Voigt, N; Heijman, J; Dobrev, D
Adverse side effects of drugs are a significantly underestimated problem in modern medicine. In this review article, we summarize common adverse side effects of cardiovascular drugs. In particular, we highlight the factors promoting these adverse side effects in patients, including reduced hepatic or renal clearance in elderly patients that often requires dosage adjustment. Pharmacodynamic and pharmacokinetic interactions between drugs (e.g. through the cytochrome P450 system or P-glycoproteins) can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. The most prominent cardiac side effects include arrhythmias, e.g. atrioventricular (AV) block, drug-induced long-QT syndrome and torsade de pointes and altered inotropy. Non-cardiac side effects are subsequently discussed grouped by drug class. A better understanding of the risks and side effects of cardiovascular drugs is expected to reduce the mortality and morbidity associated with adverse side effects.
Bell, David S H; Patil, Harshal R; O'Keefe, James H
This review discusses the current data on various antidiabetic medications and their effects on major adverse cardiovascular events (MACE). Diabetes mellitus is a potent independent risk factor for MACE, and this risk increases in proportion to the elevation of hemoglobin A1c. Available data suggest that tight glycemic control in patients with diabetes reduces microvascular complications, but has limited effect or may even increase the risk of MACE and other macrovascular complications. For individuals with type 2 diabetes mellitus (T2DM) drugs that reduce postprandial glucose (α-glucosidase inhibitors, incretin mimetics, quick-acting bromocriptine, dipeptidyl peptidase-4 inhibitors, and colesevelam) are associated with a decrease in MACE. Drugs that directly reduce insulin resistance (pioglitazone and metformin) are also associated with lesser but still significant decreases in MACE. Insulin, rosiglitazone (but not pioglitazone), and sulfonylureas (especially with glyburide and particularly the glyburide + metformin combination) are associated with increases in MACE. In summary, drugs that reduce postprandial glucose and improve insulin resistance without predisposing patients to hypoglycemia appear to both control hyperglycemia and improve cardiovascular prognosis. However, many of the traditional agents used for treating T2DM, such as insulin and sulfonylureas, do not improve cardiovascular prognosis despite improving hyperglycemia.
Artero, Enrique G; Lee, Duck-chul; Lavie, Carl J; España-Romero, Vanesa; Sui, Xuemei; Church, Timothy S; Blair, Steven N
Physical fitness is one of the strongest predictors of individual future health status. Together with cardiorespiratory fitness (CRF), muscular strength has been increasingly recognized in the pathogenesis and prevention of chronic disease. We review the most recent literature on the effect of muscular strength in the development of cardiovascular disease, with special interest in elucidating its specific benefits beyond those from CRF and body composition. Muscular strength has shown an independent protective effect on all-cause and cancer mortality in healthy middle-aged men, as well as in men with hypertension and patients with heart failure. It has also been inversely associated with age-related weight and adiposity gains, risk of hypertension, and prevalence and incidence of the metabolic syndrome. In children and adolescents, higher levels of muscular fitness have been inversely associated with insulin resistance, clustered cardiometabolic risk, and inflammatory proteins. Generally, the influence of muscular fitness was weakened but remained protective after considering CRF. Also, interestingly, higher levels of muscular fitness seems to some extent counteract the adverse cardiovascular profile of overweight and obese individuals. As many of the investigations have been conducted with non-Hispanic white men, it is important to examine how race/ethnicity and gender may affect these relationships. To conclude, most important effects of resistance training are also summarized, to better understand how higher levels of muscular fitness may result in a better cardiovascular prognosis and survival.
Patelis, Nikolaos; Kouvelos, George N; Koutsoumpelis, Andreas; Moris, Demetrios; Matsagkas, Miltiadis I; Arnaoutoglou, Eleni
Cardiovascular complications signify a major cause of morbidity and mortality in patients undergoing vascular surgery adversely affecting both short- and long-term prognosis. During the last decade, unmet needs for a distinct cardiovascular risk assessment have led to an intensive research for establishment of biomarkers with sufficient predictive value. This literature review aims in examining the value of several biomarkers in predicting the incidence of major adverse cardiac events in vascular surgery patients. We reviewed the English language literature and analyzed the biomarkers as independent predictors or in correlation with other factors. We found several biomarkers showing a significant predictive value for a major adverse cardiovascular event in patients undergoing vascular surgery. These biomarkers can be used in clinical practice as outcome predictors, although sensitivity and specificity varies. Detection of subclinical cardiovascular damage may improve total risk estimation and facilitate clinical assessment of patients at risk for future cardiovascular events. The wide variety of sensitivity and specificity in predicting a MACE of these biomarkers exert the need for future trials in which these markers will be tested as adjunctive tools of cardiovascular risk estimation scoring systems.
Ramirez-Villegas, Juan F.; Lam-Espinosa, Eric; Ramirez-Moreno, David F.; Calvo-Echeverry, Paulo C.; Agredo-Rodriguez, Wilfredo
Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis. PMID:21386966
Udell, Jacob A.; Lu, Hong; Redelmeier, Donald A.
BACKGROUND: Infertility may indicate an underlying predisposition toward premature cardiovascular disease, yet little is known about potential long-term cardiovascular events following fertility therapy. We investigated whether failure of fertility therapy is associated with subsequent adverse cardiovascular events. METHODS: We performed a population-based cohort analysis of women who received gonadotropin-based fertility therapy between Apr. 1, 1993, and Mar. 31, 2011, distinguishing those who subsequently gave birth and those who did not. Using multivariable Poisson regression models, we estimated the relative rate ratio of adverse cardiovascular events associated with fertility therapy failure, accounting for age, year, baseline risk factors, health care history and number of fertility cycles. The primary outcome was subsequent treatment for nonfatal coronary ischemia, stroke, transient ischemic attack, heart failure or thromboembolism. RESULTS: Of 28 442 women who received fertility therapy, 9349 (32.9%) subsequently gave birth and 19 093 (67.1%) did not. The median number of fertility treatments was 3 (interquartile range 1–5). We identified 2686 cardiovascular events over a median 8.4 years of follow-up. The annual rate of cardiovascular events was 19% higher among women who did not give birth after fertility therapy than among those who did (1.08 v. 0.91 per 100 patient-years, p < 0.001), equivalent to a 21% relative increase in the annual rate (95% confidence interval 13%–30%). We observed no association between event rates and number of treatment cycles. INTERPRETATION: Fertility therapy failure was associated with an increased risk of long-term adverse cardiovascular events. These women merit surveillance for subsequent cardiovascular events. PMID:28385819
Chin, Michael T.
Air pollution is a significant cause of cardiovascular morbidity and mortality worldwide. Although the epidemiologic association between air pollution exposures and exacerbation of cardiovascular disease is well established, the mechanisms by which these exposures promote cardiovascular disease are incompletely understood. In this review I will give an overview of the components of air pollution, an overview of the cardiovascular effects of air pollution exposure and a review of the basic mechanisms that are activated by exposure to promote cardiovascular disease. PMID:25552258
Silkjaer, Trine; Nyvold, Charlotte Guldborg; Juhl-Christensen, Caroline; Hokland, Peter; Nørgaard, Jan Maxwell
Alterations in the two catalytic genes cytochrome c oxidase subunits I and II (COI and COII) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia (AML). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML. In 37 (16%) patients, a non-synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non-synonymous variations. Twenty-four (10%) patients had non-synonymous variations in COI, whereas 13 (6%) patients had non-synonymous variations in COII. The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation (CN-AML) treated with curative intent, the presence of a non-synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease-free survival (DFS) in both univariate (DFS; hazard ratio (HR) 4.4, P = 0.006) and multivariate analyses (DFS; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML, and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN-AML should be explored further.
Nakamura, Shunichi; Kato, Koji; Yoshida, Asuka; Fukuma, Nagaharu; Okumura, Yasuyuki; Ito, Hiroto; Mizuno, Kyoichi
Although attention has recently been focused on the role of psychosocial factors in patients with cardiovascular disease (CVD), the factors that have the greatest influence on prognosis have not yet been elucidated. The aim of this study was to evaluate the effects of depression, anxiety, and anger on the prognosis of patients with CVD. Four hundred fourteen consecutive patients hospitalized with CVD were prospectively enrolled. Depression was evaluated using the Patient Health Questionnaire, anxiety using the Generalized Anxiety Disorder Questionnaire, and anger using the Spielberger Trait Anger Scale. Cox proportional-hazards regression was used to examine the individual effects of depression, anxiety, and anger on a combined primary end point of cardiac death or cardiac hospitalization and on a combined secondary end point of all-cause death or hospitalization during follow-up (median 14.2 months). Multivariate analysis showed that depression was a significant risk factor for cardiovascular hospitalization or death after adjusting for cardiac risk factors and other psychosocial factors (hazard ratio 2.62, p = 0.02), whereas anxiety was not significantly associated with cardiovascular hospitalization or death after adjustment (hazard ratio 2.35, p = 0.10). Anger was associated with a low rate of cardiovascular hospitalization or death (hazard ratio 0.34, p <0.01). In conclusion, depression in hospitalized patients with CVD is a stronger independent risk factor for adverse cardiac events than either anxiety or anger. Anger may help prevent adverse outcomes. Routine screening for depression should therefore be performed in patients with CVD, and the potential effects of anger in clinical practice should be reconsidered.
Palaniappan, Muthiah; George, Melvin; Subramaniyan, Ganesan; Dkhar, Steven Aibor; Pillai, Ajith Ananthakrishna; Jayaraman, Balachander; Chandrasekaran, Adithan
Background Cardiovascular diseases (CVD) are one of the leading causes of non-communicable disease related deaths globally. Patients with cardiovascular diseases are often prescribed multiple drugs and have higher risk for developing more adverse drug reactions due to polypharmacy. Aim To evaluate the pattern of adverse drug reactions reported with cardiovascular drugs in an adverse drug reaction monitoring centre (AMC) of a tertiary care hospital. Settings and Design Adverse drug reactions related to cardiovascular drugs reported to an AMC of a tertiary care hospital were included in this prospective observational study. Materials and Methods All cardiovascular drugs related adverse drug reactions (ADRs) received in AMC through spontaneous reporting system and active surveillance method from January 2011 to March 2013 were analysed for demographic profile, ADR pattern, severity and causality assessment. Statistical Analysis used The study used descriptive statistics and the values were expressed in numbers and percentages. Results During the study period, a total of 463 ADRs were reported from 397 patients which included 319 males (80.4%) and 78 females (19.6%). The cardiovascular drug related reports constituted 18.1% of the total 2188 ADR reports. In this study, the most common ADRs observed were cough (17.3%), gastritis (7.5%) and fatigue (6.5%). Assessment of ADRs using WHO-causality scale revealed that 62% of ADRs were possible, 28.2% certain and 6.8% probable. As per Naranjo’s scale most of the reports were possible (68.8%) followed by probable (29.7%). According to Hartwig severity scale majority of the reports were mild (95%) followed by moderate (4.5%). A system wise classification of ADRs showed that gastrointestinal system (20.7%) related reactions were the most frequently observed adverse reactions followed by respiratory system (18.4%) related adverse effects. From the reported ADRs, the drugs most commonly associated with ADRs were found to be
Ocio, E M; Schop, R F J; Gonzalez, B; Van Wier, S A; Hernandez-Rivas, J M; Gutierrez, N C; Garcia-Sanz, R; Moro, M J; Aguilera, C; Hernandez, J; Xu, R; Greipp, P R; Dispenzieri, A; Jalal, S M; Lacy, M Q; Gonzalez-Paz, N; Gertz, M A; San Miguel, J F; Fonseca, R
Fluorescence in situ hybridisation (FISH) is an effective technique for the cytogenetic analysis of Waldenström macroglobulinemia (WM), but the potential impact of molecular cytogenetics on disease evolution and as a prognostic marker is still unknown. Deletion of the long arm of chromosome 6 (6q-) is the most frequent cytogenetic abnormality in WM. This study analysed the prevalence of this aberration in 102 WM patients, and correlated it with disease characteristics. The incidence of 6q21 deletion was 7% by conventional cytogenetics and 34% when analysed by FISH (54% when cytoplasmic immunoglobulin M-FISH was used). Patients with deletion of 6q displayed features of adverse prognosis, such as higher levels of beta2-microglobulin and monoclonal paraprotein and a greater tendency to display anaemia and hypoalbuminemia. Interestingly, there was a correlation between the presence of 6q deletion and the International Staging System prognostic index (incidence of 6q- among patients stratified in stages 1, 2 and 3 was 24%, 42% and 67% respectively). Those patients diagnosed with smouldering WM who displayed the abnormality showed a trend to an earlier requirement of treatment. Finally, the survival analysis did not show differences between the two groups of patients, probably due to the short follow up of our series.
Pistelli, R; Lange, P; Miller, D L
In this paper, the authors update the present knowledge about three risk factors for the prognosis of chronic obstructive pulmonary disease (COPD), which may be particularly relevant in elderly people: mucus hypersecretion, respiratory infections, and cardiovascular comorbidity. Chronic mucus hypersecretion (CMH) is a common respiratory symptom in old age, the relevance of which is analysed on the basis of data collected during the first three rounds of the Copenhagen City Heart Study. In subjects aged > or = 65 yrs, CMH was a strong predictor of the incidence of respiratory infections in a 10-yr follow-up period and it was also a strong predictor of death from COPD (relative risk=2.5). However, CMH was associated with consistently lower forced expiratory volume in one second (FEV1) values, but not with an accelerated decline of FEV1 in this sample of an elderly population. Acute respiratory infections (ARI) are extremely common at all ages, mostly mild self-limiting illnesses at a young age, but severe often fatal illnesses in elderly people already affected by a chronic disease such as COPD. This paper summarises the present knowledge about aetiology, pathology, prognostic relevance, and prevention of ARI. Furthermore, the areas in which further research is needed are listed. Clinical cohort studies clearly support the relevance of cardiovascular comorbidity for the short-and long-term prognosis of elderly subjects affected by severe COPD. In this paper, the recently demonstrated association between particulate air pollution and cardiovascular events is reported to suggest the presence of an extremely susceptible cluster of elderly subjects in the population identified by the copresence of chronic obstructive pulmonary disease and cardiovascular comorbidity.
Park, Ki; Wei, Janet; Minissian, Margo; Merz, C. Noel Bairey
Adverse pregnancy conditions in women are common and have been associated with adverse cardiovascular and metabolic outcomes such as myocardial infarction and stroke. As risk stratification in women is often suboptimal, recognition of non-traditional risk factors such as hypertensive disorders of pregnancy and premature delivery has become increasingly important. Additionally, such conditions may also increase the risk of cardiovascular disease in the children of afflicted women. In this review, we aim to highlight these conditions, along with infertility, and the association between such conditions and various cardiovascular outcomes and related maternal risk along with potential translation of risk to offspring. We will also discuss proposed mechanisms driving these associations as well as potential opportunities for screening and risk modification. PMID:26037616
Fardet, Laurence; Fève, Bruno
The prevalence of use of long-term systemic glucocorticoid therapy in the general adult population is 1 %. This figure increases to up to 3 % in elderly women. Metabolic (i.e. diabetes mellitus, dyslipidemia, weight gain, lipodystrophy) and cardiovascular (i.e. hypertension, cardiovascular events) adverse events are commonly observed in these patients and can be life threatening. Paradoxically, there is very few data on some of these adverse events and many of the available studies remain inconclusive. Incidence of and risk factors for dyslipidemia, weight gain and lipodystrophy are poorly defined. The optimal treatment plan for patients diagnosed with glucocorticoid-induced diabetes or hypertension is undetermined. Finally, there is no medical consensus on the best strategies for the prevention and detection of these complications. However, certain of these questions can be answered by looking at available data on patients with endogenous hypercortisolism (i.e. Cushing's syndrome). This article reviews the pathophysiology, incidence, risk factors, screening, and treatment of glucocorticoid-induced weight gain, lipodystrophy, diabetes, dyslipidemia, hypertension, and cardiovascular events. It also focuses on the possible prevention of these adverse events by targeting the glucocorticoid receptor using selective glucocorticoid receptor modulators.
Vlasova, Maria A; Tarasova, Olga S; Riikonen, Joakim; Raula, Janne; Lobach, Anatoly S; Borzykh, Anna A; Smirin, Boris V; Kauppinen, Esko I; Eletskii, Alexander V; Herzig, Karl-Heinz; Salonen, Jarno; Tavi, Pasi; Lehto, Vesa-Pekka; Järvinen, Kristiina
When nanocarriers are used for drug delivery they can often achieve superior therapeutic outcomes over standard drug formulations. However, concerns about their adverse effects are growing due to the association between exposure to certain nanosized particles and cardiovascular events. Here we examine the impact of intravenously injected drug-free nanocarriers on the cardiovasculature at both the systemic and organ levels. We combine in vivo and in vitro methods to enable monitoring of hemodynamic parameters in conscious rats, assessments of the function of the vessels after sub-chronic systemic exposure to nanocarriers and evaluation of the direct effect of nanocarriers on vascular tone. We demonstrate that nanocarriers can decrease blood pressure and increase heart rate in vivo via various mechanisms. Depending on the type, nanocarriers induce the dilation of the resistance arteries and/or change the responses induced by vasoconstrictor or vasodilator drugs. No direct correlation between physicochemical properties and cardiovascular effects of nanoparticles was observed. The proposed combination of methods empowers the studies of cardiovascular adverse effects of the nanocarriers.
Song, Wei; Zhang, Tianyang; Li, Wei; Mu, Rui; Zhang, Lingyi; Li, Yan; Jin, Baofeng; Wang, Na; Li, Ailing; Cui, Jiuwei
This study aimed to investigate the expression of Friend leukemia virus integration 1 (Fli-1) and its correlation with the prognosis of endometrial cancer (EC). Thirty-two EC tissue samples were evaluated for Fli-1 expression using immunohistochemistry. Fli-1 showed significantly high expression in EC cells, followed by hyperplasia cells, and was negative in adjacent normal tissues. The high expression of Fli-1 was significantly associated with a high differentiation grade, mutated P53 expression, and histological subtype (p < .05). Downregulation of Fli-1 in AN3CN cells using RNA interference inhibited cell clone formation and proliferation but did not affect apoptosis and migration of the cells. This study provides the first evidence that Fli-1 expression gradually increases in parallel with disease progression, and its overexpression might predict poor prognosis in EC.
Li, Wen-Feng; Zhang, Dan-Dan; Xia, Ji-Tian; Wen, Shan-Fan; Guo, Jun; Li, Zi-Cheng
This study is to explore the association of adverse cardiovascular events with B vitamins supplementation. Rev.Man 5.1 and Stata 11.0 software were applied for the meta-analysis. The number of cardiovascular events was collected and calculated using indicates of odds ratio and 95% confidence intervals in a fixed-effects or a random-effects model when appropriate. The study includes 15 studies which consists of 37,358 study objects (experimental group: 19,601; control group: 17,757). This study showed that the pooled ORs was 1.01 (95% CI = 0.96~1.06, P > 0.05) for objects with Experimental group (B vitamins supplementation) vs. Control group (placebo or regular treatment), which suggests no significant differences were found in the overall effect of the number of cardiovascular events between the two groups. Further stratification of subgroup analysis indicates no significant differences were found between the two groups as well. There were also no publication bias existing by the Egger’s linear regression test (P > 0.05). Our result indicates that the number of cardiovascular events in experimental group using B vitamins supplementation during the treatment is equal to placebo or regular treatment group thus further studies is necessary. PMID:25232372
Pasala, Tilak; Hoo, Jennifer Soo; Lockhart, Mary Kate; Waheed, Rehan; Sengodan, Prasanna; Alexander, Jeffrey
Antiplatelet therapy reduces the risk of myocardial infarction, stroke, and vascular death in patients who have symptomatic peripheral artery disease. However, a subset of patients who take aspirin continues to have recurrent cardiovascular events. There are few data on cardiovascular outcomes in patients with peripheral artery disease who manifest aspirin resistance. Patients with peripheral artery disease on long-term aspirin therapy (≥4 wk) were tested for aspirin responsiveness by means of the VerifyNow Aspirin Assay. The mean follow-up duration was 22.6 ± 8.3 months. The primary endpoint was a composite of death, myocardial infarction, or ischemic stroke. Secondary endpoints were the incidence of vascular interventions (surgical or percutaneous), or of amputation or gangrene caused by vascular disease. Of the 120 patients enrolled in the study, 31 (25.8%) were aspirin-resistant and 89 (74.2%) were aspirin-responsive. The primary endpoint occurred in 10 (32.3%) patients in the aspirin-resistant group and in 13 (14.6%) patients in the aspirin-responsive group (hazard ratio=2.48; 95% confidence interval, 1.08–5.66; P=0.03). There was no significant difference in the secondary outcome of revascularization or tissue loss. By multivariate analysis, aspirin resistance and history of chronic kidney disease were the only independent predictors of long-term adverse cardiovascular events. Aspirin resistance is highly prevalent in patients with symptomatic peripheral artery disease and is an independent predictor of adverse cardiovascular risk. Whether intervening in these patients with additional antiplatelet therapies would improve outcomes needs to be explored. PMID:28100965
Wong, Li-Fan; Lee, Jang-Ming
Esophageal squamous cell carcinoma (ESCC) is a frequently recurrent deadly cancer for which no efficient targeted drug exists. AXL is an adverse prognostic factor in some cancers. Strong clinical evidence to support the prognostic role of AXL in ESCC is lacking. A total of 116 patients diagnosed with operable primary ESCC were enrolled. Both AXL and HER2 expression were detected by immunohistochemistry (IHC) in esophageal tissue and were correlated with the clinical outcome of patients. The efficacy of the AXL targeted drug foretinib was also evaluated in ESCC cells. Expression of AXL was found in about 80 % of ESCC tissue, and was significantly correlated with progression of tumor (P<0.001), increased risk of death (Hazard ratio HR [95 % CI=2.09[1.09-4.04], P=0.028], and distant metastasis (odds ratio OR [95 %CI]=3.96 (1.16-13.60), P=0.029). The adverse clinical impact of AXL was more evident when cumulatively expressed with HER2. In cell model, ESCC cells were more sensitive to AXL inhibitor foretinib than to the HER2 inhibitor lapatinib. Meanwhile, the AXL inhibitor foretinib showed a synergistic effect with HER2 inhibitors and the potential to overcome drug resistance to lapatinib. We thus concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. PMID:27172793
Xia, Yu; Liu, Li; Bai, Qi; Wang, Jiajun; Xi, Wei; Qu, Yang; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming
Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases. Moreover, Kaplan-Meier method was conducted and high expression of tumoral dectin-1 was associated with shorter patient recurrence free survival (RFS) and overall survival (OS) (P < 0.001 for both). In multivariate analyses, tumoral dectin-1 expression was also confirmed as an independent prognostic factor for patients’ survival together with other clinical parameters (P < 0.001 for RFS and OS). After incorporating these characteristics including tumoral dectin-1 expression, two nomograms were constructed to predict ccRCC patients’ RFS and OS (c-index 0.796 and 0.812, respectively) and performed better than existed integrated models (P < 0.001 for all models comparisons). In conclusion, high tumoral dectin-1 expression was an independent predictor of adverse clinical outcome in ccRCC patients. This molecule and established nomograms might help clinicians in future decision making and therapeutic developments. PMID:27600310
Pugsley, Michael K; Authier, Simon; Curtis, Michael J
Cationic compounds are diverse and atypical therapeutic substances. In the present study we examined whether a prototypical class effect of cationic drugs in the cardiovascular system exists and whether this might be predictable on the basis of chemistry. The dose-dependent effects of cationic compounds of varying molecular weights and charge were examined on the blood pressure (BP), heart rate (HR) and the ECG in anesthetized rats. The compounds examined were protamine, hexadimethrine, tetraethylammonium (TEA), low molecular weight poly-L-lysine (LMW-PLL) and high molecular weight PLL (HMW-PLL). All of the compounds examined except TEA produced a dose-dependent reduction in BP. No changes occurred in HR even when high doses were administered. The ECG effects of these cationic compounds included a dose-dependent prolongation of the QT interval, especially at higher doses. All compounds transiently decreased the size of the P-wave after i.v. bolus administration whereas only protamine and hexadimethrine prolonged the PR and QRS intervals and only at the highest dose (32 mg/kg) administered. All cationic compounds, except TEA and saline, evoked ventricular premature beats (VPB), and protamine and HMW-PLL also evoked brief episodes of ventricular tachycardia (VT). The incidence and frequency of arrhythmias was not dose-dependent and no animals experienced protracted episodes of arrhythmia incidence. These dose dependent effects of the polycationic compounds tested suggest a collective mechanism of action that relates the effect of charge of the compound to the onset and persistence of observed cardiovascular toxicity, and adverse cardiovascular effect risk appears to be predictable on this basis.
Farina, Francesca; Sancini, Giulio; Longhin, Eleonora; Mantecca, Paride; Camatini, Marina; Palestini, Paola
Recent studies have suggested a link between inhaled particulate matter (PM) exposure and increased mortality and morbidity associated with cardiorespiratory diseases. Since the response to PM1 has not yet been deeply investigated, its impact on mice lungs and cardiovascular system is here examined. A repeated exposure to Milan PM1 was performed on BALB/c mice. The bronchoalveolar lavage fluid (BALf) and the lung parenchyma were screened for markers of inflammation (cell counts, tumor necrosis factor-α (TNF-α); macrophage inflammatory protein-2 (MIP-2); heme oxygenase-1 (HO-1); nuclear factor kappa-light-chain-enhancer of activated B cells p50 subunit (NFκB-p50); inducible nitric oxide synthetase (iNOS); endothelial-selectin (E-selectin)), cytotoxicity (lactate dehydrogenase (LDH); alkaline phosphatase (ALP); heat shock protein 70 (Hsp70); caspase-8-p18), and a putative pro-carcinogenic marker (cytochrome 1B1 (Cyp1B1)). Heart tissue was tested for HO-1, caspase-8-p18, NFκB-p50, iNOS, E-selectin, and myeloperoxidase (MPO); plasma was screened for markers of platelet activation and clot formation (soluble platelet-selectin (sP-selectin); fibrinogen; plasminogen activator inhibitor 1 (PAI-1)). PM1 triggers inflammation and cytotoxicity in lungs. A similar cytotoxic effect was observed on heart tissues, while plasma analyses suggest blood-endothelium interface activation. These data highlight the importance of lung inflammation in mediating adverse cardiovascular events following increase in ambient PM1 levels, providing evidences of a positive correlation between PM1 exposure and cardiovascular morbidity. PMID:23509745
Exposure to ambient levels of air pollution increases cardiovascular morbidity and mortality. Advanced age is among the factors associated with susceptibility to the adverse effects of air pollution. Dietary fatty acid supplementation has been shown to decrease cardiovascular ris...
Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen
The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications.
