risk of developing pathological IMT during the study (OR 6.0, 95% CI 0.9-36.9), as compared to EFV ones. CV risk was elevated in advanced naïve patients and tended to remain high in the first year of therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Skin Autofluorescence and the Association with Renal and Cardiovascular Risk Factors in Chronic Kidney Disease Stage 3

PubMed Central

McIntyre, Natasha J.; Fluck, Richard J.; McIntyre, Christopher W.

2011-01-01

Summary Background and objectives Tissue advanced glycation end products (AGE) accumulation is a measure of cumulative metabolic stress. Assessment of tissue AGE by skin autofluorescence (SAF) correlates well with cardiovascular (CV) outcomes in diabetic, transplant, and dialysis patients, and may be a useful marker of CV risk in earlier stages of chronic kidney disease (CKD). Design, setting, participants, & measurements 1707 patients with estimated GFR 59 to 30ml/min per 1.73 m2 were recruited from primary care practices for the Renal Risk In Derby (RRID) study. Detailed medical history was obtained, and each participant underwent clinical assessment as well as urine and serum biochemistry tests. SAF was assessed (mean of three readings) as a measure of skin AGE deposition using a cutaneous AF device (AGE Reader™, DiagnOptics, Groningen, The Netherlands). Results Univariate analysis revealed significant correlations between AF readings and several potential risk factors for cardiovascular disease (CVD) and progression of CKD. SAF readings (arbitrary units) were also significantly higher among males (2.8 ± 0.7 versus 2.7 ± 0.6), diabetics (3.0 ± 0.7 versus 2.7 ± 0.6), patients with evidence of self-reported CVD (2.9 ± 0.7 versus 2.7 ± 0.6), and those with no formal educational qualifications (2.8 ± 0.6 versus 2.6 ± 0.6; P < 0.01 for all). Multivariable linear regression analysis identified hemoglobin, diabetes, age, and eGFR as the most significant independent determinants of higher SAF (standardized coefficients −0.16, 0.13, 0.12, and −0.10, respectively; R2 = 0.17 for equation). Conclusion Increased SAF is independently associated with multiple CV and renal risk factors in CKD 3. Long-term follow-up will assess the value of SAF as a predictor of CV and renal risk in this population. PMID:21885790

The International Childhood Cardiovascular Cohort (i3C) consortium outcomes study of childhood cardiovascular risk factors and adult cardiovascular morbidity and mortality: Design and recruitment.

PubMed

Sinaiko, Alan R; Jacobs, David R; Woo, Jessica G; Bazzano, Lydia; Burns, Trudy; Hu, Tian; Juonala, Markus; Prineas, Ronald; Raitakari, Olli; Steinberger, Julia; Urbina, Elaine; Venn, Alison; Jaquish, Cashell; Dwyer, Terry

2018-04-22

Although it is widely thought that childhood levels of cardiovascular (CV) risk factors are related to adult CV disease, longitudinal data directly linking the two are lacking. This paper describes the design and organization of the International Childhood Cardiovascular Cohort Consortium Outcomes Study (i3C Outcomes), the first longitudinal cohort study designed to locate adults with detailed, repeated, childhood biological, physical, and socioeconomic measurements and a harmonized database. I3C Outcomes uses a Heart Health Survey (HHS) to obtain information on adult CV endpoints, using mail, email, telephone, and clinic visits in the United States (U.S.) and Australia and a national health database in Finland. Microsoft Access, REsearch Data Capture (REDCap) (U.S.), LimeSurvey (Australia), and Medidata™ Rave data systems are used to collect, transfer and organize data. Self-reported CV events are adjudicated via hospital and doctor-released medical records. After the first two study years, participants (N = 10,968) were more likely to be female (56% vs. 48%), non-Hispanic white (90% vs. 80%), and older (10.4 ± 3.8 years vs. 9.4 ± 3.3 years) at their initial childhood study visit than the currently non-recruited cohort members. Over 48% of cohort members seen during both adulthood and childhood have been found and recruited, to date, vs. 5% of those not seen since childhood. Self-reported prevalences were 0.7% Type 1 Diabetes, 7.5% Type 2 Diabetes, 33% hypertension, and 12.8% CV event. 32% of CV events were judged to be true. I3C Outcomes is uniquely able to establish evidence-based guidelines for child health care and to clarify relations to adult CV disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Model-observational bridging study on the effectiveness of ezetimibe on cardiovascular morbidity and mortality in France: A population-based study.

PubMed

Ferrières, Jean; Dallongeville, Jean; Rossignol, Michel; Bénichou, Jacques; Caro, J Jaime; Getsios, Denis; Hernandez, Luis; Abenhaim, Lucien; Grimaldi-Bensouda, Lamiae

To evaluate the real-life impact of ezetimibe on cardiovascular (CV) morbidity and mortality in France. To estimate the number of non-fatal and fatal CV events that could be prevented and corresponding number of patients needed to treat (NNT) with ezetimibe to prevent one CV event over 5 years. Non-interventional 48-month follow-up cohort conducted in hypercholesterolemic patients starting on ezetimibe <3 months at study entry, either as monotherapy or combined with statins. Prediction modeling using discrete event simulation with calibrated Framingham CV risk equations was applied to data from pivotal clinical trials on ezetimibe and real-life data derived from the cohort. A total of 3215 patients in the cohort accumulated 9314 person-years of follow-up for an average of 2.9 years. Mean age was 61.5 (standard deviation [SD] = 10.7), 54.6% were males, and 27.0% had a history of CV disease. Baseline LDL-cholesterol averaged 4.1 mmol/L (159 mg/dL; SD = 1.0) and HDL-C 1.6 mmol/L (62 mg/dL; SD = 0.5). LDL-C decreased in the first 12 months in ezetimibe-LLT (lipid-lowering therapy) initiators, switchers (monotherapy), and combination therapy with a statin by respectively 21.3%, 6.4%, and 29.1%. The corresponding predicted rate reductions of CV events (non-fatal and fatal) compared to no treatment or to a statin (combination therapy) were respectively 8, 2, and 12 per 1000 patients treated over 5 years, with a global NNT of 143 patients over 5 years. These results, accounting for observed CV event rates, risk factors evolution over time and adherence to treatment in real life, were consistent with those from clinical trials. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Contingent Vouchers and Motivational Interviewing for Cigarette Smokers in Residential Substance Abuse Treatment

PubMed Central

Rohsenow, Damaris J.; Tidey, Jennifer W.; Martin, Rosemarie A.; Colby, Suzanne M.; Sirota, Alan D.; Swift, Robert M.; Monti, Peter M.

2015-01-01

Residential drug treatment provides an opportunity to intervene with smokers substance use disorders (SUD). A randomized controlled clinical trial compared: (1) Contingent Vouchers (CV) for smoking abstinence to Noncontingent Vouchers (NCV), crossed with (2) Motivational Interviewing (MI) or Brief Advice (BA), for 184 smokers in SUD treatment. During the voucher period, 36% of carbon monoxide readings indicated smoking abstinence for those receiving CV versus 13% with NCV (p < .001). Post-treatment point-prevalence abstinence rates were low (3–4% at each follow up), with more abstinence when CV was combined with MI (6.6% on average) than with BA (0% on average). No differential effects on drug use or motivation to quit smoking occurred. Thus, CV had limited effects on long-term smoking abstinence in this population but effects were improved when CV was combined with MI. More effective methods are needed to increase motivation to quit smoking and quit rates in this high-risk population. PMID:25805668

Bio-effect of nanoparticles in the cardiovascular system.

PubMed

Yu, Xiaohong; Hong, Fashui; Zhang, Yu-Qing

2016-11-01

Nanoparticles (NPs; < 100 nm) are increasingly being applied in various fields due to their unique physicochemical properties. The increase in human exposure to NPs has raised concerns regarding their health and safety profiles. The potential correlation between NP exposure and several cardiovascular (CV) events has been demonstrated. The aim of this review is to provide a comprehensive evaluation of the current knowledge regarding the bio-toxic impacts of titanium oxide, silver, silica, carbon black, carbon nanotube, and zinc oxide NPs exposure on the CV system in terms of in vivo and in vitro experiments, which is not fully understood presently. Moreover, the potential toxic mechanisms of NPs in the CV system that are still being questioned are elaborately discussed, and the underlying capacity of NPs used in medicine for CV events are summarized. It will be an important instrument to extrapolate relevant data for human CV risk evaluation and management. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2881-2897, 2016. © 2016 Wiley Periodicals, Inc.

Diagnosis, Treatment, and Prevention of Cardiovascular Toxicity Related to Anti-Cancer Treatment in Clinical Practice: An Opinion Paper from the Working Group on Cardio-Oncology of the Korean Society of Echocardiography

PubMed Central

Kim, Hyungseop; Chung, Woo-Baek; Cho, Kyoung Im; Kim, Bong-Joon; Seo, Jeong-Sook; Park, Seong-Mi; Kim, Hak Jin; Lee, Ju-Hee; Kim, Eun Kyoung

2018-01-01

Cardiovascular (CV) toxicity associated with anti-cancer treatment is commonly encountered and raises critical problems that often result in serious morbidity or mortality. Most cardiac toxicities are related to the cumulative dose of chemotherapy; however, the type of chemotherapy, concomitant agents, and/or conventional CV risk factors have been frequently implicated in CV toxicity. Approximately half of the patients exhibiting CV toxicity receive an anthracycline-based regimen. Therefore, serologic biomarkers or cardiac imagings are important during anti-cancer treatment for early detection and the decision of appropriate management of cardiotoxicity. However, given the difficulty in determining a causal relationship, a multidisciplinary collaborative approach between cardiologists and oncologists is required. In this review, we summarize the CV toxicity and focus on the role of cardiac imaging in management strategies for cardiotoxicity associated with anti-cancer treatment. PMID:29629020

Targeted cardiopulmonary resuscitation training focused on the family members of high-risk patients at a regional medical center: A comparison between family members of high-risk and no-risk patients.

PubMed

Han, Kap Su; Lee, Ji Sung; Kim, Su Jin; Lee, Sung Woo

2018-05-01

We developed a hospital-based cardiopulmonary resuscitation (CPR) training model focused on the target population (family members of patients with potential risks for cardiac arrest) and compared the outcome of CPR training between target and non-target populations for validity. Family members of patients in training were divided into three groups on the basis of patients' diseases, as follows: 1) the cardio-specific (CS) risk group, including family members of patients with cardiac disease at risk of cardiac arrest; 2) the cardiovascular (CV) risk group, including family members of patients with risk factors for cardiovascular disease; and 3) the no-risk group. Pre- and posttraining surveys and skill tests as well as a post-training 3-month telephone survey were conducted. Educational outcomes were analyzed. A total of 203 family members were enrolled into 21 CPR training classes. The CS group (n=88) included elderly persons and housewives with a lower level of education compared with the CV (n=79) and no-risk groups (n=36). The CS group was motivated by healthcare professionals and participated in the training course. The CS, CV, and no-risk groups showed improvements in knowledge, willingness to perform CPR, and skills. Despite the older age and lower level of education in the CS group, the effects of education were similar to those in the other groups. A high rate of response and secondary propagation of CPR training were observed in the CS group. Family members of patients with heart disease could be an appropriate target population for CPR training, particularly in terms of recruitment and secondary propagation. Targeted intervention may be an effective training strategy to improve bystander CPR rates.

Use of observed within-person variation of cardiac troponin in emergency department patients for determination of biological variation and percentage and absolute reference change values.

PubMed

Simpson, Aaron J; Potter, Julia M; Koerbin, Gus; Oakman, Carmen; Cullen, Louise; Wilkes, Garry J; Scanlan, Samuel L; Parsonage, William; Hickman, Peter E

2014-06-01

Many patients presenting to the emergency department (ED) for assessment of possible acute coronary syndrome (ACS) have low cardiac troponin concentrations that change very little on repeat blood draw. It is unclear if a lack of change in cardiac troponin concentration can be used to identify acutely presenting patients at low risk of ACS. We used the hs-cTnI assay from Abbott Diagnostics, which can detect cTnI in the blood of nearly all people. We identified a population of ED patients being assessed for ACS with repeat cTnI measurement who ultimately were proven to have no acute cardiac disease at the time of presentation. We used data from the repeat sampling to calculate total within-person CV (CV(T)) and, knowing the assay analytical CV (CV(A)), we could calculate within-person biological variation (CV(i)), reference change values (RCVs), and absolute RCV delta cTnI concentrations. We had data sets on 283 patients. Men and women had similar CV(i) values of approximately 14%, which was similar at all concentrations <40 ng/L. The biological variation was not dependent on the time interval between sample collections (t = 1.5-17 h). The absolute delta critical reference change value was similar no matter what the initial cTnI concentration was. More than 90% of subjects had a critical reference change value <5 ng/L, and 97% had values of <10 ng/L. With this hs-cTnI assay, delta cTnI seems to be a useful tool for rapidly identifying ED patients at low risk for possible ACS. © 2014 The American Association for Clinical Chemistry.

HbA1c variability in type 2 diabetes is associated with the occurrence of new-onset albuminuria within three years.

PubMed

Dorajoo, Sreemanee Raaj; Ng, Joceline Shi Ling; Goh, Jessica Hui Fen; Lim, Su Chi; Yap, Chun Wei; Chan, Alexandre; Lee, Joyce Yu Chia

2017-06-01

To evaluate the association between HbA1c coefficient of variation (HbA1c-CV) and 3-year new-onset albuminuria risk. A retrospective cohort study involving 716 normoalbuminuric type 2 diabetes patients was conducted between 2010 and 2014. HbA1c-CV was used to categorize patients into low, moderate or high variability groups. Multivariate logistic models were constructed and validated. Integrated discrimination (IDI) and net reclassification (NRI) improvement indices were used to quantify the added predictive value of HbA1c-CV. The mean age of our cohort was 56.1±12.9years with a baseline HbA1c of 8.3±1.3%. Over 3-years of follow-up, 35.2% (n=252) developed albuminuria. An incremental risk of albuminuria was observed with moderate (6.68-13.43%) and high (above 13.44%) HbA1c-CV categories demonstrating adjusted odds ratios of 1.63 (1.12-2.38) and 3.80 (2.10-6.97) for 3-year new-onset albuminuria, respectively. Including HbA1c-CV for 3-year new-onset albuminuria prediction improved model discrimination (IDI: 0.023, NRI: 0.293, p<0.05). The final model had a C-statistic of 0.760±0.018 on validation. HbA1c-CV improves 3-year prediction of new-onset albuminuria. Together with mean HbA1c, baseline urine albumin-to-creatinine ratio and presence of hypertension, accurate 3-year new-onset albuminuria prediction may be possible. Copyright © 2017 Elsevier B.V. All rights reserved.

The molecular epidemiology of HIV-1 in the Comunidad Valenciana (Spain): analysis of transmission clusters.

PubMed

Patiño-Galindo, Juan Ángel; Torres-Puente, Manoli; Bracho, María Alma; Alastrué, Ignacio; Juan, Amparo; Navarro, David; Galindo, María José; Ocete, Dolores; Ortega, Enrique; Gimeno, Concepción; Belda, Josefina; Domínguez, Victoria; Moreno, Rosario; González-Candelas, Fernando

2017-09-14

HIV infections are still a very serious concern for public heath worldwide. We have applied molecular evolution methods to study the HIV-1 epidemics in the Comunidad Valenciana (CV, Spain) from a public health surveillance perspective. For this, we analysed 1804 HIV-1 sequences comprising protease and reverse transcriptase (PR/RT) coding regions, sampled between 2004 and 2014. These sequences were subtyped and subjected to phylogenetic analyses in order to detect transmission clusters. In addition, univariate and multinomial comparisons were performed to detect epidemiological differences between HIV-1 subtypes, and risk groups. The HIV epidemic in the CV is dominated by subtype B infections among local men who have sex with men (MSM). 270 transmission clusters were identified (>57% of the dataset), 12 of which included ≥10 patients; 11 of subtype B (9 affecting MSMs) and one (n = 21) of CRF14, affecting predominately intravenous drug users (IDUs). Dated phylogenies revealed these large clusters to have originated from the mid-80s to the early 00 s. Subtype B is more likely to form transmission clusters than non-B variants and MSMs to cluster than other risk groups. Multinomial analyses revealed an association between non-B variants, which are not established in the local population yet, and different foreign groups.

A safety assessment of Coriolus versicolor biomass as a food supplement

PubMed Central

Barros, Ana B.; Ferrão, Jorge; Fernandes, Tito

2016-01-01

Background Coriolus versicolor (CV) is a common mushroom with antitumor, anti-inflammatory, antioxidant, antiviral, antibacterial, and immunomodulatory properties. The existence of these properties has been extensively proven mainly using CV extract; research on the biomass form is scarce. Objective The aim of this study was to investigate the safety of the CV biomass form, as it is commonly used as a food supplement. Design CV biomass powder was dissolved in distilled water and administered daily (2.5, 5.0, and 7.5 g/kg live weight) in single doses by gavage to both female and male Charles River albino rats. Results No adverse or lethal effects were observed as a consequence of the daily administration of CV biomass. In addition, compared with the control group, no abnormal findings were observed at necropsy and histopathological examination. Conclusions A safe profile of CV biomass for human consumption can be inferred from the absence of any remarkable adverse effects in rats. PMID:26969586

Functional characterization of contractile vacuole isolated from Amoeba proteus.

PubMed

Nishihara, Eri; Shimmen, Teruo; Sonobe, Seiji

2004-12-01

Contractile vacuoles (CVs) released from cells of Amoeba proteus were used to analyze its function in vitro. When CV was transferred to a hypertonic medium, its volume decreased within 10 sec. When it was subsequently returned to its original medium, it quickly started swelling. However, it ruptured before recovering its initial volume. These results suggested that the CV membrane is semi-permeable and that the fluid is collected by the osmotic gradient in vivo. The water permeability of membrane of isolated CV was calculated from the rate of osmotic volume change to be 0.94 microm/sec . OsM. This high value suggested that CV membrane is equipped with water channel. CV contracted (or burst) quickly upon addition of 1 mM ATP. Contraction was induced by ATP, but not by other nucleotides, GTP, ITP, ADP, or the analogues of ATP, AMP-PNP and ATPgammaS. It was suggested that the contraction of isolated CV was caused by increase in the tension of its membrane by ATP.

Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials

PubMed Central

2014-01-01

Background It is important to establish the cardiovascular (CV) safety profile of novel antidiabetic drugs. Methods Pooled analyses were performed of 20 randomized controlled studies (N = 9156) of saxagliptin as monotherapy or add-on therapy in patients with type 2 diabetes mellitus (T2DM) as well as a subset of 11 saxagliptin + metformin studies. Adjudicated major adverse CV events (MACE; CV death, myocardial infarction [MI], and stroke) and investigator-reported heart failure were assessed, and incidence rates (IRs; events/100 patient-years) and IR ratios (IRRs; saxagliptin/control) were calculated (Mantel-Haenszel method). Results In pooled datasets, the IR point estimates for MACE and individual components of CV death, MI, and stroke favored saxagliptin, but the 95% CI included 1. IRR (95% CI) for MACE in the 20-study pool was 0.74 (0.45, 1.25). The Cox proportional hazard ratio (95% CI) was 0.75 (0.46, 1.21), suggesting no increased risk of MACE in the 20-study pool. In the 11-study saxagliptin + metformin pool, the IRR for MACE was 0.93 (0.44, 1.99). In the 20-study pool, the IRR for heart failure was 0.55 (0.27, 1.12). Conclusions Analysis of pooled data from 20 clinical trials in patients with T2DM suggests that saxagliptin is not associated with an increased CV risk. PMID:24490835

Variability of segment coordination using a vector coding technique: Reliability analysis for treadmill walking and running.

PubMed

Hafer, Jocelyn F; Boyer, Katherine A

2017-01-01

Coordination variability (CV) quantifies the variety of movement patterns an individual uses during a task and may provide a measure of the flexibility of that individual's motor system. While there is growing popularity of segment CV as a marker of motor system health or adaptability, it is not known how many strides of data are needed to reliably calculate CV. This study aimed to determine the number of strides needed to reliably calculate CV in treadmill walking and running, and to compare CV between walking and running in a healthy population. Ten healthy young adults walked and ran at preferred speeds on a treadmill and a modified vector coding technique was used to calculate CV for the following segment couples: pelvis frontal plane vs. thigh frontal plane, thigh sagittal plane vs. shank sagittal plane, thigh sagittal plane vs. shank transverse plane, and shank transverse plane vs. rearfoot frontal plane. CV for each coupling of interest was calculated for 2-15 strides for each participant and gait type. Mean CV was calculated across the entire gait cycle and, separately, for 4 phases of the gait cycle. For running and walking 8 and 10 strides, respectively, were sufficient to obtain a reliable CV estimate. CV was significantly different between walking and running for the thigh vs. shank couple comparisons. These results suggest that 10 strides of treadmill data are needed to reliably calculate CV for walking and running. Additionally, the differences in CV between walking and running suggest that the role of knee (i.e., inter-thigh- shank) control may differ between these forms of locomotion. Copyright © 2016 Elsevier B.V. All rights reserved.

Hyaluronan synthesis in cultured tobacco cells (BY-2) expressing a chlorovirus enzyme: cytological studies.

PubMed

Rakkhumkaew, Numfon; Shibatani, Shigeo; Kawasaki, Takeru; Fujie, Makoto; Yamada, Takashi

2013-04-01

Extraction of hyaluronan from animals or microbial fermentation has risks including contamination with pathogens and microbial toxins. In this work, tobacco cultured-cells (BY-2) were successfully transformed with a chloroviral hyaluronan synthase (cvHAS) gene to produce hyaluronan. Cytological studies revealed accumulation of HA on the cells, and also in subcellular fractions (protoplasts, miniplasts, vacuoplasts, and vacuoles). Transgenic BY-2 cells harboring a vSPO-cvHAS construct containing the vacuolar targeting signal of sporamin connected to the N-terminus of cvHAS accumulated significant amounts of HA in vacuoles. These results suggested that cvHAS successfully functions on the vacuolar membrane and synthesizes/transports HA into vacuoles. Efficient synthesis of HA using this system provides a new method for practical production of HA. Copyright © 2012 Wiley Periodicals, Inc.

Cardiovascular risk assessment in rheumatoid arthritis – controversies and the new approach

PubMed Central

Głuszko, Piotr

2016-01-01

The current methods of cardiovascular (CV) risk assessment in the course of inflammatory connective tissue diseases are a subject of considerable controversy. Comparing different methods of CV risk assessment in current rheumatoid arthritis (RA) guidelines, only a few of them recommend the use of formal risk calculators. These are the EULAR guidelines suggesting the use of SCORE and the British Society for Rheumatology guidelines performed in collaboration with NICE preferring the use of QRISK-2. Analyzing the latest American and British reports, two main concepts could be identified. The first one is to focus on risk calculators developed for the general population taking into account RA, and the calculator that might fulfill this role is the new QRISK-2 presented by NICE in 2014. The second concept is to create RA-specific risk calculators, such as the Expanded Cardiovascular Risk Prediction Score for RA. In this review we also discuss the efficiency of a new Pooled Cohort Equation and other calculators in the general and RA population. PMID:27504023

Can Cardiovascular Epidemiology and Clinical Trials Close the Risk Management Gap Between Diabetes and Prediabetes?

PubMed

Perreault, Leigh; Færch, Kristine; Gregg, Edward W

2017-09-01

We reviewed published literature to determine the relationship between A1c and cardiovascular disease (CVD) and summarize the need and implications for CVD risk reduction with interventions, focusing in the prediabetic A1c range (<6.5%). Strong evidence supports a continuous relationship between A1c and CVD-even below the current levels of A1c-defined prediabetes and after adjustment for known risk factors for CVD. Clinical trials have demonstrated a reduction in CV morbidity and/or mortality when interventions are invoked in the prediabetic A1c range. Guidelines advocating CV risk factor management in prediabetes have not been widely adopted, subsequently leading to comparable coronary heart disease risk between people with prediabetes (HR = 1.9, 95% CI 1.7-2.1 vs normoglycemia) and diabetes itself (HR=2.0, 95% CI 1.8-2.2 vs no diabetes). This review highlights the missed opportunity to utilize multiple risk factor interventions to reduce CVD in high-risk people with prediabetes.

Ambulatory Blood Pressure Variability Increases Over a 10-Year Follow-Up in Community-Dwelling Older People

PubMed Central

Pearce, Mark S.; Wincenciak, Joanna; Kerr, Simon R.J.; Newton, Julia L.

2016-01-01

Abstract BACKGROUND Greater ambulatory blood pressure variability (ABPV) is associated with end-organ damage and increased mortality. Age-related changes in the cardiovascular and autonomic nervous systems make age-associated increases in ABPV likely. Cross-sectional studies support this hypothesis, showing greater ABPV among older compared to younger adults. The only longitudinal study to examine changes in ABPV, however, found ABPV decreased over 5 years follow-up. This unexpected observation probably reflected the highly selected nature of the study participants. METHODS In this longitudinal study, we assessed changes in ABPV over 10 years in a community-cohort of older people. In addition, we examined the extent to which ABPV was predicted by demographics, cardiovascular risk factors, and medication. Clinical examination and 24-hour ambulatory blood pressure monitoring were carried out at baseline and at 10 years follow-up in 83 people, median age 70 years. ABPV was calculated using SD and coefficient of variation (Cv). Three time periods were examined: daytime, nighttime, and 24 hours. RESULTS Daytime and 24-hour, systolic and diastolic, SD, and Cv were significantly greater at follow-up than at baseline ( P < 0.001 in all cases). Mean BP did not change. CONCLUSIONS Multilevel modeling showed follow-up interval had a significant, positive effect on SD and Cv ( P < 0.004), independent of age, sex, and medication. ABPV increased over a 10-year follow-up despite stable mean BP. ABPV may therefore be an additional target for treatment in older people. Future studies should examine what degree of ABPV is harmful and if control of ABPV reduces adverse outcome. PMID:26310662

Balancing cardiovascular and gastrointestinal risks in patients with osteoarthritis receiving nonsteroidal anti‑inflammatory drugs. A summary of guidelines from an international expert group.

PubMed

Mosleh, Wassim; Farkouh, Michael E

2016-01-01

Over the past 2 decades, extensive research has assessed the use of traditional nonsteroidal anti‑inflammatory drugs (NSAIDs), and the newer cyclooxygenase‑2 (COX-2) inhibitor drugs, in the treatment of chronic pain syndromes. The proper use of NSAIDs has been the subject of significant debate, bringing together multidisciplinary researchers and clinicians to discuss the risks and benefits of these therapies. Current guidelines discussing the proper use of NSAIDs do not address the issue of the risks of COX‑2‑selective NSAIDs and nonselective NSAIDs for both the gastrointestinal (GI) and cardiovascular (CV) systems in patients on low‑dose aspirin. Accordingly, a multidisciplinary expert group was organized to review the current evidence with the aim of developing statements devoted to guide clinicians in making evidence‑based and individualized selections of NSAIDs. This review will discuss and summarize the most recent evidence on this topic to give an insight into the most effective and safest therapeutic options, thus preventing serious adverse CV and GI events. NSAIDs should be used cautiously and as infrequently as possible, with nonpharmacological approaches prescribed first. If the use of NSAIDs is required, the choice should balance the possible CV and GI risks.

Potential benefits of eicosapentaenoic acid on atherosclerotic plaques.

PubMed

Nelson, J R; Wani, O; May, H T; Budoff, M

2017-04-01

Residual cardiovascular (CV) risk remains in some patients despite optimized statin therapy and may necessitate add-on therapy to reduce this risk. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, lowers plasma triglyceride levels without raising low-density lipoprotein cholesterol levels and has potential beneficial effects on atherosclerotic plaques. Animal studies have shown that EPA reduces levels of pro-inflammatory cytokines and chemokines. In clinical trials utilizing a wide spectrum of plaque imaging modalities, EPA has shown beneficial effects on plaque characteristics. Studies of patients with coronary artery disease receiving statin therapy suggest that EPA may decrease plaque vulnerability and prevent plaque progression. EPA also decreased pentraxin-3 and macrophage accumulation. A large, randomized, Japanese study reported that EPA plus a statin resulted in a 19% relative reduction in major coronary events at 5years versus a statin alone in patients with hypercholesterolemia (P=0.011). Icosapent ethyl, a high-purity prescription form of EPA ethyl ester, has been shown to reduce triglyceride levels and markers of atherosclerotic inflammation. Results of an ongoing CV outcomes study will further define the potential clinical benefits of icosapent ethyl in reducing CV risk in high-risk patients receiving statin therapy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Autonomic nervous system function assessed by conventional and spectral analysis might be useful in terms of predicting retinal deterioration in persons with type 1 diabetes mellitus.

PubMed

Duvnjak, L; Tomić, M; Blaslov, K; Vučković Rebrina, S

2016-06-01

To determine whether cardiac autonomic dysfunction represents a risk factor for diabetic retinopathy (DR) development and progression in persons with type 1 diabetes mellitus (T1DM). The study comprised 154 normoalbuminuric persons with T1DM divided into two groups according to the DR presence: with and without DR. Cardiovascular autonomic functioning was measured at baseline using conventional and spectral analysis. Participants were re-examined for the DR presence 18months after. The group with DR had longer disease duration compared to the group without DR (20 vrs 11.5years, p<0.001), heart rate coefficient of variation (HRV-CV) at rest and during deep breathing were lower in participants with DR (p=0.001 and 0.004), as well did spectral indices of HRV: low frequency (LF) band, high frequency (HF) band (p=0.003 and 0.022) while LF/HF ratio indicating sympathovagal balance was higher (p=0.037). No difference in glycaemic control or blood pressure value were observed. Twenty-one (13.36%) participants developed non proliferative DR or progressed to proliferative DR. Cox proportional regression showed that the 18months risk from retinal deterioration was reduced by 33.4% by each increase in the HRV-CV of 1%, 12.7% for the same HRV-CV increase during deep breathing while LF band of 1ms(2) results in 8.6% risk reduction. This study provides evidence that DR should not be considered merely a metabolic control manifestation and that HRV-CV as well as spectral indices of HRV might serve as a practical tool to identify a subgroup of T1DM patients with higher risk of retinal deterioration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Heat Shock Proteins, L-Arginine, and Asymmetric Dimethylarginine Levels in Patients With Obstructive Sleep Apnea Syndrome.

PubMed

İn, Erdal; Özdemir, Cengiz; Kaman, Dilara; Sökücü, Sinem Nedime

2015-11-01

Vascular endothelial inflammation and enhanced oxidative stress are important factors in the pathogenesis of obstructive sleep apnea syndrome (OSAS). The aim of this study was to determine the levels of heat shock protein (HSP) 27, HSP70, HSP90, L-arginine, and asymmetric dimethylarginine (ADMA) in patients with OSAS and determine their relationship with cardiovascular (CV) risk factors. Forty patients with OSAS, comprising 26 with and 14 without traditional CV risk factors (obesity, hypercholesterolemia, diabetes, hypertension, and smoking), and 20 control subjects without OSAS were included. All patients underwent a full polysomnographic evaluation, and blood samples were obtained in the morning after the night the diagnostic study was performed. No significant differences were found in serum HSP27 and HSP70 levels between the groups. HSP90 and ADMA levels increased significantly, whereas L-arginine levels decreased significantly in patients with OSAS, both with and without CV risk factors, compared with controls, but were not different among the subgroups. In all patients with OSAS, serum HSP70 levels were positively correlated with a percent time with saturation<90% (r=.349, P=.027). Serum L-arginine levels were negatively correlated with desaturation number (r=-.360, P=.022) and apnea-hypopnea index (r=-.354, P=.025) and positively correlated with mean oxygen saturation (r=.328, P=.039). Serum levels of HSP90 and ADMA increased, whereas those of L-arginine decreased in patients with OSAS regardless of CV risk factors. These findings indicate the presence of oxidative stress and endothelial dysfunction in patients with OSAS. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Symptomatic atrial fibrillation and risk of cardiovascular events: data from the Euro Heart Survey.

PubMed

Guerra, Federico; Brambatti, Michela; Nieuwlaat, Robby; Marcucci, Maura; Dudink, Elton; Crijns, Harry J G M; Matassini, Maria Vittoria; Capucci, Alessandro

2017-12-01

Atrial fibrillation (AF) is associated with a wide range of clinical presentations. Whether and how AF symptoms can affect prognosis is still unclear. Aims of the present analysis were to investigate potential predictors of symptomatic AF and to determine if symptoms are associated with higher incidence of cardiovascular (CV) events at 1-year follow-up. The Euro Heart Survey on Atrial Fibrillation included 3607 consecutive patients with documented AF and available follow-up regarding symptoms status. Patients found symptomatic at baseline were classified into still symptomatic (SS group; n = 896) and asymptomatic (SA; n = 1556) at 1 year. Similarly, asymptomatic patients at baseline were classified into still asymptomatic (AA group; n = 903) and symptomatic (AS group; n = 252) at 1 year. Demographics, as well as clinical variables and medical treatments, were tested as potential predictors of symptoms persistence/development at 1-year. We also compared CV events between SS and SA groups, and AS and AA groups at 1-year follow-up. Both persistence and development of AF symptoms were associated with an increased risk of CV hospitalization, stroke, heart failure worsening, and thrombo-embolism. AF type, hypothyroidism, chronic heart failure, and chronic obstructive pulmonary disease (COPD), were independently associated with an increased risk of symptomatic status at 1-year follow-up between SS and SA groups. Persistence or development of symptoms after medical treatment are associated with an increased risk of CV events during a 1-year follow-up. Type of AF, along with hypothyroidism, COPD and chronic heart failure are significantly associated with symptoms persistence despite medical treatment. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

Testosterone Replacement Therapy: Long-Term Safety and Efficacy.

PubMed

Corona, Giovanni; Sforza, Alessandra; Maggi, Mario

2017-08-01

Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH). The former is the consequence of congenital or acquired "organic" damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T) therapy (TTh). In addition, concerns related to cardiovascular (CV) safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an "ex-juvantibus" criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented. Copyright © 2017 Korean Society for Sexual Medicine and Andrology.

Cardiovascular Health: Associations with Race-ethnicity, Nativity, and Education in a Diverse, Population-based Sample of Californians

PubMed Central

Bostean, Georgiana; Roberts, Christian K.; Crespi, Catherine M.; Prelip, Michael; Peters, Anne; Belin, Thomas R.; McCarthy, William J.

2013-01-01

Purpose This study examined how race-ethnicity, nativity, and education interact to influence disparities in cardiovascular (CV) health, a new concept defined by the American Heart Association (AHA). We assessed whether race-ethnicity and nativity disparities in CV health vary by education, and whether the foreign-born differ in CV health from their US-born race-ethnic counterparts with comparable education. Methods We used data from the 2009 California Health Interview Survey to determine the prevalence of optimal CV health metrics (based on selected AHA guidelines) among adults ages 25 and over (n = 42,014). We examined the interaction between education and ethnicity-nativity, comparing predicted probabilities of each CV health measure between US-born and foreign-born Whites, Asians, and Latinos. Results All groups were at high risk of suboptimal physical activity levels, fruit and vegetable and fast food consumption, and overweight/obesity. Those with higher education were generally better-off, except among Asians. Ethnicity-nativity differences were more pronounced among those with less than a college degree. The foreign-born exhibited both advantages and disadvantages in CV health compared to their US-born counterparts that varied by ethnicity-nativity. Conclusions Education influences ethnicity-nativity disparities in CV health, with most race-ethnic and nativity differences occurring among the less educated. Studies of nativity differences in CV health should stratify by education in order to adequately address SES differences. PMID:23726820

Cardiovascular health: associations with race-ethnicity, nativity, and education in a diverse, population-based sample of Californians.

PubMed

Bostean, Georgiana; Roberts, Christian K; Crespi, Catherine M; Prelip, Michael; Peters, Anne; Belin, Thomas R; McCarthy, William J

2013-07-01

This study examined how race-ethnicity, nativity, and education interact to influence disparities in cardiovascular (CV) health, a new concept defined by the American Heart Association. We assessed whether race-ethnicity and nativity disparities in CV health vary by education and whether the foreign-born differ in CV health from their U.S.-born race-ethnic counterparts with comparable education. We used data from the 2009 California Health Interview Survey to determine the prevalence of optimal CV health metrics (based on selected American Heart Association guidelines) among adults ages 25 and older (n = 42,014). We examined the interaction between education and ethnicity-nativity, comparing predicted probabilities of each CV health measure between U.S.-born and foreign-born White, Asian, and Latino respondents. All groups were at high risk of suboptimal physical activity levels, fruit and vegetable and fast food consumption, and overweight/obesity. Those with greater education were generally better off except among Asian respondents. Ethnicity-nativity differences were more pronounced among those with less than a college degree. The foreign-born respondents exhibited both advantages and disadvantages in CV health compared with their U.S.-born counterparts that varied by ethnicity-nativity. Education influences ethnicity-nativity disparities in CV health, with most race-ethnic and nativity differences occurring among the less educated. Studies of nativity differences in CV health should stratify by education in order to adequately address SES differences. Copyright © 2013 Elsevier Inc. All rights reserved.

Vascular calcification on plain radiographs is associated with carotid intima media thickness, malnutrition and cardiovascular events in dialysis patients: a prospective observational study

PubMed Central

2013-01-01

Background Vascular calcification (VC) and carotid intima media thickness (CIMT) are strongly associated with cardiovascular (CV) disease. We hypothesized that significant VC on plain radiographs is associated with CIMT and CV events in dialysis patients. In addition, we evaluated risk factors for VC progression on plain radiographs in dialysis patients. Methods In this 2-year observational, prospective study, 67 dialysis patients were included. We checked plain radiographs at baseline and after 2 years. Laboratory tests and malnutrition score were obtained at baseline, after 12 months, and after 24 months. Results The mean age of patients was 56.3 ± 10.3 years and duration of dialysis was 41.3 ± 34.5 months. The prevalence of significant VC was 61.2% and the prevalence of carotid artery atheromatous plaques was 55.6%. Mean CIMT, malnutrition scores, CRP level and prevalence of carotid atheromatous plaques were significantly higher in patients with significant VC. Serum albumin and total iron binding capacity were significantly lower in patients with significant VC compared to patients without significant VC. During a mean observational period of 22 months, patients without significant VC showed lower CV events by the Kaplan-Meyer method (p = 0.010). Progression of VC was found in 35.7% among 56 patients followed up. Hemoglobin after 24 months was an independent factor for progression of VC (Exp(B) = 0.344, 95% Confidence Interval = 0.13 – 0.96, p = 0.034). Conclusions Significant VC on plain radiograph was associated with CIMT, malnutrition, inflammation, and CV events in dialysis patients. Conditions which increase hemoglobin level may retard progression of VC in dialysis patients. PMID:23360132

The Role of Cardiovascular Risk Factors and Stroke in Familial Alzheimer Disease.

PubMed

Tosto, Giuseppe; Bird, Thomas D; Bennett, David A; Boeve, Bradley F; Brickman, Adam M; Cruchaga, Carlos; Faber, Kelley; Foroud, Tatiana M; Farlow, Martin; Goate, Alison M; Graff-Radford, Neill R; Lantigua, Rafael; Manly, Jennifer; Ottman, Ruth; Rosenberg, Roger; Schaid, Daniel J; Schupf, Nicole; Stern, Yaakov; Sweet, Robert A; Mayeux, Richard

2016-10-01

The contribution of cardiovascular disease (CV) and cerebrovascular disease to the risk for late-onset Alzheimer disease (LOAD) has been long debated. Investigations have shown that antecedent CV risk factors increase the risk for LOAD, although other investigations have failed to validate this association. To study the contribution of CV risk factors (type 2 diabetes, hypertension, and heart disease) and the history of stroke to LOAD in a data set of large families multiply affected by LOAD. The National Institute on Aging Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease family study (hereinafter referred to as NIA-LOAD study) is a longitudinal study of families with multiple members affected with LOAD. A multiethnic community-based longitudinal study (Washington Heights-Inwood Columbia Aging Project [WHICAP]) was used to replicate findings. The 6553 participants in the NIA-LOAD study were recruited from 23 US Alzheimer disease centers with ongoing data collection since 2003; the 5972 WHICAP participants were recruited at Columbia University with ongoing data collection since 1992. Data analysis was performed from 2003 to 2015. Generalized mixed logistic regression models tested the association of CV risk factors (primary association) with LOAD. History of stroke was used for the secondary association. A secondary model adjusted for the presence of an apolipoprotein E (APOE) ε4 allele. A genetic risk score, based on common variants associated with LOAD, was used to account for LOAD genetic risk beyond the APOE ε4 effect. Mediation analyses evaluated stroke as a mediating factor between the primary association and LOAD. A total of 6553 NIA-LOAD participants were included in the analyses (4044 women [61.7%]; 2509 men [38.3%]; mean [SD] age, 77.0 [9] years), with 5972 individuals from the WHICAP study included in the replication sample (4072 women [68.2%]; 1900 men [31.8%]; mean [SD] age, 76.5 [7.0] years). Hypertension was associated with decreased LOAD risk (odds ratio [OR], 0.63; 95% CI, 0.55-0.72); type 2 diabetes and heart disease were not. History of stroke conferred greater than 2-fold increased risk for LOAD (OR, 2.23; 95% CI, 1.75-2.83). Adjustment for APOE ε4 did not alter results. The genetic risk score was associated with LOAD (OR, 2.85; 95% CI, 2.05-3.97) but did not change the independent association of LOAD with hypertension or stroke. In the WHICAP sample, hypertension was not associated with LOAD (OR, 0.99; 95% CI, 0.88-1.11), whereas history of stroke increased the risk for LOAD (OR, 1.96; 95% CI, 1.56-2.46). The effect of hypertension on LOAD risk was also mediated by stroke in the NIA-LOAD and the WHICAP samples. In familial and sporadic LOAD, a history of stroke was significantly associated with increased disease risk and mediated the association between selected CV risk factors and LOAD, which appears to be independent of the LOAD-related genetic background.

The Role of Cardiovascular Risk Factors and Stroke in Familial Alzheimer Disease

PubMed Central

Tosto, Giuseppe; Bird, Thomas D.; Bennett, David A.; Boeve, Bradley F.; Brickman, Adam M.; Cruchaga, Carlos; Faber, Kelley; Foroud, Tatiana M.; Farlow, Martin; Goate, Alison M.; Graff-Radford, Neill R.; Lantigua, Rafael; Manly, Jennifer; Ottman, Ruth; Rosenberg, Roger; Schaid, Daniel J.; Schupf, Nicole; Stern, Yaakov; Sweet, Robert A.; Mayeux, Richard

2016-01-01

Importance The contribution of cardiovascular disease (CV) and cerebrovascular disease to the risk for late-onset Alzheimer disease (LOAD) has been long debated. Investigations have shown that antecedent CV risk factors increase the risk for LOAD, although other investigations have failed to validate this association. Objective To study the contribution of CV risk factors (type 2 diabetes, hypertension, and heart disease) and the history of stroke to LOAD in a data set of large families multiply affected by LOAD. Design, Setting, and Participants The National Institute on Aging Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease family study (hereinafter referred to as NIA-LOAD study) is a longitudinal study of families with multiple members affected with LOAD. A multiethnic community-based longitudinal study (Washington Heights–Inwood Columbia Aging Project [WHICAP]) was used to replicate findings. The 6553 participants in the NIA-LOAD study were recruited from 23 US Alzheimer disease centers with ongoing data collection since 2003; the 5972 WHICAP participants were recruited at Columbia University with ongoing data collection since 1992. Data analysis was performed from 2003 to 2015. Main Outcomes and Measures Generalized mixed logistic regression models tested the association of CV risk factors (primary association) with LOAD. History of stroke was used for the secondary association. A secondary model adjusted for the presence of an apolipoprotein E (APOE) ε4 allele. A genetic risk score, based on common variants associated with LOAD, was used to account for LOAD genetic risk beyond the APOE ε4 effect. Mediation analyses evaluated stroke as a mediating factor between the primary association and LOAD. Results A total of 6553 NIA-LOAD participants were included in the analyses (4044 women [61.7%]; 2509 men [38.3%]; mean [SD] age, 77.0 [9] years), with 5972 individuals from the WHICAP study included in the replication sample (4072 women [68.2%]; 1900 men [31.8%]; mean [SD] age, 76.5 [7.0] years). Hypertension was associated with decreased LOAD risk (odds ratio [OR], 0.63; 95% CI, 0.55-0.72); type 2 diabetes and heart disease were not. History of stroke conferred greater than 2-fold increased risk for LOAD (OR, 2.23; 95% CI, 1.75-2.83). Adjustment for APOE ε4 did not alter results. The genetic risk score was associated with LOAD (OR, 2.85; 95% CI, 2.05-3.97) but did not change the independent association of LOAD with hypertension or stroke. In the WHICAP sample, hypertension was not associated with LOAD (OR, 0.99; 95% CI, 0.88-1.11), whereas history of stroke increased the risk for LOAD (OR, 1.96; 95% CI, 1.56-2.46). The effect of hypertension on LOAD risk was also mediated by stroke in the NIA-LOAD and the WHICAP samples. Conclusions and Relevance In familial and sporadic LOAD, a history of stroke was significantly associated with increased disease risk and mediated the association between selected CV risk factors and LOAD, which appears to be independent of the LOAD-related genetic background. PMID:27533593

[Screening of asymptomatic left ventricular systolic dysfunction in a population sample at high cardiovascular risk in Lombardy (Italy): the DAVID-Berg study].

PubMed

Gavazzi, Antonello; De Maria, Renata; Grosu, Aurelia; Iacovoni, Attilio; Fontana, Alessandra; Gori, Mauro; Ferrari, Paola; Canova, Paolo; Calabrese, Alice; Filippi, Alessandro; Rutili, Maria Rosaria; Donzelli, Luigi; Parolini, Marina; Senni, Michele

2014-05-01

Prevalence of asymptomatic left ventricular systolic dysfunction (ALVSD) increases with age and cardiovascular (CV) risk exposure. Early diagnosis and treatment allow reducing heart failure and fatal and non-fatal event rates. Data on ALVSD prevalence in Italy are still scarce and ALVSD remains commonly under-diagnosed in primary care, where diagnostic facilities are limited. Among subjects at high CV risk in primary care, we assessed the prevalence of ALVSD and the relative predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the Framingham Heart Failure Risk Score (FHFRS). Records of 4047 subjects aged 55-80 years, without history, symptoms or signs of heart failure, registered at three primary care practices in Lombardy, Northern Italy, were reviewed; 623 subjects at high CV risk underwent visit, ECG, echocardiography, NT-proBNP and FHFRS calculation. ALVSD, defined as left ventricular ejection fraction <50%, was detected in 33 subjects (5.3%) who showed higher NT-proBNP (p<0.001) and FHFRS (p=0.013) than those without ALVSD. NT-proBNP levels beyond normal age and gender-specific 95th percentile had a 97.7% negative predictive value for ALVSD and were associated with a 6-fold increase in ALVSD risk. Adding NT-proBNP to FHFRS significantly improved prediction (C-statistic 0.76, 95% confidence interval [CI] 0.67-0.84 vs 0.63, 95% CI 0.53-0.73, p=0.04; net reclassification improvement 38.4%). The combination of FHFRS and major ECG abnormalities was not superior to stand alone NT-proBNP (C-statistic 0.71, 95% CI 0.63-0.80 vs 0.74, 95% CI 0.64-0.83, p=0.61). In subjects at high CV risk in primary care, prevalence of ALVSD is 5.3%; for diagnosis NT-proBNP adds predictive value to the FHFRS and is equivalent to the combination of FHFRS and ECG. Because of its practical advantages, NT-proBNP might be routinely used for ALVSD screening in primary care.

Multiple antibacterial histone H2B proteins are expressed in tissues of American oyster.

PubMed

Seo, Jung-Kil; Stephenson, Jeana; Noga, Edward J

2011-03-01

We have previously identified a histone H2B isomer (cvH2B-1) from tissue extracts of the bivalve mollusk, the American oyster (Crassostrea virginica). In this paper, we isolate an additional three antibacterial proteins from acidified gill extract by preparative acid-urea-polyacrylamide gel electrophoresis and reversed-phase high performance liquid chromatography. Extraction of these proteins from tissue was best accomplished by briefly boiling the tissues in a weak acetic acid solution. Addition of protease inhibitors while boiling resulted in somewhat lower yields, with one protein being totally absent with this method. Via mass spectrometry, the masses of one of these purified proteins was 13607.0Da (peak 2), which is consistent with the molecular weight of histone H2B. In addition, via western-blotting using anti-calf histone H2B antibody, all three proteins were positive and were thus named cvH2B-2, cvH2B-3 and cvH2B-4. The antibacterial activity of cvH2B-2 was similar to that of cvH2B-1, with activity against a Gram-positive bacterium (Lactococcus lactis subsp. lactis; minimum effective concentration [MEC] 52-57μg/mL) but inactive against Staphylococcus aureus (MEC>250μg/mL). However, both proteins had relatively potent activity against the Gram-negative oyster pathogen Vibrio parahemolyticus (MEC 11.5-14μg/mL) as well as the human pathogen Vibrio vulnificus (MEC 21.3-25.3μg/mL). cvH2B-3 and cvH2B-4 also had similarly strong activity against Vibrio vulnificus. These data provide further evidence for the antimicrobial function of histone H2B isomers in modulating bacterial populations in oyster tissues. The combined estimated concentrations of these histone H2B isomers were far above the inhibitory concentrations for the tested vibrios, including human pathogens. Our results indicate that the highly conserved histone proteins might be important components not only of immune defenses in oysters but have the potential to influence the abundance of a ubiquitous microbial resident of oyster tissues that is the major source of seafood-borne illness in humans. Published by Elsevier Inc.

Expanding the Evidence Base: Comparing Randomized Controlled Trials and Observational Studies of Statins.

PubMed

Atar, Dan; Ong, Seleen; Lansberg, Peter J

2015-01-01

It is widely accepted that randomized controlled trials (RCTs) are the gold standard for demonstrating the efficacy of a given therapy (results under ideal conditions). Observational studies, on the other hand, can complement this by demonstrating effectiveness (results under real-world conditions). To examine the role that observational studies can play in complementing data from RCTs, we reviewed published studies for statins, a class of drugs that have been widely used to reduce the risk of cardiovascular (CV) events by lowering low-density lipoprotein cholesterol levels. RCTs have consistently demonstrated the benefits of statin treatment in terms of CV risk reduction and have demonstrated that more intensive statin therapy has incremental benefits over less intensive treatment. Observational studies of statin use in 'real-world' populations have served to augment the evidence base generated from statin RCTs in preselected populations of patients who are often at high CV risk and have led to similar safety and efficacy findings. They have also raised questions about factors affecting medication adherence, under-treatment, switching between statins, and failure to reach low-density lipoprotein cholesterol target levels, questions for which the answers could lead to improved patient care.

Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients.

PubMed

McInnes, G; Evans, M; Del Prato, S; Stumvoll, M; Schweizer, A; Lukashevich, V; Shao, Q; Kothny, W

2015-11-01

To report the cardiovascular (CV) safety profile and heart failure (HF) risk of vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-vildagliptin treatments) was calculated using the Mantel-Haenszel (M-H) method. Of the 17 446 patients, 9599 received vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m(2) (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61-1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M-H RR 1.08 (95% CI 0.68-1.70). This large meta-analysis indicates that vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in vildagliptin-treated patients. © 2015 John Wiley & Sons Ltd.

Tomato and lycopene supplementation and cardiovascular risk factors: A systematic review and meta-analysis.

PubMed

Cheng, Ho Ming; Koutsidis, Georgios; Lodge, John K; Ashor, Ammar; Siervo, Mario; Lara, José

2017-02-01

Epidemiological evidence suggests an association between consumption of tomato products or lycopene and lower risk for cardiovascular diseases (CVD). Our aim was to evaluate the state of the evidence from intervention trials on the effect of consuming tomato products and lycopene on markers of cardiovascular (CV) function. We undertook a systematic review and meta-analysis on the effect of supplementing tomato and lycopene on CV risk factors. Three databases including Medline, Web of science, and Scopus were searched from inception to August 2016. Inclusion criteria were: intervention trials reporting effects of tomato products and lycopene supplementation on CV risk factors among adult subjects >18 years of age. The outcomes of interest included blood lipids (total-, HDL-, LDL-cholesterol, triglycerides, oxidised-LDL), endothelial function (flow-mediated dilation (FMD), pulse wave velocity (PWV)) and blood pressure (BP) inflammatory factors (CRP, IL-6) and adhesion molecules (ICAM-1). Random-effects models were used to determine the pooled effect sizes. Out of 1189 publications identified, 21 fulfilled inclusion criteria and were meta-analysed. Overall, interventions supplementing tomato were associated with significant reductions in LDL-cholesterol (-0.22 mmol/L; p = 0.006), IL-6 (standardised mean difference -0.25; p = 0.03), and improvements in FMD (2.53%; p = 0.01); while lycopene supplementation reduced systolic-BP (-5.66 mmHg; p = 0.002). No other outcome was significantly affected by these interventions. The available evidence on the effects of tomato products and lycopene supplementation on CV risk factors supports the view that increasing the intake of these has positive effects on blood lipids, blood pressure and endothelial function. These results support the development of promising individualised nutritional strategies involving tomatoes to tackle CVD. Copyright © 2017 Elsevier B.V. All rights reserved.

Predialysis and Postdialysis pH and Bicarbonate and Risk of All-Cause and Cardiovascular Mortality in Long-term Hemodialysis Patients.

PubMed

Yamamoto, Tadashi; Shoji, Shigeichi; Yamakawa, Tomoyuki; Wada, Atsushi; Suzuki, Kazuyuki; Iseki, Kunitoshi; Tsubakihara, Yoshiharu

2015-09-01

To date, very few studies have been carried out on the associations of pre- and postdialysis acid-base parameters with mortality in hemodialysis patients. An observational study including cross-sectional and 1-year analyses. Data from the renal registry of the Japanese Society of Dialysis Therapy (2008-2009), including 15,132 dialysis patients 16 years or older. Predialysis pH<7.30, 7.30 to 7.34 (reference), 7.35 to 7.39, or ≥7.40 (1,550, 4,802, 6,023, and 2,757 patients, respectively); predialysis bicarbonate level < 18.0, 18.0 to 21.9 (reference), 22.0 to 25.9, or ≥26.0 mEq/L (2,724, 7,851, 4,023, and 534 patients, respectively); postdialysis pH<7.40, 7.40 to 7.44, 7.45 to 7.49 (reference), or ≥7.50 (2,114, 5,331, 4,975, and 2,712 patients, respectively); and postdialysis bicarbonate level < 24.0, 24.0 to 25.9, 26.0 to 27.9 (reference), or ≥28.0 mEq/L (5,087, 4,330, 3,451, and 2,264 patients, respectively). All-cause and cardiovascular (CV) mortality during the 1-year follow-up. HRs were estimated using unadjusted models and models adjusted for age, sex, dialysis vintage, history of CV disease, diabetes, weight gain ratio, body mass index, calcium-phosphorus product, serum albumin level, serum total cholesterol level, blood hemoglobin level, single-pool Kt/V, and normalized protein catabolic rate. Of 15,132 patients, during follow-up, 1,042 died of all causes, including 408 CV deaths. In the adjusted analysis for all-cause mortality, HRs compared to the reference group were significantly higher in patients with predialysis pH≥7.40 (HR, 1.36; 95% CI, 1.13-1.65) and postdialysis pH<7.40 (HR, 1.22; 95% CI, 1.00-1.49). Predialysis pH≥7.40 was also associated with higher risk of CV mortality (HR, 1.34; 95% CI, 1.01-1.79). No association of pre- or postdialysis bicarbonate level with all-cause and CV mortality was observed. Single measurements of acid-base parameters, short duration of follow-up, small number of CV deaths. Predialysis pH≥7.40 was associated with significantly elevated risk of all-cause and CV mortality. However, pre- and postdialysis bicarbonate levels were not associated with all-cause and CV mortality. Predialysis pH may be the most appropriate reference for accurate correction of metabolic acidosis in dialysis patients. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study.

PubMed

Szenborn, L; Osipova, I V; Czajka, H; Kharit, S M; Jackowska, T; François, N; Habib, M A; Borys, D

2017-09-25

Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. PHiD-CV was immunogenic and well tolerated in 2-17-year-old children with asplenia or splenic dysfunction. Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108. Copyright © 2017. Published by Elsevier Ltd.

Metabolic syndrome, diet and exercise.

PubMed

De Sousa, Sunita M C; Norman, Robert J

2016-11-01

Polycystic ovary syndrome (PCOS) is associated with a range of metabolic complications including insulin resistance (IR), obesity, dyslipidaemia, hypertension, obstructive sleep apnoea (OSA) and non-alcoholic fatty liver disease. These compound risks result in a high prevalence of metabolic syndrome and possibly increased cardiovascular (CV) disease. As the cardiometabolic risk of PCOS is shared amongst the different diagnostic systems, all women with PCOS should undergo metabolic surveillance though the precise approach differs between guidelines. Lifestyle interventions consisting of increased physical activity and caloric restriction have been shown to improve both metabolic and reproductive outcomes. Pharmacotherapy and bariatric surgery may be considered in resistant metabolic disease. Issues requiring further research include the natural history of PCOS-associated metabolic disease, absolute CV risk and comparative efficacy of lifestyle interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Predicting Risk Sensitivity in Humans and Lower Animals: Risk as Variance or Coefficient of Variation

ERIC Educational Resources Information Center

Weber, Elke U.; Shafir, Sharoni; Blais, Ann-Renee

2004-01-01

This article examines the statistical determinants of risk preference. In a meta-analysis of animal risk preference (foraging birds and insects), the coefficient of variation (CV), a measure of risk per unit of return, predicts choices far better than outcome variance, the risk measure of normative models. In a meta-analysis of human risk…

History dependence of human muscle-fiber conduction velocity during voluntary isometric contractions.

PubMed

McGill, Kevin C; Lateva, Zoia C

2011-09-01

The conduction velocity (CV) of a muscle fiber is affected by the fiber's discharge history going back ∼1 s. We investigated this dependence by measuring CV fluctuations during voluntary isometric contractions of the human brachioradialis muscle. We recorded electromyogram (EMG) signals simultaneously from multiple intramuscular electrodes, identified potentials belonging to the same motor unit using EMG decomposition, and estimated the CV of each discharge from the interpotential interval. In 12 of 14 subjects, CV increased by ∼10% during the first second after recruitment and then fluctuated by about ±2% in a way that mirrored the fluctuations in the instantaneous firing rate. The CV profile could be precisely described in terms of the discharge history by a simple mathematical model. In the other two subjects, and one subject retested after cooling the arm, the CV fluctuations were inversely correlated with instantaneous firing rate. In all subjects, CV was additionally affected by very short interdischarge intervals (<25 ms): it was increased in doublets at recruitment, but decreased in doublets during continuous firing and after short interdischarge intervals in doubly innervated fibers. CV also exhibited a slow trend of about -0.05%/s that did not depend on the immediate discharge history. We suggest that measurements of CV fluctuations during voluntary contractions, or during stimulation protocols that involve longer and more complex stimulation patterns than are currently being used, may provide a sensitive approach for estimating the dynamic characteristics of ion channels in the human muscle-fiber membrane.

History dependence of human muscle-fiber conduction velocity during voluntary isometric contractions

PubMed Central

Lateva, Zoia C.

2011-01-01

The conduction velocity (CV) of a muscle fiber is affected by the fiber's discharge history going back ∼1 s. We investigated this dependence by measuring CV fluctuations during voluntary isometric contractions of the human brachioradialis muscle. We recorded electromyogram (EMG) signals simultaneously from multiple intramuscular electrodes, identified potentials belonging to the same motor unit using EMG decomposition, and estimated the CV of each discharge from the interpotential interval. In 12 of 14 subjects, CV increased by ∼10% during the first second after recruitment and then fluctuated by about ±2% in a way that mirrored the fluctuations in the instantaneous firing rate. The CV profile could be precisely described in terms of the discharge history by a simple mathematical model. In the other two subjects, and one subject retested after cooling the arm, the CV fluctuations were inversely correlated with instantaneous firing rate. In all subjects, CV was additionally affected by very short interdischarge intervals (<25 ms): it was increased in doublets at recruitment, but decreased in doublets during continuous firing and after short interdischarge intervals in doubly innervated fibers. CV also exhibited a slow trend of about −0.05%/s that did not depend on the immediate discharge history. We suggest that measurements of CV fluctuations during voluntary contractions, or during stimulation protocols that involve longer and more complex stimulation patterns than are currently being used, may provide a sensitive approach for estimating the dynamic characteristics of ion channels in the human muscle-fiber membrane. PMID:21565985

An object-oriented, knowledge-based system for cardiovascular rehabilitation--phase II.

PubMed Central

Ryder, R. M.; Inamdar, B.

1995-01-01

The Heart Monitor is an object-oriented, knowledge-based system designed to support the clinical activities of cardiovascular (CV) rehabilitation. The original concept was developed as part of graduate research completed in 1992. This paper describes the second generation system which is being implemented in collaboration with a local heart rehabilitation program. The PC UNIX-based system supports an extensive patient database organized by clinical areas. In addition, a knowledge base is employed to monitor patient status. Rule-based automated reasoning is employed to assess risk factors contraindicative to exercise therapy and to monitor administrative and statutory requirements. PMID:8563285

Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin (CARMELINA®): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk.