Kuerer, Henry M; Lari, Sara A; Arun, Banu K; Hu, Chung-Yuan; Brewster, Abenaa; Mittendorf, Elizabeth A; Albarracin, Constance T; Babiera, Gildy V; Caudle, Abigail S; Wagner, Jamie L; Litton, Jennifer K; Bedrosian, Isabelle; Meric-Bernstam, Funda; Lucci, Anthony; Hunt, Kelly K
Obesity is associated with adverse biologic features and poor outcome in patients with invasive breast cancer, yet this relationship has not been evaluated in patients with ductal carcinoma in situ (DCIS). From 1996 to 2009, body mass index (BMI) was recorded at initial diagnosis for 1,885 patients with DCIS treated at our institution. Patients were categorized as obese (BMI ≥ 30 kg/m(2)), overweight (BMI 25 to <30 kg/m(2)), or of normal weight or underweight (BMI < 25 kg/m(2)). Logistic regression was used to examine associations between BMI and patient, clinical, and pathologic features and treatment. Local-regional recurrence was calculated using the Kaplan-Meier method. All statistical tests were two-sided. Of the 1,885 patients, 514 (27.7%) were obese, 510 (27.5%) were overweight, and 831 (44.8%) were normal/underweight. In multivariate analysis, overweight and obese patients were significantly more likely to be African American (odds ratio [OR], 3.93; 95% confidence interval [CI], 2.66-5.80) or Hispanic (OR, 1.44; CI, 1.02-2.04), be postmenopausal (OR, 1.63; CI, 1.28-2.07), have diabetes (OR, 4.60; CI, 2.60-8.12), have estrogen-receptor-positive DCIS (OR, 1.39; CI, 1.00-192), and present with a radiologic abnormality rather than clinical symptoms (OR, 1.35; CI, 1.01-1.80). At a median follow-up time of 4.96 years (range, 1.0-14.34 years), no significant differences in local recurrence rates were detected based on patients' initial BMI category. Furthermore, there was no significant difference in risk of recurrence between diabetic patients receiving metformin or not. In conclusion, higher BMI is not associated with adverse biologic features or prognosis in patients with DCIS.
Goodman, Julie E; Prueitt, Robyn L; Sax, Sonja N; Pizzurro, Daniella M; Lynch, Heather N; Zu, Ke; Venditti, Ferdinand J
The US Environmental Protection Agency (EPA) recently concluded that there is likely to be a causal relationship between short-term (< 30 days) ozone exposure and cardiovascular (CV) effects; however, biological mechanisms to link transient effects with chronic cardiovascular disease (CVD) have not been established. Some studies assessed changes in circulating levels of biomarkers associated with inflammation, oxidative stress, coagulation, vasoreactivity, lipidology, and glucose metabolism after ozone exposure to elucidate a biological mechanism. We conducted a weight-of-evidence (WoE) analysis to determine if there is evidence supporting an association between changes in these biomarkers and short-term ozone exposure that would indicate a biological mechanism for CVD below the ozone National Ambient Air Quality Standard (NAAQS) of 75 parts per billion (ppb). Epidemiology findings were mixed for all biomarker categories, with only a few studies reporting statistically significant changes and with no consistency in the direction of the reported effects. Controlled human exposure studies of 2 to 5 hours conducted at ozone concentrations above 75 ppb reported small elevations in biomarkers for inflammation and oxidative stress that were of uncertain clinical relevance. Experimental animal studies reported more consistent results among certain biomarkers, although these were also conducted at ozone exposures well above 75 ppb and provided limited information on ozone exposure-response relationships. Overall, the current WoE does not provide a convincing case for a causal relationship between short-term ozone exposure below the NAAQS and adverse changes in levels of biomarkers within and across categories, but, because of study limitations, they cannot not provide definitive evidence of a lack of causation.
WANG, SHUAI; WANG, ZHOU; YANG, YU; SHI, MO; SUN, ZHENGUO
Ku80, a subunit of the heterodymeric Ku protein, is clearly implicated in nonhomologous end joining DNA repair, chemoresistance and radioresistance in malignant tumors. In the present study, the clinicopathological significance of Ku80 in esophageal squamous cell carcinoma (ESCC) was investigated. The expression levels of Ku80 were determined by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry in ESCC specimens and normal esophageal mucosa. The mRNA and protein levels of Ku80 were significantly higher in ESCC tissues than in normal esophageal mucosa, and were significantly associated with tumor differentiation, local invasion, lymph node metastasis and tumor-node-metastasis (TNM) stage. However, overexpression of Ku80 mRNA and protein levels were not significantly correlated with age, gender, tumor site or tumor size. Cox proportional hazards regression model demonstrated that tumor local invasion, lymph node metastasis, TNM stage and Ku80 mRNA and protein levels were independent risk factors indicating the overall survival of patients with ESCC. The present study demonstrated that aberrant Ku80 overexpression is observed in ESCC. In addition, high expression levels of Ku80 are associated with adverse clinicopathological features and unfavorable prognosis in ESCC patients. PMID:26722230
Lari, Sara A.; Arun, Banu K.; Hu, Chung-Yuan; Brewster, Abenaa; Mittendorf, Elizabeth A.; Albarracin, Constance T.; Babiera, Gildy V.; Caudle, Abigail S.; Wagner, Jamie L.; Litton, Jennifer K.; Bedrosian, Isabelle; Meric-Bernstam, Funda; Lucci, Anthony; Hunt, Kelly K.
Obesity is associated with adverse biologic features and poor outcome in patients with invasive breast cancer, yet this relationship has not been evaluated in patients with ductal carcinoma in situ (DCIS). From 1996 to 2009, body mass index (BMI) was recorded at initial diagnosis for 1,885 patients with DCIS treated at our institution. Patients were categorized as obese (BMI ≥ 30 kg/m2), overweight (BMI 25 to<30 kg/m2), or of normal weight or underweight (BMI <25 kg/m2). Logistic regression was used to examine associations between BMI and patient, clinical, and pathologic features and treatment. Local–regional recurrence was calculated using the Kaplan–Meier method. All statistical tests were two-sided. Of the 1,885 patients, 514 (27.7%) were obese, 510 (27.5%) were overweight, and 831 (44.8%) were normal/underweight. In multivariate analysis, overweight and obese patients were significantly more likely to be African American (odds ratio [OR], 3.93; 95% confidence interval [CI], 2.66–5.80) or Hispanic (OR, 1.44; CI, 1.02–2.04), be postmenopausal (OR, 1.63; CI, 1.28–2.07), have diabetes (OR, 4.60; CI, 2.60–8.12), have estrogen-receptor-positive DCIS (OR, 1.39; CI, 1.00–192), and present with a radiologic abnormality rather than clinical symptoms (OR, 1.35; CI, 1.01–1.80). At a median follow-up time of 4.96 years (range, 1.0–14.34 years), no significant differences in local recurrence rates were detected based on patients’ initial BMI category. Furthermore, there was no significant difference in risk of recurrence between diabetic patients receiving metformin or not. In conclusion, higher BMI is not associated with adverse biologic features or prognosis in patients with DCIS. PMID:22392043
Manini, Alex F.; Hoffman, Robert S.; Stimmel, Barry; Vlahov, David
Objectives It was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses. Methods This prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In-hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest. Results There were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] 27.6), bicarbonate < 20 mEql/L (5.4% prevalence, OR 4.4), and prior cardiac disease (7.1% prevalence, OR 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value; while presence of two or more risk factors had 90.9% positive predictive value. Conclusions The authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings. PMID:25903997
Arnab, Banerjee; Biswadip, Ghosh; Arindam, Pande; Shyamash, Mandal; Anirban, Ghosh; Rajan, Palui
Background Rheumatoid arthritis (RA) is an independent risk factor for adverse cardiovascular (CV) events that accounts for a significant proportion of mortality among these patients. Anti-CCP antibodies are associated with higher frequency of extra-articular manifestations and poorer outcomes in RA. Aims To determine the role of anti-cyclic citrullinated peptide (CCP) antibody as an independent risk factor for developing CV complications as documented by carotid intima medial thickness and abnormal echocardiography in established RA patients. Materials and methods Eighty patients of RA having disease duration of at least 3 years participated in this hospital-based, cross-sectional, and observational study. Forty patients were anti-CCP antibody positive. Patients of established RA having known CV risk factors, known heart disease, or family history of premature ischemic heart disease were excluded. Results Anti-CCP positive group had early morning stiffness, tender and swollen joint count, and c-reactive protein (CRP) level significantly higher than those in anti-CCP negative group. Average intima-medial thicknesses of common carotid arteries were also significantly higher among anti-CCP positive group (P = 0.029) and were positively correlated with patients' age and disease duration. Lower left ventricular ejection fraction and left ventricular diastolic dysfunction were more commonly dispersed among the anti-CCP positive patients with P values of 0.01 and 0.034, respectively. Mild pericardial thickening was documented among 12.5% patients of anti-CCP positive group, while none of the anti-CCP negative patients had similar findings in echocardiography. Conclusion This study stressed on the important role of anti-CCP antibody in myocardial dysfunction due to inflammation in RA patients. Both atherosclerotic vascular involvement and cardiac abnormalities including pericardial, myocardial, and endocardial involvements were higher among anti-CCP positive RA patients
Golyadkina, Anastasiya A.; Kalinin, Aleksey A.; Kirillova, Irina V.; Kossovich, Elena L.; Kossovich, Leonid Y.; Menishova, Liyana R.; Polienko, Asel V.
Object of study: Improvement of life quality of patients with high stroke risk ia the main goal for development of system for patient-specific modeling of cardiovascular system. This work is dedicated at increase of safety outcomes for surgical treatment of brain blood supply alterations. The objects of study are common carotid artery, internal and external carotid arteries and bulb. Methods: We estimated mechanical properties of carotid arteries tissues and patching materials utilized at angioplasty. We studied angioarchitecture features of arteries. We developed and clinically adapted computer biomechanical models, which are characterized by geometrical, physical and mechanical similarity with carotid artery in norm and with pathology (atherosclerosis, pathological tortuosity, and their combination). Results: Collaboration of practicing cardiovascular surgeons and specialists in the area of Mathematics and Mechanics allowed to successfully conduct finite-element modeling of surgical treatment taking into account various features of operation techniques and patching materials for a specific patient. Numerical experiment allowed to reveal factors leading to brain blood supply decrease and atherosclerosis development. Modeling of carotid artery reconstruction surgery for a specific patient on the basis of the constructed biomechanical model demonstrated the possibility of its application in clinical practice at approximation of numerical experiment to the real conditions.
Yi, Tie-ci; Li, Jian-ping
Cardiovascular disease is one of the major threats to human. Air pollution, which , as it become a problem too serious to be ignored in China, is known to be an important risk factor for cardiovascular disease. Among all pollutants, ultrafine particles ( UFPs) , defined as particles with their diameter less than 0. 1 f.Lm, are a specific composition. They are very small in size, large in quantity and surface area, and most important, capable of passing through the air-blood barrier. These unique features of UFPs make them special in their impact on cardiovascular system. Nowadays, the influence of UFPs on the cardiovascular system has become a hot topic. On the one side, studies have shown that UFPs can cause inflammation and oxidative stress in the lung, and then induce systemic inflammation by releasing cytokine and reactive oxygen species into the circulation. On the other side, UFPs themselves can "spillout"into the circulation and interact with their targets. By this way, UFPs directly affect endothelial cells, myocardial cells and the autonomic nervous system, which ultimately result in increased cardiovascular events. We intend to make an overview about the recent progress about the influence of UFPs on human cardiovascular disease and the related mechanisms, and argue for more attention to this issue.
Eguaras, Sonia; Toledo, Estefanía; Hernández-Hernández, Aitor; Cervantes, Sebastián; Martínez-González, Miguel A.
Strong observational evidence supports the association between obesity and cardiovascular events. In elderly high-risk subjects, the Mediterranean diet (MedDiet) was reported to counteract the adverse cardiovascular effects of adiposity. Whether this same attenuation is also present in younger subjects is not known. We prospectively examined the association between obesity and cardiovascular clinical events (myocardial infarction, stroke or cardiovascular death) after 10.9 years follow-up in 19,065 middle-aged men and women (average age 38 year) according to their adherence to the MedDiet (<6 points or ≥6 points in the Trichopoulou’s Mediterranean Diet Score). We observed 152 incident cases of cardiovascular disease (CVD). An increased risk of CVD across categories of body mass index (BMI) was apparent if adherence to the MedDiet was low, with multivariable-adjusted hazard ratios (HRs): 1.44 (95% confidence interval: 0.93–2.25) for ≥25 – <30 kg/m2 of BMI and 2.00 (1.04–3.83) for ≥30 kg/m2 of BMI, compared to a BMI < 25 kg/m2. In contrast, these estimates were 0.77 (0.35–1.67) and 1.15 (0.39–3.43) with good adherence to MedDiet. Better adherence to the MedDiet was associated with reduced CVD events (p for trend = 0.029). Our results suggest that the MedDiet could mitigate the harmful cardiovascular effect of overweight/obesity. PMID:26556370
Su, Shaoyong; Jimenez, Marcia P.; Roberts, Cole T. F.; Loucks, Eric B.
Childhood adversity, characterized by abuse, neglect, and household dysfunction, is a problem that exerts a significant impact on individuals, families, and society. Growing evidence suggests that adverse childhood experiences (ACEs) are associated with health decline in adulthood, including cardiovascular disease (CVD). In the current review, we first provide an overview of the association between ACEs and CVD risk, with updates on the latest epidemiological evidence. Second, we briefly review plausible pathways by which ACEs could influence CVD risk, including traditional risk factors and novel mechanisms. Finally, we highlight the potential implications of ACEs in clinical and public health. Information gleaned from this review should help physicians and researchers in better understanding potential long-term consequences of ACEs and considering adapting current strategies in treatment or intervention for patients with ACEs. PMID:26289252
Cullinan, Mary P; Palmer, Janet E; Carle, Anne D; West, Malcolm J; Westerman, Bill; Seymour, Gregory J
Adverse effects of long-term usage of triclosan-containing toothpaste in humans are currently unknown. We assessed the effect of long-term use of 0.3% triclosan-toothpaste on serious adverse events (SAEs) in patients with cardiovascular disease (CVD). 438 patients with a history of stable CVD were entered into the 5-year longitudinal Cardiovascular and Periodontal Study at Prince Charles Hospital, Brisbane, Australia and randomised into test (triclosan) or placebo groups. There were no significant differences in demographics or clinical features between the groups. Patients were examined at baseline, and annually for 5-years. SAEs were classified according to the System Organ Classes defined by MedDRA (Medical Dictionary for Regulatory Activities). Results were analysed using chi square and Kaplan Meier analysis. Overall, 232 patients (123 in the triclosan group; 109 in the placebo group) experienced 569 SAEs (288 in the triclosan group and 281 in the placebo group). There was no significant difference between the groups in numbers of patients experiencing SAEs (p=0.35) or specific cardiovascular SAEs (p=0.82), nor in time to the first SAE or first cardiovascular SAE, irrespective of gender, age or BMI after adjusting for multiple comparisons (p>0.05). The adjusted odds of experiencing an SAE were estimated to increase by 2.7% for each year of age (p=0.02) and the adjusted odds of experiencing a cardiovascular SAE were estimated to increase by 5.1% for each unit increase in BMI (p=0.02). Most cardiovascular events were related to unstable angina or myocardial infarcts, 21 were associated with arrhythmia and 41 were vascular events such as aortic aneurysm and cerebrovascular accident. Within the limitations of the present study the data suggest that the use of triclosan-toothpaste may not be associated with any increase in SAEs in this CVD population. The long-term impact of triclosan on hormone-related disease, such as cancer, in humans remains to be determined.
Heidecker, Bettina; Hare, Joshua M
In the last half century, epidemiologic studies and basic science investigations revealed that hypertension (Kannel et al., Ann Intern Med 55:33-50, 1961), hyperlipidemia (Dawber et al., Am J Public Health Nations Health 49:1349-1356, 1959), diabetes (Kannel et al., Am J Cardiol 34(1):29-34, 1974), smoking (Dawber et al., Am J Public Health Nations Health 49:1349-1356, 1959), and inflammation (Rossmann et al., Exp Gerontol 43(3):229-237, 2008) posed increased risk for cardiovascular disease. These associations served both as risk factors and offered insight into disease pathophysiology. Currently, it is increasingly appreciated that polygenic factors may also play a role as etiologic or risk factors (Chakravarti and Little, Nature 421(6921):412-414, 2003; Dorn and Molkentin, Circulation 109(2):150-158, 2004). Recent technologic advances in genomic screening make the search for these factors possible, and robust technologies are now available for both entire genome screening for expression or single nucleotide polymorphisms. In this paper, we review the basic principles of gene expression and molecular signature analysis in the context of potential clinical applications of transcriptomics.
Fischer, Michael J; Kimmel, Paul L; Greene, Tom; Gassman, Jennifer J; Wang, Xuelei; Brooks, Deborah H; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A; Bruce, Marino A; Kusek, John W; Norris, Keith C; Lash, James P
This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease.
Fernández-Laso, Valvanera; Sastre, Cristina; Valdivielso, Jose M.; Betriu, Angels; Fernández, Elvira; Egido, Jesús; Martín-Ventura, Jose L.
Background and objectives Soluble TNF–like weak inducer of apoptosis (sTWEAK) is a proinflammatory cytokine belonging to the TNF superfamily. sTWEAK concentrations have been associated with the presence of CKD and cardiovascular disease (CVD). We hypothesized that sTWEAK levels may relate to a higher prevalence of atherosclerotic plaques, vascular calcification, and cardiovascular outcomes observed in patients with CKD. Design, setting, participants, & measurements A 4-year prospective, multicenter, longitudinal study was conducted in 1058 patients with CKD stages 3–5D (mean age =58±13 years old; 665 men) but without any history of CVD from the NEFRONA Study (a study design on the prevalence of surrogate markers of CVD). Ankle-brachial index and B-mode ultrasound were performed to detect the presence of carotid and/or femoral atherosclerotic plaques together with biochemical measurements and sTWEAK assessment. Patients were followed for cardiovascular outcomes (follow-up of 3.13±1.15 years). Results Patients with more advanced CKD had lower sTWEAK levels. sTWEAK concentrations were independently and negatively associated with carotid intima-media thickness. sTWEAK levels were lower in patients with carotid atherosclerotic plaques but not in those with femoral plaques. After adjustment by confounders, the odds ratio (OR) for presenting carotid atherosclerotic plaques in patients in the lowest versus highest tertile of sTWEAK was 4.18 (95% confidence interval [95% CI], 2.89 to 6.08; P<0.001). Furthermore, sTWEAK levels were lower in patients with calcified carotid atherosclerotic plaques. The OR for presenting calcified carotid plaques was 1.77 (95% CI, 1.06 to 2.93; P=0.02) after multivariable adjustment. After the follow-up, 41 fatal and 68 nonfatal cardiovascular events occurred. In a Cox model, after controlling for potential confounding factors, patients in the lowest tertile of sTWEAK concentrations had a higher risk of fatal and nonfatal cardiovascular
Warms, Catherine A.; Backus, Deborah; Rajan, Suparna; Bombardier, Charles H.; Schomer, Katherine G.; Burns, Stephen P.
Context There are anecdotal reports of adverse events (AEs) associated with exercise in people with spinal cord injury (SCI) and consequent concern by people with SCI and their providers about potential risks of exercise. Enumeration of specific events has never been performed and the extent of risk of exercise to people with SCI is not understood. Objective To systematically review published evidence to identify and enumerate reports of adverse events or AEs associated with training in persons with SCI. Methods Review was limited to peer-reviewed studies published in English from 1970 to 2011: (1) in adults with SCI, (2) evaluating training protocols consisting of repeated sessions over at least 4 weeks to maintain or improve cardiovascular health, (3) including volitional exercise modalities and functional electrical stimulation (FES)-enhanced exercise modalities, and (4) including a specific statement about AEs. Trained reviewers initially identified a total of 145 studies. After further screening, 38 studies were included in the review. Quality of evidence was evaluated using established procedures. Results There were no serious AEs reported. There were no common AEs reported across most types of interventions, except for musculoskeletal AEs related to FES walking. There were few AEs in volitional exercise studies. Conclusion There is no evidence to suggest that cardiovascular exercise done according to guidelines and established safety precautions is harmful. To improve the strength of these conclusions, future publications should include definition of AEs, information about pre-intervention screening, and statements of the nature and extent of AEs. PMID:24090603
Han, Jie; Wang, Xiaona; Ye, Ping; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei
Objectives Despite growing evidence that arterial stiffness has important predictive value for cardiovascular disease in patients with advanced stages of chronic kidney disease, the predictive significance of arterial stiffness in individuals with mildly impaired renal function has not been established. The aim of this study was to evaluate the predictive value of arterial stiffness on cardiovascular disease in this specific population. Materials and methods We analyzed measurements of arterial stiffness (carotid–femoral pulse-wave velocity [cf-PWV]) and the incidence of major adverse cardiovascular events (MACEs) in 1,499 subjects from a 4.8-year longitudinal study. Results A multivariate Cox proportional-hazard regression analysis showed that in individuals with normal renal function (estimated glomerular filtration rate [eGFR] ≥90 mL/min/1.73 m2), the baseline cf-PWV was not associated with occurrence of MACEs (hazard ratio 1.398, 95% confidence interval 0.748–2.613; P=0.293). In individuals with mildly impaired renal function (eGFR <90 mL/min/1.73 m2), a higher baseline cf-PWV level was associated with a higher risk of MACEs (hazard ratio 2.334, 95% confidence interval 1.082–5.036; P=0.031). Conclusion Arterial stiffness is a moderate and independent predictive factor for MACEs in individuals with mildly impaired renal function (eGFR <90 mL/min/1.73 m2). PMID:27621605
Khasawneh, Fadi T.; Shankar, Gollapudi S.
The use of atypical antipsychotic agents has rapidly increased in the United States and worldwide in the last decade. Nonetheless, many health care practitioners do not appreciate the significance of the cardiovascular side effects that may be associated with their use and the means to minimize them. Thus, atypical antipsychotic medications can cause cardiovascular side effects such as arrhythmias and deviations in blood pressure. In rare cases, they may also cause congestive heart failure, myocarditis, and sudden death. Patients with schizophrenia have a higher risk of cardiovascular mortality than healthy individuals, possibly because of excessive smoking, the underlying disorder itself, or a combination of both factors. Increased awareness of these potential complications can allow pharmacists and physicians to better manage and monitor high risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. Additionally, monitoring patients regularly via blood draws and checking blood pressure, heart rate, and electrocardiogram can help catch any clinical problems and prevent further complications. Finally, patient and family-member education, which pharmacists in particular can play key roles in, is central for the management and prevention of side effects, which is known to reflect positively on morbidity and mortality in these patients. PMID:24649390
Petersen, John W; Douglas, J Yellowlees
Long thought to be two separate syndromes, Ehlers-Danlos syndrome hypermobility type (EDS-HT) and benign joint hypermobility syndrome (BJHS) appear on close examination to represent the same syndrome, with virtually identical clinical manifestations. While both EDS-HT and BJHS were long thought to lack the genetic loci of other connective tissue disorders, including all other types of EDS, researchers have discovered a genetic locus that accounts for manifestations of both EDS-HT and BJHS in a small population of patients. However, given the modest sample size of these studies and the strong correlation between serum levels of tenascin-X with clinical symptoms of both EDS-HT and BJHS, strong evidence exists for the origins of both types of hypermobility originating in haploinsufficiency or deficiency of the gene TNXB, responsible for tenascin-X. Tenascin-X regulates both the structure and stability of elastic fibers and organizes collagen fibrils in the extra-cellular matrix (ECM), impacting the rigidity or elasticity of virtually every cell in the body. While the impacts of tenascin-X insufficiency or deficiency on the skin and joints have received some attention, its potential cardiovascular impacts remain relatively unexplored. Here we set forth two novel hypotheses. First, TNXB haploinsufficiency or deficiency causes the range of clinical manifestations long identified with both EDS-HT and BJHS. And, second, that haploinsufficiency or deficiency of TNXB may provide some benefits against adverse cardiovascular events, including heart attack and stroke, by lowering levels of arterial stiffness associated with aging, as well as by enhancing accommodation of accrued atherosclerotic plaques. This two-fold hypothesis provides insights into the mechanisms underlying the syndromes previous identified with joint hypermobility, at the same time the hypothesis also sheds light on the role of the composition of the extracellular matrix and its impacts on endothelial sheer
Chida, Yoichi; Vedhara, Kavita
There is a growing epidemiological literature focusing on the association between psychosocial stress and human immunodeficiency virus (HIV) disease progression or acquired immunodeficiency syndrome (AIDS), but inconsistent findings have been published. We aimed to quantify the association between adverse psychosocial factors and HIV disease progression. We searched Medline; PsycINFO; Web of Science; PubMed up to 19 January 2009, and included population studies with a prospective design that investigated associations between adverse psychosocial factors and HIV disease progression or AIDS. Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. The overall meta-analysis examined 36 articles including 100 psychosocial and disease related relationships. It exhibited a small, but robust positive association between adverse psychosocial factors and HIV progression (correlation coefficient as combined size effect 0.059, 95% confidence interval 0.043-0.074, p<0.001). Notably, sensitivity analyses showed that personality types or coping styles and psychological distress were more strongly associated with greater HIV disease progression than stress stimuli per se, and that all of the immunological and clinical outcome indicators (acquired immunodeficiency syndrome stage, CD4+ T-cell decline, acquired immunodeficiency syndrome diagnosis, acquired immunodeficiency syndrome mortality, and human immunodeficiency virus disease or acquired immunodeficiency syndrome symptoms) except for viral load exhibited detrimental effects by adverse psychosocial factors. In conclusion, the current review reveals a robust relationship between adverse psychosocial factors and HIV disease progression. Furthermore, there would appear to be some evidence for particular psychosocial factors to be most strongly associated with HIV disease progression.
Xiao, Xiang-sheng; Cai, Mu-yan; Chen, Jie-wei; Guan, Xin-yuan; Kung, Hsiang-fu; Zeng, Yi-xin; Xie, Dan
Objective Transcriptional coactivator p300 has been shown to play a variety of roles in the transcription process and mutation of p300 has been found in certain types of human cancers. However, the expression dynamics of p300 in breast cancer (BC) and its effect on BC patients’ prognosis are poorly understood. Methods In the present study, the methods of tissue microarray and immunohistochemistry (IHC) were used to investigate the protein expression of p300 in BCs. Receiver operating characteristic (ROC) curve analysis, Spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were utilized to analyze the data. Results Based on the ROC curve analysis, the cutoff value for p300 high expression was defined when the H score for p300 was more than 105. High expression of p300 could be observed in 105/193 (54.4%) of BCs, in 6/25 (24.0%) of non-malignant breast tissues, respectively (P=0.004). Further correlation analysis showed that high expression of p300 was positively correlated with higher histological grade, advanced clinical stage and tumor recurrence (P<0.05). In univariate survival analysis, a significant association between high expression of p300 and shortened patients’ survival and poor progression-free survival was found (P<0.05). Importantly, p300 expression was evaluated as an independent prognostic factor in multivariate analysis (P<0.05). Conclusion Our findings provide a basis for the concept that high expression of p300 in BC may be important in the acquisition of a recurrence phenotype, suggesting that p300 high expression, as examined by IHC, is an independent biomarker for poor prognosis of patients with BC. PMID:23467396
Triant, V A; Josephson, F; Rochester, C G; Althoff, K N; Marcus, K; Munk, R; Cooper, C; D'Agostino, R B; Costagliola, D; Sabin, C A; Williams, P L; Hughes, S; Post, W S; Chandra-Strobos, N; Guaraldi, G; Young, S S; Obenchain, R; Bedimo, R; Miller, V; Strobos, J
Clinical decisions are ideally based on randomized trials but must often rely on observational data analyses, which are less straightforward and more influenced by methodology. The authors, from a series of expert roundtables convened by the Forum for Collaborative HIV Research on the use of observational studies to assess cardiovascular disease risk in human immunodeficiency virus infection, recommend that clinicians who review or interpret epidemiological publications consider 7 key statistical issues: (1) clear explanation of confounding and adjustment; (2) handling and impact of missing data; (3) consistency and clinical relevance of outcome measurements and covariate risk factors; (4) multivariate modeling techniques including time-dependent variables; (5) how multiple testing is addressed; (6) distinction between statistical and clinical significance; and (7) need for confirmation from independent databases. Recommendations to permit better understanding of potential methodological limitations include both responsible public access to de-identified source data, where permitted, and exploration of novel statistical methods.