PubMed

Rosenstock, Julio; Perkovic, Vlado; Alexander, John H; Cooper, Mark E; Marx, Nikolaus; Pencina, Michael J; Toto, Robert D; Wanner, Christoph; Zinman, Bernard; Baanstra, David; Pfarr, Egon; Mattheus, Michaela; Broedl, Uli C; Woerle, Hans-Juergen; George, Jyothis T; von Eynatten, Maximilian; McGuire, Darren K

2018-03-14

Cardiovascular (CV) outcome trials in type 2 diabetes (T2D) have underrepresented patients with chronic kidney disease (CKD), leading to uncertainty regarding their kidney efficacy and safety. The CARMELINA ® trial aims to evaluate the effects of linagliptin, a DPP-4 inhibitor, on both CV and kidney outcomes in a study population enriched for cardio-renal risk. CARMELINA ® is a randomized, double-blind, placebo-controlled clinical trial conducted in 27 countries in T2D patients at high risk of CV and/or kidney events. Participants with evidence of CKD with or without CV disease and HbA1c 6.5-10.0% (48-86 mmol/mol) were randomized 1:1 to receive linagliptin once daily or matching placebo, added to standard of care adjusted according to local guidelines. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. The key secondary outcome is a composite of time to first sustained occurrence of end-stage kidney disease, ≥ 40% decrease in estimated glomerular filtration rate (eGFR) from baseline, or renal death. CV and kidney events are prospectively adjudicated by independent, blinded clinical event committees. CARMELINA ® was designed to continue until at least 611 participants had confirmed primary outcome events. Assuming a hazard ratio of 1.0, this provides 90% power to demonstrate non-inferiority of linagliptin versus placebo within the pre-specified non-inferiority margin of 1.3 at a one-sided α-level of 2.5%. If non-inferiority of linagliptin for the primary outcome is demonstrated, then its superiority for both the primary outcome and the key secondary outcome will be investigated with a sequentially rejective multiple test procedure. Between July 2013 and August 2016, 6980 patients were randomized and took ≥ 1 dose of study drug (40.6, 33.1, 16.9, and 9.4% from Europe, South America, North America, and Asia, respectively). At baseline, mean ± SD age was 65.8 ± 9.1 years, HbA1c 7.9 ± 1.0%, BMI 31.3 ± 5.3 kg/m 2 , and eGFR 55 ± 25 mL/min/1.73 m 2 . A total of 5148 patients (73.8%) had prevalent kidney disease (defined as eGFR < 60 mL/min/1.73 m 2 or macroalbuminuria [albumin-to-creatinine ratio > 300 mg/g]) and 3990 patients (57.2%) had established CV disease with increased albuminuria; these characteristics were not mutually exclusive. Microalbuminuria (n = 2896 [41.5%]) and macroalbuminuria (n = 2691 [38.6%]) were common. CARMELINA ® will add important information regarding the CV and kidney disease clinical profile of linagliptin by including an understudied, vulnerable cohort of patients with T2D at highest cardio-renal risk. Trial registration ClinicalTrials.gov identifier-NCT01897532; registered July 9, 2013.

Thermal stability of oils added with avocado (Persea americana cv. Hass) or olive (Olea europaea cv. Arbequina) leaf extracts during the French potatoes frying.

PubMed

Jiménez, Paula; García, Paula; Bustamante, Andrés; Barriga, Andrés; Robert, Paz

2017-04-15

Effect of the addition of avocado (Persea americana cv. Hass) or olive (Olea europaea cv. Arbequina) hydroalcoholic leaf extracts (AHE and OHE, respectively) on thermal stability of canola oil (CO) and high oleic sunflower oil (HOSO) during French potatoes frying at 180°C was studied. The extracts were characterized by the total phenolic content, phenol chromatographic profiles and antioxidant activity. B-type trimer procyanidins were the major phenolic compounds identified in AHE. OHE showed higher phenol content, antioxidant activity regarding AHE. CO+OHE and HOSO+OHE decreased the formation of polar compounds and showed an anti-polymeric effect with respect to oils without extracts, whereas AHE extract showed a prooxidant effect on HOSO. Therefore, OHE showed an antioxidant effect on HOSO and CO under the studied conditions. In addition, all systems (CO+AHE, HOSO+AHE, CO+OHE and HOSO+OHE) increased the retention of tocopherols. These results demonstrate the potential utility of OHE as natural antioxidant for oils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Arterial calcification: friend or foe?

PubMed

Nicoll, Rachel; Henein, Michael Y

2013-07-31

There is a significant relationship between the presence, extent and progression of coronary artery calcification (CAC) and cardiovascular (CV) events and mortality in both CV and renal patients and CAC scoring can provide improved predictive ability over risk factor scoring alone. There is also a close relationship between CAC presence and atherosclerotic plaque burden, with angiography studies showing very high sensitivity but poor specificity of CAC score for predicting obstructive disease. Nevertheless, there are objections to CAC screening because of uncertainties and lack of studies showing improved outcome. Furthermore, histopathology studies indicate that heavily calcified plaque is unlikely to result in a CV event, while the vulnerable plaque tends to be uncalcified or 'mixed', suggesting that calcification may be protective. This scenario highlights a number of paradoxes, which may indicate that the association between CAC and CV events is spurious, following from the adoption of CAC as a surrogate for high plaque burden, which itself is a surrogate for the presence of vulnerable plaque. Since studies indicate that arterial calcification is a complex, organised and regulated process similar to bone formation, there is no particular reason why it should be a reliable indicator of either the plaque burden or the risk of a future CV event. We suggest that it is time to divorce arterial calcification from atherosclerosis and to view it as a distinct pathology in its own right, albeit one which frequently coexists with atherosclerosis and is related to it for reasons which are not yet fully understood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

CCN2 (CTGF) gene polymorphism is a novel prognostic risk factor for cardiovascular outcomes in hemodialysis patients.

PubMed

Cozzolino, Mario; Biondi, Maria Luisa; Banfi, Elena; Riser, Bruce L; Mehmeti, Florjan; Cusi, Daniele; Gallieni, Maurizio

2010-01-01

The very high cardiovascular (CV) mortality and morbidity rates in hemodialysis (HD) patients are greatly related to atherosclerosis. CCN2 (connective tissue growth factor/CTGF) is a profibrotic factor that is secreted by endothelial cells, involved in atherogenesis, promoting fibroblast proliferation and matrix production. CCN2 protein is significantly increased in complicated fibrous plaques and enhances monocyte migration into atherosclerotic lesions. The aim of this study was to investigate a possible association between CCN2 gene polymorphism and CV morbidity and mortality in HD patients. 98 HD patients, followed for 24 months, were genotyped for the common polymorphism on the CCN2 gene (G-945C). HD patient characteristics were: age 64 ± 13 years, males 64%, diabetes 24%, hypertension 62%, smokers 38%, dyslipidemia 28%, all undergoing standard HD three times weekly. All-cause mortality was not associated with CCN2 polymorphism (G-945C). In contrast, however, the GG genotype was strongly associated with CV mortality: OR 13 (1.49-155), p = 0.0048. Interestingly, the GG genotype was also greatly associated with the serious CV events of stroke and myocardial infarction in surviving HD patients: OR 13.3 (2.5-87.08), p = 0.0001. We demonstrate for the first time that CCN2 gene polymorphism is a prognostic risk factor for CV morbidity and mortality in HD patients. These data may have important implications for better understanding the link between accelerated atherosclerosis and increased mortality in HD population. Copyright © 2010 S. Karger AG, Basel.

Sexual murderers with adult or child victims: are they different?

PubMed

Spehr, Aranke; Hill, Andreas; Habermann, Niels; Briken, Peer; Berner, Wolfgang

2010-09-01

This study investigates characteristics differentiating sexually motivated murderers targeting child victims (CV; n = 35) from those with only adult victims (AV; n = 100). In the initial phase, psychiatric court reports were evaluated using standardized instruments (SCID-II, PCL-R, HCR-20, SVR-20, Static-99). In the second phase, data on duration of detention and reconviction rates were obtained from German federal criminal records. The CV group showed more often diagnostic criteria of pedophilia (43% vs. 4%) and less often alcohol abuse and drug dependency (31% vs. 55%), sexual dysfunctions (9% vs. 29%) and narcissistic personality disorder (0% vs. 13%). No significant differences were found regarding PCL-R and total risk assessment scores. Child victim perpetrators were more likely to have committed acts of sexual child abuse before the sexual homicide (46% vs. 16%) but were less likely to have committed rape or sexual assault (17% vs. 42%) or caused bodily injury (26% vs. 50%). The CV group was detained more frequently in forensic psychiatric hospitals (59% vs. 26%), but the two groups showed the same rates of release and reconviction for sexual (22% for both groups), nonsexual violent (CV 25% vs. AV 15%) and nonviolent offenses (CV 63% vs. AV 59%). Although well-known differences between nonhomicidal sexual child abusers and rapists were replicated in this study on sexual homicide perpetrators, the groups showed more similarities than differences. The high prevalence of violence and antisocial personality disorder in both groups seem to be important risk factors for committing a (sexual) homicide and might have outweighed other differences.

'Work it out': evaluation of a chronic condition self-management program for urban Aboriginal and Torres Strait Islander people, with or at risk of cardiovascular disease.

PubMed

Mills, Kyly; Gatton, Michelle L; Mahoney, Ray; Nelson, Alison

2017-09-26

Chronic diseases disproportionately burden Aboriginal and Torres Strait Islander people in Australia, with cardiovascular (CV) diseases being the greatest contributor. To improve quality of life and life expectancy for people living with CV disease, secondary prevention strategies such as rehabilitation and self-management programs are critical. However, there is no published evidence examining the effect of chronic condition self-management (CCSM) group programs for Aboriginal and Torres Strait Islander people who have, or are at risk of, CV disease specifically. This study evaluates the Work It Out program for its effect on clinical outcome measures in urban Aboriginal and Torres Strait Islander participants with or at risk of CV disease. This study was underpinned by a conceptual framework based on Aboriginal and Torres Strait Islander community control. Participants had at least one diagnosed CV disease, or at least one CV disease risk factor. Short-term changes in clinical outcome measures over (approximately) 12 weeks were evaluated with a quasi-experimental, pre-post test design, using paired t-tests. Factors contributing to positive changes were tested using general linear models. The outcome measures included blood pressure (mmHg), weight (kg), body mass index (kg/m 2 ), waist and hip circumference (cm), waist to hip ratio (waist cm/hip cm) and six minute walk test (6MWT). Changes in several clinical outcome measures were detected, either within the entire group (n = 85) or within specific participant sub-groups. Participant's 6MWT distance improved by an average 0.053 km (95% CI: 0.01-0.07 km). The change in distance travelled was influenced by number of social and emotional wellbeing conditions participants presented with. The weight of participants classified with extreme obesity decreased on average by 1.6 kg (95% CI: 0.1-3.0 kg). Participants with high baseline systolic blood pressure demonstrated a mean decrease of 11 mmHg (95% CI: 3.2-18.8 mmHg). Change in blood pressure was influenced by the number of cardiovascular conditions participants experienced. Short-term improvements seen in some measures could indicate a trend for improvement in other indicators over the longer term. These results suggest the Work It Out program could be a useful model for cardiovascular rehabilitation and prevention for other urban Aboriginal and Torres Strait Islander populations.

Women with preterm birth have a distinct cervicovaginal metabolome.

PubMed

Ghartey, Jeny; Bastek, Jamie A; Brown, Amy G; Anglim, Laura; Elovitz, Michal A

2015-06-01

Metabolomics has the potential to reveal novel pathways involved in the pathogenesis of preterm birth (PTB). The objective of this study was to investigate whether the cervicovaginal (CV) metabolome was different in asymptomatic women destined to have a PTB compared with term birth. A nested case-control study was performed using CV fluid collected from a larger prospective cohort. The CV fluid was collected between 20-24 weeks (V1) and 24-28 weeks (V2). The metabolome was compared between women with a spontaneous PTB (n = 10) to women who delivered at term (n = 10). Samples were extracted and prepared for analysis using a standard extraction solvent method. Global biochemical profiles were determined using gas chromatography/mass spectrometry and ultra-performance liquid chromatography/tandem mass spectrometry. An ANOVA was used to detect differences in biochemical compounds between the groups. A false discovery rate was estimated to account for multiple comparisons. A total of 313 biochemicals were identified in CV fluid. Eighty-two biochemicals were different in the CV fluid at V1 in those destined to have a PTB compared with term birth, whereas 48 were different at V2. Amino acid, carbohydrate, and peptide metabolites were distinct between women with and without PTB. These data suggest that the CV space is metabolically active during pregnancy. Changes in the CV metabolome may be observed weeks, if not months, prior to any clinical symptoms. Understanding the CV metabolome may hold promise for unraveling the pathogenesis of PTB and may provide novel biomarkers to identify women most at risk. Copyright © 2015 Elsevier Inc. All rights reserved.

ROLE OF INSULIN SENSITIZERS ON CARDIOVASCULAR RISK FACTORS IN POLYCYSTIC OVARIAN SYNDROME: A META-ANALYSIS.

PubMed

Thethi, Tina K; Katalenich, Bonnie; Nagireddy, Prathima; Chabbra, Pankdeep; Kuhadiya, Nitesh; Fonseca, Vivian

2015-06-01

Polycystic ovarian syndrome (PCOS) is associated with an increase in cardiovascular (CV) risk factors such as insulin resistance, with accompanying hyperinsulinemia and hyperlipidemia, which are predisposing factors for type 2 diabetes mellitus and CV disease. The aim of this meta-analysis is to examine the effect of insulin sensitizers on clinical and biochemical features of PCOS and risk factors for CV disease. A systematic literature review was conducted, and randomized controlled clinical trials were identified by a search of bibliographic databases: Medline database (from 1966 forward), EMBASE (January 1985 forward), and Cochrane Central Register of Controlled Trials. Reviews of reference lists further identified candidate trials. Data was independently abstracted in duplicate by 2 investigators using a standardized data-collection form. Articles without a comparison group and randomization allocation were excluded. Reviewers worked independently and in duplicate to determine the methodological quality of trials, then collected data on patient characteristics, interventions, and outcomes. Of 455 studies, 44 trials were eligible. A random effects model was used. Significant unadjusted results favoring treatment with insulin sensitizers were obtained for body mass index (BMI) (effect size [ES] of 0.58), waist to hip ratio (WHR) (ES of 0.02), low-density-lipoprotein cholesterol (LDL-C) (ES of 0.11), fasting insulin (ES of 2.82), fasting glucose (ES of 0.10), free testosterone (ES of 1.88), and androstenedione level (ES of 0.76). Treatment with insulin sensitizers in women with PCOS results in improvement in CV factors such as BMI, WHR, LDL-C, fasting insulin, glucose, free testosterone, and androstenedione.

Depression in Cardiovascular Patients in Middle Eastern Populations: A Literature Review.

PubMed

Donnelly, Tam Truong; Al Suwaidi, Jassim Mohd; Al-Qahtani, Awad; Asaad, Nidal; Qader, Najlaa Abdul; Singh, Rajvir; Fung, Tak Shing; Mueed, Irem; Sharara, Shima; El Banna, Noha; Omar, Sarah

2015-08-01

Cardiovascular disease (CVD) is increasing in Middle Eastern countries. Depression is associated with increased morbidity and mortality rates among cardiovascular (CV) patients. Early detection of and intervention for depression among CV patients can reduce morbidity and mortality and save health care costs. Public information on mental health care needs of Arab CV patients living in Middle East regions is scattered and limited. This literature review surveyed and summarized research studies to learn what is known about the relationship between depression and CVD in Middle Eastern populations. The information will raise awareness among health care professionals and policy makers regarding the clinical significance of depression in Arab CV patients. It might contribute to development of culturally appropriate and effective mental health care services. Multiple databases were searched and 60 articles were assessed, including studies that investigated depression in Arab CV patient populations, physiological mechanisms of depression-CVD comorbidity, and intervention strategies that affect CV risk in depressed Arab patients. We discuss the extent to which this issue has been explored in Arab populations living in Middle East regions and Arab populations living abroad. We recommend that more comprehensive and in-depth research studies be conducted with Arab cardiac patients to enable implementation of culturally appropriate and effective mental health care interventions.

A Cluster-randomized Trial of a Centralized Clinical Pharmacy Cardiovascular Risk Service to Improve Guideline Adherence

PubMed Central

Carter, Barry L.; Coffey, Christopher S.; Chrischilles, Elizabeth A.; Ardery, Gail; Ecklund, Dixie; Gryzlak, Brian; Vander Weg, Mark W.; James, Paul A.; Christensen, Alan J.; Parker, Christopher P.; Gums, Tyler; Finkelstein, Rachel J; Uribe, Liz; Polgreen, Linnea A.

2015-01-01

Background Numerous studies have demonstrated the value of including pharmacists in team-based care to improve adherence to cardiovascular (CV) guidelines, medication adherence and risk factor control but there is limited information on whether these models can be successfully implemented more widely in diverse settings and populations. The purpose of this study is to evaluate whether a centralized, web-based CV risk service (CVRS) managed by clinical pharmacists will improve guideline adherence in multiple primary care medical offices with diverse geographic and patient characteristics. Methods This study is a prospective trial in 20 primary care offices stratified by the percent of under-represented minorities and then randomized to either the CVRS intervention or usual care. The intervention will last for 12 months and all subjects will have research visits at baseline and 12 months. The primary outcome is the difference in guideline adherence between groups. Data will also be abstracted from the medical record at 24 months to determine if the intervention effect is sustained after it is discontinued. Conclusions This study expects to enroll subjects through 2016 with results expected in 2019. This study will provide information on whether a distant, centralized CV risk service can be implemented in large numbers of medical offices, if it is effective in diverse populations, and if the effect can be sustained long-term. PMID:26111939

Simultaneously measured inter-arm and inter-leg systolic blood pressure differences and cardiovascular risk stratification: a systemic review and meta-analysis.

PubMed

Singh, Sukhchain; Sethi, Ankur; Singh, Mukesh; Khosla, Kavia; Grewal, Navsheen; Khosla, Sandeep

2015-08-01

Association of inter-arm systolic blood pressure difference (IASBPD) with cardiovascular (CV) morbidity and mortality remains controversial. We aimed to thoroughly examine all available evidence on inter-limb blood pressure (BP) difference and its association with CV risk and outcomes. We searched PubMed, EMBASE, CINAHL, Cochrane library, and Ovid for studies reporting bilateral simultaneous BP measurements in arms or legs and risk of peripheral arterial disease (PAD), coronary artery disease, cerebrovascular disease, subclavian stenosis, or mortality. Random-effect meta-analysis was performed to compare effect estimates. Twenty-seven studies met inclusion criteria, but only 17 studies (18 cohorts) were suitable for analysis. IASBPD of 10 mmHg or more was associated with PAD (risk ratios, 2.22; 1.41-3.5; P = .0006; sensitivity 16.6%; 6.7-35.4; specificity 91.9%; 83.1-96.3; 8 cohorts; 4774 subjects), left ventricular mass index (standardized mean difference 0.21; 0.03-0.39; P = .02; 2 cohort; 1604 subjects), and brachial-ankle pulse wave velocity (PWV) (one cohort). Association of PAD remained significant at cutoff of 15 mmHg (risk ratios, 1.91; 1.28-2.84; P = .001; 5 cohorts; 1914 subjects). We could not find statistically significant direct association of coronary artery disease, cerebrovascular disease, CV, and all-cause mortality in subjects with IASBPD of 10 mmHg or more, 15 mmHg or more, and inter-leg systolic BP difference of 15 mmHg or more. Inter-leg BP difference of 15 mmHg or more was strong predictor of PAD (P = .0001) and brachial-ankle PWV (P = .0001). Two invasive studies showed association of IASBPD and subclavian stenosis (estimates could not be combined). In conclusion, inter-arm and leg BP differences are strong predictors of PAD. IASBPD may be associated with subclavian stenosis, high left ventricular mass effect, and higher brachial-ankle PWVs. Inter-leg BP difference may also be associated with high left ventricular mass effect and higher brachial-ankle PWVs. Presence of inter-limb BP difference may indicate higher global CV risk. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Adiposity has no direct effect on carotid intima-media thickness in adolescents and young adults: Use of structural equation modeling to elucidate indirect & direct pathways.

PubMed

Gao, Zhiqian; Khoury, Philip R; McCoy, Connie E; Shah, Amy S; Kimball, Thomas R; Dolan, Lawrence M; Urbina, Elaine M

2016-03-01

Carotid intima-media thickness (cIMT) is associated with CV events in adults. Thicker cIMT is found in youth with CV risk factors including obesity. Which risk factors have the most effect upon cIMT in youth and whether obesity has direct or indirect effects is not known. We used structural equation modeling to elucidate direct and indirect pathways through which obesity and other risk factors were associated with cIMT. We collected demographics, anthropometrics and laboratory data on 784 subjects age 10-24 years (mean 18.0 ± 3.3 years). Common, bulb and internal carotid cIMT were measured by ultrasound. Multivariable regression analysis was performed to assess independent determinants of cIMT. Analyses were repeated with structural equation modeling to determine direct and indirect effects. Multivariable regression models explained 11%-22% of variation of cIMT. Age, sex and systolic blood pressure (BP) z-score were significant determinants of all cIMT segments. Body mass index (BMI) z-score, race, presence of type 2 diabetes mellitus (T2DM), hemoglobin A1c (HbA1c) and non-HDL were significant for some segments (all p = 0.05). The largest direct effect on cIMT was age (0.312) followed by BP (0.228), Blood glucose control (0.108) and non-HDL (0.134). BMI only had a significant indirect effect through blood glucose control, BP & non-HDL. High sensitivity C-reactive protein (CRP) had a small indirect effect through blood glucose control (all p = 0.05). Age and BP are the major factors with direct effect on cIMT. Glucose and non-HDL were also important in this cohort with a high prevalence of T2DM. BMI only has indirect effects, through other risk factors. Traditional CV risk factors have important direct effects on cIMT in the young, but adiposity exerts its influence only through other CV risk factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cardiovascular effects of urate-lowering therapies in patients with chronic gout: a systematic review and meta-analysis.

PubMed

Zhang, Tony; Pope, Janet E

2017-07-01

To determine if urate-lowering treatment (ULT) in gout can reduce cardiovascular (CV) outcomes. Randomized trials were searched for treatment with ULT in gout. Eligible trials had to report CV safety of a ULT. Potential medications included allopurinol, febuxostat, pegloticase, rasburicase, probenecid, benzbromarone, sulphinpyrazone, losartan, fenofibrate and sodium-glucose linked transporter 2 inhibitors. A total of 3084 citations were found, with 642 duplicates. After the primary screen, 35 studies were selected for review. Several trials did not report CV events. Six were not randomized controlled trials (RCTs). Four studies reported no events in either intervention arm while the other four had 40 events in the febuxostat group ( n = 3631) and 5 in allopurinol group ( n = 1154). Overall, the pooled analysis did not show a significant difference between the two [febuxostat vs allopurinol: relative risk (RR) 1.69 (95% CI 0.54, 5.34), P = 0.37]. CV events did not decrease over time. Comparing shorter studies (<52 weeks) to longer ones did not reveal any statistical differences. However, in long-term studies with febuxostat vs allopurinol, results were nearly significant, with more CVE occurring with febuxostat treatment. Comparing any ULT to placebo (eight studies, n = 2221 patients) did not demonstrate a significant difference in non-Anti-Platelet Trialists' Collaboration events [any ULT vs placebo: RR 1.47 (95% CI 0.49, 4.40), P = 0.49] or all-cause mortality [any ULT vs placebo: RR 1.45 (95% CI 0.35, 5.77), P = 0.60]. RCT data do not suggest differences in CV events among ULTs in gout. Trials had few events despite high-risk patients being enrolled and may have been too short to show CV reduction by controlling inflammatory attacks and lowering uric acid. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Cyclic Voltammetry Probe Approach Curves with Alkali Amalgams at Mercury Sphere-Cap Scanning Electrochemical Microscopy Probes.

PubMed

Barton, Zachary J; Rodríguez-López, Joaquín

2017-03-07

We report a method of precisely positioning a Hg-based ultramicroelectrode (UME) for scanning electrochemical microscopy (SECM) investigations of any substrate. Hg-based probes are capable of performing amalgamation reactions with metal cations, which avoid unwanted side reactions and positive feedback mechanisms that can prove problematic for traditional probe positioning methods. However, prolonged collection of ions eventually leads to saturation of the amalgam accompanied by irreversible loss of Hg. In order to obtain negative feedback positioning control without risking damage to the SECM probe, we implement cyclic voltammetry probe approach surfaces (CV-PASs), consisting of CVs performed between incremental motor movements. The amalgamation current, peak stripping current, and integrated stripping charge extracted from a shared CV-PAS give three distinct probe approach curves (CV-PACs), which can be used to determine the tip-substrate gap to within 1% of the probe radius. Using finite element simulations, we establish a new protocol for fitting any CV-PAC and demonstrate its validity with experimental results for sodium and potassium ions in propylene carbonate by obtaining over 3 orders of magnitude greater accuracy and more than 20-fold greater precision than existing methods. Considering the timescales of diffusion and amalgam saturation, we also present limiting conditions for obtaining and fitting CV-PAC data. The ion-specific signals isolated in CV-PACs allow precise and accurate positioning of Hg-based SECM probes over any sample and enable the deployment of CV-PAS SECM as an analytical tool for traditionally challenging conditions.

Evaluation of cardiovascular risk in stages of gout by a complex multimodal ultrasonography.

PubMed

Gancheva, Rada; Kundurdjiev, Atanas; Ivanova, Mariana; Kundurzhiev, Todor; Kolarov, Zlatimir

2017-01-01

The aim of our work was to assess ultrasound features of cardiovascular (CV) risk in stages of gout. Cross-sectional complex multimodal ultrasound study of 169 age-matched patients, with similar distribution of arterial hypertension, diabetes mellitus, obesity and chronic renal failure, was divided into four groups: 41 with asymptomatic hyperuricemia, 52 gout without tophi, 42 gouty tophi and 34 controls with osteoarthritis. Parameters independently associated with CV risk were measured: renal resistive index (RRI), left ventricular mass index (LVMi), mitral annulus early diastolic velocity (e'), intima-media thickness (IMT) and common carotid artery resistive index (CCARI). Multivariate analyses were performed to evaluate the impact of gout stages and CV risk factors on ultrasound alterations. Gouty tophi increased the risk of having IMT >0.90 mm with an OR 11.51 (95 % CI 2.32-57.21, p = 0.003), gout without tophi raised the risk with an OR 6.25 (95 % CI 1.37-28.44, p = 0.018), while asymptomatic hyperuricemia had no effect on IMT. The category of CCARI >0.70 was influenced by tophi with an OR 11.18 (95 % CI 2.61-47.83, p = 0.001) and by arterial hypertension with an OR 3.22 (95 % CI 1.11-9.36, p = 0.032). Neither asymptomatic hyperuricemia nor gout without tophi modified the development of abnormally high CCARI. Gout stages had no impact on LVMi, e' and RRI. Tophi are related to worsened ultrasonographic parameters evaluating target organs in gout, relative to earlier stages of the disease. They create a strong risk of carotid arteries' changes even beyond arterial hypertension.

78 FR 61000 - Additional Designations, Foreign Narcotics Kingpin Designation Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... To: OPERADORA Y ADMINISTRADORA DE RESTAURANTES Y BARES RUDU, S.A. DE C.V.; Linked To: ROOL EUROPE AG... REMF671011QH1 (Mexico) (individual) [SDNTK] (Linked To: OPERADORA Y ADMINISTRADORA DE RESTAURANTES Y BARES RUDU... Y ADMINISTRADORA DE RESTAURANTES Y BARES RUDU, S.A. DE C.V., Vallarta No. 2380, Col. Colinas De San...

75 FR 42485 - Additional Designation of Entities and Individuals Pursuant to Executive Order 12978

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

... President, invoking the authority, inter alia, of the International Emergency Economic Powers Act (50 U.S.C. 1701-1706), issued the Order. In the Order, the President declared a national emergency to deal with.... DE C.V., Mexico, Distrito Federal, Mexico; c/o GRUPO JEZINNE, S.A. DE C.V., Mexico, Distrito Federal...

Prevalence of chronic kidney disease and its determinants in coronary heart disease patients in 24 European countries: Insights from the EUROASPIRE IV survey of the European Society of Cardiology.

PubMed

Wagner, Martin; Wanner, Christoph; Kotseva, Kornelia; Wood, David; De Bacquer, Dirk; Rydén, Lars; Störk, Stefan; Heuschmann, Peter U

2017-07-01

Aims Chronic kidney disease (CKD) is associated with the development and progression of coronary heart disease (CHD), in addition to classic cardiovascular risk factors. We analysed the prevalence of CKD in CHD patients from 24 European countries in the ambulatory setting and in a preceding hospital stay for CHD (index). Methods and results A total of 7998 EUROASPIRE IV participants (median 65 years of age, 76% male) attended a study visit 6-36 months after the index hospitalisation. CKD was classified according to stages of estimated glomerular filtration rate (eGFR) and albuminuria (urinary albumin/creatinine ratio). In stable CHD conditions (study visit), 17.3% had CKD (eGFR <60 mL/min/1.73 m 2 ) with variation among participating countries (range 13.1-26.4%). A further 12% presented with preserved eGFR but significant albuminuria. During the hospital stay due to a coronary event, impaired kidney function was observed in 17.6% (range 7.5-38.2%). Risk factors for impaired kidney function included older age, female gender, classic cardiovascular (CV) risk factors, details of CHD history and congestive heart failure (multivariate regression). Of all patients, 38.9% had declined, 31.3% were stable and 29.8% had improved kidney function between hospital discharge and the study visit, dependent on age, gender, CV risk factors, CHD history and cardiac dysfunction (multivariate regression). Conclusions Every fifth CHD patient had CKD, while every tenth exhibited albuminuria as the sole indicator of kidney damage. These subjects are at increased risk of progression of CKD and CHD complications. After hospital stays due to CHD, there is potential of recovery of kidney function, but our findings underline the importance of identifying patients who are at high risk of developing CKD in order to counteract disease progression.

Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly.

PubMed

Alehagen, Urban; Aaseth, Jan; Alexander, Jan; Johansson, Peter

2018-01-01

Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function. From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results, mortality was registered. After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group. A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95%CI 0.42-0.81; P = 0.001). In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk. This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years. Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity. The results thus validate the results obtained in the 10-year evaluation. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanisms behind this effect remain to be fully elucidated, although various effects on cardiac function, oxidative stress, fibrosis and inflammation have previously been identified. Since this was a small study, the observations should be regarded as hypothesis-generating. Clinicaltrials.gov NCT01443780.

A Pragmatic Approach to Guide Implementation Evaluation Research: Strategy Mapping for Complex Interventions.

PubMed

Huynh, Alexis K; Hamilton, Alison B; Farmer, Melissa M; Bean-Mayberry, Bevanne; Stirman, Shannon Wiltsey; Moin, Tannaz; Finley, Erin P

2018-01-01

Greater specification of implementation strategies is a challenge for implementation science, but there is little guidance for delineating the use of multiple strategies involved in complex interventions. The Cardiovascular (CV) Toolkit project entails implementation of a toolkit designed to reduce CV risk by increasing women's engagement in appropriate services. The CV Toolkit project follows an enhanced version of Replicating Effective Programs (REP), an evidence-based implementation strategy, to implement the CV Toolkit across four phases: pre-conditions, pre-implementation, implementation, and maintenance and evolution. Our current objective is to describe a method for mapping implementation strategies used in real time as part of the CV Toolkit project. This method supports description of the timing and content of bundled strategies and provides a structured process for developing a plan for implementation evaluation. We conducted a process of strategy mapping to apply Proctor and colleagues' rubric for specification of implementation strategies, constructing a matrix in which we identified each implementation strategy, its conceptual group, and the corresponding REP phase(s) in which it occurs. For each strategy, we also specified the actors involved, actions undertaken, action targets, dose of the implementation strategy, and anticipated outcome addressed. We iteratively refined the matrix with the implementation team, including use of simulation to provide initial validation. Mapping revealed patterns in the timing of implementation strategies within REP phases. Most implementation strategies involving the development of stakeholder interrelationships and training and educating stakeholders were introduced during the pre-conditions or pre-implementation phases. Strategies introduced in the maintenance and evolution phase emphasized communication, re-examination, and audit and feedback. In addition to its value for producing valid and reliable process evaluation data, mapping implementation strategies has informed development of a pragmatic blueprint for implementation and longitudinal analyses and evaluation activities. We update recent recommendations on specification of implementation strategies by considering the implications for multi-strategy frameworks and propose an approach for mapping the use of implementation strategies within complex, multi-level interventions, in support of rigorous evaluation. Developing pragmatic tools to aid in operationalizing the conduct of implementation and evaluation activities is essential to enacting sound implementation research.

High concentrations of anthocyanins in genuine cherry-juice of old local Austrian Prunus avium varieties.

PubMed

Schüller, Elisabeth; Halbwirth, Heidi; Mikulic-Petkovsek, Maja; Slatnar, Ana; Veberic, Robert; Forneck, Astrid; Stich, Karl; Spornberger, Andreas

2015-04-15

Antioxidant activity and polyphenols were quantified in vapour-extracted juice of nine Austrian, partially endemic varieties of sweet cherry (Prunus avium): cv. 'Spätbraune von Purbach', cv. 'Early Rivers', cv. 'Joiser Einsiedekirsche', cv. 'Große Schwarze Knorpelkirsche' and four unidentified local varieties. Additionally the effect of storage was evaluated for six of the varieties. A variety showing the highest antioxidant capacity (9.64 μmol Trolox equivalents per mL), total polyphenols (2747 mg/L) and total cyanidins (1085 mg/L) was suitable for mechanical harvest and its juice did not show any losses of antioxidant capacity and total anthocyanin concentration during storage. The juice of cv. 'Große Schwarze Knorpelkirsche' had also high concentrations of total anthocyanins (873 mg/L), but showed substantial losses through storage. The local Austrian sweet cherry varieties from the Pannonian climate zone are particularly suitable for the production of processed products like cherry juice with high content of anthocyanins and polyphenols. Copyright © 2014 Elsevier Ltd. All rights reserved.

PlantCV v2: Image analysis software for high-throughput plant phenotyping

PubMed Central

Abbasi, Arash; Berry, Jeffrey C.; Callen, Steven T.; Chavez, Leonardo; Doust, Andrew N.; Feldman, Max J.; Gilbert, Kerrigan B.; Hodge, John G.; Hoyer, J. Steen; Lin, Andy; Liu, Suxing; Lizárraga, César; Lorence, Argelia; Miller, Michael; Platon, Eric; Tessman, Monica; Sax, Tony

2017-01-01

Systems for collecting image data in conjunction with computer vision techniques are a powerful tool for increasing the temporal resolution at which plant phenotypes can be measured non-destructively. Computational tools that are flexible and extendable are needed to address the diversity of plant phenotyping problems. We previously described the Plant Computer Vision (PlantCV) software package, which is an image processing toolkit for plant phenotyping analysis. The goal of the PlantCV project is to develop a set of modular, reusable, and repurposable tools for plant image analysis that are open-source and community-developed. Here we present the details and rationale for major developments in the second major release of PlantCV. In addition to overall improvements in the organization of the PlantCV project, new functionality includes a set of new image processing and normalization tools, support for analyzing images that include multiple plants, leaf segmentation, landmark identification tools for morphometrics, and modules for machine learning. PMID:29209576

PlantCV v2: Image analysis software for high-throughput plant phenotyping.

PubMed

Gehan, Malia A; Fahlgren, Noah; Abbasi, Arash; Berry, Jeffrey C; Callen, Steven T; Chavez, Leonardo; Doust, Andrew N; Feldman, Max J; Gilbert, Kerrigan B; Hodge, John G; Hoyer, J Steen; Lin, Andy; Liu, Suxing; Lizárraga, César; Lorence, Argelia; Miller, Michael; Platon, Eric; Tessman, Monica; Sax, Tony

2017-01-01

Systems for collecting image data in conjunction with computer vision techniques are a powerful tool for increasing the temporal resolution at which plant phenotypes can be measured non-destructively. Computational tools that are flexible and extendable are needed to address the diversity of plant phenotyping problems. We previously described the Plant Computer Vision (PlantCV) software package, which is an image processing toolkit for plant phenotyping analysis. The goal of the PlantCV project is to develop a set of modular, reusable, and repurposable tools for plant image analysis that are open-source and community-developed. Here we present the details and rationale for major developments in the second major release of PlantCV. In addition to overall improvements in the organization of the PlantCV project, new functionality includes a set of new image processing and normalization tools, support for analyzing images that include multiple plants, leaf segmentation, landmark identification tools for morphometrics, and modules for machine learning.

PlantCV v2: Image analysis software for high-throughput plant phenotyping

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

Gehan, Malia A.; Fahlgren, Noah; Abbasi, Arash

Systems for collecting image data in conjunction with computer vision techniques are a powerful tool for increasing the temporal resolution at which plant phenotypes can be measured non-destructively. Computational tools that are flexible and extendable are needed to address the diversity of plant phenotyping problems. We previously described the Plant Computer Vision (PlantCV) software package, which is an image processing toolkit for plant phenotyping analysis. The goal of the PlantCV project is to develop a set of modular, reusable, and repurposable tools for plant image analysis that are open-source and community-developed. Here in this paper we present the details andmore » rationale for major developments in the second major release of PlantCV. In addition to overall improvements in the organization of the PlantCV project, new functionality includes a set of new image processing and normalization tools, support for analyzing images that include multiple plants, leaf segmentation, landmark identification tools for morphometrics, and modules for machine learning.« less

PlantCV v2: Image analysis software for high-throughput plant phenotyping

DOE PAGES

Gehan, Malia A.; Fahlgren, Noah; Abbasi, Arash; ...

2017-12-01

Systems for collecting image data in conjunction with computer vision techniques are a powerful tool for increasing the temporal resolution at which plant phenotypes can be measured non-destructively. Computational tools that are flexible and extendable are needed to address the diversity of plant phenotyping problems. We previously described the Plant Computer Vision (PlantCV) software package, which is an image processing toolkit for plant phenotyping analysis. The goal of the PlantCV project is to develop a set of modular, reusable, and repurposable tools for plant image analysis that are open-source and community-developed. Here in this paper we present the details andmore » rationale for major developments in the second major release of PlantCV. In addition to overall improvements in the organization of the PlantCV project, new functionality includes a set of new image processing and normalization tools, support for analyzing images that include multiple plants, leaf segmentation, landmark identification tools for morphometrics, and modules for machine learning.« less

Patterns of Statin Use in a Real-World Population of Patients at High Cardiovascular Risk.

PubMed

Lin, Iris; Sung, Jennifer; Sanchez, Robert J; Mallya, Usha G; Friedman, Mark; Panaccio, Mary; Koren, Andrew; Neumann, Peter; Menzin, Joseph

2016-06-01

Widespread use of statins has improved hypercholesterolemia management, yet a significant proportion of patients remain at risk for cardiovascular (CV) events. Analyses of treatment patterns reveal inadequate intensity and duration of statin therapy among patients with hypercholesterolemia, and little is known about real-world statin use, specifically in subgroups of patients at high risk for CV events. To examine patterns of statin use and outcomes among patients with high-risk features who newly initiated statin monotherapy. Adult patients (aged > 18 years) at high CV risk who received > 1 prescription for statin monotherapy and who had not received lipid-modifying therapy during the previous 12 months were identified from the Truven MarketScan Commercial and Medicare Supplemental databases (from January 2007 to June 2013). Patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes were hierarchically classified into 5 mutually exclusive CV risk categories (listed here in order from highest to lowest risk): (1) recent CV event (subcategorized by hospitalization for acute coronary syndrome [ACS] or other non-ACS CV event within 90 days of index); (2) coronary heart disease (CHD); (3) history of ischemic stroke; (4) peripheral artery disease (PAD); and (5) diabetes. Outcomes of interest included changes in therapy, proportion of days covered (PDC), time to discontinuation, and proportion of patients with ASCVD-related inpatient visit during the follow-up period. Statin therapy was subdivided into high-intensity treatment (atorvastatin 40 mg or 80 mg, rosuvastatin 20 mg or 40 mg, or simvastatin 80 mg) or moderate- to low-intensity treatment (all other statins and statin dosing regimens). Follow-up data were obtained from the index date (statin initiation) until the end of continuous enrollment. A total of 541,221 patients were included in the analysis. The majority of patients were stratified in the diabetes cohort (61.1%), followed in frequency by recent ACS event (15.8%), recent non-ACS CV event (9.9%), PAD (4.7%), CHD (4.4%), and history of ischemic stroke (4.1%). Only 15.0% of the population initiated therapy with a high-intensity statin, and 22.5% of these high-intensity statin initiators switched to a moderate- to low-intensity regimen during the follow-up period. Median time to statin discontinuation was approximately 15 months. Duration of treatment was longer among those who were treated with a high-intensity versus a moderate- to low-intensity statin regimen (21 and 15 months, respectively). The PDC was highest in the recent ACS hospitalization cohort (66.4%) and lowest in the diabetes cohort (55.5%). The PDC was significantly greater among patients who initiated treatment with a high-intensity statin regimen than with a moderate- to low-intensity statin regimen (62.1% vs. 57.5%, respectively; P< 0.001). At 1 year, Kaplan-Meier estimates of the cumulative rates for ASCVD-related hospitalizations ranged from 3.5% (diabetes) to 21.8% (recent ACS hospitalization). Patients at high risk for CV events are suboptimally dosed with statins, have high rates of discontinuation, and have low rates of adherence. Despite the use of statin therapy, ASCVD-related inpatient visit rates were high, particularly among those patients at highest risk because of a recent ACS hospitalization. Future interventions are required to ensure that high-risk patients are effectively managed to reduce subsequent morbidity and mortality. Support for this research was provided by Regeneron Pharmaceuticals, Tarrytown, New York, and Sanofi US, Bridgewater, New Jersey. Menzin and Lin are employees of Boston Health Economics, which received consulting fees from Sanofi. Friedman is a consultant to Boston Health Economics. Lin, Friedman, and Menzin have received research support from Sanofi US. Sung, Mallya, Panaccio, and Koren are employees of Sanofi US and also have ownership interest in Sanofi US. Sanchez is an employee of and has ownership interest in Regeneron Pharmaceuticals. Neumann has served on advisory boards for Merck & Co, Takeda Pharmaceutical Company, Genentech, Novartis, Bayer AG, UCB, Sanofi US, Robert Wood Johnson Foundation, and Cubist and serves as consultant for Boston Health Economics, Forrest, P urdue, and Smith and Nephew. This research has been presented in part at the International Society for Pharmacoeconomics and Outcomes Research, 20th Annual International Meeting, May 16-20, 2015, Philadelphia, Pennsylvania. All authors contributed to the study design, protocol development, and results interpretation. Lin and Menzin were responsible for conducting the study analyses. All authors were involved in manuscript development and approved the submitted version.

Prospective Validation of a Screening Biomarker Approach Combining Amino-Terminal Pro-Brain Natriuretic Peptide With Galectin-3 Predicts Death and Cardiovascular Events in Asymptomatic Hemodialysis Patients.

PubMed

Voroneanu, Luminita; Siriopol, Dimitrie; Apetrii, Mugurel; Hogas, Simona; Onofriescu, Mihai; Nistor, Ionut; Kanbay, Mehmet; Dumea, Raluca; Cusai, Silvia; Cianga, Petru; Constantinescu, Daniela; Covic, Adrian

2018-05-01

Cardiovascular (CV) disease is a major cause of death in hemodialysis patients. Biomarkers used to identify high-risk asymptomatic patients would allow early evaluation of cardiac dysfunction and appropriate therapeutic intervention. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 (Gal-3) may serve this purpose. Plasma levels of NT-proBNP and Gal-3 were measured in 173 patients. Patients were prospectively followed for occurrences of major CV events or death. The association of NT-proBNP and Gal-3 with outcome was analyzed. The prognostic abilities for the combined outcome of Gal-3 and/or NT-proBNP were evaluated. During a median follow-up of 36 months, there were 47 incident outcomes (death and CV events). In the univariable Cox analysis, age, hypertension, albumin, phosphorus levels, and combined elevation of NT-proBNP with Gal-3 above the median (hazard ratio [HR] = 3.65, 95% confidence interval [CI] = 1.45-9.21) were associated with outcomes. In multivariable Cox analysis, both NT-proBNP and Gal-3 values above the median remained associated with outcomes (HR = 3.34, 95% CI = 1.30-8.56). In clinically asymptomatic dialysis patients, combined use of NT-proBNP and Gal-3 may improve risk stratification for death and CV events.

Sports and exercise cardiology in the United States: cardiovascular specialists as members of the athlete healthcare team.

PubMed

Lawless, Christine E; Olshansky, Brian; Washington, Reginald L; Baggish, Aaron L; Daniels, Curt J; Lawrence, Silvana M; Sullivan, Renee M; Kovacs, Richard J; Bove, Alfred A

2014-04-22

In recent years, athletic participation has more than doubled in all major demographic groups, while simultaneously, children and adults with established heart disease desire participation in sports and exercise. Despite conferring favorable long-term effects on well-being and survival, exercise can be associated with risk of adverse events in the short term. Complex individual cardiovascular (CV) demands and adaptations imposed by exercise present distinct challenges to the cardiologist asked to evaluate athletes. Here, we describe the evolution of sports and exercise cardiology as a unique discipline within the continuum of CV specialties, provide the rationale for tailoring of CV care to athletes and exercising individuals, define the role of the CV specialist within the athlete care team, and lay the foundation for the development of Sports and Exercise Cardiology in the United States. In 2011, the American College of Cardiology launched the Section of Sports and Exercise Cardiology. Membership has grown from 150 to over 4,000 members in just 2 short years, indicating marked interest from the CV community to advance the integration of sports and exercise cardiology into mainstream CV care. Although the current athlete CV care model has distinct limitations, here, we have outlined a new paradigm of care for the American athlete and exercising individual. By practicing and promoting this new paradigm, we believe we will enhance the CV care of athletes of all ages, and serve the greater athletic community and our nation as a whole, by allowing safest participation in sports and physical activity for all individuals who seek this lifestyle. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Testosterone Replacement Therapy and Cardiovascular Risk: A Review

PubMed Central

Corona G, Giovanni; Rastrelli, Giulia; Maseroli, Elisa; Sforza, Alessandra

2015-01-01

Recent reports in the scientific and lay press have suggested that testosterone (T) replacement therapy (TRT) is likely to increase cardiovascular (CV) risk. In a final report released in 2015, the Food and Drug Administration (FDA) cautioned that prescribing T products is approved only for men who have low T levels due to primary or secondary hypogonadism resulting from problems within the testis, pituitary, or hypothalamus (e.g., genetic problems or damage from surgery, chemotherapy, or infection). In this report, the FDA emphasized that the benefits and safety of T medications have not been established for the treatment of low T levels due to aging, even if a man's symptoms seem to be related to low T. In this paper, we reviewed the available evidence on the association between TRT and CV risk. In particular, data from randomized controlled studies and information derived from observational and pharmacoepidemiological investigations were scrutinized. The data meta-analyzed here do not support any causal role between TRT and adverse CV events. This is especially true when hypogonadism is properly diagnosed and replacement therapy is correctly performed. Elevated hematocrit represents the most common adverse event related to TRT. Hence, it is important to monitor hematocrit at regular intervals in T-treated subjects in order to avoid potentially serious adverse events. PMID:26770933

Indicators of Cardiovascular Risk in Metabolic Syndrome: Long Term Follow-up in Italian Patients.

PubMed

Mombelli, Giuliana; Pavanello, Chiara; Castelnuovo, Samuela; Bosisio, Raffaella; Simonelli, Sara; Pazzucconi, Franco; Sirtori, Cesare Riccardo

2017-01-01

Cardiovascular risk (CV) factors associated with the metabolic syndrome (MetS) may vary in different populations. In some, hypertension may be the major determinant, in others are low high-density lipoprotein cholesterol (HDL-C), high triglycerides, or another component. Subjects included in this analysis were identified in 2006, among those attending the Lipid Clinic of the Niguarda Hospital, and followed up through to 2013. Patient characteristics (including the occurrence of CV events) were obtained from electronic medical records. MetS was diagnosed according to the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) guidelines. The carotid intima media thickness (cIMT) was also followed in these patients over the years. After 7 years a total of 858 subjects had a complete follow-up; 271 of those had MetS. Patients developing a CV event showed elevated baseline cIMT (e.g. cIMTmax ≥ 2.4 mm in males and ≥ 2.2 mm in females); moreover the cIMT in MetS patients was higher at baseline and the rise over 7 years was larger compared with patients without MetS. By examining each body variable for MetS we found that a waist to height ratio (WHtR) ≥ 0.5 was present in nearly all subjects with a CV event. The follow-up data of a series of Italian patients with and without MetS, clearly indicates that the former have a raised cIMT and their arterial IMT progression is greater and the presence of a larger WHtR is apparently linked to a higher incidence of CV events. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mortality in primary angioplasty patients starting antiplatelet therapy with prehospital prasugrel or clopidogrel: a 1-year follow-up from the European MULTIPRAC Registry

PubMed Central

Goldstein, Patrick; Grieco, Niccolò; Ince, Hüseyin; Danchin, Nicolas; Ramos, Yvonne; Goedicke, Jochen; Clemmensen, Peter

2016-01-01

Aim MULTIPRAC was designed to provide insights into the use and outcomes associated with prehospital initiation of antiplatelet therapy with either prasugrel or clopidogrel in the context of primary percutaneous coronary intervention. After a previous report on efficacy and safety outcomes during hospitalization, we report here the 1-year follow-up data, including cardiovascular (CV) mortality. Methods and results MULTIPRAC is a multinational, prospective registry of patients with ST-elevation myocardial infarction (STEMI) from 25 hospitals in nine countries, all of which had an established practice of prehospital start of dual antiplatelet therapy in place. The key outcome was CV death at 1 year. Among 2,036 patients followed-up through 1 year, 49 died (2.4%), 10 during the initial hospitalization and 39 within 1 year after hospital discharge. The primary analysis was based on the P2Y12-inhibitor, used from prehospital loading dose through hospital discharge. Prasugrel (n=824) was more commonly used than clopidogrel (n=425). The observed 1-year rates for CV death were 0.5% with prasugrel and 2.6% with clopidogrel. After adjustment for differences in baseline characteristics, treatment with prasugrel was associated with a significantly lower risk of CV death than treatment with clopidogrel (odds ratio 0.248; 95% confidence interval 0.06–0.89). Conclusion In STEMI patients from routine practice undergoing primary angioplasty, who were able to start oral antiplatelet therapy prehospital, treatment with prasugrel as compared to clopidogrel was associated with a lower risk of CV death at 1-year follow-up. PMID:27143908

Are generic and brand-name statins clinically equivalent? Evidence from a real data-base.

PubMed

Corrao, Giovanni; Soranna, Davide; Arfè, Andrea; Casula, Manuela; Tragni, Elena; Merlino, Luca; Mancia, Giuseppe; Catapano, Alberico L

2014-10-01

Use of generic drugs can help contain drug spending. However, there is concern among patients and physicians that generic drugs may be clinically inferior to brand-name ones. This study aimed to compare patients treated with generic and brand-name statins in terms of therapeutic interruption and cardiovascular (CV) outcomes. 13,799 beneficiaries of the health care system of Lombardy, Italy, aged 40 years or older who were newly treated with generic or brand-name simvastatin during 2008, were followed until 2011 for the occurrence of two outcomes: 1) therapeutic discontinuation and 2) hospitalization for CV events. Hazard ratios (HR) associated with use of generic or brand-name at starting therapy (intention-to-treat analysis) and during follow-up (as-treated analysis) were estimated by fitting proportional hazard Cox models. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. Patients who started on generic did not experience a different risk of discontinuation (HR: 0.98; 95% CI 0.94 to 1.02) nor of CV outcomes (HR: 0.98; 95% CI 0.79 to 1.22) from those starting on brand-name. Patients who spent >75% of time of follow-up with statin available on generics did not experience a different risk of discontinuation (HR: 0.94; 95% CI 0.87 to 1.01), nor of CV outcomes (HR: 1.06; 95% CI 0.83 to 1.34), compared with those who mainly or only used brand-name statin. Our findings do not support the notion that in the real world clinical practice brand-name statins are superior to generics for keeping therapy and preventing CV outcomes. Copyright © 2014. Published by Elsevier B.V.

Effects of hypocaloric diets with different glycemic indexes on endothelial function and glycemic variability in overweight and in obese adult patients at increased cardiovascular risk.

PubMed

Buscemi, Silvio; Cosentino, Loretta; Rosafio, Giuseppe; Morgana, Manuela; Mattina, Alessandro; Sprini, Delia; Verga, Salvatore; Rini, Giovam Battista

2013-06-01

The role of glycemic index of the diet in glucose control and cardiovascular prevention is still not clear. The aim of this study was to determine the effects of hypocaloric diets with different glycemic indexes and glycemic loads on endothelial function and glycemic variability in nondiabetic participants at increased cardiovascular risk. Forty nondiabetic obese participants were randomly assigned to a three-month treatment with either a low glycemic index (LGI; n=19) or high glycemic index (HGI; n=21) hypocaloric diet with similar macronutrient and fiber content. Endothelial function was measured as flow-mediated dilatation (FMD) of the brachial artery before and after dieting. In addition, 48-h continuous subcutaneous glucose monitoring was done before and after dieting in a subgroup of 24 participants. The amount of weight loss after dieting was similar in both groups. The glycemic index of the diet significantly influenced the FMD (P<0.005). In particular, the change of FMD was 2.3±2.6% following the LGI diet, and -0.9±3.6% after the HGI diet (P<0.005). The mean 48-h glycemia decreased significantly after dietary treatment (P<0.05), but no significant effect of the glycemic index of the diet on results was observed. The glycemic index of the diet significantly influenced the 48-h glycemic variability measured as coefficient of variability (CV%; P<0.001). The CV% decreased after the LGI diet (from 23.5 to 20.0%) and increased after the HGI diet (from 23.6 to 26.6%). The change in percentage of FMD was inversely correlated with the change in the 48-h glycemic CV% (r=-0.45; P<0.05). Endothelial function and glycemic variability ameliorate in association with the adherence to an LGI hypocaloric diet in nondiabetic obese persons. ISRCTN56834511. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Red Cell Distribution Width and Mortality in Patients With Acute Coronary Syndrome: A Meta-Analysis on Prognosis.

PubMed

Abrahan, Lauro L; Ramos, John Daniel A; Cunanan, Elleen L; Tiongson, Marc Denver A; Punzalan, Felix Eduardo R

2018-06-01

Red cell distribution width (RDW), a routine component of the complete blood count (CBC), measures variation in the size of circulating erythrocytes. It has been associated with several clinical outcomes in cardiovascular disease. We sought to strengthen the association between RDW and mortality in patients admitted for acute coronary syndrome (ACS) by pooling together data from available studies. Studies that fulfilled the following were identified for analysis: 1) observational; 2) included patients admitted for ACS; 3) reported data on all-cause or cardiovascular (CV) mortality in association with a low or high RDW; and 4) used logistic regression analysis to control for confounders. Using MEDLINE, Clinical Key, ScienceDirect, Scopus, and Cochrane Central Register of Controlled Trials databases, a search for eligible studies was conducted until January 9, 2017. The quality of each study was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Our primary outcome of interest was all-cause or CV mortality. We also investigated the impact of RDW on major adverse cardiovascular events (MACEs) for the studies that reported these outcomes. Review Manager (RevMan) 5.3 was utilized to perform Mantel-Haenzel analysis of random effects and compute for relative risk. We identified 13 trials involving 10,410 patients, showing that in ACS, a low RDW is associated with a statistically significant lower all-cause or CV mortality (RR 0.35, (95% CI 0.30 to 0.40), P < 0.00001, I 2 = 53%), a finding that was consistent both in the short- and long-term. A low RDW is also associated with lower risk for MACEs after an ACS (RR 0.56, (95% CI 0.51 to 0.61), P < 0.00001, I 2 = 91%). A low RDW during an ACS is associated with lower all-cause or CV mortality and lower risk of subsequent MACEs, providing us with a convenient and inexpensive risk stratification tool in ACS patients.

Efficacy and safety of glucagon-like peptide-1 agonists on macrovascular and microvascular events in type 2 diabetes mellitus: A meta-analysis.

PubMed

Gargiulo, P; Savarese, G; D'Amore, C; De Martino, F; Lund, L H; Marsico, F; Dellegrottaglie, S; Marciano, C; Trimarco, B; Perrone-Filardi, P

2017-12-01

Glucagon-like peptide-1 (GLP-1) agonists improve glycaemic control in type 2 diabetes mellitus (DM). Outcome trials investigating macro and microvascular effects of GLP-1 agonists reported conflicting results. The aim of this study was to assess, in a meta-analysis, the effects of GLP-1 agonists on mortality, major nonfatal cardiovascular (CV) events, renal and retinal events. MEDLINE, Cochrane, ISI Web of Science, SCOPUS and ClinicalTrial.gov databases were searched for articles published until June 2017. Randomized trials enrolling more than 200 patients, comparing GLP-1 versus placebo or active treatments in patients with DM, and assessing outcomes among all-cause death, CV death, MI, stroke, HF, diabetic retinopathy and nephropathy were included. 77 randomized trials enrolling 60,434 patients were included. Compared to control, treatment with GLP-1 significantly reduced the risk of all-cause death (RR: 0.888; CI: 0.804-0.979; p = 0.018) and the risk of CV death (RR: 0.858; CI: 0.757-0.973; p = 0.017). GLP-1 agonists did not affect the risk of MI (RR: 0.917; CI: 0.830-1.014; p = 0.092) as well as the risk of stroke (RR: 0.882; CI: 0.759-1.023; p = 0.097), HF (RR: 0.967; CI: 0.803-1.165; p = 0.725), retinopathy (RR: 1.000; CI: 0.807-1.238; p = 0.997) and nephropathy (RR: 0.866; CI: 0.625-1.199; p = 0.385). Treatment with GLP-1 agonists in DM patients is associated with a significant reduction of all cause and CV mortality. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Cryopreservation of banana's cv Grand Naine in vitro rhizomes.

PubMed

Londe, Luciana C N; Vendrame, Wagner A; Sanaei, Massy; Oliveira, Alexandre B DE

2018-01-01

The preservation of banana genetic material is usually performed through seedlings. However, most banana cultivars do not produce seed and are propagated vegetatively. Therefore, cryopreservation is a feasible technique that allows the preservation of banana genotypes indefinitely. For the success of cryopreservation protocols, the selection of cryoprotectants and pre-freezing techniques are important factor. Therefore, the objective of this study was to verify the effects of different cryoprotectants with and without 1% phloroglucinol and pre-cooling periods on the development of a protocol for cryopreservation of in vitro rhizomes ofMusa accuminata(AAA) cv Grand Naine banana. The addition of 1% phloroglucinol to the cryoprotective solutions, such as PVS2 enhanced recovery of cryopreserved banana rhizomes. In addition, pre-cooling of explants in ice for 3 hours in PVS2 + 1% of phloroglucinol allowed efficient cryopreservation of banana rhizomes, followed by successful recovery and regeneration of in vitro shoots of banana cv Grand Naine.

ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients.

PubMed

Gellen, Barnabas; Thorin-Trescases, Nathalie; Sosner, Philippe; Gand, Elise; Saulnier, Pierre-Jean; Ragot, Stéphanie; Fraty, Mathilde; Laugier, Stéphanie; Ducrocq, Grégory; Montaigne, David; Llaty, Pierre; Rigalleau, Vincent; Zaoui, Philippe; Halimi, Jean-Michel; Roussel, Ronan; Thorin, Eric; Hadjadj, Samy

2016-11-01

A high serum angiopoietin-like 2 (ANGPTL2) concentration is an independent risk factor for developing diabetes and is associated with insulin resistance and atherosclerosis. In this work, we have examined the impact of serum ANGPTL2 on improving cardiovascular (CV) risk stratification in patients with type 2 diabetes. A prospective, monocentric cohort of consecutive type 2 diabetes patients (the SURDIAGENE cohort; total of 1353 type 2 diabetes patients; 58% men, mean ± SD age 64 ± 11 years) was followed for a median of 6.0 years for death as primary endpoint and major adverse CV events (MACE; i.e. CV death, myocardial infarction or stroke) as a secondary endpoint. Patients with end-stage renal disease, defined as a requirement for dialysis or a history of kidney transplantation, were excluded. Patients were grouped into quartiles according to ANGPTL2 concentrations at inclusion: <11.2 (Q1), 11.2-14.7 (Q2), 14.8-19.5 (Q3) or >19.5 (Q4) ng/ml. During follow up, 367 patients (representing 4.5% of the total person-years) died and 290 patients (representing 3.7% of the total person-years) presented with MACE. Both the survival and MACE-free survival rates were significantly different between ANGPTL2 quartiles (logrank 82.12, p < 0.0001 for death; and logrank 65.14, p < 0.0001 for MACE). Patients with ANGPTL2 concentrations higher than 19.5 ng/ml (Q4) had a significantly higher risk of death and MACE than those with ANGPTL2 levels of 19.5 ng/ml or less (Q1-3) (HR for death 2.44 [95% CI 1.98, 3.00], p < 0.0001; HR for MACE 2.43 [95% CI 1.92, 3.06], p < 0.0001) after adjustment for sex, age and established CV risk factors. Using ANGPTL2 concentrations, prediction of the risk of mortality, as assessed by integrated discrimination improvement (IDI), was significantly improved (IDI 0.006 ± 0.002, p = 0.0002). In patients with type 2 diabetes, serum ANGPTL2 concentrations were independently associated with death and MACE. Therefore, ANGPTL2 is a promising candidate biomarker for improving risk stratification in type 2 diabetes patients, and may prove to be a valuable therapeutic target.

Clinical update on benefit versus risks of oral paracetamol alone or with codeine: still a good option?

PubMed

Kress, Hans Georg; Untersteiner, Gerald

2017-02-01

After decades of worldwide use of paracetamol/acetaminophen as a popular and apparently safe prescription and over-the-counter medicine, the future role of this poorly understood analgesic has been seriously questioned by recent concerns about prenatal, cardiovascular (CV) and hepatic safety, and also about its analgesic efficacy. At the same time the usefulness of codeine in combination products has come under debate. Based on a PubMed database literature search on the terms efficacy, safety, paracetamol, acetaminophen, codeine and their combinations up to and including June 2016, this clinical update reviews the current evidence of the benefit and risks of oral paracetamol alone and with codeine for mild-to-moderate pain in adults, and compares the respective efficacy and safety profiles with those of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas there is a clear strong association of NSAID use and gastrointestinal (GI) and CV morbidity and mortality, evidence for paracetamol with and without codeine supports the recommended use even in most vulnerable individuals, such as the elderly, pregnant women, alcoholics, and compromised GI and CV patients. The controversies and widespread misconceptions about the complex hepatic metabolism and potential hepatotoxicity have been corrected by recent reviews, and paracetamol remains the first-line nonopioid analgesic in patients with liver diseases if notes of caution are applied. Due to its safety and tolerability profile paracetamol remained a first-line treatment in many international guidelines. Alone and with codeine it is a safe and effective option in adults, whilst NSAIDs are obviously less safe as alternatives, given the risk of potentially fatal GI and CV adverse effects.