Suneja, Manish; Murry, Daryl J; Stokes, John B; Lim, Victoria S
To assess whether endocrine dysfunction may cause derangement in energy homeostasis in patients undergoing hemodialysis (HD), we profiled hormones, during a 3-day period, from the adipose tissue and the gut and the nervous system around the circadian clock in 10 otherwise healthy HD patients and 8 normal controls. The protocol included a 40-h fast. We also measured energy-protein intake and output and assessed appetite and body composition. We found many hormonal abnormalities in HD patients: 1) leptin levels were elevated, due, in part, to increased production, and nocturnal surge in response to daytime feeding, exaggerated. 2) Peptide YY (PYY), an anorexigenic gut hormone, was markedly elevated and displayed an augmented response to feeding. 3) Acylated ghrelin, an orexigenic gut hormone, was lower and did not exhibit the premeal spike as observed in the controls. 4) neuropeptide Y (NPY), a potent orexigenic peptide, was markedly elevated and did not display any circadian variation. 5) Norepinephrine, marginally elevated, did not exhibit the normal nocturnal dip. By contrast, α-melanocyte-stimulating hormone and glucagon-like peptide-1 were not different between the two groups. Despite these hormonal abnormalities, HD patients maintained a good appetite and had normal body lean and fat mass, and there was no evidence of increased energy expenditure or protein catabolism. We explain the hormonal abnormalities as well as the absence of anorexia on suppression of parasympathetic activity (vagus nerve dysfunction), a phenomenon well documented in dialysis patients. Unexpectedly, we noted that the combination of high leptin, PYY, and NPY with suppressed ghrelin may increase arterial blood pressure, impair vasodilatation, and induce cardiac hypertrophy, and thus could predispose to adverse cardiovascular events that are the major causes of morbidity and mortality in the HD population. This is the first report attempting to link hormonal abnormalities associated with
Quddus, M Ruhul; Sung, C James; Zhang, Cunxian; Lawrence, W Dwayne
Most endometrial carcinomas contain only 1 Müllerian cell type although the presence of 2 or more cell types within 1 tumor, for example a predominantly low-grade endometrioid carcinoma with a minor component (arbitrarily defined as 30% or less) of high-grade serous and/or clear cell carcinoma, is not uncommon. The current study attempts to evaluate whether the presence of minor serous or clear cell components exerts an adverse effect on the prognosis in stage-I endometrial carcinomas of ''mixed-type.'' The study cases include 22 cases of stage-I endometrioid carcinoma with a minor component of serous carcinoma and 14 cases of endometrioid carcinoma with a minor component of clear cell carcinoma. Minor components were arbitrarily defined as representing anywhere between 5% and 30% of the total tumor. The study cases were compared with 56 cases of histologically pure age-matched and stage-matched endometrioid carcinomas, 6 pure serous carcinomas, and 13 pure clear cell carcinomas. All study and control cases were fully staged. Treatment history and outcome status were obtained and follow-up ranged from 56 to 140 months. Our study suggests that the presence of minor components of serous and clear cell carcinoma, defined as between 5% and 30%, within a mixed-type endometrial carcinoma appears to adversely influence the long-term survival of stage-I tumors, although a larger study is needed to corroborate our findings.
Garg, Sonia; de Lemos, James A.; Ayers, Colby; Khouri, Michel G.; Pandey, Ambarish; Berry, Jarett D.; Peshock, Ronald M.; Drazner, Mark H.
Objectives This study was performed to determine whether a 4-tiered classification of left ventricular hypertrophy (LVH) defines subgroups in the general population which are at variable risk of adverse cardiovascular outcomes. Background We recently proposed a 4-tiered classification of LVH where eccentric LVH is subdivided into “indeterminate hypertrophy” and “dilated hypertrophy” and concentric LVH into “thick hypertrophy” and “both thick and dilated hypertrophy,” based on the presence of increased left ventricular end-diastolic volume. Methods Participants from the Dallas Heart study who underwent cardiac magnetic resonance imaging and did not have LV dysfunction or history of heart failure (HF) (n = 2,458) were followed for a median of 9 years for the primary outcome of HF or cardiovascular (CV) death. Multivariable Cox proportional hazard models were used to adjust for age, sex, African-American race, hypertension, diabetes, and history of cardiovascular disease (CVD). Results In the cohort, 70% had no LVH, 404 (16%) had indeterminate hypertrophy, 30 (1%) had dilated hypertrophy, 289 (12%) had thick hypertrophy, and 7 (0.2%) had both thick and dilated hypertrophy. The cumulative incidence of HF or CV death was 2% with no LVH, 1.7% with indeterminate, 16.7% with dilated, 11.1% with thick, and 42.9% with both thick and dilated hypertrophy (log rank p< 0.0001). Compared with participants without LVH, those with dilated (HR 7.3, 95% CI 2.8–18.8), thick (HR 2.4, 95% CI 1.4–4.0), and both thick and dilated (HR 5.8, 95% CI 1.7–19.5) hypertrophy remained at increased risk for HF or CV death after multivariable adjustment, whereas the group with indeterminate hypertrophy was not (HR 0.9, 95% CI 0.4–2.2). Conclusion In the general population, the 4-tiered classification system for LVH stratified LVH into subgroups with differential risk of adverse CV outcomes. Unstructured Abstract: Participants from the Dallas Heart Study were stratified using
Chai, Chi-Yung; Zhang, Yimin; Song, Junlong; Lin, Shih-Chun; Sun, Shengrong; Chang, I-Wei
Background: Colorectal cancer is prevalent worldwide and it is also the fourth most common cause of cancer mortality. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a public dataset of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that VNN1 was the most significantly upregulated gene among those related to nitrogen compound metabolic process (GO:0006807). Therefore, we analyzed the clinicopathological correlation and prognostic impact of VNN1 protein (pantetheinase), which encoded by VNN1 gene. Methods: VNN1 immunostaining was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by surgery, which were bisected into high- and low-expression subgroups. Furthermore, statistical analyses were performed to correlate the relationship between VNN1 immunoreactivity and clinicopathological features, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: High VNN1 immunoexpression was significantly associated with advanced pre-treatment and post-treatment disease and poor response to CCRT (all P ≤ .026). In addition, VNN1 overexpression was linked to adverse DSS, LRFS and MeFS in univariate analysis and served as an independent prognosticator indicating worse DSS and LRFS in multivariate analysis (all P ≤ .019). Conclusion: VNN1 may play a crucial role in rectal cancer progression and responsiveness to CCRT, and serve as a novel prognostic biomarker. Additional studies to clarify the molecular pathway are essential for developing potential VNN1-targeted therapies for rectal cancer. PMID:27830030
Carpéné, Christian; Schaak, Stéphane; Guilbeau-Frugier, Céline; Mercader, Josep; Mialet-Perez, Jeanne
Tyramine is naturally occurring in food and induces pressor responses. Low-tyramine diets are recommended for patients treated with MAO inhibitors to avoid the fatal hypertensive crisis sadly known as "cheese effect". Hence, tyramine intake is suspected to have toxicological consequences in humans, while its administration to type 1 diabetic rodents has been reported to improve glucose tolerance. We investigated in mice whether prolonged tyramine ingestion could alter glucose homeostasis, insulin sensitivity, adipose tissue physiology or cardiovascular functions. Tyramine was added at 0.04 or 0.14 % in the drinking water since this was estimated to increase by 10- to 40-fold the spontaneous tyramine intake of control mice fed a standard diet. Ten to 12 weeks of such tyramine supplementation did not influence body weight gain, adiposity or food consumption. Both doses (reaching approx. 300 and 1100 μmol tyramine/kg bw/day) decreased nonfasting blood glucose but did not modify glucose tolerance or fasting levels of glucose, insulin or circulating lipids. Blood pressure was not increased in tyramine-drinking mice, while only the higher tested dose moderately increased heart rate without change in its variability. Markers of cardiac tissue injury or oxidative stress remained unaltered, except an increased hydrogen peroxide production in heart preparations. In isolated adipocytes, tyramine inhibited lipolysis similarly in treated and control groups, as did insulin. The lack of serious adverse cardiovascular effects of prolonged tyramine supplementation in normoglycemic mice together with the somewhat insulin-like effects found on adipose cells should lead to reconsider favourably the risk/benefit ratio of the intake of this dietary amine.
Overview of Cardiovascular research which addresses risks of space flight, including adaptive changes to the cephalad fluid shift (such as reduced circulating blood volume), potential for heart rhy...
Rajagopalan, Viswanathan; Zhang, Youhua; Ojamaa, Kaie; Chen, Yue-feng; Pingitore, Alessandro; Pol, Christine J.; Saunders, Debra; Balasubramanian, Krithika; Towner, Rheal A.; Gerdes, A. Martin
Background A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI. Methods and Results Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy. Conclusions Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans. PMID:26981865
Mitchell, Patricia L; Karakach, Tobias K; Currie, Deborah L; McLeod, Roger S
Animal and human studies have indicated that fatty acids such as the conjugated linoleic acids (CLA) found in milk could potentially alter the risk of developing metabolic disorders including diabetes and cardiovascular disease (CVD). Using susceptible rodent models (apoE(-/-) and LDLr(-/-) mice) we investigated the interrelationship between mouse strain, dietary conjugated linoleic acids and metabolic markers of CVD. Despite an adverse metabolic risk profile, atherosclerosis (measured directly by lesion area), was significantly reduced with t-10, c-12 CLA and mixed isomer CLA (Mix) supplementation in both apoE(-/-) (p<0.05, n = 11) and LDLr(-/-) mice (p<0.01, n = 10). Principal component analysis was utilized to delineate the influence of multiple plasma and tissue metabolites on the development of atherosclerosis. Group clustering by dietary supplementation was evident, with the t-10, c-12 CLA supplemented animals having distinct patterns, suggestive of hepatic insulin resistance, regardless of mouse strain. The effect of CLA supplementation on hepatic lipid and fatty acid composition was explored in the LDLr(-/-) strain. Dietary supplementation with t-10, c-12 CLA significantly increased liver weight (p<0.05, n = 10), triglyceride (p<0.01, n = 10) and cholesterol ester content (p<0.01, n = 10). Furthermore, t-10, c-12 CLA also increased the ratio of 18∶1 to 18∶0 fatty acid in the liver suggesting an increase in the activity of stearoyl-CoA desaturase. Changes in plasma adiponectin and liver weight with t-10, c-12 CLA supplementation were evident within 3 weeks of initiation of the diet. These observations provide evidence that the individual CLA isomers have divergent mechanisms of action and that t-10, c-12 CLA rapidly changes plasma and liver markers of metabolic syndrome, despite evidence of reduction in atherosclerosis.
Stergiou, George S; Asayama, Kei; Thijs, Lutgarde; Kollias, Anastasios; Niiranen, Teemu J; Hozawa, Atsushi; Boggia, José; Johansson, Jouni K; Ohkubo, Takayoshi; Tsuji, Ichiro; Jula, Antti M; Imai, Yutaka; Staessen, Jan A
Home blood pressure monitoring is useful in detecting white-coat and masked hypertension and is recommended for patients with suspected or treated hypertension. The prognostic significance of white-coat and masked hypertension detected by home measurement was investigated in 6458 participants from 5 populations enrolled in the International Database of HOme blood pressure in relation to Cardiovascular Outcomes. During a median follow-up of 8.3 years, 714 fatal plus nonfatal cardiovascular events occurred. Among untreated subjects (n=5007), cardiovascular risk was higher in those with white-coat hypertension (adjusted hazard ratio 1.42; 95% CI [1.06-1.91]; P=0.02), masked hypertension (1.55; 95% CI [1.12-2.14]; P<0.01) and sustained hypertension (2.13; 95% CI [1.66-2.73]; P<0.0001) compared with normotensive subjects. Among treated patients (n=1451), the cardiovascular risk did not differ between those with high office and low home blood pressure (white-coat) and treated controlled subjects (low office and home blood pressure; 1.16; 95% CI [0.79-1.72]; P=0.45). However, treated subjects with masked hypertension (low office and high home blood pressure; 1.76; 95% CI [1.23-2.53]; P=0.002) and uncontrolled hypertension (high office and home blood pressure; 1.40; 95% CI [1.02-1.94]; P=0.04) had higher cardiovascular risk than treated controlled patients. In conclusion, white-coat hypertension assessed by home measurements is a cardiovascular risk factor in untreated but not in treated subjects probably because the latter receive effective treatment on the basis of their elevated office blood pressure. In contrast, masked uncontrolled hypertension is associated with increased cardiovascular risk in both untreated and treated patients, who are probably undertreated because of their low office blood pressure.
Tzeng, Sheng-Tai; Tsai, Ming-Hong; Chen, Chi-Long; Lee, Jing-Xing; Jao, Tzu-Ming; Yu, Sung-Liang; Yen, Sou-Jhy; Yang, Ya-Chien
Background Genomic deletion at tumor suppressor loci is a common genetic aberration in human cancers. The study aimed to explore candidate tumor suppressor genes at chromosome 4q25-q28.2 and to delineate novel prognostic biomarkers associated with colorectal cancer (CRC). Methods Deletion mapping of chromosome 4q25-q28.2 was conducted in 114 sporadic CRC by loss of heterozygosity study with 11 microsatellite markers. A novel candidate tumor suppressor gene, namely NDST4, was identified at 4q26. Gene expression of NDST4 was investigated in 52 pairs of primary CRC tissues by quantitative reverse transcription-polymerase chain reaction. Allelic loss of NDST4 gene was further determined in 174 colorectal carcinomas by loss of heterozygosity analysis, and then was assessed for clinical relevance. Results One minimal deletion region was delineated between D4S2297 and D4S2303 loci at 4q26, where NDST4 was the only gene that had markedly been downregulated in CRC tumors. By laser capture microdissection, NDST4 RNA expression was demonstrated in colonic epithelial cells, but was undetectable in tumor cells. In total, 30 (57.7%) of 52 colorectal carcinomas showed a dramatic reduction in NDST4 gene expression compared with matched normal mucosae. The genetic loss of NDST4 was significantly associated with advanced pathological stage (P = 0.039) and poorer overall survival of patients (P = 0.036). Conclusions NDST4 gene is a novel candidate tumor suppressor gene in human cancer, and the loss of its function might be involved in CRC progression. In addition, the loss of heterozygosity assay, which was established to determine the allelic loss of NDST4 gene, could be a cost-effective tool for providing a useful biomarker of adverse prognosis in CRC. PMID:23825612
[Clinical usefulness of ondansetron hydrochloride for nausea and vomiting during repeated courses of chemotherapy for malignant lymphoma--impact of prognosis announcement on anti-emetic effect and evaluation of patient perception of chemotherapy-associated adverse events].
Kodama, Fumio; Mohri, Hiroshi; Motomura, Shigeki; Fukawa, Hitoshi; Tanabe, Juichi; Koharasawa, Hideyuki; Kanamori, Heiwa; Hashimoto, Yoshimi; Harano, Hiroshi; Sakai, Rika; Tomita, Naoto; Fujimaki, Katsumichi; Takemura, Sachiya; Hattori, Michiko
We evaluated the efficacy and safety of ondansetron hydrochloride (OND) on nausea and vomiting during repeated courses of CHOP or ACOMP-B therapy in patients with malignant lymphoma. The impact of the prognosis announcement on the anti-emetic effect and chemotherapy-associated adverse events was also investigated. Forty-two subjects with malignant lymphoma who underwent CHOP or ACOMP-B therapy including cyclophosphamide 600 mg/m2 and adriamycin 40 mg/m2 were investigated for a maximum of 6 courses. For acute nausea and vomiting, ondansetron was injected intravenously before the start of chemotherapy on the first day of each course of chemotherapy. For delayed emesis, ondansetron was administered orally for 4 days from the following day. The efficacy on acute nausea and vomiting was found to be 95.0% (1st course), 95.0% (2nd course), 90.9% (3rd course), 88.2% (4th course), 92.3% (5th course) and 91.7% (6th course), respectively. A high efficacy of > or = 85% was also obtained for delayed nausea and vomiting on each day. Though the adverse event of elevated GPT value developed in one subject. It was mild and resolved. No difference in efficacy was seen with or without announcement of prognosis to patients. Following the investigation on antiemetic effect, patient perception of chemotherapy-induced adverse events was evaluated. The most common event was hair loss, followed by taste abnormality and numbness and hyposthesia of the tips of the fingers. The incidence of nausea and vomiting was the 4th and 5th most common, which are less frequent than in the report of Coates in 1983. In conclusion, ondansetron is considered clinically useful with stable anti-emetic effect on both acute and delayed nausea and vomiting over repeated courses of chemotherapy, without any significant safety problem.
Du, Jinling; Zhang, Danyang; Yin, Yue; Zhang, Xiaofei; Li, Jifu; Liu, Dexiang; Pan, Fang; Chen, Wenqiang
To investigate the effects of personality type and psychological stress on the occurrence of major adverse cardiovascular events (MACEs) at 5 years in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Two hundred twenty patients with stable angina (SA) or non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with PCI completed type A behavioral questionnaire, type D personality questionnaire, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Trait Coping Style Questionnaire (TCSQ), and Symptom Checklist 90 (SCL-90) at 3 days after PCI operation. Meanwhile, biomedical markers (cTnI, CK-MB, LDH, LDH1) were assayed. MACEs were monitored over a 5-year follow-up. NSTE-ACS group had higher ratio of type A behavior, type A/D behavior, and higher single factor scores of type A personality and type D personality than control group and SAP group. NSTE-ACS patients had more anxiety, depression, lower level of mental health (P < 0.05; P < 0.01), more negative coping styles and less positive coping styles. The plasma levels of biomedical predictors had positive relation with anxiety, depression, and lower level of mental health. Type D patients were at a cumulative increased risk of adverse outcome compared with non-type D patients (P < 0.05). Patients treated with PCI were more likely to have type A and type D personality and this tendency was associated with myocardial injury. They also had obvious anxiety, depression emotion, and lower level of mental health, which were related to personality and coping style. Type D personality was an independent predictor of adverse events.
Stewart, Ralph A. H.; Wallentin, Lars; Benatar, Jocelyne; Danchin, Nicolas; Hagström, Emil; Held, Claes; Husted, Steen; Lonn, Eva; Stebbins, Amanda; Chiswell, Karen; Vedin, Ola; Watson, David; White, Harvey D.
Objectives To determine whether dietary pattern assessed by a simple self-administered food frequency questionnaire is associated with major adverse cardiovascular events (MACE) in high-risk patients with stable coronary artery disease. Background A Mediterranean dietary pattern has been associated with lower cardiovascular (CV) mortality. It is less certain whether foods common in western diets are associated with CV risk. Methods At baseline, 15 482 (97.8%) patients (mean age 67 ± 9 years) with stable coronary heart disease from 39 countries who participated in the Stabilisation of atherosclerotic plaque by initiation of darapladib therapy (STABILITY) trial completed a life style questionnaire which included questions on common foods. A Mediterranean diet score (MDS) was calculated for increasing consumption of whole grains, fruits, vegetables, legumes, fish, and alcohol, and for less meat, and a ‘Western diet score’ (WDS) for increasing consumption of refined grains, sweets and deserts, sugared drinks, and deep fried foods. A multi-variable Cox proportional hazards models assessed associations between MDS or WDS and MACE, defined as CV death, non-fatal myocardial infarction, or non-fatal stroke. Results After a median follow-up of 3.7 years MACE occurred in 7.3% of 2885 subjects with an MDS ≥15, 10.5% of 4018 subjects with an MDS of 13–14, and 10.8% of 8579 subjects with an MDS ≤12. A one unit increase in MDS >12 was associated with lower MACE after adjusting for all covariates (+1 category HR 0.95, 95% CI 0.91, 0.98, P = 0.002). There was no association between WDS (adjusted model +1 category HR 0.99, 95% CI 0.97, 1.01) and MACE. Conclusion Greater consumption of healthy foods may be more important for secondary prevention of coronary artery disease than avoidance of less healthy foods typical of Western diets. PMID:27109584
Kuo, Te-Hui; Tseng, Chien-Tzu; Lin, Wei-Hung; Chao, Jo-Yen; Wang, Wei-Ming; Li, Chung-Yi; Wang, Ming-Cheng
The association between dialysis vascular access dysfunction and the risk of developing major adverse cardiovascular events (MACE) in hemodialysis patients is unclear and has not yet been investigated. We analyzed data from the National Health Insurance Research Database of Taiwan to quantify this association. Adopting a case-control design nested within a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9711 incident cases of MACE during the stage of stable maintenance dialysis and 19,422 randomly selected controls matched to cases on age, gender, and duration of dialysis. Events of vascular access dysfunction in the 6-month period before the date of MACE onset (ie, index date) for cases and before index dates for controls were evaluated retrospectively. The presence of vascular access dysfunction was associated with a 1.385-fold higher odds of developing MACE as estimated from the logistic regression analysis. This represents a significantly increased adjusted odds ratio (OR) at 1.268 (95% confidence interval [CI] = 1.186-1.355) after adjustment for comorbidities and calendar years of initiating dialysis. We also noted a significant exposure-response trend (P < 0.001) between the frequency of vascular access dysfunction and MACE, with the greatest risk (adjusted OR = 1.840, 95% CI = 1.549-2.186) noted in patients with ≥3 vascular access events. We concluded that dialysis vascular access dysfunction was significantly associated with an increased risk of MACE. Hence, vascular access failure can be an early sign for MACE in patients receiving maintenance hemodialysis. Active monitoring and treatment of cardiovascular risk factors and related diseases, not merely managing vascular access dysfunction, would be required to reduce the risk of MACE.
Shen, Zhi-Yong; Fang, Yuan; Zhen, Li; Zhu, Xian-Jun; Chen, Hao; Liu, Hao; Jiang, Bo; Li, Guo-Xin; Deng, Hai-Jun
Elevated expression of S100P has been detected in several tumor types. To analyze the potential use of S100P for the prediction of colorectal cancer (CRC) metastasis and prognosis, S100P expression was detected in 125 patients with colon adenocarcinoma by immunohistochemistry, followed by correlation and survival analysis. High S100P expression was correlated with metastasis, as demonstrated by clinically relevant data, and predicted poor survival more effectively than preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in colon adenocarcinoma. Stable S100P knockdown CRC cell lines were established to elucidate the relationship between S100P expression and tumor progression in vitro and in vivo. S100P knockdown resulted in reductions in the invasiveness and metastasis of CRC cells. Xenograft growth in nude mice also demonstrated that down-regulated S100P dramatically inhibited peritoneal metastasis of CRC cells. S100P promoted the invasion and metastasis of CRC by activating RAGE/ERK signaling and promoting the epithelial-mesenchymal transition (EMT). RAGE was found to be crucial for S100P-mediated EMT in colon cancer. Knockdown of RAGE in S100P-overexpressing colon cancer cells dramatically suppressed EMT process. Our results indicate that overexpression of S100P is related with an invasive and metastatic phenotype of CRC which is EMT-involved and RAGE dependent.
Burandt, Eike; Bari Noubar, Tanaz; Lebeau, Annette; Minner, Sarah; Burdelski, Christoph; Jänicke, Fritz; Müller, Vollkmar; Terracciano, Luigi; Simon, Ronald; Sauter, Guido; Wilczak, Waldemar; Lebok, Patrick
Activated leukocyte cell adhesion molecule (ALCAM) is a membranous cell adhesion protein that is often expressed in breast cancer. Data on the prognostic impact of ALCAM expression is highly controversial in this cancer. To evaluate the clinical impact of ALCAM expression in a sufficiently large patient cohort, we utilized a tissue microarray (TMA) containing more than 2,100 primary breast cancers with clinical follow-up data by immunohistochemistry. TMA spots containing normal breast epithelium showed moderate to strong membranous ALCAM staining. ALCAM staining was strong in 66.2%, moderate in 10.9%, weak in 11.1% and absent in 11.8% of 1,778 (80.9%) interpretable breast cancer tissue spots. Decreased ALCAM expression was significantly associated with advanced tumor size (p=0.0017), unfavorable tumor grade (p<0.0001), negative ER and PR status (p<0.0001 each) as well as high Ki67 labeling index (p<0.0001). Cancers with ACLAM expression loss had a significantly poorer overall (p<0.0001) and disease-specific survival (p=0.0088). This association also held true in the subset of nodal positive cancers (p<0.0001). In conclusion, these data demonstrate that ALCAM is generally expressed in normal and cancerous breast epithelium and that a marked reduction of ALCAM expression characterizes a subset of breast cancer patients with adverse tumor characteristics and unfavorable clinical outcome.
Wang, Shao-Li; Wang, Cheng-Long; Wang, Pei-Li; Xu, Hao; Du, Jian-Peng; Zhang, Da-Wu; Gao, Zhu-Ye; Zhang, Lei; Fu, Chang-Geng; Chen, Ke-Ji; Shi, Da-Zhuo
The study was to access the association between resting heart rate (RHR) and one-year risk of major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). Patients with ACS after PCI (n = 808) were prospectively followed-up for MACE. RHR was obtained from electrocardiogram. MACE was defined as a composite of cardiac death, nonfatal recurrent myocardial infarction, ischemic-driven revascularization, and ischemic stroke. The association between RHR and one-year risk of MACE was assessed using Cox proportional hazards regression model. Compared with patients with RHR >76 bpm, the adjusted hazard ratio (AHR) was 0.51 (95% confidence intervals [CI]: 0.23-1.14; P = 0.100) for patients with RHR < 61 bpm, and 0.44 (95%CI: 0.23-0.85; P = 0.014) for those with RHR 61-76 bpm. For patients with RHR ≥ 61 bpm, an increase of 10 bpm in RHR was associated with an increase by 38.0% in the risk of MACE (AHR: 1.38; 95% CI: 1.04-1.83; P = 0.026). ACS patients after PCI with RHR >76 bpm were at higher risk of MACE during one-year follow-up compared with patients with RHR 61-76 bpm. An elevated RHR ≥ 61 bpm was associated with increased risk of one-year MACE in ACS patients.
Zeus, Tobias; Ketterer, Ulrike; Leuf, Daniela; Dannenberg, Lisa; Wagstaff, Rabea; Bönner, Florian; Gliem, Michael; Jander, Sebastian; Kelm, Malte; Polzin, Amin
Troponin T (TnT) elevation above the 99th percentile upper reference limit (URL) is considered diagnostic of acute myocardial infarction (MI). Non-specific increases of TnT are frequent in acute stroke patients. However, in these patients, correct diagnosis of MI is crucial because the antithrombotic medications used to treat acute MI might be harmful and produce intracranial bleeding. In this study, we aimed to associate enhanced TnT levels defined by different cutoff values with occurrence of culprit lesion coronary artery disease (CAD) as well as 1-year major adverse cerebral and cardiovascular events (MACCEs). In this cohort study, we investigated 84 consecutive patients with acute ischemic stroke and concomitant MI. TnT levels were measured using a fourth-generation TnT assay. The incidence of culprit lesion CAD was determined by coronary angiography. MACCEs were recorded during 1-year follow-up. Culprit lesion CAD occurred in 55 % of patients, and 1-year MACCE in 37 %. TnT levels above the manufacturers' provided 99th URL (TnT > 0.01) were not associated with culprit lesion CAD (relative risk [RR], 1.3; 95 % confidence interval [CI] 0.96-1.8; P = 0.09). Slightly increased cutoff level (TnT > 0.03) increased specificity and was associated with culprit lesion CAD without decreasing sensitivity (RR, 1.5; 95 % CI 1.1-2.2; P = 0.021) and 1-year MACCE (RR, 1.7; 95 % CI 1.3-2.3; P < 0.001). Slightly increasement of the TnT cutoff level predicted MACCEs and is superior in prediction of culprit lesion CAD in stroke patients without being less sensitive. This finding has to be confirmed in large-scale clinical trials.