Implications of the cardiovascular safety of febuxostat and allopurinol in patients with gout and cardiovascular morbidities (CARES) trial and associated FDA public safety alert.

PubMed

Choi, Hyon; Neogi, Tuhina; Stamp, Lisa; Dalbeth, Nicola; Terkeltaub, Robert

2018-06-05

Recently, the FDA issued a public safety alert, responding to results of the now-published Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities (CARES) trial. CARES showed no significant difference between allopurinol and febuxostat in the primary composite endpoint of cardiovascular (CV) events in subjects with gout and established cardiovascular comorbidities at baseline. However, there was significantly increased risk of cardiac and all-cause mortality with febuxostat. Urate lowering therapy (ULT) is central to long-term management of gout, and xanthine oxidoreductase inhibitor (XOI) therapy is the consensus first line approach. Allopurinol is generally the first XOI employed, but febuxostat is an effective XOI option, and is commonly used when allopurinol is not tolerated. These data are further relevant since CV co-morbidities are common in gout. Here, we examine why the CARES trial was done, and discuss other, ongoing comparative studies of febuxostat and allopurinol whose results are awaited. We assess strengths and limitations of CARES, and appraise robustness and biologic plausibility of the results. CARES does not prove that febuxostat raises CV mortality risk, but suggests greater risk with febuxostat than allopurinol. CARES results do not support first line use of febuxostat ULT, and raise questions on febuxostat placement at various pharmacologic ULT decision tree branches. Alternatives to febuxostat that are frequently effective include allopurinol dose-escalation, and uricosuric therapy alone or combined with allopurinol. The FDA safety alert highlights the need for shared ULT medical decision with gout patients, including discussion of CV safety of febuxostat. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The optimal strategy of percutaneous coronary intervention for ST-elevation myocardial infarction patients with multivessel disease: an updated meta-analysis of 9 randomized controlled trials.

PubMed

Fan, Zhong G; Gao, Xiao F; Li, Xiao B; Mao, Wen X; Chen, Li W; Tian, Nai L

2017-04-01

The optimal strategy of percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) still remains controversial. This study sought to explore the optimal PCI strategy for those patients. Medline, EMBASE and the Cochrane Controlled Trials Registry were searched for relevant studies. We analyzed the comparison of major adverse cardiac events (MACEs) as the primary end point between the preventive PCI strategy and the culprit only PCI strategy (CV-PCI). The further analysis of two subgroups described as the complete multivessel PCI strategy during primary procedure (CMV-PCI) and the staged PCI strategy (S-PCI) was also performed. Nine randomized trials were identified. The risk of MACEs was reduced significantly regarding to preventive PCI strategy (OR=0.41, 95% CI: 0.31-0.53, P<0.001) compared to CV-PCI strategy. There were lower risks of long-term mortality, reinfarction and repeat revascularization in the preventive PCI group compared to the CV-PCI group (OR=0.41, 95% CI: 0.27-0.62, P<0.001; OR=0.54, 95% CI: 0.32-0.91, P=0.021; OR=0.37, 95% CI: 0.26-0.51, P<0.001). Subgroup analysis showed that staged PCI strategy reduced the incidence of long-term mortality versus CMV-PCI strategy. The preventive PCI is associated with the lower risk of MACEs in STEMI patients with MVD compared to the CV-PCI strategy, and the S-PCI strategy seems to be an optimal choice for these patients rather than the CMV-PCI.

Assessment of local carotid stiffness in seronegative and seropositive rheumatoid arthritis.

PubMed

Aslan, Abdullah Nabi; Şirin Özcan, Ayşe Nur; Erten, Şükran; Alsancak, Yakup; Durmaz, Tahir

2017-10-01

Rheumatoid arthritis (RA) is a chronic, inflammatory disease associated with increased risk of cardiovascular (CV) disease. Arterial stiffness (AS) is an independent predictor of CV events. This study aimed to analyse local carotid AS parameters in seronegative and seropositive RA patients. Of 347 consecutive RA patients, we selected specifically those who were free of established CV diseases and risk factors. As a result, 140 patients (126 women, 52.2 ± 10 years) and 140 healthy controls (122 women, 52.7 ± 8.0 years) were enrolled into this study. The common carotid AS was evaluated using radio frequency echo-tracking system to determine the local carotid pulse wave velocity (cPWV) and carotid intima-media thickness (cIMT). Based on rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) positivity, RA patients were categorized into seronegative and seropositive subgroups. Carotid PWV was determined to be significantly higher in all patients and subgroups than controls (p < .001 for all). Although cIMT was similar between the patients, controls and seropositive subgroup, seronegative patients had significantly higher cIMT compared to controls (p = .035) and seropositive group (p = .010). Moreover, a significant positive correlation was found between cPWV and age (r: 0.603, p < .001), ESR (r: 0.297, p = .004), ACPA (r: 0.346, p = .001) and cIMT (r: 0.290, p = .005) in seropositive patients. RA per se is sufficient to cause arteriosclerosis in the absence of classical CV risk factors. However, arterial hypertrophy is only increased in seronegative patients but not in seropositive group.

Physiological responses at five estimates of critical velocity.

PubMed

Bull, Anthony J; Housh, Terry J; Johnson, Glen O; Rana, Sharon R

2008-04-01

The purpose of this study was to compare critical velocity (CV) estimates from five mathematical models, and to examine the oxygen uptake (VO(2)) and heart rate (HR) responses during treadmill runs at the five estimates of CV. Ten subjects (six males and four females) performed one incremental test to determine maximal oxygen consumption (VO(2max)) and four or five randomly ordered constant-velocity trials on a treadmill for the estimation of CV. Five mathematical models were used to estimate CV for each subject including two linear, two nonlinear, and an exponential model. Up to five randomly ordered runs to exhaustion were performed by each subject at treadmill velocities that corresponded to the five CV estimates, and VO(2) and HR responses were monitored throughout each trial. The 3-parameter, nonlinear (Non-3) model produced CV estimates that were significantly (P < 0.05) less than the other four models. During runs at CV estimates, five subjects did not complete 60 min at the their estimate from the Non-3 model, nine did not complete 60 min at their estimate from the Non-2 model, and no subjects completed 60 min at any estimate from the other three models. The mean HR value (179 +/- 18 beats min(-1), HR(peak)) at the end of runs at CV using the Non-3 model was significantly less than the maximal HR (195 +/- 7 beats min(-1), HR(max)) achieved during the incremental trial to exhaustion. However, mean HR(peak) values from runs at all other CV estimates were not significantly different from HR(max). Furthermore, data indicated that mean HR(peak) values increased during runs at CV estimates from the third minute to the end of exercise for all models, and that these increases in VO(2) (range = 367-458 ml min(-1)) were significantly greater than that typically associated with O(2) drift ( approximately 200 ml min(-1)) for all but the exponential model, indicating a VO(2) slow component associated with CV estimates from four of the five models. However, the mean VO(2) values at the end of exercise during the runs at CV estimates for all five mathematical models were significantly less than the mean VO(2max) value. These results suggest that, in most cases, CV estimated from the five models does not represent a fatigueless task. In addition, the mean CV estimates from the five models varied by 18%, and four of the five mean CV estimates were within the heavy exercise domain. Therefore, CV would not represent the demarcation point between heavy and severe exercise domains.

The concept of psoriasis as a systemic inflammation: implications for disease management.

PubMed

Reich, K

2012-03-01

Psoriasis is a systemic, immune-mediated disorder, characterized by inflammatory skin and joint manifestations. A range of co-morbidities is associated with psoriasis, including metabolic diseases, such as diabetes, and psychological disorders. Although the systemic nature of psoriasis often remains unrecognized, the inflammatory processes involved may be associated with the development of co-morbidities, which, themselves, have a significant impact on the patient's health and quality of life. The relative risks of myocardial infarction (MI) and stroke are increased in patients with psoriasis compared with the general population. These are especially seen in younger patients with more severe disease, and are believed to contribute to the 3- to 4-year reduction in life expectancy among patients with severe psoriasis. The recent results of large studies indicate that the increased cardiovascular (CV) risk is at least partially attributable to psoriasis and independent of the presence of metabolic co-morbidities. The possible interplay between psoriasis and CV disease is complex. Metabolic diseases such as obesity and diabetes have overlapping genetic predispositions with psoriasis. Both conditions are likely to also interact at a functional level because obesity and the up-regulation of pro-inflammatory mediators in psoriasis appear to influence adipocyte homoeostasis, inducing non-professional immune functions. This may perpetuate psoriatic inflammation, displaying similarities to the immunopathogenesis of atherosclerosis. Finally, the disturbed adipokine profile and inflammation associated with psoriasis enhances insulin resistance, causing subsequent endothelial dysfunction, atherosclerosis and eventual coronary events. The differential contribution of psoriasis and uncontrolled classical CV risk factors to the increased CV risk seen in psoriasis patients is not clear. Successful treatment with methotrexate appears to lower the rates of MI in patients with psoriasis. Tumour necrosis factor-α (TNF-α) inhibitors are known to counteract insulin resistance and emerging studies demonstrate an even higher protective effect of TNF-α antagonist therapy against the development of diabetes or CV co-morbidities in patients. The recent data reviewed here indicate a role for earlier and more appropriate treatment of psoriasis with drugs such as TNF-α antagonists. Such an approach has the potential to significantly improve patient outcomes through the treatment of psoriasis itself and possibly also in protection against co-morbidities. © 2012 The Author. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

The long-term prognostic value of the Q wave criteria for prior myocardial infarction recommended in the universal definition of myocardial infarction.

PubMed

Perino, Alexander C; Soofi, Muhammad; Singh, Nikhil; Aggarwal, Sonya; Froelicher, Victor

2015-01-01

We sought to characterize the prognostic value of the third universal definition of myocardial infarction (UDMI) and ≥40msec Q wave criteria. We evaluated hazard ratios (HR) with 95% confidence intervals (CI) for cardiovascular (CV) death for computerized Q wave measurements from the electrocardiograms of 43,661 patients collected from 1987 to 1999 at the Palo Alto VA. There were 3929 (9.0%) CV deaths over a mean follow-up of 7.6 (±3.8) years. The risk of CV death for Q waves ≥40msec in any two contiguous leads in any lead group was equivalent to or higher than that for contiguous UDMI Q waves, with HR 2.44 (95% CI 2.15-4.11) and HR 2.42 (95% CI (2.18-3.42), respectively. The UDMI Q wave criteria do not provide an advantage over ≥40msec Q waves at predicting CV death. Copyright © 2015. Published by Elsevier Inc.

The rationale/design of the Guimarães/Vizela study: a multimodal population-based cohort study to determine global cardiovascular risk and disease.

PubMed

Cunha, Pedro Guimarães; Cotter, Jorge; Oliveira, Pedro; Vila, Isabel; Sousa, Nuno

2014-06-01

Cardiovascular disease and dementia are growing medical and social problems in aging societies. Appropriate knowledge of cardiovascular disease and cognitive decline risk factors (RFs) are critical for global CVR health preventive intervention. Many epidemiological studies use case definition based on data collected/measured in a single visit, a fact that can overestimate prevalence rates and distant from clinical practice demanding criteria. Portugal displays an elevated stroke mortality rate. However, population's global CV risk characterization is limited, namely, considering traditional/nontraditional RF and new intermediate phenotypes of CV and renal disease. Association of hemodynamic variables (pulse wave velocity and central blood pressure) with global CVR stratification, cognitive performance, and kidney disease are practically inexistent at a dwelling population level. After reviewing published data, we designed a population-based cohort study to analyze the prevalence of these cardiovascular RFs and intermediate phenotypes, using random sampling of adult dwellers living in 2 adjacent cities. Strict definition of phenotypes was planned: subjects were observed twice, and several hemodynamic and other biological variables measured at least 3 months apart. Three thousand thirty-eight subjects were enrolled, and extensive data collection (including central and peripheral blood pressure, pulse wave velocity), sample processing, and biobank edification were carried out. One thousand forty-seven cognitive evaluations were performed. Seeking for CV risk reclassification, early identification of subjects at risk, and evidence of early vascular aging and cognitive and renal function decline, using the strict daily clinical practice criteria, will lead to better resource allocation in preventive measures at a population level.

Most significant reduction of cardiovascular events in patients undergoing lipoproteinapheresis due to raised Lp(a) levels - A multicenter observational study.

PubMed

Schatz, U; Tselmin, S; Müller, G; Julius, U; Hohenstein, B; Fischer, S; Bornstein, S R

2017-11-01

Lipoprotein(a) (Lp(a)) is an independent cardiovascular (CV) risk factor, predisposing to premature and progressive CV events. Lipoproteinapheresis (LA) is the only efficacious therapy for reducing Lp(a). Data comparing the clinical efficacy of LA with respect to reduction of CV events in subjects with elevated Lp(a) versus LDL-C versus both disorders is scarce. We aimed to perform this comparison in a multicenter observational study. 113 LA patients from 8 apheresis centers were included (mean age 56.3 years). They were divided into 3 groups: Group I: Lp(a) < 600 mg/l, LDL-C > 2.6 mmol/l, Group II: Lp(a) > 600 mg/l, LDL-C < 2.6 mmol/l, and Group III: Lp(a) > 600 mg/l, LDL-C > 2.6 mmol/l. CV events were documented 2 years before versus 2 years after LA start. Before start of LA Group II showed the highest CV event rate (p 0.001). Group III had a higher CV event rate than Group I (p 0.03). During LA there was a significant reduction of CV events/patient in all vessel beds (1.22 ± 1.16 versus 0.33 ± 0.75, p < 0.001). The highest CV event rate during LA was seen in coronaries followed by peripheral arteries, cerebrovascular events were least common. Greater CV event reduction rates were achieved in patients with isolated Lp(a) elevation (-77%, p < 0.001) and in patients with Lp(a) and LDL-C elevation (-74%, p < 0.001) than in subjects with isolated hypercholesterolemia (-53%, p 0.06). This study demonstrates that patients with Lp(a) elevation benefit most from LA treatment. Prospective trials to confirm these data are warranted. Copyright © 2017. Published by Elsevier B.V.

Metabolic syndrome cluster does not provide incremental prognostic information in patients with stable cardiovascular disease: A post hoc analysis of the AIM-HIGH trial.

PubMed

Lyubarova, Radmila; Robinson, Jennifer G; Miller, Michael; Simmons, Debra L; Xu, Ping; Abramson, Beth L; Elam, Marshall B; Brown, Todd M; McBride, Ruth; Fleg, Jerome L; Desvigne-Nickens, Patrice; Ayenew, Woubeshet; Boden, William E

Metabolic syndrome (MS) is a well-known risk factor for the development of cardiovascular (CV) disease; yet, controversy persists whether it adds incremental prognostic value in patients with established CV disease. This study was performed to determine if MS is associated with worse CV outcomes in patients with established CV disease treated intensively with statins. We performed a post hoc analysis of the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial, in which patients with established CV disease and atherogenic dyslipidemia (n = 3414) were randomly assigned to receive extended release niacin or placebo during a mean 36-month follow-up, to assess whether the presence of MS or the number of MS components contributed to CV outcomes. The composite primary end point of CV events occurred in 15.1% of patients without MS vs 13.8%, 16.9%, and 16.8% of patients with MS in the subsets with 3, 4, and 5 MS components, respectively (corresponding adjusted hazard ratios 0.9, 1.1, and 1.1 relative to patients without MS), P = .55. Comparing subgroups with 3 vs 4 or 5 MS components, there was no significant difference in either the composite primary end point or secondary end points. Patients with diabetes mellitus had higher event rates, with or without the presence of MS. The presence of MS was not associated with worse CV outcomes in the AIM-HIGH population. The rate of CV events in statin-treated Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes patients with MS was not significantly influenced by the number of MS components. Copyright © 2017 National Lipid Association. All rights reserved.

High prevalence of cardiovascular risk factors in Asian Indians: A community survey - Chandigarh Urban Diabetes Study (CUDS)

PubMed Central

Walia, Rama; Bhansali, Anil; Ravikiran, Muthuswamy; Ravikumar, Padala; Bhadada, Sanjay K.; Shanmugasundar, G.; Dutta, Pinaki; Sachdeva, Naresh

2014-01-01

Background & objectives: Studies conducted to assess the prevalence of cardiovascular (CV) risk factors among different regions of the country show variation in risk factors in different age groups and urban and rural population. We undertook this study to determine the prevalence of cardiovascular risk factors among urban adults in a north Indian city. Methods: In a cross-sectional survey, 2227 subjects aged ≥ 20 yr were studied from April 2008 to June 2009 in Urban Chandigarh, a north Indian city. Demographic history, anthropometry and blood pressure were assessed. Fasting, and 2 h capillary plasma glucose after 75 g glucose load, HDL-C and triglycerides were estimated. Results: The most prevalent cardiovascular risk factors in the age group of 20-29 yr was sedentary lifestyle (63%), while from fourth decade and onwards, it was overweight/obesity (59-85%). The second most common prevalent cardiovascular risk factor in the age group of 20-29 yr was overweight/obesity, in 30-49 yr sedentary lifestyle, in 50-69 yr hypertension and in subjects ≥70 yr, it was hypertriglyceridaemia. The prevalence of overweight/obesity, hypertension, dysglycaemia and smoking was almost double in subjects in the fourth decade of life, as compared to those in the third decade of life. The prevalence of CV risk factors significantly increased with age irrespective of gender and prevalence of low HDL-C was significantly more common in women as compared to men. Interpretation & conclusions: Sedentary lifestyle, obesity and low HDL-C are the most prevalent CV risk factors in subjects in the third and fourth decade of life in this north Indian population and clustering of these cardiovascular risk factors increases with advancing age. Strategies need to be formulated to target this population to prevent the epidemic of cardiovascular disease. PMID:24718400

Modeling hard clinical end-point data in economic analyses.

PubMed

Kansal, Anuraag R; Zheng, Ying; Palencia, Roberto; Ruffolo, Antonio; Hass, Bastian; Sorensen, Sonja V

2013-11-01

The availability of hard clinical end-point data, such as that on cardiovascular (CV) events among patients with type 2 diabetes mellitus, is increasing, and as a result there is growing interest in using hard end-point data of this type in economic analyses. This study investigated published approaches for modeling hard end-points from clinical trials and evaluated their applicability in health economic models with different disease features. A review of cost-effectiveness models of interventions in clinically significant therapeutic areas (CV diseases, cancer, and chronic lower respiratory diseases) was conducted in PubMed and Embase using a defined search strategy. Only studies integrating hard end-point data from randomized clinical trials were considered. For each study included, clinical input characteristics and modeling approach were summarized and evaluated. A total of 33 articles (23 CV, eight cancer, two respiratory) were accepted for detailed analysis. Decision trees, Markov models, discrete event simulations, and hybrids were used. Event rates were incorporated either as constant rates, time-dependent risks, or risk equations based on patient characteristics. Risks dependent on time and/or patient characteristics were used where major event rates were >1%/year in models with fewer health states (<7). Models of infrequent events or with numerous health states generally preferred constant event rates. The detailed modeling information and terminology varied, sometimes requiring interpretation. Key considerations for cost-effectiveness models incorporating hard end-point data include the frequency and characteristics of the relevant clinical events and how the trial data is reported. When event risk is low, simplification of both the model structure and event rate modeling is recommended. When event risk is common, such as in high risk populations, more detailed modeling approaches, including individual simulations or explicitly time-dependent event rates, are more appropriate to accurately reflect the trial data.

Cardiovascular risk profile and management of atrial fibrillation in India: Real world data from RealiseAF survey.

PubMed

Narasimhan, C; Verma, Jagmohan Singh; Ravi Kishore, A G; Singh, Balbir; Dani, Sameer; Chawala, Kamaldeep; Haque, Azizul; Khan, Aftab; Nair, Mohan; Vora, Amit; Rajasekhar, V; Thomas, Joy M; Gupta, Anoop; Naik, Ajay; Prakash, V S; Naditch, Lisa; Gabriel Steg, P

Atrial fibrillation (AF) is the most common sustained arrhythmia with high risk for many cardiovascular (CV) complications. Adherence to recommended management guidelines is important to avoid complications. In India, there is little knowledge on how AF is managed in real world. This is a cross-sectional study of patients in India enrolled in RealiseAF survey between February 2010 and March 2010 with a diagnosis of AF within the last 12 months. From 15 centers, 301 patients {mean age 59.9 years (14.4); 52.5% males} were recruited. AF was controlled in 50% of patients with 77 (26.7%) in sinus rhythm and 67 (23.3%) with heart rate <80beats/min. Hypertension (50.8%), valvular heart disease (40.7%), heart failure (25.9%), and diabetes (20.4%) were the most common underlying CV diseases. Increased risk for stroke (CHADS 2 score≥2) was present in 36.6%. Most of the patients (85%) were symptomatic. AF was paroxysmal, persistent, and permanent in 28.7%, 22.7%, and 34.3% respectively. In 14%, AF was diagnosed as first episode. Forty-six percent of patients had rate control, 35.2% rhythm control, 0.3% both strategies, and 18.4% received no therapy for AF before the visit. At the end of the visit, adoption to rate control strategy increased to 52.3% and patients with no therapy decreased to 7%. AF in India is not adequately controlled. Concomitant CV risk factors and risk of stroke are high. The study underscores the need for improved adoption of guideline-directed management for optimal control of AF and reducing the risk of stroke. Copyright © 2016. Published by Elsevier B.V.

A Discrete Event Simulation Model to Assess the Economic Value of a Hypothetical Pharmacogenomics Test for Statin-Induced Myopathy in Patients Initiating a Statin in Secondary Cardiovascular Prevention.

PubMed

Mitchell, Dominic; Guertin, Jason R; Dubois, Anick; Dubé, Marie-Pierre; Tardif, Jean-Claude; Iliza, Ange Christelle; Fanton-Aita, Fiorella; Matteau, Alexis; LeLorier, Jacques

2018-04-01

Statin (HMG-CoA reductase inhibitor) therapy is the mainstay dyslipidemia treatment and reduces the risk of a cardiovascular (CV) event (CVE) by up to 35%. However, adherence to statin therapy is poor. One reason patients discontinue statin therapy is musculoskeletal pain and the associated risk of rhabdomyolysis. Research is ongoing to develop a pharmacogenomics (PGx) test for statin-induced myopathy as an alternative to the current diagnosis method, which relies on creatine kinase levels. The potential economic value of a PGx test for statin-induced myopathy is unknown. We developed a lifetime discrete event simulation (DES) model for patients 65 years of age initiating a statin after a first CVE consisting of either an acute myocardial infarction (AMI) or a stroke. The model evaluates the potential economic value of a hypothetical PGx test for diagnosing statin-induced myopathy. We have assessed the model over the spectrum of test sensitivity and specificity parameters. Our model showed that a strategy with a perfect PGx test had an incremental cost-utility ratio of 4273 Canadian dollars ($Can) per quality-adjusted life year (QALY). The probabilistic sensitivity analysis shows that when the payer willingness-to-pay per QALY reaches $Can12,000, the PGx strategy is favored in 90% of the model simulations. We found that a strategy favoring patients staying on statin therapy is cost effective even if patients maintained on statin are at risk of rhabdomyolysis. Our results are explained by the fact that statins are highly effective in reducing the CV risk in patients at high CV risk, and this benefit largely outweighs the risk of rhabdomyolysis.

Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic review of risk factors in clinical practice.

PubMed

Baig, Shanat; Edward, Nicky C; Kotecha, Dipak; Liu, Boyang; Nordin, Sabrina; Kozor, Rebecca; Moon, James C; Geberhiwot, Tarekegn; Steeds, Richard P

2017-10-17

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A enzyme. Cardiovascular (CV) disease is a common cause of mortality in FD, in particular as a result of heart failure and arrhythmia, with a significant proportion of events categorized as sudden. There are no clear models for risk prediction in FD. This systematic review aims to identify the risk factors for ventricular arrhythmia (VA) and sudden cardiac deaths (SCD) in FD. A systematic search was performed following PRISMA guidelines of EMBASE, Medline, PubMed, Web of Science, and Cochrane from inception to August 2016, focusing on identification of risk factors for the development of VA or SCD. Thirteen studies were included in the review (n = 4185 patients) from 1189 articles, with follow-up of 1.2-10 years. Weighted average age was 37.6 years, and 50% were male. Death from any cause was reported in 8.3%. Of these, 75% was due to CV problems, with the majority being SCD events (62% of reported deaths). Ventricular tachycardia was reported in 7 studies, with an average prevalence of 15.3%. Risk factors associated with SCD events were age, male gender, left ventricular hypertrophy, late gadolinium enhancement on CV magnetic resonance imaging, and non-sustained ventricular tachycardia. Although a multi-system disease, FD is a predominantly cardiac disease from a mortality perspective, with death mainly from SCD events. Limited evidence highlights the importance of clinical and imaging risk factors that could contribute to improved decision-making in the management of FD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

An integrated biochemical prediction model of all-cause mortality in patients undergoing lower extremity bypass surgery for advanced peripheral artery disease.

PubMed

Owens, Christopher D; Kim, Ji Min; Hevelone, Nathanael D; Gasper, Warren J; Belkin, Michael; Creager, Mark A; Conte, Michael S

2012-09-01

Patients with advanced peripheral artery disease (PAD) have a high prevalence of cardiovascular (CV) risk factors and shortened life expectancy. However, CV risk factors poorly predict midterm (<5 years) mortality in this population. This study tested the hypothesis that baseline biochemical parameters would add clinically meaningful predictive information in patients undergoing lower extremity bypass operations. This was a prospective cohort study of patients with clinically advanced PAD undergoing lower extremity bypass surgery. The Cox proportional hazard model was used to assess the main outcome of all-cause mortality. A clinical model was constructed with known CV risk factors, and the incremental value of the addition of clinical chemistry, lipid assessment, and a panel of 11 inflammatory parameters was investigated using the C statistic, the integrated discrimination improvement index, and Akaike information criterion. The study monitored 225 patients for a median of 893 days (interquartile range, 539-1315 days). In this study, 50 patients (22.22%) died during the follow-up period. By life-table analysis (expressed as percent surviving ± standard error), survival at 1, 2, 3, 4, and 5 years, respectively, was 90.5% ± 1.9%, 83.4% ± 2.5%, 77.5% ± 3.1%, 71.0% ± 3.8%, and 65.3% ± 6.5%. Compared with survivors, decedents were older, diabetic, had extant coronary artery disease, and were more likely to present with critical limb ischemia as their indication for bypass surgery (P < .05). After adjustment for the above, clinical chemistry and inflammatory parameters significant (hazard ratio [95% confidence interval]) for all-cause mortality were albumin (0.43 [0.26-0.71]; P = .001), estimated glomerular filtration rate (0.98 [0.97-0.99]; P = .023), high-sensitivity C-reactive protein (hsCRP; 3.21 [1.21-8.55]; P = .019), and soluble vascular cell adhesion molecule (1.74 [1.04-2.91]; P = .034). Of the inflammatory molecules investigated, hsCRP proved most robust and representative of the integrated inflammatory response. Albumin, eGFR, and hsCRP improved the C statistic and integrated discrimination improvement index beyond that of the clinical model and produced a final C statistic of 0.82. A risk prediction model including traditional risk factors and parameters of inflammation, renal function, and nutrition had excellent discriminatory ability in predicting all-cause mortality in patients with clinically advanced PAD undergoing bypass surgery. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination

PubMed Central

Takahashi, Saki; Liao, Qiaohong; Van Boeckel, Thomas P.; Xing, Weijia; Sun, Junling; Hsiao, Victor Y.; Metcalf, C. Jessica E.; Chang, Zhaorui; Liu, Fengfeng; Zhang, Jing; Wu, Joseph T.; Cowling, Benjamin J.; Leung, Gabriel M.; Farrar, Jeremy J.; van Doorn, H. Rogier; Grenfell, Bryan T.; Yu, Hongjie

2016-01-01

Background Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus. Methods and Findings Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible–infected–recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R 0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the post-EV-A71-vaccination period remained either comparable to or only slightly increased from levels prior to vaccination. The duration and strength of cross-protection following infection with EV-A71 or CV-A16 was estimated to be 9.95 wk (95% confidence interval [CI]: 3.31, 23.40) in 68% of the population (95% CI: 37%, 96%). Our predictions are limited by the necessarily short and under-sampled time series and the possible circulation of unidentified serotypes, but, nonetheless, sensitivity analyses indicate that our results are robust in predicting that the vaccine should drastically reduce incidence of EV-A71 without a substantial competitive release of CV-A16. Conclusions The ability of our models to capture the observed epidemic cycles suggests that herd immunity is driving the epidemic dynamics caused by the multiple serotypes of enterovirus. Our results predict that the EV-A71 and CV-A16 serotypes provide a temporary immunizing effect against each other. Achieving high coverage rates of EV-A71 vaccination would be necessary to eliminate the ongoing transmission of EV-A71, but serotype replacement by CV-A16 following EV-A71 vaccination is likely to be transient and minor compared to the corresponding reduction in the burden of EV-A71-associated HFMD. Therefore, a mass EV-A71 vaccination program of infants and young children should provide significant benefits in terms of a reduction in overall HFMD burden. PMID:26882540

Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination.

PubMed

Takahashi, Saki; Liao, Qiaohong; Van Boeckel, Thomas P; Xing, Weijia; Sun, Junling; Hsiao, Victor Y; Metcalf, C Jessica E; Chang, Zhaorui; Liu, Fengfeng; Zhang, Jing; Wu, Joseph T; Cowling, Benjamin J; Leung, Gabriel M; Farrar, Jeremy J; van Doorn, H Rogier; Grenfell, Bryan T; Yu, Hongjie

2016-02-01

Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus. Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible-infected-recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the post-EV-A71-vaccination period remained either comparable to or only slightly increased from levels prior to vaccination. The duration and strength of cross-protection following infection with EV-A71 or CV-A16 was estimated to be 9.95 wk (95% confidence interval [CI]: 3.31, 23.40) in 68% of the population (95% CI: 37%, 96%). Our predictions are limited by the necessarily short and under-sampled time series and the possible circulation of unidentified serotypes, but, nonetheless, sensitivity analyses indicate that our results are robust in predicting that the vaccine should drastically reduce incidence of EV-A71 without a substantial competitive release of CV-A16. The ability of our models to capture the observed epidemic cycles suggests that herd immunity is driving the epidemic dynamics caused by the multiple serotypes of enterovirus. Our results predict that the EV-A71 and CV-A16 serotypes provide a temporary immunizing effect against each other. Achieving high coverage rates of EV-A71 vaccination would be necessary to eliminate the ongoing transmission of EV-A71, but serotype replacement by CV-A16 following EV-A71 vaccination is likely to be transient and minor compared to the corresponding reduction in the burden of EV-A71-associated HFMD. Therefore, a mass EV-A71 vaccination program of infants and young children should provide significant benefits in terms of a reduction in overall HFMD burden.