Medar, Shivanand; Hsu, Daphne T.; Ushay, H. Michael; Lamour, Jacqueline M.; Cohen, Hillel W; Killinger, James S.
Introduction In children, elevated amino terminal pro B-type naturetic peptide (NT-proBNP) levels are associated with impaired heart function. The predictive value of serial monitoring of NT-proBNP levels in acute decompensated heart failure (ADHF) is unclear. Methods This prospective observational study enrolled patients ≤ 21 years with primary myocardial dysfunction and ADHF. NT-proBNP levels were obtained on enrollment (D0), day 2 (D2) and day 7 (D7). Clinical, laboratory and imaging data were collected on enrollment. CV outcome was defined as Heart Transplant (HTx), Ventricular Assist Device (VAD) placement, Extracorporeal Membrane Oxygenation or death at 1 year after admission. NT-proBNP levels and the percent change from D0 to D2 and D0 to D7 were calculated and compared between those with and without adverse cardiovascular (ACV) outcome. Results Sixteen consecutive patients were enrolled. ACV outcome occurred in 6 (37.5%, 4 HTx and 2 VAD). In patients with an ACV outcome, median NT-ProBNP levels at D7 were significantly higher (7,365 Vs. 1,196 pg/ml; p= 0.02) and the percent decline in NT-proBNP was significantly smaller (28% vs. 73%, p=0.02) compared to those without an ACV outcome. ROC curve analysis revealed that a less than 55% decline in NT-proBNP levels at D7 had a sensitivity and specificity of 83% and 90% respectively in predicting an ACV [AUC 0.86, CI (0.68,1.0), p=0.02]. Conclusions In conclusion, children with primary myocardial dysfunction and ADHF, a persistently elevated NT-proBNP and/or a lesser degree of decline in NT-proBNP during the first week of presentation were strongly associated with ACV outcome. Serial NT-proBNP monitoring may allow the early identification of children at risk for worse outcome. PMID:25856472
Li, Zejuan; Huang, Hao; Li, Yuanyuan; Jiang, Xi; Chen, Ping; Arnovitz, Stephen; Radmacher, Michael D; Maharry, Kati; Elkahloun, Abdel; Yang, Xinan; He, Chunjiang; He, Miao; Zhang, Zhiyu; Dohner, Konstanze; Neilly, Mary Beth; Price, Colles; Lussier, Yves A; Zhang, Yanming; Larson, Richard A; Le Beau, Michelle M; Caligiuri, Michael A; Bullinger, Lars; Valk, Peter J M; Delwel, Ruud; Lowenberg, Bob; Liu, Paul P; Marcucci, Guido; Bloomfield, Clara D; Rowley, Janet D; Chen, Jianjun
Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially.
Expression of the potential therapeutic target CXXC5 in primary acute myeloid leukemia cells - high expression is associated with adverse prognosis as well as altered intracellular signaling and transcriptional regulation
Bruserud, Øystein; Reikvam, Håkon; Fredly, Hanne; Skavland, Jørn; Hagen, Karen-Marie; van Hoang, Tuyen Thy; Brenner, Annette K.; Kadi, Amir; Astori, Audrey; Gjertsen, Bjørn Tore; Pendino, Frederic
The CXXC5 gene encodes a transcriptional activator with a zinc-finger domain, and high expression in human acute myeloid leukemia (AML) cells is associated with adverse prognosis. We now characterized the biological context of CXXC5 expression in primary human AML cells. The global gene expression profile of AML cells derived from 48 consecutive patients was analyzed; cells with high and low CXXC5 expression then showed major differences with regard to extracellular communication and intracellular signaling. We observed significant differences in the phosphorylation status of several intracellular signaling mediators (CREB, PDK1, SRC, STAT1, p38, STAT3, rpS6) that are important for PI3K-Akt-mTOR signaling and/or transcriptional regulation. High CXXC5 expression was also associated with high mRNA expression of several stem cell-associated transcriptional regulators, the strongest associations being with WT1, GATA2, RUNX1, LYL1, DNMT3, SPI1, and MYB. Finally, CXXC5 knockdown in human AML cell lines caused significantly increased expression of the potential tumor suppressor gene TSC22 and genes encoding the growth factor receptor KIT, the cytokine Angiopoietin 1 and the selenium-containing glycoprotein Selenoprotein P. Thus, high CXXC5 expression seems to affect several steps in human leukemogenesis, including intracellular events as well as extracellular communication. PMID:25605239
Gransar, Heidi; Lin, Fay; Valenti, Valentina; Cho, Iksung; Berman, Daniel; Callister, Tracy; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Al-Mallah, Mouaz; Budoff, Matthew; Kaufmann, Philipp; Achenbach, Stephan; Raff, Gilbert; Chinnaiyan, Kavitha; Cademartiri, Filippo; Maffei, Erica; Villines, Todd; Kim, Yong-Jin; Leipsic, Jonathon; Feuchtner, Gudrun; Rubinshtein, Ronen; Pontone, Gianluca; Andreini, Daniele; Marques, Hugo; Shaw, Leslee; Min, James K.
Objective To examine sex-specific associations, if any, between per-vessel CAD extent and the risk of major adverse cardiovascular events (MACE) over a five-year study duration. Background The presence and extent of coronary artery disease (CAD) diagnosed by coronary computed tomography angiography (CCTA) is associated with increased short-term mortality and MACE. Nevertheless, some uncertainty remains regarding the influence of gender on these findings. Methods 5,632 patients (mean age 60.2 + 11.8 years, 36.5% female) from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry were followed over the course of 5 years. Obstructive CAD was defined as ≥50% luminal stenosis in a coronary vessel. Using Cox proportional-hazards models, we calculated the hazard ratio (HR) for incident MACE among women and men, defined as death or myocardial infarction (MI). Results Obstructive CAD was more prevalent in men (42% vs. 26%, p<0.001) whereas women were more likely to have normal coronary arteries (43% vs. 27%, p<0.001). There were a total of 798 incident MACE events. After adjustment, there was a strong association between increased MACE risk and non-obstructive CAD (HR 2.16 for women, 2.56 for men, p<0.001 for both), obstructive one-vessel CAD (HR 3.69 and 2.66, p<0.001), two-vessel CAD (HR 3.92 and 3.55, p<0.001) and three-vessel/left-main CAD (HR 5.94 and 4.44, p<0.001). Further exploratory analyses of atherosclerotic burden did not identify gender-specific patterns predictive of MACE. Conclusion In a large prospective CCTA cohort followed long-term, we did not observe an interaction of gender for the association between MACE risk and increased per-vessel extent of obstructive CAD. These findings highlight the persistent prognostic significance of anatomic CAD subsets as detected by CCTA for the risk of MACE in both women and men. PMID:27056154
Godkar, Darshan; Bachu, Kalyan; Dave, Bijal; Niranjan, Selva; Khanna, Ashok
Over the last decade, one group of neurohormonal markers, including atrial natriuretic peptide (ANP), N-terminal pro-ANP, B-type natriuretic peptide (BNP), and N-terminal proBNP, has generated much interest in the evaluation and management of heart failure and acute coronary syndrome. There has been so much literature on the subject, especially concerning BNP and proBNP, that it leaves us confused at times about what the literature has to say about these markers. In this article, we have made an honest attempt to examine all the available literature in relation to the impact of BNP and proBNP on cardiovascular disease and present it to the reader in an assimilated fashion.
Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population
Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T)...
Corella, Dolores; Carrasco, Paula; Sorlí, Jose V.; Estruch, Ramón; Rico-Sanz, Jesús; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Covas, M. Isabel; Coltell, Oscar; Arós, Fernando; Lapetra, José; Serra-Majem, Lluís; Ruiz-Gutiérrez, Valentina; Warnberg, Julia; Fiol, Miquel; Pintó, Xavier; Ortega-Azorín, Carolina; Muñoz, Miguel Ángel; Martínez, J. Alfredo; Gómez-Gracia, Enrique; González, José I.; Ros, Emilio; Ordovás, José M.
OBJECTIVE Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet. RESEARCH DESIGN AND METHODS A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events. RESULTS The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 [95% CI 1.62–2.17] for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 [95% CI 1.36–6.19]; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 [95% CI 0.49–1.87]; P = 0.892 for TT compared with CC). CONCLUSIONS Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence. PMID:23942586
Myburgh, Renier; Hochfeld, Warren E; Dodgen, Tyren M; Ker, James; Pepper, Michael S
Human genetic variation in the form of single nucleotide polymorphisms as well as more complex structural variations such as insertions, deletions and copy number variants, is partially responsible for the clinical variation seen in response to pharmacotherapeutic drugs. This affects the likelihood of experiencing adverse drug reactions and also of achieving therapeutic success. In this paper, we review key studies in cardiovascular pharmacogenetics that reveal genetic variations underlying the outcomes of drug treatment in cardiovascular disease. Examples of genetic associations with drug efficacy and toxicity are described, including the roles of genetic variability in pharmacokinetics (e.g. drug metabolizing enzymes) and pharmacodynamics (e.g. drug targets). These findings have functional implications that could lead to the development of genetic tests aimed at minimizing drug toxicity and optimizing drug efficacy in cardiovascular medicine.
Krzyzanowska, Katarzyna; Mittermayer, Friedrich; Wolzt, Michael; Schernthaner, Guntram
The endogenous competitive nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is an emerging risk marker for future cardiovascular events. Elevated ADMA concentrations have been described in patients with an adverse cardiovascular risk profile. Recently, various studies investigated the independent role of ADMA as a cardiovascular risk predictor in several patient cohorts. In addition, ADMA might not only be a risk marker but also a causative factor for cardiovascular disease. This review summarizes the literature on the relationship between ADMA, cardiovascular disease and diabetes.
The Impact of Educational Status on 10-Year (2004-2014) Cardiovascular Disease Prognosis and All-cause Mortality Among Acute Coronary Syndrome Patients in the Greek Acute Coronary Syndrome (GREECS) Longitudinal Study
Notara, Venetia; Kogias, Yannis; Stravopodis, Petros; Antonoulas, Antonis; Zombolos, Spyros; Mantas, Yannis; Pitsavos, Christos
Objectives: The association between educational status and 10-year risk for acute coronary syndrome (ACS) and all-cause mortality was evaluated. Methods: From October 2003 to September 2004, 2172 consecutive ACS patients from six Greek hospitals were enrolled. In 2013 to 2014, a 10-year follow-up (2004-2014) assessment was performed for 1918 participants (participation rate, 88%). Each patient’s educational status was classified as low (<9 years of school), intermediate (9 to 14 years), or high (>14 years). Results: Overall all-cause mortality was almost twofold higher in the low-education group than in the intermediate-education and high-education groups (40% vs. 22% and 19%, respectively, p<0.001). Additionally, 10-year recurrent ACS events (fatal and non-fatal) were more common in the low-education group than in the intermediate-education and high-education groups (42% vs. 30% and 35%, p<0.001), and no interactions between sex and education on the investigated outcomes were observed. Moreover, patients in the high-education group were more physically active, had a better financial status, and were less likely to have hypertension, diabetes, or ACS than the participants with the least education (p<0.001); however, when those characteristics and lifestyle habits were accounted for, no moderating effects regarding the relationship of educational status with all-cause mortality and ACS events were observed. Conclusions: A U-shaped association may be proposed for the relationship between ACS prognosis and educational status, with participants in the low-education and high-education groups being negatively affected by other factors (e.g., job stress, depression, or loneliness). Public health policies should be aimed at specific social groups to reduce the overall burden of cardiovascular disease morbidity. PMID:27499164
Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei
Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values < 0.05). For every reduction of 5% in left ventricular ejection fraction induced by mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.
Tsai, H-T; Isaacs, C; Fu, A Z; Warren, J L; Freedman, A N; Barac, A; Huang, C-Y; Potosky, A L
Randomized controlled trials have reported a 4-5 times increased risk of heart failure (HF) in breast cancer patients receiving trastuzumab (Herceptin (®) ) compared to patients who do not receive trastuzumab. However, data regarding the cardiac effects of trastuzumab on elderly patients treated in general practice remain very limited. Using the US surveillance, epidemiology, and end results (SEER)-Medicare database, we conducted a retrospective cohort study on the cardiac effects of trastuzumab use in all incident breast cancer patients diagnosed from 1998 to 2007 who were 66 years and older, had no prior recent claims for cardiomyopathy (CM) or HF, and were followed through 2009. We defined our outcome as the first CM/HF event after diagnosis. We performed Cox-proportional hazard models with propensity score adjustment to estimate CM/HF risk associated with trastuzumab use. A total of 6,829 out of 68,536 breast cancer patients (median age: 75) had an incident CM/HF event. Patients who received trastuzumab tended to be younger, non-white, diagnosed more recently, and had a stage IV diagnosis. Trastuzumab use was associated with an increased risk of CM/HF (HR = 2.08, 95 % CI 1.77-2.44, p < 0.001). The trastuzumab-associated CM/HF risk was stronger in patients who were younger (HR = 2.52 for 66-75 years and HR = 1.44 for 76 years and older, p < 0.001) and diagnosed in recent years (HR = 2.58 for 2006-2007 vs. 1.86 for 1998-2005, p = 0.01). The twofold risk of CM/HF associated with trastuzumab remained regardless of patients' diagnosis stage, presence of hypertension, cardiovascular comorbidities, or receipt of anthracyclines, taxanes, or radiation. Trastuzumab may double CM/HF risk among elderly breast cancer patients. Our findings reinforce the need to prevent and manage cardiac risk among elderly breast cancer patients receiving trastuzumab.
Angelopoulos, Theodore J; Lowndes, Joshua; Sinnett, Stephanie; Rippe, James M
The objective of the current study was to explore our hypothesis that average consumption of fructose and fructose containing sugars would not increase risk factors for cardiovascular disease (CVD) and the metabolic syndrome (MetS). A randomized, double blind, parallel group study was conducted where 267 individuals with BMI between 23 and 35 kg/m² consumed low fat sugar sweetened milk, daily for ten weeks as part of usual weight-maintenance diet. One group consumed 18% of calories from high fructose corn syrup (HFCS), another group consumed 18% of calories from sucrose, a third group consumed 9% of calories from fructose, and the fourth group consumed 9% of calories from glucose. There was a small change in waist circumference (80.9 ± 9.5 vs. 81.5 ± 9.5 cm) in the entire cohort, as well as in total cholesterol (4.6 ± 1.0 vs. 4.7 ± 1.0 mmol/L, p < 0.01), triglycerides (TGs) (11.5 ± 6.4 vs. 12.6 ± 8.9 mmol/L, p < 0.01), and systolic (109.2 ± 10.2 vs. 106.1 ± 10.4 mmHg, p < 0.01) and diastolic blood pressure (69.8 ± 8.7 vs. 68.1 ± 9.7 mmHg, p < 0.01). The effects of commonly consumed sugars on components of the MetS and CVD risk factors are minimal, mixed and not clinically significant.
Angelopoulos, Theodore J.; Lowndes, Joshua; Sinnett, Stephanie; Rippe, James M.
The objective of the current study was to explore our hypothesis that average consumption of fructose and fructose containing sugars would not increase risk factors for cardiovascular disease (CVD) and the metabolic syndrome (MetS). A randomized, double blind, parallel group study was conducted where 267 individuals with BMI between 23 and 35 kg/m2 consumed low fat sugar sweetened milk, daily for ten weeks as part of usual weight-maintenance diet. One group consumed 18% of calories from high fructose corn syrup (HFCS), another group consumed 18% of calories from sucrose, a third group consumed 9% of calories from fructose, and the fourth group consumed 9% of calories from glucose. There was a small change in waist circumference (80.9 ± 9.5 vs. 81.5 ± 9.5 cm) in the entire cohort, as well as in total cholesterol (4.6 ± 1.0 vs. 4.7 ± 1.0 mmol/L, p < 0.01), triglycerides (TGs) (11.5 ± 6.4 vs. 12.6 ± 8.9 mmol/L, p < 0.01), and systolic (109.2 ± 10.2 vs. 106.1 ± 10.4 mmHg, p < 0.01) and diastolic blood pressure (69.8 ± 8.7 vs. 68.1 ± 9.7 mmHg, p < 0.01). The effects of commonly consumed sugars on components of the MetS and CVD risk factors are minimal, mixed and not clinically significant. PMID:27023594
Mäenpää, Jukka; Volotinen-Maja, Marjo; Kautiainen, Hannu; Neuvonen, Mikko; Niemi, Mikko; Neuvonen, Pertti J; Backman, Janne T
Although ophthalmic timolol is generally well tolerated, a significant fraction of topically administered timolol can be systemically absorbed. We investigated the effect of the strong CYP2D6 inhibitor paroxetine on the pharmacokinetics of timolol after ophthalmic administration. In a four-phase crossover study, 12 healthy volunteers ingested either paroxetine (20 mg) or placebo daily for 3 days. In phases 1-2, timolol 0.1% gel, and in phases 3-4, timolol 0.5% drops were administered to both eyes. Paroxetine increased the plasma concentrations of timolol with both timolol formulations to a similar degree. The geometric mean ratio (95% confidence interval) of timolol peak concentration was 1.53-fold (1.23-1.91) with 0.1% timolol and 1.49-fold (0.94-2.36) with 0.5% timolol, and that of timolol area under the plasma concentration-time curve (AUC) from time 0 to 12 hours was 1.61-fold (1.26- to 2.06-fold) and 1.78-fold (1.21-2.62), respectively. During paroxetine administration, six subjects on 0.5% timolol drops, but none on 0.1% timolol gel, had plasma timolol concentrations exceeding 0.7 ng/ml, which can cause systemic adverse effects in patients at risk. There was a positive correlation between the AUC from time 0 to 13 hours of paroxetine and the placebo phase AUC from time 0 to infinity of timolol after timolol 0.5% drops (P < 0.05), and a nonsignificant trend after timolol 0.1% gel, consistent with the role of CYP2D6 in the metabolism of both agents. In the orthostatic test, heart rate immediately after upright standing was significantly lower (P < 0.05) during the paroxetine phase than during the placebo phase at 1 and 3 hours after 0.5% timolol dosing. In conclusion, paroxetine and other CYP2D6 inhibitors can have a clinically important interaction with ophthalmic timolol, particularly when patients are using 0.5% timolol formulations.
Payne, Rupert A
Cardiovascular disease is a major, growing, worldwide problem. It is important that individuals at risk of developing cardiovascular disease can be effectively identified and appropriately stratified according to risk. This review examines what we understand by the term risk, traditional and novel risk factors, clinical scoring systems, and the use of risk for informing prescribing decisions. Many different cardiovascular risk factors have been identified. Established, traditional factors such as ageing are powerful predictors of adverse outcome, and in the case of hypertension and dyslipidaemia are the major targets for therapeutic intervention. Numerous novel biomarkers have also been described, such as inflammatory and genetic markers. These have yet to be shown to be of value in improving risk prediction, but may represent potential therapeutic targets and facilitate more targeted use of existing therapies. Risk factors have been incorporated into several cardiovascular disease prediction algorithms, such as the Framingham equation, SCORE and QRISK. These have relatively poor predictive power, and uncertainties remain with regards to aspects such as choice of equation, different risk thresholds and the roles of relative risk, lifetime risk and reversible factors in identifying and treating at-risk individuals. Nonetheless, such scores provide objective and transparent means of quantifying risk and their integration into therapeutic guidelines enables equitable and cost-effective distribution of health service resources and improves the consistency and quality of clinical decision making. PMID:22348281
Lavie, Carl J; McAuley, Paul A; Church, Timothy S; Milani, Richard V; Blair, Steven N
Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed.
Khorana, Alok A.
Venous thromboembolism (VTE) is a frequent complication of malignancy, and its incidence has increased markedly in recent years. VTE itself can directly lead to patient mortality, and is the second leading cause of death in patients with cancer. Furthermore, emerging data suggest that activation of coagulation in malignancy is integrally linked with tumor biology, particularly with angiogenesis. The development of the clinical hypercoagulable state is also linked with adverse prognosis in patients with cancer, including patients receiving systemic chemotherapy. This review focuses on the clinical evidence documenting a link between VTE and adverse short-term and long-term prognosis in patients with cancer. PMID:20097409
Prognostic Value of Combined CT Angiography and Myocardial Perfusion Imaging versus Invasive Coronary Angiography and Nuclear Stress Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events: The CORE320 Multicenter Study.
Chen, Marcus Y; Rochitte, Carlos E; Arbab-Zadeh, Armin; Dewey, Marc; George, Richard T; Miller, Julie M; Niinuma, Hiroyuki; Yoshioka, Kunihiro; Kitagawa, Kakuya; Sakuma, Hajime; Laham, Roger; Vavere, Andrea L; Cerci, Rodrigo J; Mehra, Vishal C; Nomura, Cesar; Kofoed, Klaus F; Jinzaki, Masahiro; Kuribayashi, Sachio; Scholte, Arthur J; Laule, Michael; Tan, Swee Yaw; Hoe, John; Paul, Narinder; Rybicki, Frank J; Brinker, Jeffrey A; Arai, Andrew E; Matheson, Matthew B; Cox, Christopher; Clouse, Melvin E; Di Carli, Marcelo F; Lima, João A C
Purpose To compare the prognostic importance (time to major adverse cardiovascular event [MACE]) of combined computed tomography (CT) angiography and CT myocardial stress perfusion imaging with that of combined invasive coronary angiography (ICA) and stress single photon emission CT myocardial perfusion imaging. Materials and Methods This study was approved by all institutional review boards, and written informed consent was obtained. Between November 2009 and July 2011, 381 participants clinically referred for ICA and aged 45-85 years were enrolled in the Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) prospective multicenter diagnostic study. All images were analyzed in blinded independent core laboratories, and a panel of physicians adjudicated all adverse events. MACE was defined as revascularization (>30 days after index ICA), myocardial infarction, or cardiac death; hospitalization for chest pain or congestive heart failure; or arrhythmia. Late MACE was defined similarly, except for patients who underwent revascularization within the first 182 days after ICA, who were excluded. Comparisons of 2-year survival (time to MACE) used standard Kaplan-Meier curves and restricted mean survival times bootstrapped with 2000 replicates. Results An MACE (49 revascularizations, five myocardial infarctions, one cardiac death, nine hospitalizations for chest pain or congestive heart failure, and one arrhythmia) occurred in 51 of 379 patients (13.5%). The 2-year MACE-free rates for combined CT angiography and CT perfusion findings were 94% negative for coronary artery disease (CAD) versus 82% positive for CAD and were similar to combined ICA and single photon emission CT findings (93% negative for CAD vs 77% positive for CAD, P < .001 for both). Event-free rates for CT angiography and CT perfusion versus ICA and single photon emission CT for either positive or negative results were not
Understanding Your Cancer Prognosis is the main video in the NCI Prognosis Video Series, which offers the perspectives of three cancer patients and their doctor, an oncologist who is also a national expert in doctor-patient communication.
Li, Wei-Ming; Huang, Chun-Nung; Ke, Hung-Lung; Li, Ching-Chia; Wei, Yu-Ching; Yeh, Hsin-Chih; Chang, Lin-Li; Huang, Chun-Hsiung; Liang, Peir-In; Yeh, Bi-Wen; Chan, Ti-Chun; Li, Chien-Feng; Wu, Wen-Jeng
Urothelial carcinoma (UC) occurs in the upper urinary tract (UTUC) and the urinary bladder (UBUC). The molecular pathogenesis of UC has not been fully elucidated. Through data mining of a published transcriptome of UBUC (GSE31684), we identified Minichromosome Maintenance Complex Component 2 (MCM2) and MCM10 as the two most significantly upregulated genes in UC progression among the MCM gene family, the key factors for the initiation of DNA replication. To validate the clinical significance of MCM2 and MCM10, immunohistochemistry, evaluated by H-score, was used in a pilot study of 50 UTUC and 50 UBUC samples. Only a high expression level of MCM10 predicted worse disease-specific survival (DSS) and inferior metastasis-free survival (MeFS) for both UTUC and UBUC. Correspondingly, evaluation of MCM10 mRNA expression in 36 UTUCs and 30 UBUCs showed significantly upregulated levels in high stage UC, suggesting its role in tumor progression. Evaluation of 340 UTUC and 296 UBUC tissue samples, respectively, demonstrated that high MCM10 immunoexpression was significantly associated with advanced primary tumors, nodal status, and the presence of vascular invasion in both groups of UCs. In multivariate Cox regression analyses, adjusted for standard clinicopathological features, MCM10 overexpression was independently associated with DSS (UTUC hazard ratio [HR]=2.401, P = 0.013; UBUC HR=4.323, P=0.001) and with MeFS (UTUC HR=3.294, P<0.001; UBUC HR=1.972, P=0.015). In vitro, knockdown of MCM10 gene significantly suppressed cell proliferation in both J82 and TCCSUP cells. In conclusion, MCM10 overexpression was associated with unfavorable clinicopathological characteristics and independent negative prognostic effects, justifying its potential theranostic value in UC. PMID:27780919
Graham, Susan M; Mwilu, Regina; Liles, W Conrad
Introduction: HIV infection is associated with vascular dysfunction and adverse cardiovascular outcomes. Our objective was to review the evidence regarding the clinical utility of endothelial activation and coagulation biomarkers for the prognosis of HIV-infected patients. Methods: We searched PubMed and Embase for publications using the keywords “HIV” or “HIV infection” and “endothelium” or “coagulation”. We reviewed reference lists and hand-searched for additional relevant articles. All clinical studies that enrolled non-pregnant, HIV-infected adults, measured biomarkers reflecting endothelial activation or coagulation, and prospectively evaluated their associations with vascular dysfunction or clinical outcomes were included. Results: Seventeen studies were identified that fulfilled the inclusion criteria, of which 11 investigated endothelial activation biomarkers and 12 investigated coagulation biomarkers. Biomarkers and outcomes varied widely across studies. Overall, published studies support an association between P-selectin and venous thromboembolism in HIV-infected patients, an association between tissue-type plasminogen activator and death, and associations between D-dimer and several clinical outcomes, including venous thromboembolism, cardiovascular disease, and all-cause mortality. Conclusions: Several studies have demonstrated associations between biomarkers of endothelial activation and coagulation and clinically important outcomes in HIV-1 infection. Additional large-scale prospective investigations to determine the utility of endothelial activation and coagulation biomarkers for risk stratification and prediction of adverse outcomes are clearly warranted. PMID:23732995
Summers, Gregory D; Metsios, Giorgos S; Stavropoulos-Kalinoglou, Antonios; Kitas, George D
Both cachexia and cardiovascular disease are strongly associated with rheumatoid arthritis (RA) and linked to the chronic inflammatory process. Typically, rheumatoid cachexia occurs in individuals with normal or increased BMI (reduced muscle mass and increased fat mass). Classic cachexia (reduced muscle mass and reduced fat mass) is rare in RA but is associated with high inflammatory activity and aggressive joint destruction in patients with a poor cardiovascular prognosis. Conversely, obesity is linked to hypertension and dyslipidemia but, paradoxically, lower RA disease activity and less cardiovascular disease-related mortality. Rheumatoid cachexia might represent the 'worst of both worlds' with respect to cardiovascular outcome, but until diagnostic criteria for this condition are agreed upon, its effect on cardiovascular disease risk remains controversial.