Circulation of multiple serotypes of highly divergent enterovirus C in the Xinjiang Uighur Autonomous Region of China

PubMed Central

Zhang, Yong; Sun, Qiang; Cui, Hui; Yan, Dongmei; Fan, Qin; Song, Yang; Zhu, Shuangli; Li, Xiaolei; Huang, Guohong; Ji, Tianjiao; Hu, Lan; Wang, Dongyan; Yang, Qian; Xu, Wenbo

2016-01-01

Poliomyelitis associated with circulating vaccine-derived polioviruses (cVDPVs) is a serious public health issue in the post-eradication era, and the occurrence of recombinant cVDPVs emphasizes the need to elucidate enterovirus C (EV-C) epidemiology. Stool samples were collected from 826 healthy children in Southern Xinjiang in 2011 to investigate EV-C circulation and epidemiology. Thirty-six EV-Cs were isolated and assigned to eight EV-C serotypes by molecular serotyping, suggesting the circulation of diverse EV-Cs in Xinjiang. Phylogenetic analysis showed that the Xinjiang EV-C strains had larger variation compared to the prototype and other modern strains. Additionally, the results showed unique characteristics of Xinjiang EV-Cs, such as the cytopathicity of CV-A1 strains to RD cells; the high divergence in CV-A11, CV-A13, CV-A17, and CV-A20 strains; the divergence of Xinjiang CV-A24 from AHC-related CV-A24 variant stains distributed worldwide; and the circulation of two novel EV-C serotypes (EV-C96 and EV-C99). Evaluations of this dense and diverse EV-C ecosystem will help elucidate the processes shaping enteroviral biodiversity. This study will improve our understanding of the evolution of enteroviruses and the recombination potential between polioviruses and other EV-Cs. PMID:27642136

Lack of efficacy of resveratrol on C-reactive protein and selected cardiovascular risk factors--Results from a systematic review and meta-analysis of randomized controlled trials.

PubMed

Sahebkar, Amirhossein; Serban, Corina; Ursoniu, Sorin; Wong, Nathan D; Muntner, Paul; Graham, Ian M; Mikhailidis, Dimitri P; Rizzo, Manfredi; Rysz, Jacek; Sperling, Laurence S; Lip, Gregory Y H; Banach, Maciej

2015-01-01

Numerous studies have suggested that oral supplementation with resveratrol exerts cardioprotective effects, but evidence of the effects on C-reactive protein (CRP) plasma levels and other cardiovascular (CV) risk factors is inconclusive. Therefore, we performed a meta-analysis to evaluate the efficacy of resveratrol supplementation on plasma CRP concentrations and selected predictors of CV risk. The search included PUBMED, Cochrane Library, Web of Science, Scopus, and EMBASE (up to August 31, 2014) to identify RCTs investigating the effects of resveratrol supplementation on selected CV risk factors. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence intervals (CI) as summary statistics. Meta-analysis of data from 10 RCTs (11 treatment arms) did not support a significant effect of resveratrol supplementation in altering plasma CRP concentrations (WMD: -0.144 mg/L, 95% CI: -0.968-0.680, p = 0.731). Resveratrol supplementation was not found to alter plasma levels of total cholesterol (WMD: 1.49 mg/dL, 95% CI: -14.96-17.93, p = 0.859), low density lipoprotein cholesterol (WMD: -0.31 mg/dL, 95% CI: -9.57-8.95, p = 0.948), triglycerides (WMD: 2.67 mg/dL, 95% CI: -28.34-33.67, p = 0.866), and glucose (WMD: 1.28 mg/dL, 95% CI: -5.28-7.84, p = 0.703). It also slightly reduced high density lipoprotein cholesterol concentrations (WMD: -4.18 mg/dL, 95% CI: -6.54 to -1.82, p = 0.001). Likewise, no significant effect was observed on systolic (WMD: 0.82 mmHg, 95% CI: -8.86-10.50, p = 0.868) and diastolic blood pressure (WMD: 1.72 mm Hg, 95% CI: -6.29-9.73, p=0.674). This meta-analysis of available RCTs does not suggest any benefit of resveratrol supplementation on CV risk factors. Larger, well-designed trials are necessary to confirm these results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Object-based attention modulates the discrimination of level increments in stop-consonant noise bursts

PubMed Central

2018-01-01

This study tested the hypothesis that object-based attention modulates the discrimination of level increments in stop-consonant noise bursts. With consonant-vowel-consonant (CvC) words consisting of an ≈80-dB vowel (v), a pre-vocalic (Cv) and a post-vocalic (vC) stop-consonant noise burst (≈60-dB SPL), we measured discrimination thresholds (LDTs) for level increments (ΔL) in the noise bursts presented either in CvC context or in isolation. In the 2-interval 2-alternative forced-choice task, each observation interval presented a CvC word (e.g., /pæk/ /pæk/), and normal-hearing participants had to discern ΔL in the Cv or vC burst. Based on the linguistic word labels, the auditory events of each trial were perceived as two auditory objects (Cv-v-vC and Cv-v-vC) that group together the bursts and vowels, hindering selective attention to ΔL. To discern ΔL in Cv or vC, the events must be reorganized into three auditory objects: the to-be-attended pre-vocalic (Cv–Cv) or post-vocalic burst pair (vC–vC), and the to-be-ignored vowel pair (v–v). Our results suggest that instead of being automatic this reorganization requires training, in spite of using familiar CvC words. Relative to bursts in isolation, bursts in context always produced inferior ΔL discrimination accuracy (a context effect), which depended strongly on the acoustic separation between the bursts and the vowel, being much keener for the object apart from (post-vocalic) than for the object adjoining (pre-vocalic) the vowel (a temporal-position effect). Variability in CvC dimensions that did not alter the noise-burst perceptual grouping had minor effects on discrimination accuracy. In addition to being robust and persistent, these effects are relatively general, evincing in forced-choice tasks with one or two observation intervals, with or without variability in the temporal position of ΔL, and with either fixed or roving CvC standards. The results lend support to the hypothesis. PMID:29364931

Why are there gaps in our management of those with high cardiovascular risk?

PubMed

Doolan-Noble, Fiona; Tracey, Jocelyn; Mann, Stewart

2012-03-01

Multiple New Zealand and other international studies have identified gaps in the management of those identified at high risk of a future cardiovascular (CV) event. This study sought to explore the views of health professionals about the barriers and facilitators present within the current primary health care system to the optimal management of those at high CV risk. This qualitative study utilised a focus group methodology to examine the barriers and facilitators within primary health care (PHC), and employed a general inductive approach to analyse the text data. The analysis of text data resulted in the emergence of interrelated themes, underpinned by subthemes. The patient, their circumstances and their characteristics and perceptions provided the first key theme and subthemes. The next key theme was primary health care providers, with subthemes of communication and values and beliefs. The general practice was the third theme and included multiple subthemes: implementation planning and pathway development, time and workload and roles and responsibilities. The final main theme was the health system with the subthemes linking to funding and leadership. This study determined the factors that act as barriers and facilitators to the effective management of those at high CV risk within the New Zealand PHC sector. General practice has a pivotal role in preventive health care, but to succeed there needs to be a refocusing of the PHC sector, requiring support from policy makers, District Health Boards and Primary Health Organisations, as well as those working in the sector.

Alcohol and CV Health: Jekyll and Hyde J-Curves.

PubMed

O'Keefe, Evan L; DiNicolantonio, James J; O'Keefe, James H; Lavie, Carl J

2018-02-16

A routine of light or moderate alcohol consumption (≤1 drink/day for women and 1 to 2 drinks/day for men) is associated with a lower risk for all-cause mortality, coronary artery disease (CAD), type 2 diabetes mellitus (T2D), heart failure (HF), and stroke. Conversely, heavy drinking, (>4 drinks/day) is associated with an increased risk for death and cardiovascular (CV) disease (CVD). Excessive alcohol intake trails behind only smoking and obesity among the 3 leading causes of premature deaths in the United States (US). Heavy alcohol use is a common cause of reversible hypertension (HTN), nonischemic dilated cardiomyopathy, atrial fibrillation (AF), and stroke (both ischemic and hemorrhagic). Among males aged 15 to 59 years, alcohol abuse is perhaps the leading cause of premature death. As such, the risk-to-benefit ratio of drinking is less favorable in younger individuals. A daily habit of light to moderate drinking is ideal for those who choose to consume alcohol regularly. Red wine in particular before or during the evening meal is linked with the best long-term CV outcomes. Most of the studies on alcohol and health are observational, and correlation does not prove causation. Health care professionals should not advise nondrinkers to begin drinking because of the paucity of randomized outcome data coupled with the potential for alcohol abuse even among seemingly low risk individuals. Copyright © 2017. Published by Elsevier Inc.

Aspirin and the Primary Prevention of Cardiovascular Diseases: An Approach Based on Individualized, Integrated Estimation of Risk.

PubMed

Volpe, Massimo; Battistoni, Allegra; Gallo, Giovanna; Coluccia, Roberta; De Caterina, Raffaele

2017-09-01

While the use of aspirin in the secondary prevention of cardiovascular (CVD) is well established, aspirin in primary prevention is not systematically recommended because the absolute CV event reduction is similar to the absolute excess in major bleedings. Recently, emerging evidence suggests the possibility that the assumption of aspirin, may also be effective in the prevention of cancer. By adding to the CV prevention benefits the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in the primary prevention in favour of the latter and broaden the indication for treatment with in populations at average risk. While prospective and randomized study are currently investigating the effect of aspirin in prevention of both cancer and CVD, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention could be already based on a balanced evaluation of the benefit/risk ratio.

Efficacy of high intensity exercise on disease activity and cardiovascular risk in active axial spondyloarthritis: a randomized controlled pilot study.

PubMed

Sveaas, Silje Halvorsen; Berg, Inger Jorid; Provan, Sella Aarrestad; Semb, Anne Grete; Hagen, Kåre Birger; Vøllestad, Nina; Fongen, Camilla; Olsen, Inge C; Michelsen, Annika; Ueland, Thor; Aukrust, Pål; Kvien, Tore K; Dagfinrud, Hanne

2014-01-01

Physical therapy is recommended for the management of axial spondyloarthritis (axSpA) and flexibility exercises have traditionally been the main focus. Cardiovascular (CV) diseases are considered as a major health concern in axSpA and there is strong evidence that endurance and strength exercise protects against CV diseases. Therefore, the aim of this study was to investigate the efficacy of high intensity endurance and strength exercise on disease activity and CV health in patients with active axSpA. In a single blinded randomized controlled pilot study the exercise group (EG) performed 12 weeks of endurance and strength exercise while the control group (CG) received treatment as usual. The primary outcome was the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS). Secondary outcomes included patient reported disease activity (Bath AS Disease Activity Index [BASDAI]), physical function (Bath AS Functional Index [BASFI]), and CV risk factors measured by arterial stiffness (Augmentation Index [Alx]) and Pulse Wave Velocity [PWV]), cardiorespiratory fitness (VO2 peak) and body composition. ANCOVA on the post intervention values with baseline values as covariates was used to assess group differences, and Mann Whitney U-test was used for outcomes with skewed residuals. Twenty-eight patients were included and 24 (EG, n = 10, CG, n = 14) completed the study. A mean treatment effect of -0.7 (95%CI: -1.4, 0.1) was seen in ASDAS score. Treatment effects were also observed in secondary outcomes (mean group difference [95%CI]): BASDAI: -2.0 (-3.6, -0.4), BASFI: -1.4 (-2.6, -0.3), arterial stiffness (estimated median group differences [95% CI]): AIx (%): -5.3 (-11.0, -0.5), and for PVW (m/s): -0.3 (-0.7, 0.0), VO2 peak (ml/kg/min) (mean group difference [95%CI]: 3.7 (2.1, 5.2) and trunk fat (%): -1.8 (-3.0, -0.6). No adverse events occurred. High intensity exercise improved disease activity and reduced CV risk factors in patients with active axSpA. These effects will be further explored in a larger trial. ClinicalTrials.gov NCT01436942.

Association of computed tomography-derived left ventricular size with major cardiovascular events in the general population: the Heinz Nixdorf recall study.

PubMed

Dykun, Iryna; Geisel, Marie H; Kälsch, Hagen; Lehmann, Nils; Bauer, Marcus; Moebus, Susanne; Jöckel, Karl-Heinz; Möhlenkamp, Stefan; Erbel, Raimund; Mahabadi, Amir A

2015-05-01

To investigate the relationship between LV size as determined by non-contrast enhanced cardiac CT with incident cardiovascular disease in the general population free of clinical cardiovascular disease. LV axial area was quantified from non-contrast CT in axial, end-diastolic images at a mid-ventricular slice in participants from the population-based Heinz Nixdorf recall study, free of cardiovascular disease (n=3926, 59±8years, 53%female). LV size index (LVI) was defined as the quotient of LV area and body surface area. Major CV events (coronary events, stroke, CV death) were assessed during follow-up. Association of LVI with events was assessed using Cox regression analysis in unadjusted and multivariable adjusted models. During 8.0±1.5years of follow-up, 219 subjects developed a major CV event. Those with events had larger LVI at baseline (2258±352 vs. 2149±276 mm2/m2, p<0.0001). In univariate analysis, increase of LVI by 1 standard deviation was associated with 40% higher risk of events (HR(95%CI):1.41(1.26-1.59), p<0.0001). Associations remained statistically significant after adjustment for CV risk factors (1.24(1.10-1.40), p=0.0007) and when further adjusting for CAC (1.21(1.07-1.37), p=0.003). There was a trend towards stronger association for subjects with low CAC-score (CAC<100:1.41(1.16-1.71), p=0.0005, CAC≥100:1.24(1.06-1.44), p=0.006) in univariate analysis which persisted after multivariable adjustment (CAC<100: 1.41(1.14-1.73), p=0.001, CAC≥100: 1.12(0.96-1.31), p=0.16). CT-derived LV size is associated with incident major CV events independent of traditional risk factors and CAC-score in a population-based cohort and may improve the prediction of hard events especially in subjects with low CAC-scores. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mineralocorticoid receptor antagonists in kidney transplantation: time to consider?

PubMed

Girerd, Sophie; Jaisser, Frédéric

2018-04-17

Although patient survival is significantly improved by kidney transplantation (KT) in comparison with dialysis, it remains significantly lower than that observed in the general population. Graft function is one of the major determinants of patient survival after KT. Mineralocorticoid receptor antagonists (MRAs) could be of particular interest in this population to improve graft function and treat or prevent cardiovascular (CV) complications. In KT, ischaemia/reperfusion injury is a major factor involved in delayed graft function, which is often associated with inferior long-term graft survival. Preclinical studies suggest that MRAs may prevent ischaemia/reperfusion-related lesions in addition to having a protective effect in preventing calcineurin inhibitor-induced nephrotoxicity. Clinical data also support the anti-proteinuric effect of MRAs in chronic kidney disease (CKD). Taken together, MRAs may hence be of particular benefit in improving short- and long-term graft function. Numerous randomized controlled trials (RCTs) have shown the efficacy of MRAs in both heart failure and resistant hypertension. As these comorbidities are frequent in kidney transplant recipients before transplantation or during follow-up, MRAs could represent a useful therapeutic option in those with mild renal function impairment. However, CKD patients are under-represented in RCTs and the CV effects of MRAs in kidney transplant recipients have yet to be specifically assessed in large-scale trials. Available evidence indicates a good safety profile for MRAs in patients with a glomerular filtration rate (GFR) >30 mL/min/1.73 m2. However, as for all patients prescribed an MRA, creatinine and potassium should also be closely monitored following MRA initiation in kidney transplant patients. Given the current evidence suggesting that MRAs prevent ischaemia/reperfusion-related lesions and calcineurin inhibitor-induced nephrotoxicity in kidney transplant recipients as well as CV events in patients at high risk of CV complications (such as those in kidney transplant recipients), trials are urgently needed to fully assess the clinical impact of MRA use in this population.

Which ornamental plant species effectively remove benzene from indoor air?

NASA Astrophysics Data System (ADS)

Liu, Yan-Ju; Mu, Yu-Jing; Zhu, Yong-Guan; Ding, Hui; Crystal Arens, Nan

Phytoremediation—using plants to remove toxins—is an attractive and cost effective way to improve indoor air quality. This study screened ornamental plants for their ability to remove volatile organic compounds from air by fumigating 73 plant species with 150 ppb benzene, an important indoor air pollutant that poses a risk to human health. The 10 species found to be most effective at removing benzene from air were fumigated for two more days (8 h per day) to quantify their benzene removal capacity. Crassula portulacea, Hydrangea macrophylla, Cymbidium Golden Elf., Ficus microcarpa var. fuyuensis, Dendranthema morifolium, Citrus medica var. sarcodactylis, Dieffenbachia amoena cv. Tropic Snow; Spathiphyllum Supreme; Nephrolepis exaltata cv. Bostoniensis; Dracaena deremensis cv. Variegata emerged as the species with the greatest capacity to remove benzene from indoor air.

The effect of practical cooling strategies on physiological response and cognitive function during simulated firefighting tasks

PubMed Central

Hemmatjo, Rasoul; Motamedzade, Majid; Aliabadi, Mohsen; Kalatpour, Omid; Farhadian, Maryam

2017-01-01

Background: Firefighters often perform multiple tasks during firefighting operations under unknown and unpredictable conditions in hot and hostile environments. Methods: In this interventional study each firefighters engaged in 4 conditions: namely (1) no cooling device; control (NC), (2) cooling gel (CG), (3) cool vest (CV), and (4) CG+CV. Cooling effects of the employed interventions were evaluated based on heart rate (HR), temporal temperature (TT), reaction time (RT), and the correct response (CR). Results: HR and TT values for use of CG+CV (147.47 bpm [SD 4.8]; 37.88°C [SD 0.20]) and CV bpm (147.53 [SD 4.67]; 37.90°C [SD 0.22]) were significantly lower than the CG (153.67 bpm [SD 4.82]; 38.10°C [SD 0.22]) and NC (154.4 bpm [SD 4.91]; 38.11°C [SD 0.23]) at the end of the activity. RT and CR for use of CG + CV (389.87 ms [SD 6.12]; 143.53 [SD 1.24]) and CV (389.53 ms [SD 6.24]; 143.47 [SD 1.18]) were significantly higher than the CG (385.73 [SD 7.25] ms; 143.07 [SD 0.88]) and NC (385.67 ms [SD 7.19]; 143.00 [SD 0.84]) at the end of the activity. Conclusion: It is concluded that CV was more effective than the CG in attenuating physiological responses and cognitive functions during firefighting operations. Furthermore, combining CV with CG provides no additional benefit. PMID:28326286

On the Nature of CP Pup

NASA Technical Reports Server (NTRS)

Mason, E.; Orio, M.; Mukai, K.; Bianchini, A.; deMartino, D.; diMille, F.; Williams, R. E.

2013-01-01

We present new X-ray and optical spectra of the old nova CP Pup (nova Pup 1942) obtained with Chandra and the CTIO 4m telescope. The X-ray spectrum reveals a multi-temperature optically thin plasma reaching a maximum temperature of 36+19 keV 16 absorbed by local complex neutral material. The time resolved optical spectroscopy confirms the presence of the 1.47 hr period, with cycle-to-cycle amplitude changes, as well as of an additional long term modulation which is suggestive either of a longer pe- riod or of non-Keplerian velocities in the emission line regions. These new observational facts add further support to CP Pup as a magnetic cataclysmic variable (mCV). We compare the mCV and the non-mCV scenarios and while we cannot conclude whether CP Pup is a long period system, all observational evidences point at an intermediate polar (IP) type CV.

Light equation in eclipsing binary CV Boo: third body candidate in elliptical orbit

NASA Astrophysics Data System (ADS)

Bogomazov, A. I.; Kozyreva, V. S.; Satovskii, B. L.; Krushevska, V. N.; Kuznyetsova, Y. G.; Ehgamberdiev, S. A.; Karimov, R. G.; Khalikova, A. V.; Ibrahimov, M. A.; Irsmambetova, T. R.; Tutukov, A. V.

2016-12-01

A short period eclipsing binary star CV Boo is tested for the possible existence of additional bodies in the system with a help of the light equation method. We use data on the moments of minima from the literature as well as from our observations during 2014 May-July. A variation of the CV Boo's orbital period is found with a period of {≈}75 d. This variation can be explained by the influence of a third star with a mass of {≈}0.4 M_{⊙} in an eccentric orbit with e≈0.9. A possibility that the orbital period changes on long time scales is discussed. The suggested tertiary companion is near the chaotic zone around the central binary, so CV Boo represents an interesting example to test its dynamical evolution. A list of 14 minima moments of the binary obtained from our observations is presented.

Prognostic assessment of estimated glomerular filtration rate by the new Chronic Kidney Disease Epidemiology Collaboration equation in comparison with the Modification of Diet in Renal Disease Study equation.

PubMed

Skali, Hicham; Uno, Hajime; Levey, Andrew S; Inker, Lesley A; Pfeffer, Marc A; Solomon, Scott D

2011-09-01

Systematic reporting of estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) Study equation is recommended for detection of chronic kidney disease and prediction of cardiovascular (CV) risk. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is a newly developed and validated formula for eGFR that is more accurate at normal or near-normal eGFR. We aimed to assess the incremental prognostic accuracy of eGFR(CKD-EPI) versus eGFR(MDRD) in subjects at increased risk for CV disease. We performed a post hoc analysis of the VALIANT trial that enrolled 14,527 patients with acute myocardial infarction with signs and symptoms of heart failure and/or left ventricular systolic dysfunction. The eGFR(MDRD) and eGFR(CKD-EPI) were computed using age, gender, race, and baseline creatinine level. Patients were categorized according to their eGFR using each equation. To assess the incremental prognostic value of eGFR(CKD-EPI), the net reclassification improvement was calculated for the composite end point of CV death, recurrent myocardial infarction, heart failure, or stroke. Twenty-four percent of the subjects were reclassified into a different eGFR category using eGFR(CKD-EPI). The composite end point occurred in 33% of the subjects in this cohort. Based on eGFR(CKD-EPI), subjects reclassified into a higher eGFR experienced fewer events than those reclassified into a lower eGFR (21% vs 43%). In unadjusted analyses, the composite end point risk in subjects with eGFR between 75 and 90 mL/min per 1.73 m(2) was comparable with the referent group (eGFR between 90 and 105) using eGFR(MDRD) (hazard ratio 1.1, 95% CI 0.9-1.2) but was significantly higher using eGFR(CKD-EPI) (hazard ratio 1.2, 95% CI 1.1-1.4). The net reclassification improvement for eGFR(CKD-EPI) over eGFR(MDRD) was 8.7%. The CKD-EPI equation provides more accurate risk stratification than the MDRD Study equation in patients at high risk for CV disease, including identification of increased risk at mildly decreased eGFR. Copyright © 2011 Mosby, Inc. All rights reserved.

Income-related inequality in smoking cessation among adult patients with cardiovascular disease: a 5-year follow-up of an angiography intervention in Luxembourg.

PubMed

Tchicaya, Anastase; Lorentz, Nathalie; Demarest, Stefaan

2017-05-05

Smoking contributes to cardiovascular diseases (CVD), a leading cause of death and a large source of healthcare costs in Western countries. We examined the association between income and smoking cessation among smokers who underwent coronary angiography at the National Institute for Cardiac Surgery and Interventional Cardiology in Luxembourg. Data were derived from a follow-up study conducted in 2013/2014 among 4391 patients (of which 1001 patients were smokers) at the time of coronary angiography in 2008/2009. Four logistic regression models were applied. In three models, the predictor was income and the covariates were sex, age, nationality, marital status, diagnosis, body mass, physical activity, and awareness of tobacco as a cardiovascular (CV) risk factor. In the other model, the predictor was an interaction term composed of income and awareness of tobacco as a CV risk factor; the other variables were covariates. Among patients who were current smokers at baseline, 43.2% were current smokers at follow-up and 56.8% had quit smoking. In the multivariate logistic models, quitting smoking was associated with income even after controlling for socio-demographic, diagnostic, and behavioural risk factors. In the full model, the odds of quitting smoking among patients in the two highest income categories remained significant when compared to patients in the lowest income category: odds ratio (OR) = 2.8; 95% confidence interval (CI), 1.3-6.1 and OR = 2.8; 95% CI, 1.2-6.5, respectively. In the full model with an interaction term, quitting smoking was only associated with income when patients knew tobacco was a CV risk factor. The odds of smoking cessation were 5.62 (95% CI: 2.13-14.86) and 3.65 (95% CI: 1.51-8.86) times for patients with annual incomes of 36,000-53,999€ and ≥54,000€, respectively), compared to those for patients with an annual income of <36,000€. This study highlights the influence of income on behaviours regarding CVD risk factors after a major CVD event. Patients in the highest income groups were more likely to quit smoking, although only when they were aware of tobacco as a CV risk factor. Therefore, intervention strategies targeting lower income groups should be implemented in major health facilities.

A prospective clinical trial of specialist renal nursing in the primary care setting to prevent progression of chronic kidney: a quality improvement report.

PubMed

Walker, Rachael C; Marshall, Mark R; Polaschek, Nick R

2014-09-20

Early detection and effective management of risk factors can potentially delay progression of chronic kidney disease (CKD) to end-stage kidney disease, and decrease mortality and morbidity from cardiovascular (CV) disease. We evaluated a specialist nurse-led intervention in the primary care setting to address accepted risk factors in a study sample of adults at 'high risk of CKD progression', defined as uncontrolled type II diabetes and/or hypertension and a history of poor clinic attendance. The study was a non-controlled quality improvement study with pre- and post- intervention comparisons to test feasibility and potential effectiveness. Patients within two primary care practices were screened and recruited to the study. Fifty-two patients were enrolled, with 36 completing 12-months follow-up. The intervention involved a series of sessions led by the nephrology Nurse Practitioner with assistance from practice nurses. These sessions included assessment, education and planned medication and lifestyle changes. The primary outcome measured was proteinuria (ACR), and the secondary outcomes estimated glomerular filtration rate (eGFR) and 5-year absolute CV risk. Several 'intermediary' secondary outcomes were also measured including: blood pressure, serum total cholesterol, glycosylated haemoglobin (HbA1c), body mass index (BMI), prevalence of active smoking, a variety of self-management domains, and medication prescription. Analysis of data was performed using linear and logistic regression as appropriate. There was a significant improvement in ACR (average decrease of -6.75 mg/mmol per month) over the course of the study. There was a small but significant decrease in eGFR and a reduction in 5 year absolute CV risk. Blood pressure, serum total cholesterol, and HbA1c all decreased significantly. Adherence to lifestyle advice improved with a significant reduction in prevalence of active smoking, although there was no significant change in BMI. Self-management significantly improved across all relevant domains. The results suggest that a collaborative model of care between specialist renal nurses and primary care clinicians may improve the management of risk factors for progression of CKD and CV death. Further larger, controlled studies are warranted to definitively determine the effectiveness and costs of this intervention. Australian and New Zealand Clinical Trials Registry number: ACTRN12613000791730.

Improving Continuous-Variable Measurement-Device-Independent Multipartite Quantum Communication with Optical Amplifiers*

NASA Astrophysics Data System (ADS)

Guo, Ying; Zhao, Wei; Li, Fei; Huang, Duan; Liao, Qin; Xie, Cai-Lang

2017-08-01

The developing tendency of continuous-variable (CV) measurement-device-independent (MDI) quantum cryptography is to cope with the practical issue of implementing scalable quantum networks. Up to now, most theoretical and experimental researches on CV-MDI QKD are focused on two-party protocols. However, we suggest a CV-MDI multipartite quantum secret sharing (QSS) protocol use the EPR states coupled with optical amplifiers. More remarkable, QSS is the real application in multipartite CV-MDI QKD, in other words, is the concrete implementation method of multipartite CV-MDI QKD. It can implement a practical quantum network scheme, under which the legal participants create the secret correlations by using EPR states connecting to an untrusted relay via insecure links and applying the multi-entangled Greenberger-Horne-Zeilinger (GHZ) state analysis at relay station. Even if there is a possibility that the relay may be completely tampered, the legal participants are still able to extract a secret key from network communication. The numerical simulation indicates that the quantum network communication can be achieved in an asymmetric scenario, fulfilling the demands of a practical quantum network. Additionally, we illustrate that the use of optical amplifiers can compensate the partial inherent imperfections of detectors and increase the transmission distance of the CV-MDI quantum system.

Adenylyl Cyclase 9 Polymorphisms Reveal Potential Link to HDL Function and Cardiovascular Events in Multiple Pathologies: Potential Implications in Sickle Cell Disease.

PubMed

Niesor, Eric J; Benghozi, Renée; Amouyel, Philippe; Ferdinand, Keith C; Schwartz, Gregory G

2015-12-01

Adenylyl cyclase 9 (ADCY9) mediates β2-adrenoceptor (β2-AR) signalling. Both proteins are associated with caveolae, specialized cholesterol-rich membrane substructures. Apolipoprotein A1 (ApoA1), the major protein component of high-density lipoprotein (HDL), removes cholesterol from cell membrane and caveolae and may thereby influence β2-AR signalling, shown in vitro to be modulated by cholesterol. Patients with Sickle Cell Disease (SCD) typically have low HDL and ApoA1 levels. In patients, mainly of African origin, with SCD, β2-AR activation may trigger adhesion of red blood cells to endothelial cells, leading to vascular occlusive events. Moreover, ADCY9 polymorphism is associated with risk of stroke in SCD. In recent clinical trials, ADCY9 polymorphism was found to be a discriminant factor associated with the risk of cardiovascular (CV) events in Caucasian patients treated with the HDL-raising compound dalcetrapib. We hypothesize that these seemingly disparate observations share a common mechanism related to interaction of HDL/ApoA1 and ADCY9 on β2-AR signalling. This review also raises the importance of characterizing polymorphisms that determine the response to HDL-raising and -mimicking agents in the non-Caucasian population at high risk of CV diseases and suffering from SCD. This may facilitate personalized CV treatments.

Triglyceride to HDL-C ratio and increased arterial stiffness in children, adolescents, and young adults.

PubMed

Urbina, Elaine M; Khoury, Philip R; McCoy, Connie E; Dolan, Lawrence M; Daniels, Stephen R; Kimball, Thomas R

2013-04-01

Lipid levels are linked to early atherosclerosis. Risk stratification may be improved by using triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), which relates to arterial stiffness in adults. We tested whether TG/HDL-C was an independent predictor of arterial stiffness in youth. Subjects 10 to 26 years old (mean 18.9 years, 39% male, 56% non-Caucasian, n = 893) had laboratory, anthropometric, blood pressure, and arterial stiffness data collected (brachial distensibility, augmentation index, carotid-femoral pulse-wave velocity). Subjects were stratified into tertiles of TG/HDL-C (low, n = 227; mid, n = 288; high, n = 379). There was a progressive rise in cardiovascular (CV) risk factors and arterial stiffness across TG/HDL-C ratio. The high TG/HDL-C ratio group had the stiffest vessels (all P < .03 by analysis of variance). TG/HDL-C as a continuous variable was an independent determinant of brachial distensibility in CV risk factor adjusted model and for carotid-femoral pulse-wave velocity in obese subjects, with trend for higher augmentation index. TG/HDL-C, an estimate of small, dense low-density lipoprotein cholesterol, is an independent determinant of arterial stiffness in adolescents and young adults, especially in obese youth. These data suggest that use of TG/HDL-C may be helpful in identifying young adults requiring aggressive intervention to prevent atherosclerotic CV diseases.

Triglyceride to HDL-C Ratio and Increased Arterial Stiffness in Children, Adolescents, and Young Adults

PubMed Central

Khoury, Philip R.; McCoy, Connie E.; Dolan, Lawrence M.; Daniels, Stephen R.; Kimball, Thomas R.

2013-01-01

BACKGROUND AND OBJECTIVE: Lipid levels are linked to early atherosclerosis. Risk stratification may be improved by using triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), which relates to arterial stiffness in adults. We tested whether TG/HDL-C was an independent predictor of arterial stiffness in youth. METHODS: Subjects 10 to 26 years old (mean 18.9 years, 39% male, 56% non-Caucasian, n = 893) had laboratory, anthropometric, blood pressure, and arterial stiffness data collected (brachial distensibility, augmentation index, carotid-femoral pulse-wave velocity). Subjects were stratified into tertiles of TG/HDL-C (low, n = 227; mid, n = 288; high, n = 379). RESULTS: There was a progressive rise in cardiovascular (CV) risk factors and arterial stiffness across TG/HDL-C ratio. The high TG/HDL-C ratio group had the stiffest vessels (all P < .03 by analysis of variance). TG/HDL-C as a continuous variable was an independent determinant of brachial distensibility in CV risk factor adjusted model and for carotid-femoral pulse-wave velocity in obese subjects, with trend for higher augmentation index. CONCLUSIONS: TG/HDL-C, an estimate of small, dense low-density lipoprotein cholesterol, is an independent determinant of arterial stiffness in adolescents and young adults, especially in obese youth. These data suggest that use of TG/HDL-C may be helpful in identifying young adults requiring aggressive intervention to prevent atherosclerotic CV diseases. PMID:23460684

Executive Cognitive Functioning and Cardiovascular Autonomic Regulation in a Population-Based Sample of Working Adults.

PubMed

Stenfors, Cecilia U D; Hanson, Linda M; Theorell, Töres; Osika, Walter S

2016-01-01

Objective: Executive cognitive functioning is essential in private and working life and is sensitive to stress and aging. Cardiovascular (CV) health factors are related to cognitive decline and dementia, but there is relatively few studies of the role of CV autonomic regulation, a key component in stress responses and risk factor for cardiovascular disease (CVD), and executive processes. An emerging pattern of results from previous studies suggest that different executive processes may be differentially associated with CV autonomic regulation. The aim was thus to study the associations between multiple measures of CV autonomic regulation and measures of different executive cognitive processes. Method: Participants were 119 healthy working adults (79% women), from the Swedish Longitudinal Occupational Survey of Health. Electrocardiogram was sampled for analysis of heart rate variability (HRV) measures, including the Standard Deviation of NN, here heart beats (SDNN), root of the mean squares of successive differences (RMSSD), high frequency (HF) power band from spectral analyses, and QT variability index (QTVI), a measure of myocardial repolarization patterns. Executive cognitive functioning was measured by seven neuropsychological tests. The relationships between CV autonomic regulation measures and executive cognitive measures were tested with bivariate and partial correlational analyses, controlling for demographic variables, and mental health symptoms. Results: Higher SDNN and RMSSD and lower QTVI were significantly associated with better performance on cognitive tests tapping inhibition, updating, shifting, and psychomotor speed. After adjustments for demographic factors however (age being the greatest confounder), only QTVI was clearly associated with these executive tests. No such associations were seen for working memory capacity . Conclusion: Poorer CV autonomic regulation in terms of lower SDNN and RMSSD and higher QTVI was associated with poorer executive cognitive functioning in terms of inhibition, shifting, updating, and speed in healthy working adults. Age could largely explain the associations between the executive measures and SDNN and RMSSD, while associations with QTVI remained. QTVI may be a useful measure of autonomic regulation and promising as an early indicator of risk among otherwise healthy adults, compared to traditional HRV measures, as associations between QTVI and executive functioning was not affected by age.

Executive Cognitive Functioning and Cardiovascular Autonomic Regulation in a Population-Based Sample of Working Adults

PubMed Central

Stenfors, Cecilia U. D.; Hanson, Linda M.; Theorell, Töres; Osika, Walter S.

2016-01-01

Objective: Executive cognitive functioning is essential in private and working life and is sensitive to stress and aging. Cardiovascular (CV) health factors are related to cognitive decline and dementia, but there is relatively few studies of the role of CV autonomic regulation, a key component in stress responses and risk factor for cardiovascular disease (CVD), and executive processes. An emerging pattern of results from previous studies suggest that different executive processes may be differentially associated with CV autonomic regulation. The aim was thus to study the associations between multiple measures of CV autonomic regulation and measures of different executive cognitive processes. Method: Participants were 119 healthy working adults (79% women), from the Swedish Longitudinal Occupational Survey of Health. Electrocardiogram was sampled for analysis of heart rate variability (HRV) measures, including the Standard Deviation of NN, here heart beats (SDNN), root of the mean squares of successive differences (RMSSD), high frequency (HF) power band from spectral analyses, and QT variability index (QTVI), a measure of myocardial repolarization patterns. Executive cognitive functioning was measured by seven neuropsychological tests. The relationships between CV autonomic regulation measures and executive cognitive measures were tested with bivariate and partial correlational analyses, controlling for demographic variables, and mental health symptoms. Results: Higher SDNN and RMSSD and lower QTVI were significantly associated with better performance on cognitive tests tapping inhibition, updating, shifting, and psychomotor speed. After adjustments for demographic factors however (age being the greatest confounder), only QTVI was clearly associated with these executive tests. No such associations were seen for working memory capacity. Conclusion: Poorer CV autonomic regulation in terms of lower SDNN and RMSSD and higher QTVI was associated with poorer executive cognitive functioning in terms of inhibition, shifting, updating, and speed in healthy working adults. Age could largely explain the associations between the executive measures and SDNN and RMSSD, while associations with QTVI remained. QTVI may be a useful measure of autonomic regulation and promising as an early indicator of risk among otherwise healthy adults, compared to traditional HRV measures, as associations between QTVI and executive functioning was not affected by age. PMID:27761124

Bovine respiratory syncytial virus and bovine coronavirus in Swedish organic and conventional dairy herds.

PubMed

Wolff, Cecilia; Emanuelson, Ulf; Ohlson, Anna; Alenius, Stefan; Fall, Nils

2015-01-13

Infections with bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BoCV) are endemic to the cattle populations in most countries, causing respiratory and/or enteric disease. It has been demonstrated that herds can remain free from these infections for several years also in high prevalence areas. Organically managed (OM) dairy herds have been shown to have lower seroprevalence of both viruses compared to conventionally managed (CM) herds. The objective of this study was to challenge the hypothesis of a lower occurrence of BRSV and BoCV in OM compared to CM dairy herds. In November 2011, May 2012 and May 2013 milk samples from four homebred primiparous cows were collected in 75 to 65 OM and 69 to 62 CM herds. The antibody status regarding BRSV and BoCV was analysed with commercial indirect ELISAs. Herds were classified as positive if at least one individual sample was positive. The prevalence of positive herds ranged from 73.4% to 82.3% for BRSV and from 76.8% to 85.3% for BoCV among OM and CM herds, over the three sampling occasions. There was no statistically significant difference between OM and CM herds at any sampling occasion. The incidence risk of newly infected herds did not differ statistically between OM and CM herds at any sampling occasion, neither for BRSV nor for BoCV. The incidence of herds turning sero-negative between samplings corresponded to the incidence of newly infected. Bulk tank milk (BTM) samples were also sampled in the herds and analysed. Several herds were negative on individual samples but positive in BTM. Herd-level data on production, health and reproduction were retrieved from VÄXA Sweden and the study herds were representative of the source population. There was no difference in prevalence of or incidence risk for BRSV or BoCV between Swedish OM and CM herds. Because the incidence of herds becoming seropositive was balanced by herds becoming seronegative it should be possible to lower the prevalence of these two infections among Swedish dairy cattle herds if biosecurity is improved.

Decision-making under risk in children, adolescents, and young adults.

PubMed

Paulsen, David J; Platt, Michael L; Huettel, Scott A; Brannon, Elizabeth M

2011-01-01

Adolescents often make risky and impulsive decisions. Such behavior has led to the common assumption that a dysfunction in risk-related decision-making peaks during this age. Differences in how risk has been defined across studies, however, make it difficult to draw conclusions about developmental changes in risky decision-making. Here, we developed a non-symbolic economic decision-making task that can be used across a wide age span and that uses coefficient of variation (CV) in reward as an index of risk. We found that young children showed the strongest preference for risky compared to sure bet options of equal expected value, adolescents were intermediate in their risk preference, and young adults showed the strongest risk aversion. Furthermore, children's preference for the risky option increased for larger CVs, while adolescents and young adults showed the opposite pattern, favoring the sure bet more often as CV increased. Finally, when faced with two gambles in a risk-return tradeoff, all three age groups exhibited a greater preference for the option with the lower risk and return as the disparity in risk between the two options increased. These findings demonstrate clear age-related differences in economic risk preferences that vary with choice set and risk. Importantly, adolescence appears to represent an intermediate decision-making phenotype along the transition from childhood to adulthood, rather than an age of heightened preference for economic risk.

Stress management and dietary counseling in hypertensive patients: a pilot study of additional effect.

PubMed

Katsarou, Alexia L; Vryonis, Marios M; Protogerou, Athanassios D; Alexopoulos, Evangelos C; Achimastos, Apostolos; Papadogiannis, Dimitrios; Chrousos, George P; Darviri, Christina

2014-01-01

In Western societies, cardiovascular (CV) disease is the primary cause of mortality, and high blood pressure (BP) is the main reversible factor leading to CV disease. Dietary habits and psychosocial stress contribute to the establishment of hypertension, while its role in the control of high BP is currently examined. In this study, we examined the effect and feasibility of a combined intervention of dietary education and stress management on the control of hypertension. A randomized, controlled pilot study was designed to evaluate the effect of combined education on stress management techniques and dietary habits (Mediterranean diet principle) on office BP after eight weeks. Of the 45 randomized subjects, 36 were included in the final analysis (control group = 20 (age: 67 ± 12 years, 31.8%, males) and intervention group = 16 (age: 62 ± 12 years, 47%, males)). CV disease risk factors (except smoking), BP, dietary habits, perceived stress and physical activity (all assessed with validated questionnaires) were similar between the two groups at baseline. After eight weeks, office BP (systolic and diastolic) and perceived stress were significantly reduced, whereas the adherence in Mediterranean diet principle was significantly increased, but only in the intervention group. A combined intervention of stress management techniques and Mediterranean diet education seems to be beneficial for BP reduction. Such interventions could possibly serve as a complementary treatment along with drug therapy or in the early treatment of high normal BP. A call to action for designing epidemiological studies and evaluating the efficacy of such non-pharmacological treatment strategies is therefore warranted.

Cost-Effectiveness Analysis of Atorvastatin versus Rosuvastatin in Primary and Secondary Cardiovascular Prevention Populations in Brazil and Columbia.

PubMed

Mould-Quevedo, Joaquín F; Gutiérrez-Ardila, Magda Vianey; Ordóñez Molina, Jaime Eduardo; Pinsky, Brett; Vargas Zea, Nicolás

2014-12-01

Latin America has witnessed a marked increase in cardiovascular (CV) disease, the leading cause of death in many countries. The benefits of lipid-lowering therapy to reduce CV-related events are widely accepted. Clinical evidence suggests that rosuvastatin is associated with slightly greater reductions in low-density lipoprotein cholesterol levels than is atorvastatin at comparable doses. Rosuvastatin, however, is often priced at a premium. Our objective was to examine the cost-effectiveness of using atorvastatin versus rosuvastatin in reducing CV events in Brazil and Colombia using real-world prices. A global Markov cohort model of primary and secondary CV prevention was developed and adapted to Brazilian and Colombian settings. The risks and costs of major CV events and efficacy, adherence, and costs of statins were considered. Total gains in life-years, quality-adjusted life-years, major CV events avoided, and costs over the lifetime horizon were estimated. Several dose comparisons were considered. In the Colombian analyses, differences in drug costs between therapies were considerable while outcomes were similar. The incremental cost per quality-adjusted life-year gained for rosuvastatin versus atorvastatin was more than $700,000 and $200,000 in primary and secondary prevention, respectively. Brazilian analyses found lower incremental cost-effectiveness ratios for rosuvastatin at some dose comparisons due to similar pricing between statins. Sensitivity analyses revealed that changes in treatment efficacy and adherence had the largest impact on results. In primary and secondary CV prevention, the efficacy advantage of rosuvastatin was minimal, while its acquisition cost was higher, particularly in Colombia. The incremental cost-effectiveness ratios were, therefore, generally in favor of atorvastatin being the cost-effective option. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Assessment of American Heart Association's Ideal Cardiovascular Health Metrics Among Employees of a Large Healthcare Organization: The Baptist Health South Florida Employee Study.

PubMed

Ogunmoroti, Oluseye; Younus, Adnan; Rouseff, Maribeth; Spatz, Erica S; Das, Sankalp; Parris, Don; Aneni, Ehimen; Holzwarth, Leah; Guzman, Henry; Tran, Thinh; Roberson, Lara; Ali, Shozab S; Agatston, Arthur; Maziak, Wasim; Feldman, Theodore; Veledar, Emir; Nasir, Khurram

2015-07-01

Healthcare organizations and their employees are critical role models for healthy living in their communities. The American Heart Association (AHA) 2020 impact goal provides a national framework that can be used to track the success of employee wellness programs with a focus on improving cardiovascular (CV) health. This study aimed to assess the CV health of the employees of Baptist Health South Florida (BHSF), a large nonprofit healthcare organization. HRAs and wellness examinations can be used to measure the cardiovascular health status of an employee population. The AHA's 7 CV health metrics (diet, physical activity, smoking, body mass index, blood pressure, total cholesterol, and blood glucose) categorized as ideal, intermediate, or poor were estimated among employees of BHSF participating voluntarily in an annual health risk assessment (HRA) and wellness fair. Age and gender differences were analyzed using χ(2) test. The sample consisted of 9364 employees who participated in the 2014 annual HRA and wellness fair (mean age [standard deviation], 43 [12] years, 74% women). Sixty (1%) individuals met the AHA's definition of ideal CV health. Women were more likely than men to meet the ideal criteria for more than 5 CV health metrics. The proportion of participants meeting the ideal criteria for more than 5 CV health metrics decreased with age. A combination of HRAs and wellness examinations can provide useful insights into the cardiovascular health status of an employee population. Future tracking of the CV health metrics will provide critical feedback on the impact of system wide wellness efforts as well as identifying proactive programs to assist in making substantial progress toward the AHA 2020 Impact Goal. © 2015 Wiley Periodicals, Inc.

Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor.

PubMed

Charles-Schoeman, Christina; Wicker, Pierre; Gonzalez-Gay, Miguel A; Boy, Mary; Zuckerman, Andrea; Soma, Koshika; Geier, Jamie; Kwok, Kenneth; Riese, Richard

2016-12-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The implications of treatment with tofacitinib on cardiovascular (CV) risk in RA are unknown. Therefore, CV adverse events (AEs), and blood pressure and lipid level changes, in tofacitinib-treated patients with RA were evaluated. Data were pooled from six Phase (P)3 studies (24 months) and two open-label long-term extension (LTE) studies (60 months) of tofacitinib in patients with RA and inadequate response to DMARDs. Tofacitinib was administered alone or with non-biologic DMARDs. CV events, including major adverse CV events (MACE: CV death and non-fatal CV events) and congestive heart failure (CHF), were assessed by a blinded adjudication committee. Overall, 4271 patients from P3 studies and 4827 enrolled from P2/P3 studies into LTE studies were evaluated, representing 3942 and 8699 patient-years of exposure to tofacitinib, respectively. Blood pressure remained stable over time across studies. The number of investigator-reported hypertension-related AEs in tofacitinib-treated patients was low in P3 studies (Months 0-3: 2.8%; Months 3-6: 1.4%; >6 months: 2.8%). Across studies, lipid level increases were generally observed within 1-3 months of treatment and stabilized thereafter. Patients with events (incidence rate [IR]/100 patient-years) for MACE and CHF, respectively, were: 23 (0.58) and 9 (0.23) in P3 studies, and 32 (0.37) and 8 (0.09) in LTE studies; IRs were comparable with placebo (P3) and did not increase over time (LTE). Tofacitinib was associated with a low incidence of CV events in a large Phase 3 program, including LTE studies. Further long-term studies are underway. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Venous access and long-term pacemaker lead failure: comparing contrast-guided axillary vein puncture with subclavian puncture and cephalic cutdown.

PubMed

Chan, Ngai-Yin; Kwong, Nim-Pong; Cheong, Adrian-Piers

2017-07-01

Existing data on the relationship between venous access and long-term pacemaker lead failure (PLF) are scarce and inconsistent. We aim to study the hypothesis that contrast-guided axillary vein puncture (AP) is better than subclavian puncture (SP) and similar to cephalic vein cutdown (CV) in the incidence of PLF and the success rate of AP is higher than CV. The case records of 409 patients with 681 implantable pacemaker leads were reviewed. Two hundred and fifty-two, 217, and 212 leads were implanted via AP, CV, and SP, respectively. With a mean follow-up of 73.6 ± 33.1 months, 20 (2.9%) PLF occurred. Three (1.2%), 5 (2.3%), and 12 (5.6%) PLF occurred in the AP, CV, and SP groups, respectively. On multivariate Cox regression analysis, the only independent predictor for PLF was the use of SP instead of AP (AP vs. SP; hazard ratio: 0.261; 95% confidence interval: 0.071-0.954, P = 0.042). The success rate of CV (78.2%) was significantly lower than those of AP (97.6%) and SP (96.8%) (P < 0.001). Compared with SP, the use of AP but not CV independently predicted a lower risk of PLF. The success rates in achieving venous accesses were similar between AP and SP, but significantly lower for CV. Axillary vein puncture may thus be considered the venous access of choice for pacemaker lead implantation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Soluble urokinase plasminogen activator receptor level is an independent predictor of the presence and severity of coronary artery disease and of future adverse events.

PubMed

Eapen, Danny J; Manocha, Pankaj; Ghasemzadeh, Nima; Ghasemzedah, Nima; Patel, Riyaz S; Al Kassem, Hatem; Hammadah, Muhammad; Veledar, Emir; Le, Ngoc-Anh; Pielak, Tomasz; Thorball, Christian W; Velegraki, Aristea; Kremastinos, Dimitrios T; Lerakis, Stamatios; Sperling, Laurence; Quyyumi, Arshed A

2014-10-23

Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown. We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C-reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P<0.0001) and its severity (P<0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden's index) predicted future risk of MI (hazard ratio [HR]=3.2; P<0.0001), cardiac death (HR=2.62; P<0.0001), and the combined endpoint of death and MI (HR=1.9; P<0.0001), even after adjustment of covariates. The C-statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR. Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

PubMed Central

Eapen, Danny J.; Manocha, Pankaj; Ghasemzedah, Nima; Patel, Riyaz S.; Al Kassem, Hatem; Hammadah, Muhammad; Veledar, Emir; Le, Ngoc‐Anh; Pielak, Tomasz; Thorball, Christian W.; Velegraki, Aristea; Kremastinos, Dimitrios T.; Lerakis, Stamatios; Sperling, Laurence; Quyyumi, Arshed A.

2014-01-01

Introduction Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown. Methods and Results We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C‐reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P<0.0001) and its severity (P<0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden's index) predicted future risk of MI (hazard ratio [HR]=3.2; P<0.0001), cardiac death (HR=2.62; P<0.0001), and the combined endpoint of death and MI (HR=1.9; P<0.0001), even after adjustment of covariates. The C‐statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR. Conclusion Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD. PMID:25341887

Providing food to treat adolescents at risk for cardiovascular disease.

PubMed

de Ferranti, Sarah D; Milliren, Carly E; Denhoff, Erica Rose; Quinn, Nicolle; Osganian, Stavroula K; Feldman, Henry A; Ebbeling, Cara B; Ludwig, David S

2015-10-01

Diet modification is recommended to treat childhood cardiovascular (CV) risk factors; however, the optimal dietary strategy is unknown. In a randomized trial, the effect of a low-fat (LF) and a low-glycemic-load (LGL) reduced-calorie diet were examined in youth with overweight/obesity with CV risk factors. Using a novel intervention, we delivered LF or LGL meals and nutrition education to the home for 8 weeks (Intensive Phase), followed by 4 months Maintenance without food provision. Between-group differences in the change in insulin area under the curve (InsAUC) by oral glucose tolerance test and other risk factors were analyzed. Overall, participants (n = 27) showed substantial improvement during the Intensive Phase, including InsAUC (-59 ± 18.2 µU/ml × 120 min, P = 0.004), total cholesterol (-9.9 ± 3.6 mg/dl, P = 0.01), weight (-2.7 ± 0.5 kg, P < 0.001), waist circumference (-3.1 ± 0.8 cm, P < 0.001), HOMA-IR (-1.7 ± 0.4, P < 0.001), systolic blood pressure (-5 ± 1.4 mm Hg, P = 0.002), and CRP (-0.1 ± 0.1 mg/dl, P = 0.04). There were minimal between-group differences; the LF group showed greater declines in HDL (P = 0.005) and fasting glucose (P = 0.01) compared to the LGL group. Improvements waned during Maintenance. Home delivery of LF or LGL diets resulted in rapid and clinically important improvements in CV risk factors that diminished without food delivery and did not differ based on dietary intervention. If scalable, food provision may represent an alternative nutrition treatment strategy. © 2015 The Obesity Society.

Effect of Low-Density Lipoprotein Cholesterol Lowering by Ezetimibe/Simvastatin on Outcome Incidence: Overview, Meta-Analyses, and Meta-Regression Analyses of Randomized Trials.

PubMed

Thomopoulos, Costas; Skalis, George; Michalopoulou, Helena; Tsioufis, Costas; Makris, Thomas

2015-12-01

This analysis investigated the extent of different outcome reductions from low-density lipoprotein cholesterol (LDL-C) lowering following ezetimibe/simvastatin treatment and the proportionality of outcome to LDL-C reductions. The authors searched PubMed between 1997 and mid-June 2015 (any language) and the Cochrane Library to identify all randomized controlled trials comparing ezetimibe/simvastatin with placebo or less intensive LDL-C lowering. Risk ratios (RR) and 95% confidence intervals (CIs), standardized to 20 mg/dL LDL-C reduction, were calculated for 5 primary outcomes (fatal and nonfatal) and 4 secondary outcomes (non-cardiovascular [CV] death, cancer, myopathy, and hepatopathy). Five ezetimibe/simvastatin RCTs (30 051 individuals) were eligible, 2 comparing ezetimibe/simvastatin vs placebo and 3 vs less intensive treatment. Outcomes reduced almost to the same extent were stroke (RR: -13%, 95% CI: -21% to -3%), coronary heart disease (CHD; RR: -12%, 95% CI: -19% to -5%), and composite of stroke and CHD (RR: -14%, 95% CI: -20% to -8%). Absolute risk reductions: 5 strokes, 10 CHD events, and 16 stroke and CHD events prevented for every 1000 patients treated for 5 years. Residual risk was almost 7× higher than absolute risk reduction for all the above outcomes. All death outcomes were not reduced, and secondary outcomes did not differ between groups. Logarithmic risk ratios were not associated with LDL-C lowering. Our meta-analysis provides evidence that, in patients with different CV disease burden, major CV events are safely reduced by LDL-C lowering with ezetimibe/simvastatin, while raising the hypothesis that the extent of LDL-C lowering might not be accompanied by incremental clinical-event reduction. © 2015 Wiley Periodicals, Inc.

The Impact of Rheumatoid Arthritis Disease Characteristics on Heart Failure

PubMed Central

Myasoedova, Elena; Crowson, Cynthia S.; Nicola, Paulo J.; Maradit-Kremers, Hilal; Davis, John M.; Roger, Véronique L.; Therneau, Terry M.; Gabriel, Sherine E.

2011-01-01

Objective To examine the impact of rheumatoid arthritis (RA) characteristics and antirheumatic medications on the risk of heart failure (HF) in RA. Methods A population-based incidence cohort of RA patients aged ≥18 (1987 ACR criteria first met between 1/1/1980 and 1/1/2008) without a history of HF was followed until HF onset (defined by Framingham criteria), death, or 1/1/2008. We collected data on RA characteristics, antirheumatic medications and cardiovascular (CV) risk factors. Cox models adjusting for age, sex and calendar year were used to analyze the data. Results The study included 795 RA patients (mean age 55.3 years, 69% females, 66% rheumatoid factor [RF] positive). During the mean follow-up of 9.7 years, 92 patients developed HF. The risk of HF was associated with RF positivity (HR 1.6, 95%CI 1.0, 2.5), erythrocyte sedimentation rate (ESR) at RA incidence (HR 1.6, 95%CI 1.2, 2.0), repeatedly high ESR (HR 2.1, 95%CI 1.2, 3.5), severe extra-articular manifestations (HR 3.1, 95%CI 1.9, 5.1) and corticosteroid use (HR 2.0, 95%CI 1.3, 3.2), adjusting for CV risk factors and coronary heart disease (CHD). Methotrexate users were half as likely to have HF as non-users (HR 0.5, 95%CI 0.3, 0.9). Conclusion Several RA characteristics and the use of corticosteroids were associated with HF adjusting for CV risk factors and CHD. Methotrexate use appeared to be protective against HF. These findings suggest an independent impact of RA on HF which may be further modified by antirheumatic treatment. PMID:21572155

Cost-effectiveness analysis of a universal mass vaccination program with a PHiD-CV 2+1 schedule in Malaysia.

PubMed

Wang, Xiao Jun; Saha, Ashwini; Zhang, Xu-Hao

2017-01-01

Currently, two pediatric pneumococcal conjugate vaccines are available in the private market of Malaysia-13-valent pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide and non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). This study aimed to evaluate the cost-effectiveness of a universal mass vaccination program with a PHiD-CV 2+1 schedule versus no vaccination or with a PCV13 2+1 schedule in Malaysia. A published Markov cohort model was adapted to evaluate the epidemiological and economic consequences of programs with no vaccination, a PHiD-CV 2+1 schedule or a PCV13 2+1 schedule over a 10-year time horizon. Disease cases, deaths, direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated. Locally published epidemiology and cost data were used whenever possible. Vaccine effectiveness and disutility data were based on the best available published data. All data inputs and assumptions were validated by local clinical and health economics experts. Analyses were conducted from the perspective of the Malaysian government for a birth cohort of 508,774. Costs and QALYs were discounted at 3% per annum. One-way and probabilistic sensitivity analyses were performed. Compared with no vaccination, a PHiD-CV 2+1 program was projected to prevent 1109 invasive pneumococcal disease (IPD), 24,679 pneumonia and 72,940 acute otitis media (AOM) cases and 103 IPD/pneumonia deaths over 10 years, with additional costs and QALYs of United States dollars (USD) 30.9 million and 1084 QALYs, respectively, at an ICER of USD 28,497/QALY. Compared with a PCV13 2+1 program, PHiD-CV 2+1 was projected to result in similar reductions in IPD cases (40 cases more) but significantly fewer AOM cases (30,001 cases less), with cost savings and additional QALYs gained of USD 5.2 million and 116 QALYs, respectively, demonstrating dominance over PCV13. Results were robust to variations in one-way and probabilistic sensitivity analyses. A PHiD-CV 2+1 universal mass vaccination program could substantially reduce pneumococcal disease burden versus no vaccination, and was expected to be cost-effective in Malaysia. A PHiD-CV 2+1 program was also expected to be a dominant choice over a PCV13 2+1 program in Malaysia.

Platelet response to aspirin 50 and 100 mg in patients with coronary heart disease over a five-year period.

PubMed

Berent, Robert; Auer, Johann; Franklin, Barry; Schmid, Peter; von Duvillard, Serge P

2011-09-01

Aspirin has been shown to decrease cardiovascular (CV) events by ∼25%. Despite aspirin therapy 10% to 20% of patients with arterial vascular disease develop atherothrombotic events. A meta-analysis of antiplatelet therapy showed a progressive decrease in clinical efficacy of aspirin after 2 years. Whether this is due to a decreased sensitivity to aspirin during long-term therapy remains unclear. A prospective randomized clinical trial with serial monitoring over 5 years was conducted in 100 patients with documented coronary heart disease. We investigated whether long-term treatment with aspirin 50 and 100 mg affects platelet response similarly. Occurrence of CV events was documented. Platelet sensitivity to aspirin, prostacyclin, and adenosine diphosphate-, collagen-, and epinephrine-induced platelet aggregation were evaluated over time. In addition, β-thromboglobulin and inflammatory markers were measured. Four patients were lost to follow-up and 10 patients died. Eleven patients developed nonfatal CV events. In the 2 groups platelet response to aspirin and the referenced variables remained unchanged over 5 years. In patients who developed CV events, the last monitoring interval revealed no difference in platelet response to aspirin. However, patients with nonfatal and fatal CV events showed increased inflammatory markers versus patients without CV events independent of aspirin 50 or 100 mg intake. In conclusion, our study revealed no difference in antiplatelet response to aspirin 50 versus 100 mg or CV events over 5 years in patients with coronary heart disease. Copyright © 2011 Elsevier Inc. All rights reserved.

The clinical and nonclinical values of nonexercise estimation of cardiovascular endurance in young asymptomatic individuals.

PubMed

Alomari, Mahmoud A; Shqair, Dana M; Khabour, Omar F; Alawneh, Khaldoon; Nazzal, Mahmoud I; Keewan, Esraa F

2012-01-01

Exercise testing is associated with barriers prevent using cardiovascular (CV) endurance (CVE) measure frequently. A recent nonexercise model (NM) is alleged to estimate CVE without exercise. This study examined CVE relationships, using the NM model, with measures of obesity, physical fitness (PF), blood glucose and lipid, and circulation in 188 asymptomatic young (18-40 years) adults. Estimated CVE correlated favorably with measures of PF (r = 0.4 - 0.5) including handgrip strength, distance in 6 munities walking test, and shoulder press, and leg extension strengths, obesity (r = 0.2 - 0.7) including % body fat, body water content, fat mass, muscle mass, BMI, waist and hip circumferences and waist/hip ratio, and circulation (r = 0.2 - 0.3) including blood pressures, blood flow, vascular resistance, and blood (r = 0.2 - 0.5) profile including glucose, total cholesterol, LDL-C, HDL-C, and triglycerides. Additionally, differences (P < 0.05) in examined measures were found between the high, average, and low estimated CVE groups. Obviously the majority of these measures are CV disease risk factors and metabolic syndrome components. These results enhance the NM scientific value, and thus, can be further used in clinical and nonclinical settings.

CV-990 Landing Systems Research Aircraft (LSRA) flight #145 drilling of shuttle tire using Tire Assault Vehicle

NASA Image and Video Library

1995-07-27

Created from a 1/16th model of a German World War II tank, the TAV (Tire Assault Vehicle) was an important safety feature for the Convair 990 Landing System Research Aircraft, which tested space shuttle tires. It was imperative to know the extreme conditions the shuttle tires could tolerate at landing without putting the shuttle and its crew at risk. In addition, the CV990 was able to land repeatedly to test the tires. The TAV was built from a kit and modified into a radio controlled, video-equipped machine to drill holes in aircraft test tires that were in imminent danger of exploding because of one or more conditions: high air pressure, high temperatures, and cord wear. An exploding test tire releases energy equivalent to two and one-half sticks of dynamite and can cause severe injuries to anyone within 50 ft. of the explosion, as well as ear injury - possibly permanent hearing loss - to anyone within 100 ft. The degree of danger is also determined by the temperature pressure and cord wear of a test tire. The TAV was developed by David Carrott, a PRC employee under contract to NASA.