Tassell, Mary C; Kingston, Rosari; Gilroy, Deirdre; Lehane, Mary; Furey, Ambrose
The medicinal properties of hawthorn (Crataegus spp., a genus comprising approximately 300 species) have been utilized by many cultures for a variety of therapeutic purposes for many centuries. In the Western world cardiovascular disease (CVD) has become one of the single most significant causes of premature death. Echoing this situation, more recent research into the therapeutic benefits of hawthorn preparations has focused primarily upon its cardiovascular effects. This review covers research into the various mechanisms of action proposed for Crataegus preparations, clinical trials involving Crataegus preparations, and the herb's safety profile.Clinical trials reviewed have been inconsistent in terms of criteria used (sample size, preparation, dosage, etc) but have been largely consistent with regard to positive outcomes. An investigation into data available to date regarding hawthorn preparations and herb/drug interactions reveals that theoretical adverse interactions have not been experienced in practice. Further, adverse reactions relating to the use of hawthorn preparations are infrequent and mild, even at higher dosage ranges. A recent retrospective study by Zick et al. has suggested a negative outcome for the long-term use of hawthorn in the prognosis of heart failure. These findings are examined in this paper.Although further research is needed in certain areas, current research to date suggests that hawthorn may potentially represent a safe, effective, nontoxic agent in the treatment of CVD and ischemic heart disease (IHD).
Rationale: Epidemiological evidence suggests that ultrafine particles are associated with adverse cardiovascular effects, specifically in elderly individuals with preexisting cardiovascular disease. The objective of this study was (i) to assess cardiopulmonary responses in adult ...
establish a causal relationship in either direction, because of these methodological limitations. In Australia, the marked increase in cannabis use has not been accompanied by an increased incidence of schizophrenia. On the basis of the available data, we cannot reach firm conclusions on whether or not cannabis use causes psychosis. It seems prudent to inform apparently vulnerable individuals that cannabis may cause acute psychotic decompensation, especially at high doses. Users can feel dependent on cannabis, but this dependence is usually psychological. Withdrawal symptoms tend to occur within 48 hours following cessation of regular cannabis use, and include increased irritability, anxiety, nervousness, restlessness, sleep difficulties and aggression. Symptoms subside within 2 to 12 weeks. Driving under the influence of cannabis doubles the risk of causing a fatal road accident. Alcohol consumption plays an even greater role. A few studies and a number of isolated reports suggest that cannabis has a role in the occurrence of cardiovascular adverse effects, especially in patients with coronary heart disease. Numerous case-control studies have investigated the role of cannabis in the incidence of some types of cancer. Its role has not been ruled out, but it is not possible to determine whether the risk is distinct from that of the tobacco with which it is often smoked. Studies that have examined the influence of cannabis use on the clinical course of hepatitis C are inconclusive. Alcohol remains the main toxic agent that hepatitis C patients should avoid. In practice, the adverse effects of low-level, recreational cannabis use are generally minor, although they can apparently be serious in vulnerable individuals. The adverse effects of cannabis appear overall to be less serious than those of alcohol, in terms of neuropsychological and somatic effects, accidents and violence.
Kaliki, Swathi; Shields, Carol L; Shields, Jerry A
Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.
Šimić, Iveta; Reiner, Željko
Statins reduce cardiovascular mortality and morbidity as well as cardiovascular events in patients with a very high risk of cardiovascular disease (CVD) and also in subjects with high or moderate risk by reducing the levels of low-density lipoprotein cholesterol (LDL-C). Although they are considered to be drugs with a very good safety profile, because of their wide use there are many concerns that their adverse effects might compromise their proven beneficial effects. Therefore this article reviews all the data and provides an evidence- based insight what are the proven adverse effects of statins and what are the "myths" about them. The most important side effects include myopathy and rhabdomyolysis. Another side effect is increased activity of liver tests which occurs occasionally and is reversible. However, recent studies even suggest that statin therapy can improve hepatic steatosis. It is beyond any doubt that statins do slightly increase the incidence of type 2 diabetes mellitus in people with two or more components of metabolic syndrome but the cardiovascular benefits of such a treatment by far exceed this risk. Statin therapy has also been associated with some adverse renal effects, eg. acute renal failure, but recent data suggest even a possible protective effect of these drugs on renal dysfunction. Concerns that statins might increase cancer have not been proven. On the contrary, several studies have indicated a possible benefit of these drugs in patients with different types of cancer. Early concerns about cognitive dysfunction and memory loss associated with statins use could not be proven and most recent data even suggest a possible beneficial effect of statins in the prevention of dementia. Systematic reviews and clinical guidelines suggest that the cardiovascular benefits of statins by far out-weight non-cardiovascular harms in patients with cardiovascular risk.
Charles, John B.; Fritsch-Yelle, Janice M.; Whitson, Peggy A.; Wood, Margie L.; Brown, Troy E.; Fortner, G. William
Spaceflight causes adaptive changes in cardiovascular function that may deleteriously affect crew health and safety. Over the last three decades, symptoms of cardiovascular changes have ranged from postflight orthostatic tachycardia and decreased exercise capacity to serious cardiac rhythm disturbances during extravehicular activities (EVA). The most documented symptom of cardiovascular dysfunction, postflight orthostatic intolerance, has affected a significant percentage of U.S. Space Shuttle astronauts. Problems of cardiovascular dysfunction associated with spaceflight are a concern to NASA. This has been particularly true during Shuttle flights where the primary concern is the crew's physical health, including the pilot's ability to land the Orbiter, and the crew's ability to quickly egress and move to safety should a dangerous condition arise. The study of astronauts during Shuttle activities is inherently more difficult than most human research. Consequently, sample sizes have been small and results have lacked consistency. Before the Extended Duration Orbiter Medical Project (EDOMP), there was a lack of normative data on changes in cardiovascular parameters during and after spaceflight. The EDOMP for the first time allowed studies on a large enough number of subjects to overcome some of these problems. There were three primary goals of the Cardiovascular EDOMP studies. The first was to establish, through descriptive studies, a normative data base of cardiovascular changes attributable to spaceflight. The second goal was to determine mechanisms of cardiovascular changes resulting from spaceflight (particularly orthostatic hypotension and cardiac rhythm disturbances). The third was to evaluate possible countermeasures. The Cardiovascular EDOMP studies involved parallel descriptive, mechanistic, and countermeasure evaluations.
Cappuccio, Francesco P
Salt is one of the most important determinants of high blood pressure and increased cardiovascular risk worldwide. However, a high salt intake has other adverse effects beyond those involving the cardiovascular system, so that there is renewed interest in the relationships between high salt intake and other diseases. PMID:25019010
Kaliki, Swathi; Shields, Carol L; Shields, Jerry A
Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms “uvea,” “iris,” “ciliary body,” “choroid,” “melanoma,” “uveal melanoma” and “prognosis,” “metastasis,” “genetic testing,” “gene expression profiling.” Relevant English language articles were extracted, reviewed, and referenced appropriately. PMID:25827538
Tune, Johnathan D; Goodwill, Adam G; Sassoon, Daniel J; Mather, Kieren J
The metabolic syndrome (MetS) is defined as the concurrence of obesity-associated cardiovascular risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension. Earlier conceptualizations of the MetS focused on insulin resistance as a core feature, and it is clearly coincident with the above list of features. Each component of the MetS is an independent risk factor for cardiovascular disease and the combination of these risk factors elevates rates and severity of cardiovascular disease, related to a spectrum of cardiovascular conditions including microvascular dysfunction, coronary atherosclerosis and calcification, cardiac dysfunction, myocardial infarction, and heart failure. While advances in understanding the etiology and consequences of this complex disorder have been made, the underlying pathophysiological mechanisms remain incompletely understood, and it is unclear how these concurrent risk factors conspire to produce the variety of obesity-associated adverse cardiovascular diseases. In this review, we highlight current knowledge regarding the pathophysiological consequences of obesity and the MetS on cardiovascular function and disease, including considerations of potential physiological and molecular mechanisms that may contribute to these adverse outcomes.
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Celano, Christopher M; Daunis, Daniel J; Lokko, Hermioni N; Campbell, Kirsti A; Huffman, Jeff C
Anxiety and its associated disorders are common in patients with cardiovascular disease and may significantly influence cardiac health. Anxiety disorders are associated with the onset and progression of cardiac disease, and in many instances have been linked to adverse cardiovascular outcomes, including mortality. Both physiologic (autonomic dysfunction, inflammation, endothelial dysfunction, changes in platelet aggregation) and health behavior mechanisms may help to explain the relationships between anxiety disorders and cardiovascular disease. Given the associations between anxiety disorders and poor cardiac health, the timely and accurate identification and treatment of these conditions is of the utmost importance. Fortunately, pharmacologic and psychotherapeutic interventions for the management of anxiety disorders are generally safe and effective. Further study is needed to determine whether interventions to treat anxiety disorders ultimately impact both psychiatric and cardiovascular health.
Palma-Gómez, Samuel; González-Díaz, Sandra Nora; Arias-Cruz, Alfredo; Macías-Weinmann, Alejandra; Amaro-Vivian, Laura Elizabeth; Pérez-Vanzzini, Rafael; Gutiérrez-Mujica, José Julio; Yong-Rodríguez, Adrián
Adverse reactions to drugs are relatively frequent in clinical practice, and some of them can be life threatening. Reactions to contrast material (CM) represent an important percentage of these adverse reactions. It has been found that 70% of reactions to contrast material happen within the first five minutes of their administration. Despite the fact that hypersensitivity reactions are traditionally classified as non-allergic, in recent years investigators have reported positive skin prick tests in patients with immediate and late reactions to contrast material. This paper reports the case of a female patient with non-Hodgkin lymphoma that has presented on two distinct occasions adverse reactions to contrast material. We discuss on the type of reaction, severity, suggested prophylaxis, prognosis and recommendations, keeping in mind the underlying disease and the need to have further image studies performed.
Sahu, Sandeep; Hemlata; Verma, Anupam
The acute blood transfusion reactions are responsible for causing most serious adverse events. Awareness about various clinical features of acute and delayed transfusion reactions with an ability to assess the serious reactions on time can lead to a better prognosis. Evidence-based medicine has changed today's scenario of clinical practice to decrease adverse transfusion reactions. New evidence-based algorithms of transfusion and improved haemovigilance lead to avoidance of unnecessary transfusions perioperatively. The recognition of adverse events under anaesthesia is always challenging. The unnecessary blood transfusions can be avoided with better blood conservation techniques during surgery and with anaesthesia techniques that reduce blood loss. Better and newer blood screening methods have decreased the infectious complications to almost negligible levels. With universal leukoreduction of red blood cells (RBCs), selection of potential donors such as use of male donors only plasma and restriction of RBC storage, most of the non-infectious complications can be avoided.
Oral disease in adults treated with hemodialysis: prevalence, predictors, and association with mortality and adverse cardiovascular events: the rationale and design of the ORAL Diseases in hemodialysis (ORAL-D) study, a prospective, multinational, longitudinal, observational, cohort study
Background People with end-stage kidney disease treated with dialysis experience high rates of premature death that are at least 30-fold that of the general population, and have markedly impaired quality of life. Despite this, interventions that lower risk factors for mortality (including antiplatelet agents, epoetins, lipid lowering, vitamin D compounds, or dialysis dose) have not been shown to improve clinical outcomes for this population. Although mortality outcomes may be improving overall, additional modifiable determinants of health in people treated with dialysis need to be identified and evaluated. Oral disease is highly prevalent in the general population and represents a potential and preventable cause of poor health in dialysis patients. Oral disease may be increased in patients treated with dialysis due to their lower uptake of public dental services, as well as increased malnutrition and inflammation, although available exploratory data are limited by small sample sizes and few studies evaluating links between oral health and clinical outcomes for this group, including mortality and cardiovascular disease. Recent data suggest periodontitis may be associated with mortality in dialysis patients and well-designed, larger studies are now required. Methods/design The ORAL Diseases in hemodialysis (ORAL-D) study is a multinational, prospective (minimum follow-up 12 months) study. Participants comprise consecutive adults treated with long-term in-center hemodialysis. Between July 2010 and February 2012, we recruited 4500 dialysis patients from randomly selected outpatient dialysis clinics in Europe within a collaborative network of dialysis clinics administered by a dialysis provider, Diaverum, in Europe (France, Hungary, Italy, Poland, Portugal, and Spain) and South America (Argentina). At baseline, dental surgeons with training in periodontology systematically assessed the prevalence and characteristics of oral disease (dental, periodontal, mucosal, and
Diethelm, U; Schüler, G
Based on the literature we describe the prognosis and natural history of ankylosing spondylitis. The data on mortality are controversial and it seems that only a small group of patient show a decreased survival. It is a chronic disease with most prominent features of pain and increasing stiffness during the first decade. After a course of 40 years 90% of patients have none or only mild disability. Generally quality of life is slightly reduced. Most patients remain engaged in full-time employment, but job adaptations are often unavoidable and vocational counseling seems to be worthwhile.
Researchers at the NIH, National Institute on Aging, Cardiovascular Biology Unit-Vascular Group have discovered a method for the diagnosis and prognosis of cardiovascular aging, and is seeking parties interested in in-licensing or collaborative research to co-develop, evaluate, or commercialize novel methods for diagnosing age-related cardiovascular disorders.
Yun, Jaesuk; Chung, Eunyong; Choi, Ki Hwan; Cho, Dae Hyun; Song, Yun Jeong; Han, Kyoung Moon; Cha, Hey Jin; Shin, Ji Soon; Seong, Won-Keun; Kim, Young-Hoon; Kim, Hyung Soo
Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation. PMID:26157557
Background: Millions of people are at risk from the adverse effects of waterborne arsenic. Although the cardiovascular effects of high exposures to arsenic have been well documented, few individual level prospective studies have assessed cardiovascular risk at moderate exposures....
Ohno-Machado, Lucila; Resnic, Frederic S; Matheny, Michael E
Prognostic risk prediction models have been employed in the intensive care unit (ICU) setting since the 1980s and provide health care providers with important information to help inform decisions related to treatment and prognosis, as well as to compare outcomes across institutions. Prognostic models for critical care are among the most widely utilized and tested predictive models in healthcare. In this article, we review and compare mortality prediction models, including the APACHE (1981), SAPS (1984), APACHE-II (1985), MPM (1987), APACHE-III (1991), SAPS-II (1993), and MPM-II (1993). We emphasize the importance of model calibration in this domain. In addition, we present a brief review of the statistical methodology, multiple logistic regression, which underlies most of the models currently used in critical care.
Asher, Elad; Fefer, Paul; Sabbag, Avi; Herscovici, Romana; Regev, Ehud; Mazin, Israel; Shlomo, Nir; Zahger, Doron; Atar, Shaul; Hammerman, Haim; Polak, Arthur; Beigel, Roy; Matetzky, Shlomi
Despite the growing use of clopidogrel, limited data exist regarding the prognostic significance of chronic clopidogrel therapy in patients sustaining acute coronary syndrome (ACS). Our aim was to determine whether patients sustaining ACS while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients. A total of 5,386 consecutive ACS patients were prospectively characterised and followed-up for 30 days. Of them, 680 (13%) were treated with clopidogrel prior to the index ACS. Major adverse cardiovascular events (MACE) were defined as death, recurrent ACS, stroke and/or stent thrombosis. Compared with clopidogrel-naïve, chronic clopidogrel-treated patients were older (66 ± 12 vs 63 ± 13, respectively; p<0.01), suffered more from diabetes mellitus, hypertension, dyslipidaemia, prior cardiovascular history, including prior myocardial infarction, revascularisation, coronary artery bypass graft and stroke (p<0.01 for all), and were less likely to present with ST-elevation myocardial infarction (21% vs 45%; respectively; p < 0.001). Prior clopidogrel therapy was associated with a two-fold increase in in-hospital (1.6% vs 0.6%, respectively; p =0.006) as well as 30-day stent thrombosis (2.2% vs 1.0%, respectively; p=0.007). MACE at 30 days was also higher among chronic clopidogrel-treated compared with clopidogrel-naïve patients [12.3% vs 9.4%, respectively; p<0.01]. In multivariate log regression analysis chronic clopidogrel treatment was an independent predictor of stent thrombosis [OR=2.6 (95%CI 1.2-5.6), p=0.001]. Patients sustaining ACS while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes, including stent thrombosis.
Cardiovascular disease (CVD), particularly CHD (coronary heart disease) and stroke, remain the leading causes of death of women in America and most developed countries. In recent years the rate of CVD has declined in men but not in women. This is contributed to by an under-recognition of women’s C...
Brunner, Eric John
Recent progress in population health at aggregate level, measured by life expectancy, has been accompanied by lack of progress in reducing the difference in health prospects between groups defined by social status. Cardiovascular disease is an important contributor to this undesirable situation. The stepwise gradient of higher risk with lower status is accounted for partly by social gradients in health behaviors. The psychosocial hypothesis provides a stronger explanation, based on social patterning of living and working environments and psychological assets that individuals develop during childhood. Three decades of research based on Whitehall II and other cohort studies provide evidence for psychosocial pathways leading to cardiovascular morbidity and mortality. Job stress is a useful paradigm because exposure is long term and depends on occupational status. Studies of social-biological translation implicate autonomic and neuroendocrine function among the biological systems that mediate between chronic adverse psychosocial exposures and increased cardiometabolic risk and cardiovascular disease incidence.
Sobel, Burton E
This article presents a series of take-home statements, compiled by a multidisciplinary steering committee, concerning significant aspects of macrovascular disease in patients with diabetes mellitus, including the extent of risk, pathogenetic mechanisms, and optimal management for risk reduction. The discussion focuses in particular on the impact of diabetes medications beyond blood glucose control. In summary, these statements are as follows: (1) Patients with diabetes have an increased risk for cardiovascular disease that contributes to decreased life expectancy; (2) prognosis after a cardiovascular event is poorer in patients with diabetes; (3) pathogenetic mechanisms include insulin resistance, endothelial dysfunction, dyslipidemia, chronic inflammation, procoagulability, and impaired fibrinolysis; (4) management of established cardiovascular risk factors, for example with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and antihypertensive therapy, reduces cardiovascular event rates in diabetes; (5) correction of hyperglycemia can reduce macrovascular event rates, but the coupling to hyperglycemia is less tight for macrovascular events than it is for reduction of microvascular complications; (6) patients with diabetes should be screened for additional cardiovascular risk factors and appropriate interventions should be initiated; (7) results of observational and interventional studies have indicated that some insulin sensitizers appear to reduce the incidence of cardiovascular events and improve survival; (8) thiazolidinediones have beneficial effects on metabolism that may improve cardiovascular risk, and a randomized clinical trial in patients with advanced atherosclerosis indicates that addition of pioglitazone to therapy for hyperglycemia may reduce the incidence of cardiovascular events such as myocardial infarction and stroke.
Scibona, Paula; Angriman, Federico; Simonovich, Ventura; Heller, Martina M; Belloso, Waldo H
Cardiovascular disease remains a major cause of morbidity and mortality worldwide. Current medical practice takes into account information based on population studies and benefits observed in large populations or cohorts. However, individual patients present great differences in both toxicity and clinical efficacy that can be explained by variations in adherence, unknown drug to drug interactions and genetic variability. The latter seems to explain from 20% up to 95% of patient to patient variability. Treating patients with cardiovascular disorders faces the clinician with the challenge to include genomic analysis into daily practice. There are several examples within cardiovascular disease of treatments that can vary in toxicity or clinical usefulness based on genetic changes. One of the main factors affecting the efficacy of Clopidogrel is the phenotype associated with polymorphisms in the gene CYP 2C9. Furthermore, regarding oral anticoagulants, changes in CYP2C9 and VKORC1 play an important role in changing the clinical response to anticoagulation. When analyzing statin treatment, one of their main toxicities (myopathy) can be predicted by the SLCO1B1 polymorphism. The potential for prediction of toxicity and clinical efficacy from the use of genetic analysis warrants further studies aiming towards its inclusion in daily clinical practice.
Hall, Wayne; Degenhardt, Louisa
This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment.
Reinhard, A; Maire, R
Vestibular neuritis is a sudden unilateral peripheral vestibular deficit of unknown origin without associated hearing loss. It is the second cause of peripheral vertigo after Benign Paroxysmal Positional Vertigo (BPPV). The etiology remains unclear and some treatments are still controversial. The prognosis is good. The differential diagnosis of the disease mainly includes an acute vertigo of central origin. This article summarizes the management and prognosis of vestibular neuritis.
Ferreira, Cátia; Providência, Rui; Ferreira, Maria João; Gonçalves, Lino Manuel
Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an unfavorable prognosis, increasing the risk of stroke and death. Although traditionally associated with cardiovascular diseases, there is increasing evidence of high incidence of AF in patients with highly prevalent noncardiovascular diseases, such as cancer, sepsis, chronic obstructive pulmonary disease, obstructive sleep apnea and chronic kidney disease. Therefore, considerable number of patients has been affected by these comorbidities, leading to an increased risk of adverse outcomes. The authors performed a systematic review of the literature aiming to better elucidate the interaction between these conditions. Several mechanisms seem to contribute to the concomitant presence of AF and noncardiovascular diseases. Comorbidities, advanced age, autonomic dysfunction, electrolyte disturbance and inflammation are common to these conditions and may predispose to AF. The treatment of AF in these patients represents a clinical challenge, especially in terms of antithrombotic therapy, since the scores for stratification of thromboembolic risk, such as the CHADS2 and CHA2DS2VASc scores, and the scores for hemorrhagic risk, like the HAS-BLED score have limitations when applied in these conditions. The evidence in this area is still scarce and further investigations to elucidate aspects like epidemiology, pathogenesis, prevention and treatment of AF in noncardiovascular diseases are still needed. PMID:26577719
Sukhovershin, Roman A; Cooke, John P
Proton pump inhibitors (PPIs) are among the most widely used drugs worldwide. They are used to treat a number of gastroesophageal disorders and are usually prescribed as a long-term medication or even taken without a prescription. There are a number of clinical studies that associate PPI use with an increased cardiovascular risk. In this article, we review the clinical evidence for adverse cardiovascular effects of PPIs, and we discuss possible biological mechanisms by which PPIs can impair cardiovascular health.
Sparks, Sarah D.
The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…
Li, Wenzhang; Liu, Qianqian; Tang, Yin
Recent studies have shown platelet to lymphocyte ratio (PLR) to be a potential inflammatory marker in cardiovascular diseases. We performed a meta-analysis to systematically evaluate the prognostic role of PLR in acute coronary syndrome (ACS). A comprehensive literature search up to May 18, 2016 was conducted from PUBMED, EMBASE and Web of science to identify related studies. The risk ratio (RR) with 95% confidence interval (CI) was extracted or calculated for effect estimates. Totally ten studies involving 8932 patients diagnosed with ACS were included in our research. We demonstrated that patients with higher PLR level had significantly higher risk of in-hospital adverse outcomes (RR = 2.24, 95%CI = 1.81–2.77) and long-term adverse outcomes (RR = 2.32, 95%CI = 1.64–3.28). Sensitivity analyses confirmed the stability of our results. We didn’t detect significant publication bias by Begg’s and Egger’s test (p > 0.05). In conclusion, our meta-analysis revealed that PLR is promising biomarker in predicting worse prognosis in ACS patients. The results should be validated by future large-scale, standard investigations. PMID:28071752
As a starting point, the group defined a primary goal of maintaining in flight a level of systemic oxygen transport capacity comparable to each individual's preflight upright baseline. The goal of maintaining capacity at preflight levels would seem to be a reasonable objective for several different reasons, including the maintenance of good health in general and the preservation of sufficient cardiovascular reserve capacity to meet operational demands. It is also important not to introduce confounding variables in whatever other physiological studies are being performed. A change in the level of fitness is likely to be a significant confounding variable in the study of many organ systems. The principal component of the in-flight cardiovascular exercise program should be large-muscle activity such as treadmill exercise. It is desirable that at least one session per week be monitored to assure maintenance of proper functional levels and to provide guidance for any adjustments of the exercise prescription. Appropriate measurements include evaluation of the heart-rate/workload or the heart-rate/oxygen-uptake relationship. Respiratory gas analysis is helpful by providing better opportunities to document relative workload levels from analysis of the interrelationships among VO2, VCO2, and ventilation. The committee felt that there is no clear evidence that any particular in-flight exercise regimen is protective against orthostatic hypotension during the early readaptation phase. Some group members suggested that maintenance of the lower body muscle mass and muscle tone may be helpful. There is also evidence that late in-flight interventions to reexpand blood volume to preflight levels are helpful in preventing or minimizing postflight orthostatic hypotension.
Hall, Wayne; Degenhardt, Louisa
For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest-that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.
Peroxisome proliferator-activated receptor Gamma (PPARγ), a ligand-activated transcription factor, has a role in various cellular functions as well as glucose homeostasis, lipid metabolism, and prevention of oxidative stress. The activators of PPARγ are already widely used in the treatment of diabetes mellitus. The cardioprotective effect of PPARγ activation has been studied extensively over the years making them potential therapeutic targets in diseases associated with cardiovascular disorders. However, they are also associated with adverse cardiovascular events such as congestive heart failure and myocardial infarction. This review aims to discuss the role of PPARγ in the various cardiovascular diseases and summarize the current knowledge on PPARγ agonists from multiple clinical trials. Finally, we also review the new PPARγ agonists under development as potential therapeutics with reduced or no adverse effects. PMID:28243251
Kounis, Nicholas G; Soufras, George D; Tsigkas, Grigorios; Hahalis, George
Monoclonal antibodies are currently used in the treatment of neoplastic, hematological, or inflammatory diseases, a practice that is occasionally associated with a variety of systemic and cutaneous adverse events. Cardiac adverse events include cardiomyopathy, ventricular dysfunction, arrhythmias, arrests, and acute coronary syndromes, such as acute myocardial infarction and vasospastic angina pectoris. These events generally follow hypersensitivity reactions including cutaneous erythema, pruritus chills, and precordial pain. Recently, IgE specific for therapeutic monoclonal antibodies have been detected, pointing to the existence of hypersensitivity and Kounis hypersensitivity-associated syndrome. Therefore, the careful monitoring of cardiovascular events is of paramount importance in the course of monoclonal antibody-based therapies. Moreover, further studies are needed to elucidate the pathophysiology of cardiovascular adverse events elicited by monoclonal antibodies and to identify preventive, protective, and therapeutic measures. PMID:25340003
Aursulesei, Viviana; Cozma, A; Krasniqi, A
Iron hypothesis has been a controversial subject for over 30 years as many studies support its role as a risk factor for cardiovascular disease, while other studies found no evidence to support it. The conflicting results are accounted for by the non-homogeneity of trial design in terms of population inclusion criteria and different endpoints, non-uniform use of parameters for assessing iron role, and incomplete understanding of the mechanisms of action. The nature of iron is dual, being of crucial importance for the human body, but also toxic as "free iron" induces oxidative stress. Under physiological conditions, there are efficient and complex mechanisms against iron-induced oxidative stress, which could be reproduced for creating new, intelligent antioxidants. Iron depletion improves the cardiovascular prognosis only if serum concentration is at the lowest limit of normal ranges. However, low iron levels and the type of dietary iron intake correlate with atherosclerotic cardiovascular disease, influence the ischemic endpoints in the elderly, and exert negative impact on heart failure prognosis. So far, the causal relation and involved mechanisms are not fully elucidated. Iron overload is a difficult and frequent condition, involving the cardiovascular system by specific pathogenic pathways, therefore determining a particular form of restrictive cardiomyopathy and vaso-occlusive arterial damage.