CV-990 Landing Systems Research Aircraft (LSRA) flight #145 drilling of shuttle tire using Tire Assa

NASA Technical Reports Server (NTRS)

1995-01-01

Created from a 1/16th model of a German World War II tank, the TAV (Tire Assault Vehicle) was an important safety feature for the Convair 990 Landing System Research Aircraft, which tested space shuttle tires. It was imperative to know the extreme conditions the shuttle tires could tolerate at landing without putting the shuttle and its crew at risk. In addition, the CV990 was able to land repeatedly to test the tires. The TAV was built from a kit and modified into a radio controlled, video-equipped machine to drill holes in aircraft test tires that were in imminent danger of exploding because of one or more conditions: high air pressure, high temperatures, and cord wear. An exploding test tire releases energy equivalent to two and one-half sticks of dynamite and can cause severe injuries to anyone within 50 ft. of the explosion, as well as ear injury - possibly permanent hearing loss - to anyone within 100 ft. The degree of danger is also determined by the temperature pressure and cord wear of a test tire. The TAV was developed by David Carrott, a PRC employee under contract to NASA.

Clinically feasible stratification of 1-year to 3-year post-myocardial infarction risk

PubMed Central

Muhlestein, Joseph B; Bhandary, Durgesh; Hoetzer, Greta L; Khan, Naeem D; Bair, Tami L; Lappé, Donald L

2018-01-01

Objective Post-myocardial infarction (MI) care is crucial to preventing recurrent major adverse cardiovascular events (MACE), but can be complicated to personalise. A tool is needed that effectively stratifies risk of cardiovascular (CV) events 1–3 years after MI but is also clinically usable. Methods Patients surviving ≥1 year after an index MI with ≥1 risk factor for recurrent MI (ie, age ≥65 years, prior MI, multivessel coronary disease, diabetes, glomerular filtration rate <60 mL/min/1.73 m2) were studied. Cox regression derived sex-specific Intermountain Major Adverse Cardiovascular Events (IMACE) risk scores for the composite of 1-year to 3-year MACE (CV death, MI or stroke). Derivation was performed in 70% of subjects (n=1342 women; 3047 men), with validation in the other 30% (n=576 women; 1290 men). Secondary validations were also performed. Results In women, predictors of CV events were glucose, creatinine, haemoglobin, platelet count, red cell distribution width (RDW), age and B-type natriuretic peptide (BNP); among men, they were potassium, glucose, blood urea nitrogen, haematocrit, white blood cell count, RDW, mean platelet volume, age and BNP. In the primary validation, in women, IMACE ranged from 0 to 11 (maximum possible: 12) and had HR=1.44 per +1 score (95% CI 1.29 to 1.61; P<0.001); men had IMACE range 0–14 (maximum: 16) and HR=1.29 per +1 score (95% CI 1.20 to 1.38; P<0.001). IMACE ≥5 in women (≥6 in men) showed strikingly higher MACE risk. Conclusions Sex-specific risk scores strongly stratified 1-year to 3-year post-MI MACE risk. IMACE is an inexpensive, dynamic, electronically delivered tool for evaluating and better managing post-MI patient care. PMID:29531761

Is ankylosing spondylitis a risk factor for cardiovascular disease, and how do these risks compare with those in rheumatoid arthritis?

PubMed

Eriksson, Jonas K; Jacobsson, Lennart; Bengtsson, Karin; Askling, Johan

2017-02-01

To assess and compare the incidence of cardiovascular (CV) events, by CV phenotype, between patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA) and the general population. Using linkages of national and population-based registers, we identified one cohort of prevalent patients with AS (n=5358), one with RA (n=37 245) and one with matched general population subjects (n=25 006). These cohorts were identified in 2006 through 2011 and were followed in 31 December 2012, for first ever occurrence of acute coronary syndromes (ACS), deep venous thromboembolism, pulmonary embolism and stroke, respectively. For each outcome, we calculated incidence rates standardised to the age and sex distribution of the AS cohort, as well as relative risks using Cox proportional hazards models. Based on 69 ACS events during 20 251 person-years of follow-up of the patients with AS, and 966 events during 127 014 person-years in the RA cohort, the age/sex-adjusted relative risks for ACS compared with the general population was 1.3 (95% CI 1.0 to 1.7) for AS and 1.7 (1.4 to 2.0) for RA. For thromboembolic events, the corresponding risks were 1.4 (1.1 to 1.9) in AS and 1.8 (1.5 to 2.1) in RA. Finally, for stroke, the relative risks were 1.5 (1.1 to 2.0) in AS and 1.5 (1.2 to 1.8) in RA, compared with the general population. Prevalent patients with AS are at a 30%-50% increased risk of incident CV events. When compared with patients with RA, this level of increase was similar for stroke, but only half as high for ACS and thrombotic events. 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/.

Elevated plasma levels of PAI-1 predict cardiovascular events and cardiovascular mortality in prevalent peritoneal dialysis patients.

PubMed

Arikan, Hakki; Koc, Mehmet; Tuglular, Serhan; Ozener, Cetin; Akoglu, Emel

2009-01-01

Elevated plasminogen activator inhibitor-1 (PAI-1) levels are associated with increased cardiovascular (CV) risk in the general population. It has been shown that peritoneal dialysis (PD) patients have increased plasma levels of PAI-1. The aim of this study was to investigate whether PAI-1 independently predicted CV outcome in PD patients. Seventy-two PD patients (53% females, mean age 49.9 +/- 16.1 years) were studied. Twelve patients who underwent kidney transplantation and 14 patients who transferred to hemodialysis during follow-up were excluded from the analysis. The remaining 46 patients (54% female, mean age 54 +/- 16 years, dialytic age 42 +/- 30 months) were followed a mean time of 45.4 +/- 19.4 months (range 8-71 months). Baseline PAI-1, clinical, and laboratory parameters were assessed in all patients. Survival analyses were made with Kaplan-Meier and Cox regression analysis, with all-cause mortality and CV mortality and CV events (CVEs) as clinical end points. During the follow-up, 29 patients died (17 from CV causes), and 28 fatal and non-fatal CVEs were recorded. The patients were divided according to plasma PAI-1 levels (i.e., 41 ng/mL). The significant independent predictors of all-cause of mortality were age (60 years; p = 0.018), CRP (5 mg/L; p = 0.015), and serum albumin (<3.5 g/L; p = 0.011). Multivariable Cox regression analysis showed that plasma PAI-1 41 ng/mL was independently predictive of higher CV mortality (p = 0.021) and CVEs (p = 0.001). The only other independent predictor of CV mortality was only CRP (5 mg/L; p = 0.008). Plasma levels of PAI-1 41 ng/mL is a significant predictor of CV mortality and CVEs in PD patients.

Adipokines, Biomarkers of Endothelial Activation, and Metabolic Syndrome in Patients with Ankylosing Spondylitis

PubMed Central

López-Mejías, Raquel; Miranda-Filloy, José A.; Ubilla, Begoña; Carnero-López, Beatriz; Blanco, Ricardo; Pina, Trinitario; González-Juanatey, Carlos; Llorca, Javier; González-Gay, Miguel A.

2014-01-01

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. AS patients also display a high prevalence of features clustered under the name of metabolic syndrome (MeS). Anti-TNF-α therapy was found to be effective to treat AS patients by suppressing inflammation and also improving endothelial function. Previously, it was demonstrated that a short infusion of anti-TNF-α monoclonal antibodyinfliximab induced a rapid and dramatic reduction in serum insulin levels and insulin resistance along with a rapid improvement of insulin sensitivity in nondiabetic AS patients. The role of adipokines, MeS-related biomarkers and biomarkers of endothelial cell activation and inflammation seem to be relevant in different chronic inflammatory diseases. However, its implication in AS has not been fully established. Therefore, in this review we summarize the recent advances in the study of the involvement of these molecules in CV disease or MeS in AS. The assessment of adipokines and biomarkers of endothelial cell activation and MeS may be of potential relevance in the stratification of the CV risk of patients with AS. PMID:24757680

Decision-Making Under Risk in Children, Adolescents, and Young Adults

PubMed Central

Paulsen, David J.; Platt, Michael L.; Huettel, Scott A.; Brannon, Elizabeth M.

2011-01-01

Adolescents often make risky and impulsive decisions. Such behavior has led to the common assumption that a dysfunction in risk-related decision-making peaks during this age. Differences in how risk has been defined across studies, however, make it difficult to draw conclusions about developmental changes in risky decision-making. Here, we developed a non-symbolic economic decision-making task that can be used across a wide age span and that uses coefficient of variation (CV) in reward as an index of risk. We found that young children showed the strongest preference for risky compared to sure bet options of equal expected value, adolescents were intermediate in their risk preference, and young adults showed the strongest risk aversion. Furthermore, children's preference for the risky option increased for larger CVs, while adolescents and young adults showed the opposite pattern, favoring the sure bet more often as CV increased. Finally, when faced with two gambles in a risk–return tradeoff, all three age groups exhibited a greater preference for the option with the lower risk and return as the disparity in risk between the two options increased. These findings demonstrate clear age-related differences in economic risk preferences that vary with choice set and risk. Importantly, adolescence appears to represent an intermediate decision-making phenotype along the transition from childhood to adulthood, rather than an age of heightened preference for economic risk. PMID:21687443

RAAS inhibitors and cardiovascular protection in large scale trials.

PubMed

von Lueder, Thomas G; Krum, Henry

2013-04-01

Hypertension, coronary artery disease and heart failure affect over half of the adult population in most Western societies, and are prime causes of CV morbidity and mortality. With the ever-increasing worldwide prevalence of CV disease due to ageing and the "diabetes" pandemic, guideline groups have recognized the importance of achieving cardioprotection in affected individuals as well as in those at risk for future CV events. The renin-angiotensin-aldosterone system (RAAS) is the most important system controlling blood pressure (BP), cardiovascular and renal function in man. As our understanding of the crucial role of RAAS in the pathogenesis of most, if not all, CV disease has expanded over the past decades, so has the development of drugs targeting its individual components. Angiotensin-converting enzyme inhibitors (ACEi), Ang-II receptor blockers (ARB), and mineralcorticoid receptor antagonists (MRA) have been evaluated in large clinical trials for their potential to mediate cardioprotection, singly or in combination. Direct renin inhibitors are currently under scrutiny, as well as novel dual-acting RAAS-blocking agents. Herein, we review the evidence generated from large-scale clinical trials of cardioprotection achieved through RAAS-blockade.

Critical Velocity Is Associated With Combat-Specific Performance Measures in a Special Forces Unit.

PubMed

Hoffman, Mattan W; Stout, Jeffrey R; Hoffman, Jay R; Landua, Geva; Fukuda, David H; Sharvit, Nurit; Moran, Daniel S; Carmon, Erez; Ostfeld, Ishay

2016-02-01

The purpose of this study was to examine the relationship between critical velocity (CV) and anaerobic distance capacity (ADC) to combat-specific tasks (CST) in a special forces (SFs) unit. Eighteen male soldiers (mean ± SD; age: 19.9 ± 0.8 years; height: 177.6 ± 6.6 cm; body mass: 74.1 ± 5.8 kg; body mass index [BMI]: 23.52 ± 1.63) from an SF unit of the Israel Defense Forces volunteered to complete a 3-minute all-out run along with CST (2.5-km run, 50-m casualty carry, and 30-m repeated sprints with "rush" shooting [RPTDS]). Estimates of CV and ADC from the 3-minute all-out run were determined from data downloaded from a global position system device worn by each soldier, with CV calculated as the average velocity of the final 30 seconds of the run and ADC as the velocity-time integral above CV. Critical velocity exhibited significant negative correlations with the 2.5-km run time (r = -0.62, p < 0.01) and RPTDS time (r = -0.71, p < 0.01). In addition, CV was positively correlated with the average velocity during the 2.5-km run (r = 0.64, p < 0.01). Stepwise regression identified CV as the most significant performance measure associated with the 2.5-km run time, whereas BMI and CV measures were significant predictors of RPTDS time (R(2) = 0.67, p ≤ 0.05). Using the 3-minute all-out run as a testing measurement in combat, personnel may offer a more efficient and simpler way in assessing both aerobic and anaerobic capabilities (CV and ADC) within a relatively large sample.

Comparative adsorption of Pb2+ and Cd2+ by cow manure and its vermicompost.

PubMed

Zhu, Weiqin; Du, Wenhui; Shen, Xuyang; Zhang, Hangjun; Ding, Ying

2017-08-01

Organic waste has great potential for use as an amendment to immobilize heavy metals in the environment. Therefore, this study investigates various properties of cow manure (CM) and its derived vermicompost (CV), including the pH, cationic exchangeable capacity (CEC), elemental composition and surface structure, to determine the potential of these waste products to remove Pb 2+ and Cd 2+ from solution. The results demonstrate that CV has a much higher pH, CEC and more irregular pores than CM and is enriched with minerals and ash content but has a lower C, H, O and N content. Adsorption isotherms studies shows that the adsorption of Pb 2+ and Cd 2+ onto either CM or CV follows a Langmuir model and presents maximum Pb 2+ and Cd 2+ adsorption capacities of 102.77 mg g -1 and 38.11 mg g -1 onto CM and 170.65 and 43.01 mg g -1 onto CV, respectively. Kinetic studies show that the adsorption of Pb 2+ onto CM and CV fits an Elovich model, whereas the adsorption of Cd 2+ onto CM and CV fits a pseudo-second-order model. Desorption studies indicate that CV is more effective than CM in removing Pb 2+ and Cd 2+ . FTIR analysis demonstrates that the adsorption of Pb 2+ and Cd 2+ onto CM mainly depends on existed aliphatic alcohol, aromatic acid as well as new produced carbonates, whereas that onto CV may be contributed by the existed aliphatic alcohol, aromatic acids as well as some carbonates and phosphates. Thus, vermicomposting disposal of cow manure with destination mineral addition may broaden the way of its recycle and environmental usage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Contemporary Cardiovascular Concerns after Spinal Cord Injury: Mechanisms, Maladaptations, and Management.

PubMed

Phillips, Aaron A; Krassioukov, Andrei V

2015-12-15

Cardiovascular (CV) issues after spinal cord injury (SCI) are of paramount importance considering they are the leading cause of death in this population. Disruption of autonomic pathways leads to a highly unstable CV system, with impaired blood pressure (BP) and heart rate regulation. In addition to low resting BP, on a daily basis the majority of those with SCI suffer from transient episodes of aberrantly low and high BP (termed orthostatic hypotension and autonomic dysreflexia, respectively). In fact, autonomic issues, including resolution of autonomic dysreflexia, are frequently ranked by individuals with high-level SCI to be of greater priority than walking again. Owing to a combination of these autonomic disturbances and a myriad of lifestyle factors, the pernicious process of CV disease is accelerated post-SCI. Unfortunately, these secondary consequences of SCI are only beginning to receive appropriate clinical attention. Immediately after high-level SCI, major CV abnormalities present in the form of neurogenic shock. After subsiding, new issues related to BP instability arise, including orthostatic hypotension and autonomic dysreflexia. This review describes autonomic control over the CV system before injury and the mechanisms underlying CV abnormalities post-SCI, while also detailing the end-organ consequences, including those of the heart, as well as the systemic and cerebral vasculature. The tertiary impact of CV dysfunction will also be discussed, such as the potential impediment of rehabilitation, and impaired cognitive function. In the recent past, our understanding of autonomic dysfunctions post-SCI has been greatly enhanced; however, it is vital to further develop our understanding of the long-term consequences of these conditions, which will equip us to better manage CV disease morbidity and mortality in this population.

Risk of Myocardial Infarction in Patients with Long-Term Non-Vitamin K Antagonist Oral Anticoagulant Treatment.

PubMed

Tornyos, Adrienn; Kehl, Dániel; D'Ascenzo, Fabrizio; Komócsi, András

2016-01-01

The relative cardiovascular (CV) safety of oral anticoagulants continues to be debated, and in particular concerns for risk of myocardial infarction (MI) have been raised. We analyzed the risk of MI in patients treated long term with oral anticoagulants (vitamin K antagonists [VKA], direct thrombin inhibitors or activated X factor antagonist) for atrial fibrillation, deep vein thrombosis or pulmonary embolism using a network meta-analysis (NMA). Randomized, phase 3 trials comparing novel anticoagulants to VKA were searched. Information on study design and clinical outcomes was extracted. The primary end-point of the analysis was the occurrence of MI or acute coronary syndrome. A Bayesian multiple treatment analysis was performed using fixed-effect and random-effects modeling. Twelve trials including 100,524 randomized patients were analyzed. The odds for MI in NMA were worse with dabigatran when compared to VKA, rivaroxaban, apixaban, and edoxaban (OR: 0.66 CI: 0.49-0.87; OR: 0.56 CI: 0.38-0.82, OR: 0.59 CI 0.40-0.88, and OR: 0.71 CI: 0.50-1.0, respectively).The posterior probability of being the first best choice of treatment was 53.5% for rivaroxaban, 33.8% for apixaban, 9.5% for ximelagatran, 2.0% for edoxaban, 1.2% for VKA, and 0.007% for dabigatran. There is a considerable heterogeneity regarding CV safety among oral anticoagulants. Differences in risk of MI may influence the choice of treatment. Multiple treatment NMA found 29%-44% higher odds of MI with dabigatran supporting the concerns regarding its CV safety. Copyright © 2015 Elsevier Inc. All rights reserved.

Health and economic impact of PHiD-CV in Canada and the UK: a Markov modelling exercise.

PubMed

Knerer, Gerhart; Ismaila, Afisi; Pearce, David

2012-01-01

The spectrum of diseases caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) represents a large burden on healthcare systems around the world. Meningitis, bacteraemia, community-acquired pneumonia (CAP), and acute otitis media (AOM) are vaccine-preventable infectious diseases that can have severe consequences. The health economic model presented here is intended to estimate the clinical and economic impact of vaccinating birth cohorts in Canada and the UK with the 10-valent, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared with the newly licensed 13-valent pneumococcal conjugate vaccine (PCV-13). The model described herein is a Markov cohort model built to simulate the epidemiological burden of pneumococcal- and NTHi-related diseases within birth cohorts in the UK and Canada. Base-case assumptions include estimates of vaccine efficacy and NTHi infection rates that are based on published literature. The model predicts that the two vaccines will provide a broadly similar impact on all-cause invasive disease and CAP under base-case assumptions. However, PHiD-CV is expected to provide a substantially greater reduction in AOM compared with PCV-13, offering additional savings of Canadian $9.0 million and £4.9 million in discounted direct medical costs in Canada and the UK, respectively. The main limitations of the study are the difficulties in modelling indirect vaccine effects (herd effect and serotype replacement), the absence of PHiD-CV- and PCV-13-specific efficacy data and a lack of comprehensive NTHi surveillance data. Additional limitations relate to the fact that the transmission dynamics of pneumococcal serotypes have not been modelled, nor has antibiotic resistance been accounted for in this paper. This cost-effectiveness analysis suggests that, in Canada and the UK, PHiD-CV's potential to protect against NTHi infections could provide a greater impact on overall disease burden than the additional serotypes contained in PCV-13.

Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study.

PubMed

Krinsley, James S; Egi, Moritoki; Kiss, Alex; Devendra, Amin N; Schuetz, Philipp; Maurer, Paula M; Schultz, Marcus J; van Hooijdonk, Roosmarijn T M; Kiyoshi, Morita; Mackenzie, Iain M J; Annane, Djillali; Stow, Peter; Nasraway, Stanley A; Holewinski, Sharon; Holzinger, Ulrike; Preiser, Jean-Charles; Vincent, Jean-Louis; Bellomo, Rinaldo

2013-03-01

Hyperglycemia, hypoglycemia, and increased glycemic variability have each been independently associated with increased risk of mortality in critically ill patients. The role of diabetic status on modulating the relation of these three domains of glycemic control with mortality remains uncertain. The purpose of this investigation was to determine how diabetic status affects the relation of hyperglycemia, hypoglycemia, and increased glycemic variability with the risk of mortality in critically ill patients. This is a retrospective analysis of prospectively collected data involving 44,964 patients admitted to 23 intensive care units (ICUs) from nine countries, between February 2001 and May 2012. We analyzed mean blood glucose concentration (BG), coefficient of variation (CV), and minimal BG and created multivariable models to analyze their independent association with mortality. Patients were stratified according to the diagnosis of diabetes. Among patients without diabetes, mean BG bands between 80 and 140 mg/dl were independently associated with decreased risk of mortality, and mean BG bands>or=140 mg/dl, with increased risk of mortality. Among patients with diabetes, mean BG from 80 to 110 mg/dl was associated with increased risk of mortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. An effect of center was noted on the relation between mean BG and mortality. Hypoglycemia, defined as minimum BG<70 mg/dl, was independently associated with increased risk of mortality among patients with and without diabetes and increased glycemic variability, defined as CV>or=20%, was independently associated with increased risk of mortality only among patients without diabetes. Derangements of more than one domain of glycemic control had a cumulative association with mortality, especially for patients without diabetes. Although hyperglycemia, hypoglycemia, and increased glycemic variability is each independently associated with mortality in critically ill patients, diabetic status modulates these relations in clinically important ways. Our findings suggest that patients with diabetes may benefit from higher glucose target ranges than will those without diabetes. Additionally, hypoglycemia is independently associated with increased risk of mortality regardless of the patient's diabetic status, and increased glycemic variability is independently associated with increased risk of mortality among patients without diabetes.

Association Between Socioeconomic Status and Mortality, Cardiovascular Disease, and Cancer in Patients With Type 2 Diabetes.

PubMed

Rawshani, Araz; Svensson, Ann-Marie; Zethelius, Björn; Eliasson, Björn; Rosengren, Annika; Gudbjörnsdottir, Soffia

2016-08-01

The association between socioeconomic status and survival based on all-cause, cardiovascular (CV), diabetes-related, and cancer mortality in type 2 diabetes has not been examined in a setting of persons with equitable access to health care with adjustment for important confounders. To determine whether income, educational level, marital status, and country of birth are independently associated with all-cause, CV, diabetes-related, and cancer mortality in persons with type 2 diabetes. A study including all 217 364 individuals younger than 70 years with type 2 diabetes in the Sweden National Diabetes Register (January 1, 2003, to December 31, 2010) who were monitored through December 31, 2012, was conducted. A Cox proportional hazards regression model with up to 17 covariates was used for analysis. All-cause, CV, diabetes-related, and cancer mortality. Of the 217 364 persons included in the study, mean (SD) age was 58.3 (9.3) years and 130 839 of the population (60.2%) was male. There were a total of 19 105 all-cause deaths with 11 423 (59.8%), 6984 (36.6%), and 6438 (33.7%) CV, diabetes-related, or cancer deaths, respectively. Compared with being single, hazard ratios (HRs) for married individuals, determined using fully adjusted models, for all-cause, CV, and diabetes-related mortality were 0.73 (95% CI, 0.70-0.77), 0.67 (95% CI, 0.63-0.71), and 0.62 (95% CI, 0.57-0.67), respectively. Marital status was not associated with overall cancer mortality, but married men had a 33% lower risk of prostate cancer mortality compared with single men, with an HR of 0.67 (95% CI, 0.50-0.90). Comparison of HRs for the lowest vs highest income quintiles for all-cause, CV, diabetes-related, and cancer mortality were 1.71 (95% CI, 1.60-1.83), 1.87 (95% CI, 1.72-2.05), 1.80 (95% CI, 1.61-2.01), and 1.28 (95% CI, 1.14-1.44), respectively. Compared with native Swedes, HRs for all-cause, CV, diabetes-related, and cancer mortality for non-Western immigrants were 0.55 (95% CI, 0.48-0.63), 0.46 (95% CI, 0.38-0.56), 0.38 (95% CI, 0.29-0.49), and 0.72 (95% CI, 0.58-0.88), respectively, and these HRs were virtually unaffected by covariate adjustment. Hazard ratios for those with a college/university degree compared with 9 years or less of education were 0.85 (95% CI, 0.80-0.90), 0.84 (95% CI, 0.78-0.91), and 0.84 (95% CI, 0.76-0.93) for all-cause, CV, and cancer mortality, respectively. Independent of risk factors, access to health care, and use of health care, socioeconomic status is a powerful predictor of all-cause and CV mortality but was not as strong as a predictor of death from cancer.

Relationship between lipoprotein subfraction cholesterol and residual risk for cardiovascular outcomes: A post hoc analysis of the AIM-HIGH trial.

PubMed

Toth, Peter P; Jones, Steven R; Slee, April; Fleg, Jerome; Marcovina, Santica M; Lacy, Megan; McBride, Ruth; Boden, William E

2018-03-09

The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial failed to demonstrate incremental clinical benefit of extended-release niacin (ERN) in 3414 statin-treated patients with established cardiovascular (CV) disease who had low baseline levels of high-density lipoprotein cholesterol (HDL-C) as compared to placebo. A previous secondary analysis suggested that ERN provided outcome benefits in ERN-treated patients with high triglycerides (TGs; >200 mg/dL) and very low HDL-C (<32 mg/dL) at baseline. The current analysis sought to ascertain how changes in TG-enriched lipoproteins and HDL subfractions impact residual risk in the comparator treatment arms. We evaluated the relationship between niacin treatment, lipoproteins and their subfractions, and CV outcomes in a non-prespecified, post hoc analysis of the AIM-HIGH trial. Lipoprotein subfraction analysis was performed with zonal ultracentrifugation in 2457 AIM-HIGH participants at baseline and 1 year of treatment. Hazard ratios were estimated using Cox proportional hazards models for relationships between lipoproteins and the composite primary endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization. Analyses were performed for the entire cohort and in participants with TGs > 200 mg/dL and HDL-C < 32 mg/dL. Apoprotein B-containing lipoproteins and their subfractions decreased significantly in both treatment arms but decreased more with ERN treatment. HDL-C and its subfractions increased significantly in both treatment groups, but more so in patients treated with ERN. For the entire study population, neither apoB- nor apoA1-containing lipoprotein subfractions predicted risk at baseline or at 1 year of follow-up. In the high TG and low HDL-C subgroup treated with placebo, changes at 1 year in HDL 2 -C, total cholesterol/HDL 2 -C, and non-HDL-C/HDL 2 -C may be associated with increased CV events, whereas in the ERN treatment arm, changes at 1 year in very low-density lipoprotein cholesterol and very low-density lipoprotein subfractions, total remnant lipoproteins, and various risk ratios may be associated with increased CV events, while HDL 2 -C may be associated with reduced risk. We provide hypothesis-generating findings that ERN may confer benefit in patients with coronary heart disease who have high TGs and low HDL by reducing serum levels of remnant lipoprotein cholesterol and increasing HDL 2 -C. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

PubMed Central

Scarpignato, C

2013-01-01

Although NSAIDs are very effective drugs, their use is associated with a broad spectrum of adverse reactions in the liver, kidney, cardiovascular (CV) system, skin and gut. Gastrointestinal (GI) side effects are the most common and constitute a wide clinical spectrum ranging from dyspepsia, heartburn and abdominal discomfort to more serious events such as peptic ulcer with life-threatening complications of bleeding and perforation. The appreciation that CV risk is also increased further complicates the choices of physicians prescribing anti-inflammatory therapy. Despite prevention strategies should be implemented in patients at risk, gastroprotection is often underused and adherence to treatment is generally poor. A more appealing approach would be therefore to develop drugs that are devoid of or have reduced GI toxicity. Gastro-duodenal mucosa possesses many defensive mechanisms and NSAIDs have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid load. NSAIDs cause gastro-duodenal damage, by two main mechanisms: a physiochemical disruption of the gastric mucosal barrier and systemic inhibition of gastric mucosal protection, through inhibition of cyclooxygenase (COX, PG endoperoxide G/H synthase) activity of the GI mucosa. However, against a background of COX inhibition by anti-inflammatory doses of NSAIDs, their physicochemical properties, in particular their acidity, underlie the topical effect leading to short-term damage. It has been shown that esterification of acidic NSAIDs suppresses their gastrotoxicity without adversely affecting anti-inflammatory activity. Another way to develop NSAIDs with better GI tolerability is to complex these molecules with cyclodextrins (CDs), giving rise to so-called “inclusion complexes” that can have physical, chemical and biological properties very different from either those of the drug or the cyclodextrin. Complexation of NSAIDs with β-cyclodextrin potentially leads to a more rapid onset of action after oral administration and improved GI tolerability because of minimization of the drug gastric effects. One such drug, piroxicam-β-cyclodextrin (PBC), has been used in Europe for 25 years. Preclinical and clinical pharmacology of PBC do show that the β-cyclodextrin inclusion complex of piroxicam is better tolerated from the upper GI tract than free piroxicam, while retaining all the analgesic and anti-inflammatory properties of the parent compound. In addition, the drug is endowed with a quick absorption rate, which translates into a faster onset of analgesic activity, an effect confirmed in several clinical studies. An analysis of the available trials show that PBC has a GI safety profile, which is better than that displayed by uncomplexed piroxicam. Being an inclusion complex of piroxicam, whose CV safety has been pointed out by several observational studies, PBC should be viewed as a CV safe anti-inflmmatory compound and a GI safer alternative to piroxicam. As a consequence, it should be considered as a useful addition to our therapeutic armamentarium. PMID:23394552

Ultrastructural study on the follicle-associated epithelium of nasal-associated lymphoid tissue in specific pathogen-free (SPF) and conventional environment-adapted (SPF-CV) rats

PubMed Central

JEONG, KWANG IL; SUZUKI, HODAKA; NAKAYAMA, HIROYUKI; DOI, KUNIO

2000-01-01

Membranous (M) cells in follicle-associated epithelium (FAE) play an important role in the mucosal immunity through transport of a variety of foreign antigens to the underlying mucosa-associated lymphoid tissue (MALT). We aimed to investigate the ultrastructure of M cells in the FAE covering nasal-associated lymphoid tissue (NALT) both in specific pathogen-free (SPF) rats and in conventional environment-adapted (SPF-CV) rats aged 8–38 wk. In NALT of both SPF and SPF-CV rats, FAE included the nonciliated microvillous cell, which appears to be an analogue of M cell previously described in other MALT. In SPF rats, M cells increased in number only slightly with age, and they maintained morphological uniformity irrespective of age. In SPF-CV rats, M cells selectively increased in number resulting in prominent expansion of FAE surface area in parallel with the duration of maintenance in a conventional environment. In addition, M cells in SPF-CV rats showed heterogeneity in their surface morphology such as the length and number of microvilli and cell surface area and outline. In addition, the FAE was stratified by various subtypes of M cells, which were characterised by several subcellular alterations including the presence of many keratin filaments, homogeneous dark bodies and extensive cytoplasmic interfoliation with wide intercellular spaces filled with amorphous proteinaceous material. These characteristics of M cells in SPF-CV rat were intimately related with a preferential influx of immunocompetent cells into the FAE, which was not seen or was very rare in SPF rats irrespective of age. The results suggest the possibility that NALT may effectively carry out the mucosal immune response against antigenic stimuli of different magnitude through the unique dynamics of M cells which seem to be influenced by the infiltration of immunocompetent cells. PMID:10853966