Friedman, Oded; Logan, Alexander G
Nocturnal hypertension and non-dipping of blood pressure during sleep are distinct entities that often occur together and are regarded as important harbingers of poor cardiovascular prognosis. This review addresses several aspects related to these blood pressure abnormalities including definitions, diagnostic limitations, pathogenesis and associated patient profiles, prognostic significance, and therapeutic strategies. Taken together, persistent nocturnal hypertension and non-dipping blood pressure pattern, perhaps secondary to abnormal renal sodium handling and/or altered nocturnal sympathovagal balance, are strongly associated with deaths, cardiovascular events, and progressive loss of renal function, independent of daytime and 24-hour blood pressure. Several pharmacological and non-pharmacological approaches may restore nocturnal blood pressure and circadian blood pressure rhythm to normal; however, whether this translates to a clinically meaningful reduction in unfavorable cardiovascular and renal consequences remains to be seen. PMID:21949613
Cardiovascular disease is the number one cause of death worldwide. It is broadly defined to include anything which adversely affects the heart or blood vessels. One-third of Americans have one or more forms of it. By one estimate, average human life expectancy would increase by seven years if it were eliminated. The mainstream medical model seeks mostly to "manage" cardiovascular disease with pharmaceuticals or to surgically bypass or reopen blocked vessels via angioplasty. These methods have proven highly useful and saved countless lives. Yet drug therapy may be costly and ongoing, and it carries the risk of side effects while often doing little or nothing to improve underlying health concerns. Similarly, angioplasty or surgery are invasive methods which entail risk. Laser therapy1 regenerates tissue, stimulates biological function, reduces inflammation and alleviates pain. Its efficacy and safety have been increasingly well documented in cardiovascular disease of many kinds. In this article we will explore the effects of laser therapy in angina, atherosclerosis, coronary artery disease, hypertension, hyperlipidemia, myocardial infarction, stroke and other conditions. The clinical application of various methods of laser therapy, including laserpuncture and transcutaneous, supravascular and intravenous irradiation of blood will be discussed. Implementing laser therapy in the treatment of cardiovascular disease offers the possibility of increasing the health and wellbeing of patients while reducing the costs and enhancing safety of medical care.
Passino, Claudio; Giannoni, Alberto; Milli, Massimo; Polettii, Roberta; Emdin, Michele
The pathophysiologic role of enhanced chemosensitivity to carbon dioxide and/or hypoxia has been underscored in several cardiovascular diseases, including heart failure. In the early stages of this syndrome, the chemoreflex acts as a compensatory mechanism. Later on, however, it contributes to sustain the sympathetic activation, with detrimental effects on cardiovascular function and prognosis.
What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article defined the different types of adverse drug reactions (ADRs) and explored when they can occur. It emphasised the importance of being knowledgeable about medications, considering patient safety when patients are taking medications, being alert to the possibility of ADRs, and recognising and responding to suspected ADRs.
Wood, Susan K; Valentino, Rita J
Chronic exposure to psychosocial stress has adverse effects on cardiovascular health, however the stress-sensitive neurocircuitry involved remains to be elucidated. The anatomical and physiological characteristics of the locus coeruleus (LC)-norepinephrine (NE) system position it to contribute to stress-induced cardiovascular disease. This review focuses on cardiovascular dysfunction produced by social stress and a major theme highlighted is that differences in coping strategy determine individual differences in social stress-induced cardiovascular vulnerability. The establishment of different coping strategies and cardiovascular vulnerability during repeated social stress has recently been shown to parallel a unique plasticity in LC afferent regulation, resulting in either excitatory or inhibitory input to the LC. This contrasting regulation of the LC would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The advances described suggest new directions for developing treatments and/or strategies for decreasing stress-induced cardiovascular vulnerability.
Martin, Bryan L; Nelson, Michael R; Hershey, Joyce N; Engler, Renata J M
(The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.) Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prolonged disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rare reaction risk. There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced risk communication intervention. When they occur, vaccine related adverse events must be treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.
Al-Hamoudi, Waleed K.
Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation, cirrhotic cardiomyopathy, and pulmonary vascular abnormalities. The pathogenic mechanisms of these cardiovascular changes are multifactorial and include neurohumoral and vascular dysregulations. Accumulating evidence suggests that cirrhosis-related cardiovascular abnormalities play a major role in the pathogenesis of multiple life-threatening complications including hepatorenal syndrome, ascites, spontaneous bacterial peritonitis, gastroesophageal varices, and hepatopulmonary syndrome. Treatment targeting the circulatory dysfunction in these patients may improve the short-term prognosis while awaiting liver transplantation. Careful fluid management in the immediate post-transplant period is extremely important to avoid cardiac-related complications. Liver transplantation results in correction of portal hypertension and reversal of all the pathophysiological mechanisms that lead to the cardiovascular abnormalities, resulting in restoration of a normal circulation. The following is a review of the pathogenesis and clinical implications of the cardiovascular changes in cirrhosis. PMID:20616408
The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk. PMID:25710019
The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk.
It has long been known from case series that vitamin D excess can lead to atherosclerosis and vascular calcification in humans. In the 1980s, ecological studies provided data that deficient human vitamin D status may also increase the risk of developing cardiovascular disease (CVD). The assumption of a biphasic vitamin D effect on CVD is supported by experimental studies: Numerous studies have demonstrated positive effects of the vitamin D hormone (1,25-dihydroxyviramin D) on the cardiovascular system. However, the effects and mechanisms that lead to vascular calcification by vitamin D excess could also be confirmed. Large prospective observational studies support the hypothesis of a U-shaped association between vitamin D and CVD. These studies indicate that deficient circulating 25-hydroxyvitamin D levels (<30 nmol/l) are independently-associated with increased CVD morbidity and mortality. They also suggest that those circulating 25-hydroxyvitamin D levels, which have long been considered to be safe (100-150 nmol/l), are associated with an increased CVD risk. Meanwhile, numerous randomized controlled trials have investigated the effects of vitamin D supplements or ultraviolet B radiation on biochemical cardiovascular risk markers, cardiovascular physiology, and cardiovascular outcomes. Overall, results are mixed with the majority of studies reporting neither beneficial nor adverse vitamin D effects. Several limitations in the study design, which may have prevented beneficial vitamin D effects, are discussed. In conclusion, it must be stated that the role of vitamin D in the prevention and management of CVD as well as the dose-response relationship of potentially harmful effects still remain to be established.
Al-Mohaissen, Maha A.; Ignaszewski, Martha J.; Frohlich, Jiri; Ignaszewski, Andrew P.
Statins are potent medications which reduce low-density lipoprotein cholesterol (LDL-C) levels. Their efficacy in cardiovascular risk reduction is well established and indications for their use are expanding. While statins are generally well tolerated and safe, adverse events are relatively common, particularly statin-associated muscle adverse events (SaMAEs), which are the most frequently encountered type of adverse event. Recent guidelines and guideline updates on SaMAEs and statin intolerance have included revised definitions of SaMAEs, incorporating new evidence on their pathogenesis and management. As SaMAEs emerge as a therapeutic challenge, it is important for physicians to be aware of updates on management strategies to ensure better patient outcomes. The majority of patients who are considered statin-intolerant can nevertheless tolerate some forms of statin therapy and successfully achieve optimal LDL-C levels. This review article discusses the recent classification of SaMAEs with emphasis on pathogenesis and management strategies. PMID:28003885
Frederiksen, Henrik; Christiansen, Christian Fynbo; Nørgaard, Mette
Adult immune thrombocytopenia was previously considered a benign disease affecting young people and with a low risk of severe bleeding. This view was challenged by studies published during the past decade, as the median age of adult immune thrombocytopenia patients has been found to be 55-60 years and the incidence increases with age. Recent studies reported that mortality and morbidity are increased compared with the general population. In this review, we describe patient-specific factors associated with the outcome of disease, the clinical course of immune thrombocytopenia including the potential adverse impact of some treatments and finally the overall prognosis.
Welin, L; Vedin, A; Wilhelmsson, C
Among 1809 patients with myocardial infarction, 60 (3.3%) later developed a postmyocardial infarction syndrome. These 60 patients were compared with controls with myocardial infarction but without postmyocardial infarction syndrome. Cases with postmyocardial infarction syndrome had larger and more complicated infarcts than control subjects. Five year cumulative mortality was higher among cases (26%) than among control subjects (18%) but this difference was not statistically significant. Corticosteroid treatment did not adversely affect the prognosis of the postmyocardial infarction syndrome, which we conclude is mainly determined by the severity of the underlying coronary heart disease. PMID:6882603
Roden, Dan M
Drugs are widely used and highly effective in the treatment of heart disease. Nevertheless, in some instances, even drugs effective in a population display lack of efficacy or adverse drug reactions in individual patients, often in an apparently unpredictable fashion. This review summarizes the genomic factors now known to influence variability in responses to widely used cardiovascular drugs such as clopidogrel, warfarin, heparin and statins. Genomic approaches being used to discover new pathways in common cardiovascular diseases and thus potential new targets for drug development are described. Finally, the way in which this new information is likely to be used in an electronic medical record environment is discussed. PMID:26178435
Durand, François; Valla, Dominique
Once patients with cirrhosis experience decompensation, early mortality risk increases sharply. Liver transplantation has transformed the prognosis of decompensated cirrhosis. Child-Pugh score has been the reference for many years for assessing the prognosis of cirrhosis. However, Child-Pugh score has important limitations among which is subjective interpretation of some of its variables, making it difficult to categorize patients according to their own disease severity. The model for end-stage liver disease (MELD) score, which was originally designed for assessing the prognosis of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), is a continuous score relying on three objective variables. Along with TIPS, MELD score proved to be a robust marker of early mortality across a wide spectrum of causes of cirrhosis, even though 10 to 20% of patients are still misclassified. MELD is especially useful for prioritizing candidates for transplantation according to a "sickest first" policy. However, MELD is not a universal prognostic marker of cirrhosis and several MELD exceptions require more specific approaches.
Lebrun-Vignes, B; Valeyrie-Allanore, L
Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions.
Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira
Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521
Reid, Ian R
Calcium supplements reduce bone turnover and slow the rate of bone loss. However, few studies have demonstrated reduced fracture incidence with calcium supplements, and meta-analyses show only a 10% decrease in fractures, which is of borderline statistical and clinical significance. Trials in normal older women and in patients with renal impairment suggest that calcium supplements increase the risk of cardiovascular disease. To further assess their safety, we recently conducted a meta-analysis of trials of calcium supplements, and found a 27%-31% increase in risk of myocardial infarction, and a 12%-20% increase in risk of stroke. These findings are robust because they are based on pre-specified analyses of randomized, placebo-controlled trials and are consistent across the trials. Co-administration of vitamin D with calcium does not lessen these adverse effects. The increased cardiovascular risk with calcium supplements is consistent with epidemiological data relating higher circulating calcium concentrations to cardiovascular disease in normal populations. There are several possible pathophysiological mechanisms for these effects, including effects on vascular calcification, vascular cells, blood coagulation and calcium-sensing receptors. Thus, the non-skeletal risks of calcium supplements appear to outweigh any skeletal benefits, and are they appear to be unnecessary for the efficacy of other osteoporosis treatments.
Janić, Miodrag; Lunder, Mojca; Šabovič, Mišo
The world population is aging and the number of old people is continuously increasing. Arterial structure and function change with age, progressively leading to arterial stiffening. Arterial stiffness is best characterized by measurement of pulse wave velocity (PWV), which is its surrogate marker. It has been shown that PWV could improve cardiovascular event prediction in models that included standard risk factors. Consequently, it might therefore enable better identification of populations at high-risk of cardiovascular morbidity and mortality. The present review is focused on a survey of different pharmacological therapeutic options for decreasing arterial stiffness. The influence of several groups of drugs is described: antihypertensive drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-blockers, diuretics, and nitrates), statins, peroral antidiabetics, advanced glycation end-products (AGE) cross-link breakers, anti-inflammatory drugs, endothelin-A receptor antagonists, and vasopeptidase inhibitors. All of these have shown some effect in decreasing arterial stiffness. Nevertheless, further studies are needed which should address the influence of arterial stiffness diminishment on major adverse cardiovascular and cerebrovascular events (MACCE). PMID:25170513
Frenzel, H; Roth, H; Schwartzkopff, B
Because of the high frequency of cardiovascular diseases and a steadily increasing consumption of alcohol the potentially causal relationship between alcohol and cardiovascular diseases gains great interest for public health policy. Alcohol and its metabolites induce a toxic damage of myocardial metabolism with an injury of electromechanic coupling. As a consequence of acute alcoholic intake cardiac arrhythmias and a reduced contractility of the myocardium are found not only for chronic alcoholics but also in healthy non-drinkers. Chronic abuse of alcoholic beverages for many years can be the cause of alcoholic cardiomyopathy in a small percentage of patients, who have a bad prognosis. Atria and ventricles are dilated, light and electron microscopic changes of the myocardium are unspecific. The pathogenesis of alcoholic cardiomyopathy is unknown, modulations of cardiomyocytic membranes are discussed in the course of a toxic damage. In the genesis of atherosclerosis alcohol can approach from different sites: Changings on thrombocytes and an increase of HDL-cholesterin can be protective, however an increase in blood pressure support the process of atherosclerosis. In numerous investigations a smaller degree of atherosclerosis was found for little or moderate alcohol intake, while in chronic heavy abuse of alcohol a higher extent of atherosclerosis was observed. As the amount of alcohol, assumed to be protective against the development of atherosclerosis, is consumed already by the majority of the population, there is no reason to propagate a regulate consume of moderate amount of alcoholic beverages.
Fu, Cong; Sheng, Zulong; Yao, Yuyu; Wang, Xin; Yu, Chaojun; Ma, Genshan
Coronary care unit is common in hospitals and clinical centers which offer intensive care and therapy for severe coronary artery disease patients. However, if coronary care unit could improve the long term prognosis of acute coronary syndrome patients with renal dysfunction remain unknown. Accordingly, we designed this study to evaluate the differences of incidence of major adverse cardiovascular events for acute coronary syndromes patients with renal dysfunction who treated in coronary care unit or normal unit. The primary end point was all cause mortality. A total of 414 acute coronary syndromes patients with renal dysfunction involved in the study. The results showed that during 12-48 months follow-up, death of any cause occurred in 1.8% patients (4 of 247) in coronary care unit group, as compared with 1.8% in the normal group (3 of 167) (hazard ratio, 1.098; 95% confidence interval, 0.246 to 4.904; P=0.903). Kaplan-Meier survival analysis showed that there were no significant differences between the two groups with respect to the risk of death (P=0.903), revascularization (P=0.948), stroke (P=0.542), heart failure (P=0.198). This trial firstly revealed that acute coronary syndromes patients with renal dysfunction treated in coronary care unit and normal units. Our study showed that acute coronary syndromes patients with renal dysfunction treated in coronary care unit obtained no significant benefits compared with patients in normal units, although there was a declining tendency of the risk of major adverse cardiovascular effectswith patients in coronary care unit.
Fu, Cong; Sheng, Zulong; Yao, Yuyu; Wang, Xin; Yu, Chaojun; Ma, Genshan
Coronary care unit is common in hospitals and clinical centers which offer intensive care and therapy for severe coronary artery disease patients. However, if coronary care unit could improve the long term prognosis of acute coronary syndrome patients with renal dysfunction remain unknown. Accordingly, we designed this study to evaluate the differences of incidence of major adverse cardiovascular events for acute coronary syndromes patients with renal dysfunction who treated in coronary care unit or normal unit. The primary end point was all cause mortality. A total of 414 acute coronary syndromes patients with renal dysfunction involved in the study. The results showed that during 12-48 months follow-up, death of any cause occurred in 1.8% patients (4 of 247) in coronary care unit group, as compared with 1.8% in the normal group (3 of 167) (hazard ratio, 1.098; 95% confidence interval, 0.246 to 4.904; P=0.903). Kaplan-Meier survival analysis showed that there were no significant differences between the two groups with respect to the risk of death (P=0.903), revascularization (P=0.948), stroke (P=0.542), heart failure (P=0.198). This trial firstly revealed that acute coronary syndromes patients with renal dysfunction treated in coronary care unit and normal units. Our study showed that acute coronary syndromes patients with renal dysfunction treated in coronary care unit obtained no significant benefits compared with patients in normal units, although there was a declining tendency of the risk of major adverse cardiovascular effectswith patients in coronary care unit. PMID:26770436
... Disease Venous Thromboembolism Aortic Aneurysm More Cardiovascular Disease & Diabetes Updated:Nov 4,2016 The following statistics speak ... disease. This content was last reviewed August 2015. Diabetes • Home • About Diabetes • Why Diabetes Matters Introduction Cardiovascular ...
Madani, H; Sadiki, E O; Bouziane, M; Amaarouch, S; Madani, M; Khatouf, M
Protamine is a polypeptide with low molecular weights that is used widely to reverse heparin anticoagulation during cardiac surgery. Protamine, efficient and relatively sure, can produce multiple adverse reactions after intravenous administration, including pulmonary hypertension, or systemic hypotension leading at times to cardiovascular collapse and death. Physiopathologic mechanisms, underlying these reactions, are not clear. Immunologic and non-immunologic pathways are suggested. Some risk factors expose to protamine's adverse reactions. Preoperative identification of these factors should prompt specific preventive measures. The anesthesiologist and the cardiac surgeon must be vigilant when administrating protamine. Reheparinization and reinstitution of cardiopulmonary bypass should be considered in patients with refractory shock.
Boerma, Marjan; Nelson, Gregory A; Sridharan, Vijayalakshmi; Mao, Xiao-Wen; Koturbash, Igor; Hauer-Jensen, Martin
Future long-distance space missions will be associated with significant exposures to ionizing radiation, and the health risks of these radiation exposures during manned missions need to be assessed. Recent Earth-based epidemiological studies in survivors of atomic bombs and after occupational and medical low dose radiation exposures have indicated that the cardiovascular system may be more sensitive to ionizing radiation than was previously thought. This has raised the concern of a cardiovascular disease risk from exposure to space radiation during long-distance space travel. Ground-based studies with animal and cell culture models play an important role in estimating health risks from space radiation exposure. Charged particle space radiation has dense ionization characteristics and may induce unique biological responses, appropriate simulation of the space radiation environment and careful consideration of the choice of the experimental model are critical. Recent studies have addressed cardiovascular effects of space radiation using such models and provided first results that aid in estimating cardiovascular disease risk, and several other studies are ongoing. Moreover, astronauts could potentially be administered pharmacological countermeasures against adverse effects of space radiation, and research is focused on the development of such compounds. Because the cardiovascular response to space radiation has not yet been clearly defined, the identification of potential pharmacological countermeasures against cardiovascular effects is still in its infancy.
Boerma, Marjan; Nelson, Gregory A; Sridharan, Vijayalakshmi; Mao, Xiao-Wen; Koturbash, Igor; Hauer-Jensen, Martin
Future long-distance space missions will be associated with significant exposures to ionizing radiation, and the health risks of these radiation exposures during manned missions need to be assessed. Recent Earth-based epidemiological studies in survivors of atomic bombs and after occupational and medical low dose radiation exposures have indicated that the cardiovascular system may be more sensitive to ionizing radiation than was previously thought. This has raised the concern of a cardiovascular disease risk from exposure to space radiation during long-distance space travel. Ground-based studies with animal and cell culture models play an important role in estimating health risks from space radiation exposure. Charged particle space radiation has dense ionization characteristics and may induce unique biological responses, appropriate simulation of the space radiation environment and careful consideration of the choice of the experimental model are critical. Recent studies have addressed cardiovascular effects of space radiation using such models and provided first results that aid in estimating cardiovascular disease risk, and several other studies are ongoing. Moreover, astronauts could potentially be administered pharmacological countermeasures against adverse effects of space radiation, and research is focused on the development of such compounds. Because the cardiovascular response to space radiation has not yet been clearly defined, the identification of potential pharmacological countermeasures against cardiovascular effects is still in its infancy. PMID:26730293
Tamargo, Juan; Castellano, José M; Fuster, Valentín
During the last decade, there has been a tremendous effort to develop different cardiovascular polypills in response to the upsurge in global cardiovascular disease worldwide. The pharmacological development of such a strategy has proven to be extremely complex from a formulation standpoint. Not all drugs are suitable for use in a polypill because of potential drug incompatibilities between them. Candidate agents must be safe, well tolerated, effective, guideline recommended and physiochemically compatible with the other components of the pill. The Fuster-CNIC-Ferrer cardiovascular (CV) polypill has been found to be the first-in-class polypill to be approved and commercialized in Europe and Latinamerican Countries. In this article, we review the pharmacological properties of its three components, including the clinical evidence supporting their use in patients with established cardiovascular disease, their pharmacokinetic properties, adverse effects, drug interactions and contraindications.
Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Myocardial Infarction; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Atherosclerosis
Nayak, Surajit; Acharjya, Basanti
In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR.
Background: Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is d...
Donaldson, Ken; Duffin, Rodger; Langrish, Jeremy P; Miller, Mark R; Mills, Nicholas L; Poland, Craig A; Raftis, Jennifer; Shah, Anoop; Shaw, Catherine A; Newby, David E
Nanoparticles (NPs) are tiny particles with a diameter of less than 100 nm. Traffic exhaust is a major source of combustion-derived NPs (CDNPs), which represent a significant component in urban air pollution. Epidemiological, panel and controlled human chamber studies clearly demonstrate that exposure to CDNPs is associated with multiple adverse cardiovascular effects in both healthy individuals and those with pre-existing cardiovascular disease. NPs are also manufactured from a large range of materials for industrial use in a vast array of products including for use as novel imaging agents for medical use. There is currently little information available on the impacts of manufactured NPs in humans, but experimental studies demonstrate similarities to the detrimental cardiovascular actions of CDNPs. This review describes the evidence for these cardiovascular effects and attempts to resolve the paradox between the adverse effects of the unintentional exposure of CDNPs and the intentional delivery of manufactured NPs for medical purposes.
Telithromycin is a macrolide antibiotic that has been marketed since the early 2000s. It has not been shown to be more effective against any bacteria than other macrolide antibiotics. Its antibacterial activity is in no way remarkable. In early 2014, we reviewed its adverse effect profile using data from periodic safety update reports, drug regulatory agencies, and detailed published case reports. In addition to the adverse effect profile telithromycin shares with the other macrolides, it provokes several specific adverse effects: visual disturbances due to impaired accommodation; taste and smell disorders; severe liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of consciousness. Prolongation of the QT interval with standard oral doses is a worrisome adverse effect. In practice, it is better not to use telithromycin as it exposes patients to disproportionate, serious adverse effects. When treatment with a macrolide antibiotic appears necessary, it is prudent to choose a different macrolide, such as spiramycin or azithromycin, which have fewer adverse effects.
As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.
Wang, Angela Yee Moon; Brimble, K Scott; Brunier, Gillian; Holt, Stephen G; Jha, Vivekanand; Johnson, David W; Kang, Shin-Wook; Kooman, Jeroen P; Lambie, Mark; McIntyre, Chris; Mehrotra, Rajnish; Pecoits-Filho, Roberto
Cardiovascular disease contributes significantly to the adverse clinical outcomes of peritoneal dialysis (PD) patients. Numerous cardiovascular risk factors play important roles in the development of various cardiovascular complications. Of these, loss of residual renal function is regarded as one of the key cardiovascular risk factors and is associated with an increased mortality and cardiovascular death. It is also recognized that PD solutions may incur significant adverse metabolic effects in PD patients. The International Society for Peritoneal Dialysis (ISPD) commissioned a global workgroup in 2012 to formulate a series of recommendations regarding lifestyle modification, assessment and management of various cardiovascular risk factors, as well as management of the various cardiovascular complications including coronary artery disease, heart failure, arrhythmia (specifically atrial fibrillation), cerebrovascular disease, peripheral arterial disease and sudden cardiac death, to be published in 2 guideline documents. This publication forms the first part of the guideline documents and includes recommendations on assessment and management of various cardiovascular risk factors. The documents are intended to serve as a global clinical practice guideline for clinicians who look after PD patients. The ISPD workgroup also identifies areas where evidence is lacking and further research is needed.
Vigorito, Carlo; Giallauria, Francesco
Progressive aging induces several structural and functional alterations in the cardiovascular system, among whom particularly important are a reduced number of myocardial cells and increased interstitial collagen fibers, which result in impaired left ventricular diastolic function. Even in the absence of cardiovascular disease, aging is strongly associated to a age-related reduced maximal aerobic capacity. This is due to a variety of physiological changes both at central and at peripheral level. Physical activity (PA) appears in general to have a positive effect on several health outcomes in the elderly. This review aims to illustrate the beneficial effects of exercise on the physiologic decline of cardiovascular performance occurring with age. Furthermore, it will be stressed also the positive effect of physical activity in elderly patients affected by cardiovascular diseases, such as heart failure and hypertension, and multiple comorbidities which may significantly worse prognosis in this high risk population. PMID:24600400
Vigorito, Carlo; Giallauria, Francesco
Progressive aging induces several structural and functional alterations in the cardiovascular system, among whom particularly important are a reduced number of myocardial cells and increased interstitial collagen fibers, which result in impaired left ventricular diastolic function. Even in the absence of cardiovascular disease, aging is strongly associated to a age-related reduced maximal aerobic capacity. This is due to a variety of physiological changes both at central and at peripheral level. Physical activity (PA) appears in general to have a positive effect on several health outcomes in the elderly. This review aims to illustrate the beneficial effects of exercise on the physiologic decline of cardiovascular performance occurring with age. Furthermore, it will be stressed also the positive effect of physical activity in elderly patients affected by cardiovascular diseases, such as heart failure and hypertension, and multiple comorbidities which may significantly worse prognosis in this high risk population.
Priebe, H J
factors contribute most of the increased perioperative risk related to advanced age. First, physiological ageing is accompanied by a progressive decline in resting organ function. Consequently, the reserve capacity to compensate for impaired organ function, drug metabolism and added physiological demands is increasingly impaired. Functional disability will occur more quickly and take longer to be cured. Second, ageing is associated with progressive manifestation of chronic disease which further limits baseline function and accelerates loss of functional reserve in the affected organ. Some of the age-related decline in organ function (e.g. impaired pulmonary gas exchange, diminished renal capacity to conserve and eliminate water and salt, or disturbed thermoregulation) will increase cardiovascular risk. The unpredictable interaction between age-related and disease-associated changes in organ functions, and the altered neurohumoral response to various forms of stress in the elderly may result in a rather atypical clinical presentation of a disease. This may, in turn, delay the correct diagnosis and appropriate treatment and, ultimately, worsen outcome. Third, related to the increased intake of medications and altered pharmacokinetics and pharmacodynamics, the incidence of untoward reactions to medications, anaesthetic agents, and medical and surgical interventions increases with advancing age. On the basis of various clinical studies and observations, it must be concluded that advanced age is an independent predictor of adverse perioperative cardiac outcome. It is to be expected that the aged cardiovascular risk patient carries an even higher perioperative cardiac risk than the younger cardiovascular risk patient. Although knowledge of the physiology of ageing should help reduce age-related complications, successful prophylaxis is hindered by the heterogeneity of age-related changes, unpredictable physiological and pharmacological interactions and diagnostic difficultie
Ranaivo, Irina Mamisoa; Andrianarison, Malalaniaina; Razanakoto, Naina Harinjara; Ramarozatovo, Lala Soavina
Rosai-Dorfman disease is a rare, benign histiocytic proliferative disorder that usually affects the lymph nodes. Although extranodal involvement has been reported in diverse sites, manifestation in the cardiovascular system is extremely rare. Specifically, cardiac involvement in Rosai-Dorfman disease is an extraordinarily infrequent event. We describe a case of a 36-year-old female who presented Rosai-Dorfman disease of multiple organs including the heart, with poor prognosis. PMID:27872644
AD/A-006 19U MECHANICAL FAILURE PROGNOSIS THROUGH OIL DEBRIS MONITORING Alan Beex"bower Exxon Research and Engineering Company Prepared...PERIOD COVERED Final Report 18 June 1973 to 1 August 197A 4. TITLE (•«id Subl/rl«) MECHANICAL FAILURE PROGNOSIS THROUGH OIL DEBRIS ...Company project entitled "Mechanical Failure Prognosis through Debris Analysis." This study was conducted for the Eustis Directorate, U.S. Army Air
Maravelias, C; Dona, A; Stefanidou, M; Spiliopoulou, C
Anabolic-androgenic steroids (AAS) are used as ergogenic aids by athletes and non-athletes to enhance performance by augmenting muscular development and strength. AAS administration is often associated with various adverse effects that are generally dose related. High and multi-doses of AAS used for athletic enhancement can lead to serious and irreversible organ damage. Among the most common adverse effects of AAS are some degree of reduced fertility and gynecomastia in males and masculinization in women and children. Other adverse effects include hypertension and atherosclerosis, blood clotting, jaundice, hepatic neoplasms and carcinoma, tendon damage, psychiatric and behavioral disorders. More specifically, this article reviews the reproductive, hepatic, cardiovascular, hematological, cerebrovascular, musculoskeletal, endocrine, renal, immunologic and psychologic effects. Drug-prevention counseling to athletes is highlighted and the use of anabolic steroids is must be avoided, emphasizing that sports goals may be met within the framework of honest competition, free of doping substances.
Meyer, Roger E. , Ed.
This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…
Zyubin, A.; Lavrova, A.; Babak, S.; Malaschenko, V.; Borisova, A.; Opryshko, N.
The treatment of acute lymphoblastic leukemia (ALL) can result in the side-effects such as kidney affection, hepatic failure and tissue hypoxia. We study dynamics of special biochemical marker of these pathologies - adenosine triphosphate, that is well-known substance of energy metabolism. We use methods of confocal microscopy for determining the cellular and mitochondrial concentration of adenosine triphosphate (ATP). Quantitative values of adenosine triphosphate were calculated for each patient and correlation with degree of side-effects had been done. The application of confocal microscopy for studying of side-effects and therapy of lymphoblastic leukemia is discussed.
Kohansieh, Michelle; Makaryus, Amgad N.
Sleep plays a vital role in an individual's mental, emotional, and physiological well-being. Not only does sleep deficiency lead to neurological and psychological disorders, but also the literature has explored the adverse effects of sleep deficiency on the cardiovascular system. Decreased quantity and quality of sleep have been linked to cardiovascular disease (CVD) risk factors, such as hypertension, obesity, diabetes, and dyslipidemia. We explore the literature correlating primary sleep deficiency and deprivation as a cause for cardiovascular disease and cite endothelial dysfunction as a common underlying mechanism. PMID:26495139
Fassett, Robert G; Coombes, Jeff S
Oxidative stress and inflammation are established processes contributing to cardiovascular disease caused by atherosclerosis. However, antioxidant therapies tested in cardiovascular disease such as vitamin E, C and β-carotene have proved unsuccessful at reducing cardiovascular events and mortality. Although these outcomes may reflect limitations in trial design, new, more potent antioxidant therapies are being pursued. Astaxanthin, a carotenoid found in microalgae, fungi, complex plants, seafood, flamingos and quail is one such agent. It has antioxidant and anti-inflammatory effects. Limited, short duration and small sample size studies have assessed the effects of astaxanthin on oxidative stress and inflammation biomarkers and have investigated bioavailability and safety. So far no significant adverse events have been observed and biomarkers of oxidative stress and inflammation are attenuated with astaxanthin supplementation. Experimental investigations in a range of species using a cardiac ischaemia-reperfusion model demonstrated cardiac muscle preservation when astaxanthin is administered either orally or intravenously prior to the induction of ischaemia. Human clinical cardiovascular studies using astaxanthin therapy have not yet been reported. On the basis of the promising results of experimental cardiovascular studies and the physicochemical and antioxidant properties and safety profile of astaxanthin, clinical trials should be undertaken.
Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobiological disorder exhibited by difficulty maintaining attention, as well as hyperactivity and impulsive behavior. Central nervous system (CNS) stimulants are the first line of treatment for ADHD. With the increase in number of adults on CNS stimulants, the question that arises is how well do we understand the long-term cardiovascular effects of these drugs. There has been increasing concern that adults with ADHD are at greater risk for developing adverse cardiovascular events such as sudden death, myocardial infarction, and stroke as compared to pediatric population. Cardiovascular response attributed to ADHD medication has mainly been observed in heart rate and blood pressure elevations, while less is known about the etiology of rare cardiovascular events like acute myocardial infarction (AMI), arrhythmia, and cardiomyopathy and its long-term sequelae. We present a unique case of AMI in an adult taking Adderall (mixed amphetamine salts) and briefly discuss the literature relevant to the cardiovascular safety of CNS stimulants for adult ADHD. PMID:27579185
Rationale: Epidemiological studies have shown an association between the incidence of adverse cardiovascular effects and exposure to ambient particulate matter (PM). Advanced age is among the factors identified as conferring susceptibility to PM inhalation. In order to characteri...
Thieme, D; Büttner, A
Doping -the abuse of anabolic-androgenic steroids in particular- is widespread in amateur and recreational sports and does not solely represent a problem of professional sports. Excessive overdose of anabolic steroids is well documented in bodybuilding or powerlifting leading to significant side effects. Cardiovascular damages are most relevant next to adverse endocrine effects.Clinical cases as well as forensic investigations of fatalities or steroid consumption in connection with trafficking of doping agents provide only anecdotal evidence of correlations between side effects and substance abuse. Analytical verification and self-declarations of steroid users have repeatedly confirmed the presumption of weekly dosages between 300 and 2000 mg, extra to the fact that co-administration of therapeutics to treat side-effects represent a routine procedure. Beside the most frequent use of medications used to treat erectile dysfunction or estrogenic side-effects, a substantial number of antihypertensive drugs of various classes, i.e. beta-blockers, diuretics, angiotensin II receptor antagonists, calcium channel blockers, as well as ACE inhibitors were recently confiscated in relevant doping cases. The presumptive correlation between misuse of anabolic steroids and self-treatment of cardiovascular side effects was explicitly confirmed by detailed user statements.Two representative fatalities of bodybuilders were introduced to outline characteristic, often lethal side effects of excessive steroid abuse. Moreover, illustrative autopsy findings of steroid acne, thrombotic occlusion of Ramus interventricularis anterior and signs of cardiac infarctions are presented.A potential steroid abuse should be carefully considered in cases of medical consultations of patients exhibiting apparent constitutional modifications and corresponding adverse effects. Moreover, common self-medications -as frequently applied by steroid consumers- should be taken into therapeutic considerations.
Yim, Kaitlyn M; Armstrong, April W
Psoriasis and psoriatic arthritis are associated with a significantly increased risk of cardiovascular risk factors and major adverse cardiovascular events (MACE). Active research is ongoing to elucidate this relationship between psoriatic diseases and cardiovascular comorbidities, as well as their shared pathogenic mechanisms. This review focuses on (1) the epidemiologic association between psoriasis and cardiovascular risk factors, (2) the epidemiologic association between psoriasis and MACE, (3) the epidemiologic association between psoriatic arthritis, cardiovascular risk factors, and MACE, and (4) proposed mechanisms for the contribution of psoriatic diseases to cardiovascular diseases. The proposed mechanisms for shared pathogenesis between psoriatic diseases and cardiovascular diseases are inflammation, insulin resistance, dyslipidemia, angiogenesis, oxidative stress, and endothelial dysfunction. There is complex interplay and overlap among these mechanisms and their contributions to shared pathogenesis. Future translational research is necessary to elucidate the link between psoriatic diseases and cardiovascular diseases. Such findings may be applied clinically to improve the lives of psoriasis patients.
Edmondson, Donald; von Känel, Roland
In this paper, a first in a Series of two, we look at the evidence for an association of post-traumatic stress disorder with incident cardiovascular disease risk and the mechanisms that might cause this association, as well as the prevalence of post-traumatic stress disorder due to cardiovascular disease events and its associated prognostic risk. We discuss research done after the publication of previous relevant systematic reviews, and survey currently funded research from the two most active funders in the field: the National Institutes of Health and the US Veterans Administration. We conclude that post-traumatic stress disorder is a risk factor for incident cardiovascular disease, and a common psychiatric consequence of cardiovascular disease events that might worsen the prognosis of the cardiovascular disease. There are many candidate mechanisms for the link between post-traumatic stress disorder and cardiovascular disease, and several ongoing studies could soon point to the most important behavioural and physiological mechanisms to target in early phase intervention development. Similarly, targets are emerging for individual and environmental interventions that might offset the risk of post-traumatic stress disorder after cardiovascular disease events.
Costa, Luísa Amado; Almeida, Ana G
The cardiovascular manifestations of human immunodeficiency virus (HIV) infection have changed significantly following the introduction of highly active antiretroviral therapy (HAART) regimens. On one hand, HAART has altered the course of HIV disease, with longer survival of HIV-infected patients, and cardiovascular complications of HIV infection such as myocarditis have been reduced. On the other hand, HAART is associated with an increase in the prevalence of both peripheral and coronary arterial disease. As longevity increases in HIV-infected individuals, long-term effects, such as cardiovascular disease, are emerging as leading health issues in this population. In the present review article, we discuss HIV-associated cardiovascular disease, focusing on epidemiology, etiopathogenesis, diagnosis, prognosis, management and therapy. Cardiovascular involvement in treatment-naive patients is still important in situations such as non-adherence to treatment, late initiation of treatment, and/or limited access to HAART in developing countries. We therefore describe the cardiovascular consequences in treatment-naive patients and the potential effect of antiretroviral treatment on their regression, as well as the metabolic and cardiovascular implications of HAART regimens in HIV-infected individuals.
Davidson, Sean M; Takov, Kaloyan; Yellon, Derek M
Most, if not all, cells of the cardiovascular system secrete small, lipid bilayer vesicles called exosomes. Despite technical challenges in their purification and analysis, exosomes from various sources have been shown to be powerfully cardioprotective. Indeed, it is possible that much of the so-called "paracrine" benefit in cardiovascular function obtained by stem cell therapy can be replicated by the injection of exosomes produced by stem cells. However, exosomes purified from plasma appear to be just as capable of activating cardioprotective pathways. We discuss the potential roles of endogenous exosomes in the cardiovascular system, how this is perturbed in cardiovascular disease, and evaluate their potential as therapeutic agents to protect the heart.
Torres, Tiago; Sales, Rita; Vasconcelos, Carlos; Selores, Manuela
Psoriasis is a common, chronic and systemic inflammatory disease associated with several comorbidities, such as obesity, hypertension, diabetes, dyslipidaemia and metabolic syndrome, but also with an increased risk of cardiovascular disease, like myocardial infarction or stroke. The chronic inflammatory nature of psoriasis has been suggested to be a contributing and potentially independent risk factor for the development of cardiovascular comorbidities and precocious atherosclerosis. Aiming at alerting clinicians to the need of screening and monitoring cardiovascular diseases and its risk factors in psoriatic patients, this review will focus on the range of cardiometabolic comorbidities and increased risk of cardiovascular disease associated with psoriasis.
Recent epidemiological studies indicate that exposure to ionising radiation enhances the risk of cardiovascular mortality and morbidity in a moderate but significant manner. Our goal is to identify molecular mechanisms involved in the pathogenesis of radiation-induced cardiovascular disease using cellular and mouse models. Two radiation targets are studied in detail: the vascular endothelium that plays a pivotal role in the regulation of cardiac function, and the myocardium, in particular damage to the cardiac mitochondria. Ionising radiation causes immediate and persistent alterations in several biological pathways in the endothelium in a dose- and dose-rate dependent manner. High acute and cumulative doses result in rapid, non-transient remodelling of the endothelial cytoskeleton, as well as increased lipid peroxidation and protein oxidation of the heart tissue, independent of whether exposure is local or total body. Proteomic and functional changes are observed in lipid metabolism, glycolysis, mitochondrial function (respiration, ROS production etc.), oxidative stress, cellular adhesion, and cellular structure. The transcriptional regulators Akt and PPAR alpha seem to play a central role in the radiation-response of the endothelium and myocardium, respectively. We have recently started co-operation with GSI in Darmstadt to study the effect of heavy ions on the endothelium. Our research will facilitate the identification of biomarkers associated with adverse cardiac effects of ionising radiation and may lead to the development of countermeasures against radiation-induced cardiac damage.
Ederhy, S; Hollebecque, A; Haddour, N; Massard, C; Fleury, G; Ferte, C; Adavane, S; Besse, B; Boccara, F; Soria, J-C; Cohen, A
The management of patients suffering from bronchial and lung tumors depends on conventional chemotherapy and/or targeted molecular therapies. The prescription of these chemotherapies may be accompanied by cardiovascular complications, principally congestive heart failure, arterial hypertension and arterial or venous thrombo-embolism, the frequency of which varies with the molecule administered. The management of these complications is currently poorly standardized and should take account of the patient's oncological prognosis.
Imbesi, S; Allegra, A; Calapai, G; Musolino, C; Gangemi, S
Lenalidomide is an immunomodulatory drug (IMiD) used principally in the treatment of multiple myeloma (MM), myelodysplastic syndromes (MS) and amyloidosis. Adverse reactions related to lenalidomide include myelosuppression (mainly neutropenia but also thrombocytopenia), gastrointestinal problems, skin eruption, atrial fibrillation and asthenia, decreased peripheral blood stem cell yield during stem cell collection, venous thromboembolism, and secondary malignances. In this review we focused our attention on the cutaneous adverse reactions to lenalidomide.
Cubbon, Richard M.; Abbas, Afroze; Wheatcroft, Stephen B.; Kilcullen, Niamh; Das, Raj; Morrell, Christine; Barth, Julian H.; Kearney, Mark T.; Hall, Alistair S.
Background Diabetes Mellitus (DM) is associated with adverse cardiovascular prognosis. However, the risk associated with DM may vary between individuals according to their overall cardiovascular risk burden. Therefore, we aimed to determine whether DM is associated with poor outcome in patients presenting with Acute Coronary Syndrome (ACS) according to the index episode being a first or recurrent cardiovascular event. Methods and Findings We conducted a retrospective analysis of a prospective cohort study involving 2499 consecutively admitted patients with confirmed ACS in 11 UK hospitals during 2003. Usual care was provided for all participants. Demographic factors, co-morbidity and treatment (during admission and at discharge) factors were recorded. The primary outcome was all cause mortality (median 2 year follow up), compared for cohorts with and without DM according to their prior cardiovascular disease (CVD) disease status. Adjusted analyses were performed with Cox proportional hazards regression analysis. Within the entire cohort, DM was associated with an unadjusted 45% increase in mortality. However, in patients free of a history of CVD, mortality of those with and without DM was similar (18.8% and 19.7% respectively; p = 0.74). In the group with CVD, mortality of patients with DM was significantly higher than those without DM (46.7% and 33.2% respectively; p<0.001). The age and sex adjusted interaction between DM and CVD in predicting mortality was highly significant (p = 0.002) and persisted after accounting for comorbidities and treatment factors (p = 0.006). Of patients free of CVD, DM was associated with smaller elevation of Troponin I (p<0.001). However in patients with pre-existing CVD Troponin I was similar (p = 0.992). Conclusions DM is only associated with worse outcome after ACS in patients with a pre-existing history of CVD. Differences in the severity of myocyte necrosis may account for this. Further investigation is required
Smyth, Andrew; O'Donnell, Martin; Mente, Andrew; Yusuf, Salim
Although an essential nutrient, higher sodium intake is associated with increasing blood pressure (BP), forming the basis for current population-wide sodium restriction guidelines. While short-term clinical trials have achieved low intake (<2.0 g/day), this has not been reproduced in long-term trials (>6 months). Guidelines assume that low sodium intake will reduce BP and reduce cardiovascular disease (CVD), compared to moderate intake. However, current observational evidence suggests a J-shaped association between sodium intake and CVD; the lowest risks observed with 3-5 g/day but higher risk with <3 g/day. Importantly, these observational data also confirm the association between higher intake (>5 g/day) and increased risk of CVD. Although lower intake may reduce BP, this may be offset by marked increases in neurohormones and other adverse effects which may paradoxically be adverse. Large randomised clinical trials with sufficient follow-up are required to provide robust data on the long-term effects of sodium reduction on CVD incidence. Until such trials are completed, current evidence suggests that moderate sodium intake for the general population (3-5 g/day) is likely the optimum range for CVD prevention.
da Silva, Rose M. F. L.
Syncope is a common medical problem, with a frequency between 15% and 39%. In the general population, the annual number episodes are 18.1–39.7 per 1000 patients, with similar incidence between genders. The first report of the incidence of syncope is 6.2 per 1000 person-years. However, there is a significant increase in the incidence of syncope after 70 years of age with rate annual 19.5 per thousand individuals after 80 years. It presents a recurrence rate of 35% and 29% of physical injury. Among the causes of syncope, the mediated neural reflex, known as neurocardiogenic or vasovagal syncope, is the most frequent. The others are of cardiac origin, orthostatic hypotension, carotid sinus hypersensitivity, neurological and endocrinological causes and psychiatric disorders. The diagnosis of syncope can be made by clinical method associated with the electrocardiogram in up 50% of patients. Its prognosis is determined by the underlying etiology specifically the presence and severity of cardiac disease. The annual mortality can reach between 18 and 33% if cardiac cause, and between 0 and 12% if the non-cardiac cause. Thus, it is imperative to identify its cause and risk stratification for positive impact in reducing morbidity and mortality. PMID:25538626
Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre
The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference
Bartalena, L; Bogazzi, F; Martino, E
Thyroid hormone preparations, especially thyroxine, are widely used either at replacement doses to correct hypothyroidism or at suppressive doses to abolish thyrotropin (thyroid-stimulating hormone) secretion in patients with differentiated thyroid carcinoma after total thyroidectomy or with diffuse/ nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is necessary to administer slightly supraphysiological doses of thyroxine. Possible adverse effects of this therapy include cardiovascular changes (shortening of systolic time intervals, increased frequency of atrial premature beats and, possibly, left ventricular hypertrophy) and bone changes (reduced bone density and bone mass), but the risk of these adverse effects can be minimised by carefully monitoring serum free thyroxine and free liothyronine (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely used antithyroid drugs. They are given for long periods of time and cause adverse effects in 3 to 5% of patients. In most cases, adverse effects are minor and transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life-threatening condition can now be effectively treated by granulocyte colony-stimulating factor administration. Other major adverse effects (aplastic anaemia, thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly rare.
Dasinger, John Henry; Alexander, Barbara T
Hypertension is a risk factor for cardiovascular disease, the leading cause of death worldwide. Although multiple factors contribute to the pathogenesis of hypertension, studies by Dr David Barker reporting an inverse relationship between birth weight and blood pressure led to the hypothesis that slow growth during fetal life increased blood pressure and the risk for cardiovascular disease in later life. It is now recognized that growth during infancy and childhood, in addition to exposure to adverse influences during fetal life, contributes to the developmental programming of increased cardiovascular risk. Numerous epidemiological studies support the link between influences during early life and later cardiovascular health; experimental models provide proof of principle and indicate that numerous mechanisms contribute to the developmental origins of chronic disease. Sex has an impact on the severity of cardiovascular risk in experimental models of developmental insult. Yet, few studies examine the influence of sex on blood pressure and cardiovascular health in low-birth weight men and women. Fewer still assess the impact of ageing on sex differences in programmed cardiovascular risk. Thus, the aim of the present review is to highlight current data about sex differences in the developmental programming of blood pressure and cardiovascular disease.
Pilz, Stefan; Tomaschitz, Andreas; März, Winfried; Drechsler, Christiane; Ritz, Eberhard; Zittermann, Armin; Cavalier, Etienne; Pieber, Thomas R; Lappe, Joan M; Grant, William B; Holick, Michael F; Dekker, Jacqueline M
A poor vitamin D status, i.e. low serum levels of 25-hydroxyvitamin D [25(OH)D], is common in the general population. This finding is of concern not only because of the classic vitamin D effects on musculoskeletal outcomes, but also because expression of the vitamin D receptor (VDR) and vitamin D metabolizing enzymes in the heart and blood vessels suggests a role of vitamin D in the cardiovascular system. VDR-knockout mice suffer from cardiovascular disease (CVD), and various experimental studies suggest cardiovascular protection by vitamin D, including antiatherosclerotic, anti-inflammatory and direct cardio-protective actions, beneficial effects on classic cardiovascular risk factors as well as suppression of parathyroid hormone (PTH) levels. In epidemiological studies, low levels of 25(OH)D are associated with increased risk of CVD and mortality. Data from randomized controlled trials (RCTs) are sparse and have partially, but not consistently, shown some beneficial effects of vitamin D supplementation on cardiovascular risk factors (e.g. arterial hypertension). We have insufficient data on vitamin D effects on cardiovascular events, but meta-analyses of RCTs indicate that vitamin D may modestly reduce all-cause mortality. Despite accumulating data suggesting that a sufficient vitamin D status may protect against CVD, we still must wait for results of large-scale RCTs before raising general recommendations for vitamin D in the prevention and treatment of CVD. In current clinical practice, the overall risks and costs of vitamin D supplementation should be weighed against the potential adverse consequences of untreated vitamin D deficiency.
Some myelodysplastic syndromes carry a poor prognosis. This is also the case for chronic myelomonocytic leukaemia (related to myelodysplastic syndromes), and acute myeloblastic leukaemia, a frequent complication of myelodysplasia. The only treatment capable of providing long-term remission (in about 1 in 2 patients on average) is haematopoietic stem cell transplantation, but this burdensome treatment can only be used in a minority of cases. Azacitidine (Vidaza, Celgene), an agent that blocks DNA synthesis, is the first drug to receive EU marketing authorisation in these settings. Its clinical evaluation is based on an unblinded trial that included 358 patients comparable to those discussed in the marketing authorisation. In addition to individually tailored symptomatic care, they were randomised to receive either azacitidine or conventional care regimens chosen by their physician (no treatment, low-dose cytarabine, or an anthracycline plus cytarabine). The median overall survival time was significantly longer with azacitidine (24.5 versus 15 months), and transfusion requirements were also reduced. Another comparative trial versus symptomatic treatment alone in 191 patients with various prognoses also showed an increase in survival time with azacitidine, but this study suffered from methodological flaws. The main adverse effects of azacitidine are potentially severe toxicity for various blood cells, gastrointestinal disorders, and reactions at the injection site. In practice, when haematopoietic stem cell transplantation is not feasible for poor-prognosis patients with myelodysplastic syndromes or related disorders, azacitidine can be used instead of disappointing standard treatments, even though more clinical evaluation is needed.
Nezafati, Mohammad Hassan; Eshraghi, Ali; Vojdanparast, Mohammad; Abtahi, Saeed; Nezafati, Pouya
Background: Given the importance of the role of depression in predicting the outcome of cardiovascular disorders, current medications for treating depression, particularly selective serotonin reuptake inhibitors (SSRIs), are taken into consideration. This study aimed to systematically review the published findings in the use of SSRIs and the risk for cardiac events. Materials and Methods: An independent review of the Web of Science, PubMed, Scopus, Cochrane, CINAHL, index Copernicus, and Google Scholar, up to 2014, was performed. We identified studies evaluating the effect of SSRIs, on cardiovascular events. Articles in English with full text availability, review articles, and experimental studies were included in the study. Among 150 studies reviewed based on the included keywords, 17 met the study criteria and were finally reviewed. Results: The use of some types of SSRIs may prevent platelet adhesion and aggregation; control the cardiovascular risk profile including hypertension, insulin resistance, and body weight; and also inhibit inflammatory processes. The appearance of adverse cardiac events, including cardiac arrhythmias (torsade de pointes and QT prolongation), syncope, increased systolic and diastolic right ventricular volume, and the production of pro-inflammatory cytokines leading atherosclerosis development, has also been expected with the chronic use of some types of SSRIs. Conclusion: According to our systematic review, both beneficial and adverse cardiovascular events can be established following the chronic use of various types of SSRIs. Therefore, when taking SSRIs, the cardiovascular effect of each SSRI has to be carefully considered, based on patients’ cardiovascular risk profiles. PMID:27904611
Wessel, Niels; Kurths, Jürgen; Ditto, William; Bauernschmitt, Robert
The number of patients suffering from cardiovascular diseases increases unproportionally high with the increase of the human population and aging, leading to very high expenses in the public health system. Therefore, the challenge of cardiovascular physics is to develop high-sophisticated methods which are able to, on the one hand, supplement and replace expensive medical devices and, on the other hand, improve the medical diagnostics with decreasing the patient's risk. Cardiovascular physics-which interconnects medicine, physics, biology, engineering, and mathematics-is based on interdisciplinary collaboration of specialists from the above scientific fields and attempts to gain deeper insights into pathophysiology and treatment options. This paper summarizes advances in cardiovascular physics with emphasis on a workshop held in Bad Honnef, Germany, in May 2005. The meeting attracted an interdisciplinary audience and led to a number of papers covering the main research fields of cardiovascular physics, including data analysis, modeling, and medical application. The variety of problems addressed by this issue underlines the complexity of the cardiovascular system. It could be demonstrated in this Focus Issue, that data analyses and modeling methods from cardiovascular physics have the ability to lead to significant improvements in different medical fields. Consequently, this Focus Issue of Chaos is a status report that may invite all interested readers to join the community and find competent discussion and cooperation partners.
Wessel, Niels; Kurths, Jürgen; Ditto, William; Bauernschmitt, Robert
The number of patients suffering from cardiovascular diseases increases unproportionally high with the increase of the human population and aging, leading to very high expenses in the public health system. Therefore, the challenge of cardiovascular physics is to develop high-sophisticated methods which are able to, on the one hand, supplement and replace expensive medical devices and, on the other hand, improve the medical diagnostics with decreasing the patient's risk. Cardiovascular physics-which interconnects medicine, physics, biology, engineering, and mathematics-is based on interdisciplinary collaboration of specialists from the above scientific fields and attempts to gain deeper insights into pathophysiology and treatment options. This paper summarizes advances in cardiovascular physics with emphasis on a workshop held in Bad Honnef, Germany, in May 2005. The meeting attracted an interdisciplinary audience and led to a number of papers covering the main research fields of cardiovascular physics, including data analysis, modeling, and medical application. The variety of problems addressed by this issue underlines the complexity of the cardiovascular system. It could be demonstrated in this Focus Issue, that data analyses and modeling methods from cardiovascular physics have the ability to lead to significant improvements in different medical fields. Consequently, this Focus Issue of Chaos is a status report that may invite all interested readers to join the community and find competent discussion and cooperation partners.
An NCI Cancer Currents blog about a study of a new type of cancer biomarker that measures the extent of chromosomal instability as a way to potentially predict patient prognosis and help guide cancer treatment choices.
NIU, JIAMIN; HAN, XIA; QI, HUAXIN; YIN, JIE; ZHANG, ZHIQIANG; ZHANG, ZENGTANG
The aim of the present study was to investigate the correlation between plasma the levels of vascular endothelial growth factor (VEGF) and major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI). A total of 124 patients with AMI undergoing emergency percutaneous coronary intervention (PCI) were selected, and plasma VEGF levels were measured 7 days after the onset of AMI using an enzyme-linked immunosorbent assay. The patients were divided into the L (≤190 pg/ml VEGF) and H (>190 pg/ml VEGF) groups, and were followed up every 2 months for an average of 12 months. MACE were recorded during follow-up. On the basis of these results, the patients were further divided into the MACE and non-MACE (N-MACE) groups, and the serum VEGF concentration was compared between the two groups. At the 6-month follow-up, the incidence of MACE in the H group was found to be significantly reduced compared with the L group. The serum VEGF concentration in the N-MACE group was significantly higher compared with the MACE group. Multinomial logistic regression revealed that reduced VEGF levels (β=1.243; 95% CI, 1.018–1.326; P=0.026) were independent risk factors for MACE. In conclusion, high plasma VEGF levels at 7 days after AMI onset facilitate the long-term prognosis in the same infarct zone in patients with AMI, while low plasma VEGF levels are independent risk factors for MACE. PMID:27347081
The London physician and neuroanatomist Thomas Willis in the 17th century correctly attributed the source of emotions to the brain, not the heart as believed in antiquity. Contemporary research documents the phenomenon of "triggered" heart disease, when the autonomic nervous system control of the heart by the brain goes awry, producing heart disease of sudden onset, precipitated by acute emotional upheaval. This can take the form of, variously, cardiac arrhythmias, myocardial infarction, Takotsubo cardiomyopathy and sudden death. Chronic psychological distress also can have adverse cardiovascular consequences, in the causal linkage of depressive illness to heart disease, and in the probable causation of atherosclerosis and hypertension by chronic mental stress. In patients with essential hypertension, stress biomarkers are present. The sympathetic nervous system is the usual mediator between these acute and chronic psychological substrates and cardiovascular disease.
McGrath, K-C Y; McRobb, L S; Heather, A K
Cardiovascular disease (CVD) remains the leading cause of death in Western society today. There is a striking gender difference in CVD with men predisposed to earlier onset and more severe disease. Following the recent reevaluation and ongoing debate regarding the estrogen protection hypothesis, and given that androgen use and abuse is increasing in our society, the alternate view that androgens may promote CVD in men is assuming increasing importance. Whether androgens adversely affect CVD in either men or women remains a contentious issue within both the cardiovascular and endocrinological fraternities. This review draws from basic science, animal and clinical studies to outline our current understanding regarding androgen effects on atherosclerosis, the major CVD, and asks where future directions of atherosclerosis-related androgen research may lie.
The chronic diabetes mellitus (DM) is a major risk factor for cardiovascular disease. The incidence of cardiovascular disease might be a foremost cause of morbidity and mortality in patients afflicted with DM. In fact, DM is associated with multi-factorial cardiovascular signalling alterations via significant modulation of expression pattern, activation or release of PI3K, PKB, eNOS, EDRF, NADPH oxidase, EDHF, CGRP, adenosine, iNOS, ROCK, PKC-β2, CaMKII, microRNA (miR)-126 and miR-130a, which could result in inadequate maintenance of cardiovascular physiology and subsequent development of cardiovascular pathology. This review highlights the possible adverse implications of fundamental cardiovascular signalling alteration in DM-associated cardiovascular disease pathology.
Maantay, Juliana A.; Chakraborty, Jayajit
How living near environmental hazards contributes to poorer health and disproportionate health outcomes is an ongoing concern. We conducted a substantive review and critique of the literature regarding residential proximity to environmental hazards and adverse pregnancy outcomes, childhood cancer, cardiovascular and respiratory illnesses, end-stage renal disease, and diabetes. Several studies have found that living near hazardous wastes sites, industrial sites, cropland with pesticide applications, highly trafficked roads, nuclear power plants, and gas stations or repair shops is related to an increased risk of adverse health outcomes. Government agencies should consider these findings in establishing rules and permitting and enforcement procedures to reduce pollution from environmentally burdensome facilities and land uses. PMID:22028451
Kangas, L.J.; Keller, P.E.; Hashem, S.; Kouzes, R.T.
In this paper, a novel approach to modeling and diagnosing the cardiovascular system is introduced. A model exhibits a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. Potentially, a model will be incorporated into a cardiovascular diagnostic system. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and the variables of an individual at a given time are used for diagnosis. This approach also exploits sensor fusion to optimize the utilization of biomedical sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.
Cantwell, John D.; Rose, Fred D.
The case of a 21-year-old man who suffered a myocardial infarction after using cocaine and amphetamines is reported. A brief literature review provides evidence of cocaine's potential cardiovascular effects. (Author/MT)
Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.
Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…
Spiteri, M. A.; James, D. G.
Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101
Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich
In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775
Perkins, Edward J; Chipman, J Kevin; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre
The toxicological effects of many stressors are mediated through unknown, or incompletely characterized, mechanisms of action. The application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) can be used to overcome these limitations. This approach was used to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows (FHM, Pimephales promelas). Gene expression changes in FHM ovaries in response to seven different chemicals, over different times, doses, and in vivo versus in vitro conditions, were captured in a large data set of 868 arrays. Potential AOPs of the antiandrogen flutamide were examined using two mutual information-based methods to infer gene regulatory networks and potential AOPs. Representative networks from these studies were used to predict network paths from stressor to adverse outcome as candidate AOPs. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment, thus leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biological processes, biomarkers, or alternative endpoints that can be used to monitor an AOP. Finally, the unique challenges facing the application of this approach in ecotoxicology were identified and a road map for the utilization of these tools presented.
Freeman, Andrew M; Morris, Pamela B; Barnard, Neal; Esselstyn, Caldwell B; Ros, Emilio; Agatston, Arthur; Devries, Stephen; O'Keefe, James; Miller, Michael; Ornish, Dean; Williams, Kim; Kris-Etherton, Penny
The potential cardiovascular benefits of several trending foods and dietary patterns are still incompletely understood, and nutritional science continues to evolve. However, in the meantime, a number of controversial dietary patterns, foods, and nutrients have received significant media exposure and are mired by hype. This review addresses some of the more popular foods and dietary patterns that are promoted for cardiovascular health to provide clinicians with accurate information for patient discussions in the clinical setting.
Suglia, Shakira F.; Sapra, Katherine J.; Koenen, Karestan C.
Context Violence, experienced in either childhood or adulthood, has been associated with physical health outcomes including cardiovascular disease. However, the consistency of the existing literature has not been evaluated. Evidence acquisition In 2013, the authors conducted a PubMed and Web of Science review of peer reviewed articles published prior to August 2013 on the relation between violence exposure, experienced in either childhood or adulthood, and cardiovascular outcomes. To meet inclusion criteria, articles had to present estimates for the relation between violence exposure and cardiovascular outcomes (hypertension, blood pressure, stroke, coronary disease, or myocardial infarction) adjusted for demographic factors. Articles focusing on violence from TV, video games, natural disasters, terrorism, or war were excluded. Evidence synthesis The initial search yielded 2,273 articles; after removing duplicates and applying inclusion and exclusion criteria, 30 articles were selected for review. A consistent positive relation was noted on the association between violence experienced during childhood and cardiovascular outcomes in adulthood (i.e., hypertension, coronary heart disease, and myocardial infarction). Associations across genders with varying types of violence exposure were also noted. By contrast, findings were mixed on the relation between adult violence exposure and cardiovascular outcome. Conclusions Despite varying definitions of violence exposure and cardiovascular endpoints, a consistent relation exists between childhood violence exposure, largely assessed retrospectively, and cardiovascular endpoints. Findings are mixed for the adult violence–cardiovascular health relation. The cross-sectional nature of most adult studies and the reliance of self-reported outcomes can potentially be attributed to the lack of findings among adult violence exposure studies. PMID:25599905
Vyas, Arpita K.; Hoang, Vanessa; Padmanabhan, Vasantha; Gilbreath, Ebony; Mietelka, Kristy A.
Adverse events during the prenatal and early postnatal period of life are associated with development of cardiovascular disease in adulthood. Prenatal exposure to excess testosterone (T) in sheep induces adverse reproductive and metabolic programming leading to polycystic ovarian syndrome, insulin resistance and hypertension in the female offspring. We hypothesized that prenatal T excess disrupts insulin signaling in the cardiac left ventricle leading to adverse cardiac programming. Left ventricular tissues were obtained from 2-year-old female sheep treated prenatally with T or oil (control) from days 30–90 of gestation. Molecular markers of insulin signaling and cardiac hypertrophy were analyzed. Prenatal T excess increased the gene expression of molecular markers involved in insulin signaling and those associated with cardiac hypertrophy and stress including insulin receptor substrate-1 (IRS-1), phosphatidyl inositol-3 kinase (PI3K), Mammalian target of rapamycin complex 1 (mTORC1), nuclear factor of activated T cells –c3 (NFATc3), and brain natriuretic peptide (BNP) compared to controls. Furthermore, prenatal T excess increased the phosphorylation of PI3K, AKT and mTOR. Myocardial disarray (multifocal) and increase in cardiomyocyte diameter was evident on histological investigation in T-treated females. These findings support adverse left ventricular remodeling by prenatal T excess. PMID:27328820
Padhee, Monalisa; Zhang, Song; Lie, Shervi; Wang, Kimberley C.; Botting, Kimberley J.; McMillen, I. Caroline; MacLaughlin, Severence M.; Morrison, Janna L.
Assisted Reproductive Technologies (ARTs) have revolutionised reproductive medicine; however, reports assessing the effects of ARTs have raised concerns about the immediate and long-term health outcomes of the children conceived through ARTs. ARTs include manipulations during the periconceptional period, which coincides with an environmentally sensitive period of gamete/embryo development and as such may alter cardiovascular development and health of the offspring in postnatal life. In order to identify the association between ARTs and cardiovascular health outcomes, it is important to understand the events that occur during the periconceptional period and how they are affected by procedures involved in ARTs. This review will highlight the emerging evidence implicating adverse cardiovascular outcomes before and after birth in offspring conceived through ARTs in both human and animal studies. In addition, it will identify the potential underlying causes and molecular mechanisms responsible for the congenital and adult cardiovascular dysfunctions in offspring whom were conceived through ARTs. PMID:25699984
Zhang, Ai Yuan; Ji, Xiang Wu; Zhang, Ai Juan; Guan, Li Xue; Huang, Jing; Wang, Jing Xian
Background This study was to investigate the effects of multiple genetic polymorphisms and conventional risk factors in the prognosis of coronary artery disease (CAD). Methods One hundred and fifty five patients with CAD were prospectively recruited, they were subgrouped as single vessel disease (SVD) and multiple vessel disease (MVD). All patients were detected I/D polymorphism of angiotensin-converting enzyme (ACE) gene, 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene, and G894→T mutation of endothelial nitric oxide synthase (eNOS) gene. The patients were followed up for 10-65 months, mean 35 months. End points were major adverse cardiovascular events (MACE), including angina, myocardial infarction, and cardiac sudden death. Results During the follow-up period, MACE developed in 81 patients, 73 patients with angina, seven with myocardial infarction, and one with cardiac sudden death. CAD patients with MVD were more probable of developing MACE during follow-up. Distribution of PAI-1 gene polymorphism was significantly different between SVD and MVD patients, p < 0.001. The frequency of DD genotype of ACE and 4G/4G genotype of PAI-1 in patients with MACE were significantly higher than those in patients without MACE, p < 0.001 and p = 0.002, respectively. Incidence of diabetes mellitus was significantly higher in patients with MACE than in patients without MACE, P = 0.03. Cox regression analysis showed that diabetes mellitus (HR 2.36, 95% CI 1.33-4.46, p = 0.003), 4G/4G polymorphism of PAI-1 gene (HR 3.45, 95% CI 1.71-6.56, p = 0.009), and D/D polymorphism of ACE gene (HR 2.99, 95% CI 1.84-5.76, p = 0.005), were independent predictors of the MACE. Conclusions Our results showed that the conventional risk factors and genetic polymorphisms have significant influence on prognosis of CAD patients. CAD patients with diabetes mellitus, DD genotype of ACE, and 4G/4G genotype of PAI-1 suggested poor prognosis.
The pathogenesis of cardiovascular disease is without any doubt multifactorial, and it is generally accepted, that conventional risk factors determined only about 80% of cardiovascular risk. There is accumulating evidence that vitamin D exerts important pathophysiological effects on cardiovascular system. Low vitamin D was associated with increased cardiovascular risk in several reports. This review summarizes recent epidemiological evidence and possible pathophysiological mechanism for a role of low vitamin D in cardiovascular diseases. Moreover, available data concerning vitamin D supplementation are depicted.
Rozenfeld, Suely; Giordani, Fabiola; Coelho, Sonia
OBJECTIVE To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital. METHODS A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups. RESULTS Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually. CONCLUSIONS Almost one-sixth of in-patients (16,0%) suffered an adverse drug event. The instrument used may prove useful as a technique for
Evidence of the adverse effects of industrially-produced trans fatty acids (iTFA) on risk of cardiovascular disease is consistent and well documented in the scientific literature; however, the cardiovascular effects of naturally-occurring TFA synthesized in ruminant animals (rTFA), such as vaccenic ...
Gouweleeuw, L; Naudé, P J W; Rots, M; DeJongste, M J L; Eisel, U L M; Schoemaker, R G
Depression is more common in patients with cardiovascular disease than in the general population. Conversely, depression is a risk factor for developing cardiovascular disease. Comorbidity of these two pathologies worsens prognosis. Several mechanisms have been indicated in the link between cardiovascular disease and depression, including inflammation. Systemic inflammation can have long-lasting effects on the central nervous system, which could be associated with depression. NGAL is an inflammatory marker and elevated plasma levels are associated with both cardiovascular disease and depression. While patients with depression show elevated NGAL levels, in patients with comorbid heart failure, NGAL levels are significantly higher and associated with depression scores. Systemic inflammation evokes NGAL expression in the brain. This is considered a proinflammatory effect as it is involved in microglia activation and reactive astrocytosis. Animal studies support a direct link between NGAL and depression/anxiety associated behavior. In this review we focus on the role of NGAL in linking depression and cardiovascular disease.
Rudolph, A M
After birth, gas exchange is achieved in the lung, whereas prenatally it occurs in the placenta. This is associated with differences in blood flow patterns in the fetus as compared with the postnatal circulation. Congenital cardiovascular malformations are associated with haemodynamic changes in the fetus, which differ from those occurring postnatally. Obstruction to cardiac outflow may alter myocardial development, resulting in progressive ventricular hypoplasia. Alteration of oxygen content may profoundly influence pulmonary vascular and ductus arteriosus responses. Interference in blood flow and oxygen content may affect cerebral development as a result of inadequate oxygen or energy substrate supply. The circulatory effects may be gestational dependent, related to maturation of vascular responses in different organs. These prenatal influences of congenital cardiac defects may severely affect immediate, as well as longterm, postnatal prognosis and survival. This has stimulated the development of techniques for palliation of disturbed circulation during fetal life.
Devilliers, Maïly; Busserolles, Jérôme; Lolignier, Stéphane; Deval, Emmanuel; Pereira, Vanessa; Alloui, Abdelkrim; Christin, Marine; Mazet, Bruno; Delmas, Patrick; Noel, Jacques; Lazdunski, Michel; Eschalier, Alain
Morphine is the gold-standard pain reliever for severe acute or chronic pain but it also produces adverse side effects that can alter the quality of life of patients and, in some rare cases, jeopardize the vital prognosis. Morphine elicits both therapeutic and adverse effects primarily through the same μ opioid receptor subtype, which makes it difficult to separate the two types of effects. Here we show that beneficial and deleterious effects of morphine are mediated through different signalling pathways downstream from μ opioid receptor. We demonstrate that the TREK-1 K(+) channel is a crucial contributor of morphine-induced analgesia in mice, while it is not involved in morphine-induced constipation, respiratory depression and dependence-three main adverse effects of opioid analgesic therapy. These observations suggest that direct activation of the TREK-1 K(+) channel, acting downstream from the μ opioid receptor, might have strong analgesic effects without opioid-like adverse effects.
Kowalewski, Wiesław; Hebel, Kazimiera
Cardiovascular diseases for decades have been and still are the main and current health problem of the Polish society and there are many reasons for these diseases. Hypertension is one of the major risk factors for developing cardiovascular disease. The factors significantly increasing risk the of cardiovascular disease are in addition to high blood pressure, smoking (also passive), high blood fats (cholesterol and its HDL, LDL fractions as well as triglyceride levels, obesity, lack of exercise, diabetes and hereditary features. Other important factors which play an important role are external factors such as e.g. environmental pollution, lifestyle, stress. Prediction of cardiovascular disease should start from the evaluation of the fetal period because low birth weight may be a risk of coronary heart disease, hypertension, obesity or diabetes in adulthood. The authors of the referred tests showed that the level of blood pressure observed during childhood is closely associated with the level of blood pressure in adults and is also dependent on the body weight. Since the issue of the effects of high pressure on the cardiovascular system is inherent in the issue of the metabolic syndrome, it should be mentioned also that another causative factor may be an irregularity in the removal of urine from the body and the amount of insulin. The control of hypertension is a complex problem, at least in view of the wide range of adverse factors affecting the human body: hypertension is often either a constituent of other lesions. Therefore, it is difficult to treat high blood pressure in the strict sense; more often it is a combination therapy based on pharmacology caused for other reasons.
Mishra, Prasun J
Developing more precise diagnostics approaches to predict cancer progression and prognosis is the key to precision medicine. Overwhelming evidence now suggests that small non-coding RNAs such as miRNAs can be useful tools as biomarkers for molecular diagnostics. miRNAs can serve as biomarkers in a variety of diseases, such as neurological disorders, cardiovascular disease, Type II diabetes, cancer and so on. miRNAs can not only be utilized for monitoring treatment but also for patient stratification and hence are promising predictive biomarkers in cancer progression and prognosis, as well as in predicting drug response. This article focuses on some of the recent findings in the field of miRNA biomarkers and discusses its implications for cancer diagnostics and precision medicine.
Wooten, James M
Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must be effectively practiced by all health care providers in order to avoid ADRs.
Wooten, James M
Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must effectively be practiced by all health providers in order to avoid ADRs.
In addition to the person-environment fit model (J. R. French, R. D. Caplan, & R. V. Harrison, 1982) and the demand-control model (R. A. Karasek & T. Theorell, 1990), a third theoretical concept is proposed to assess adverse health effects of stressful experience at work: the effort-reward imbalance model. The focus of this model is on reciprocity of exchange in occupational life where high-cost/low-gain conditions are considered particularly stressful. Variables measuring low reward in terms of low status control (e.g., lack of promotion prospects, job insecurity) in association with high extrinsic (e.g., work pressure) or intrinsic (personal coping pattern, e.g., high need for control) effort independently predict new cardiovascular events in a prospective study on blue-collar men. Furthermore, these variables partly explain prevalence of cardiovascular risk factors (hypertension, atherogenic lipids) in 2 independent studies. Studying adverse health effects of high-effort/low-reward conditions seems well justified, especially in view of recent developments of the labor market.
Carreño-Orellana, Néstor; Moll-Manzur, Catherina; Carrasco-Zuber, Juan Eduardo; Álvarez-Véliz, Sergio; Berroeta-Mauriziano, Daniela; Porras-Kusmanic, Ninoska
Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.
Böhmdorfer, Birgit; Schaffarzick, Daniel; Nagano, Marietta; Janowitz, Susanne Melitta; Schweitzer, Ekkehard
We present a multidisciplinary (anaesthesiology--clinical pharmacy--bioinformatics) analysis of pain as possible adverse drug reaction taking different manifestations of pain, indication groups, relevance to the Austrian drug market and possible mechanistic influence of drugs on development and apprehension of pain into consideration.We designed an overview that shows how transmitters that play a part in nociception and antinociception can be influenced by drugs. This allows conclusions to the dolorigene potential of therapeutics.
The first marathon run as an athletic event took place in the context of the Olympic Games in 1896 in Athens, Greece. Today, participation in a 'marathon run' has become a global phenomenon attracting young professional athletes as well as millions of mainly middle-aged amateur athletes worldwide each year. One of the main motives for these amateur marathon runners is the expectation that endurance exercise (EE) delivers profound beneficial health effects. However, with respect to the cardiovascular system, a controversial debate has emerged whether the marathon run itself is healthy or potentially harmful to the cardiovascular system, especially in middle-aged non-elite male amateur runners. In this cohort, exercise-induced increases in cardiac biomarkers-troponin and brain natriuretic peptide-and acute functional cardiac alterations have been observed and interpreted as potential cardiac damage. Furthermore, in the cohort of 40- to 65-year-old males engaged in intensive EE, a significant risk for the development of atrial fibrillation has been identified. Fortunately, recent studies demonstrated a normalization of the cardiac biomarkers and the functional alterations within a short time frame. Therefore, these alterations may be perceived as physiological myocardial reactions to the strenuous exercise and the term 'cardiac fatigue' has been coined. This interpretation is supported by a recent analysis of 10.9 million marathon runners demonstrating that there was no significantly increased overall risk of cardiac arrest during long-distance running races. In conclusion, intensive and long-lasting EE, e.g. running a full-distance Marathon, results in high cardiovascular strain whose clinical relevance especially for middle-aged and older athletes is unclear and remains a matter of controversy. Furthermore, there is a need for evidence-based recommendations with respect to medical screening and training strategies especially in male amateur runners over the age of
Thiocolchicoside has long been used as a muscle relaxant, despite a lack of proven efficacy beyond the placebo effect. Its chemical structure consists of colchicine, a sugar (ose) and a sulphur-containing radical (thio), and its adverse effects are therefore likely to be similar to those of colchicine. Using the standard Prescrire methodology, we reviewed the available data on the adverse effects of thiocolchicoside. Liver injury, pancreatitis, seizures, blood cell disorders, severe cutaneous disorders, rhabdomyolysis and reproductive disorders have all been recorded in the French and European pharmacovigilance databases and in the periodic updates that the companies concerned submit to regulatory agencies. These data do not specify the frequency of the disorders nor do they identify the most susceptible patient populations. Thiocolchicoside is teratogenic in experimental animals and also damages chromosomes. Human data are limited to a follow-up of about 30 pregnant women (no major malformations) and reports of altered spermatogenesis, including cases of azoospermia. In practice, there is no justification for exposing patients to the adverse effects of thiocolchicoside. It is better to use an effective, well-known analgesic for patients complaining of muscle pain, starting with paracetamol.
de Boer, Alie; van Hunsel, Florence; Bast, Aalt
Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented.
Berciano, Silvia; Ordovás, José M
A multitude of studies have been published on the relationship between cardiovascular disease risk and a variety of nutrients, foods, and dietary patterns. Despite the well-accepted notion that diet has a significant influence on the development and prevention of cardiovascular disease, the foods considered healthy and harmful have varied over the years. This review aims to summarize the current scientific evidence on the cardioprotective effect of those foods and nutrients that have been considered healthy as well as those that have been deemed unhealthy at any given time in history. For this purpose, we reviewed the most recent literature using as keywords foods and nutrients (ie, meat, omega-3) and cardiovascular disease-related terms (ie, cardiovascular diseases, stroke). Emphasis has been placed on meta-analyses and Cochrane reviews. In general, there is a paucity of intervention studies with a high level of evidence supporting the benefits of healthy foods (ie, fruits and vegetables), whereas the evidence supporting the case against those foods considered less healthy (ie, saturated fat) seems to be weakened by most recent evidence. In summary, most of the evidence supporting the benefits and harms of specific foods and nutrients is based on observational epidemiological studies. The outcome of randomized clinical trials reveals a more confusing picture with most studies providing very small effects in one direction or another; the strongest evidence comes from dietary patterns. The current status of the relationship between diet and cardiovascular disease risk calls for more tailored recommendations based on genomic technologies.
Pacher, P.; Bátkai, S.; Kunos, G.
Cannabinoids and their synthetic and endogenous analogs affect a broad range of physiological functions, including cardiovascular variables, the most important component of their effect being profound hypotension. The mechanisms of the cardiovascular effects of cannabinoids in vivo are complex and may involve modulation of autonomic outflow in both the central and peripheral nervous systems as well as direct effects on the myocardium and vasculature. Although several lines of evidence indicate that the cardiovascular depressive effects of cannabinoids are mediated by peripherally localized CB1 receptors, recent studies provide strong support for the existence of as-yet-undefined endothelial and cardiac receptor(s) that mediate certain endocannabinoid-induced cardiovascular effects. The endogenous cannabinoid system has been recently implicated in the mechanism of hypotension associated with hemorrhagic, endotoxic, and cardiogenic shock, and advanced liver cirrhosis. Furthermore, cannabinoids have been considered as novel antihypertensive agents. A protective role of endocannabinoids in myocardial ischemia has also been documented. In this chapter, we summarize current information on the cardiovascular effects of cannabinoids and highlight the importance of these effects in a variety of pathophysiological conditions. PMID:16596789
Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration. PMID:27302713
Bae, Ji Cheol
Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.
Tung, Ying-Chang; Chou, Shing-Hsien; Liu, Kuan-Liang; Hsieh, I-Chang; Wu, Lung-Sheng; Lin, Chia-Pin; Wen, Ming-Shien; Chu, Pao-Hsien
Background Heart failure (HF) readmission results in substantial expenditure on HF management. This study aimed to evaluate the readmission rate, outcome, and predictors of HF readmission. Methods Patients with reduced left ventricular ejection fraction (LVEF < 40%) who were admitted for acute decompensation of de novo HF were enrolled to analyze readmission rate, mortality and predictors of readmission. Results A total of 433 de novo HF patients with LVEF < 40% were enrolled during the period August 2013 to December 2014. The in-hospital and 6-month mortality rates were 3.9% and 15.2%, respectively. In those patients surviving the index HF hospitalization, the 30-day and 6-month readmission rates were 10.9% and 27%, respectively. At the end of the 6-month follow-up, the readmission group had higher mortality than the non-readmission group (27.66% vs. 10.36%; p = 0.001). The survivors of the 30-day readmission had similar mortality rates at 6 months, regardless of the cause of readmission (cardiovascular vs. non-cardiovascular: 25% vs. 30.43%, p = 0.677). Among all the parameters, prescription of beta blockers independently reduced the risk of 30-day readmission (odds ratio 0.15; 95% confidence interval 0.02-0.99; p = 0.049). Conclusions Those HF patients who suffered from 30-day readmission had worse prognosis at the 6-month follow-up. Regardless of the readmission causes, the patients surviving the 30-day readmission had similar mortality rates at 6-month follow-up. These results underscored the importance of reducing readmission as a means to improve HF outcome. PMID:27899857
Fornai, Francesco; Carrizzo, Albino; Forte, Maurizio; Ambrosio, Mariateresa; Damato, Antonio; Ferrucci, Michela; Biagioni, Francesca; Busceti, Carla; Puca, Annibale A; Vecchione, Carmine
The acute phase protein Pentraxin 3 (PTX3) plays a non-redundant role as a soluble pattern recognition receptor for selected pathogens and it represents a rapid biomarker for primary local activation of innate immunity and inflammation. Recent evidence indicates that PTX3 exerts an important role in modulating the cardiovascular system in humans and experimental models. In particular, there are conflicting points concerning the effects of PTX3 in cardiovascular diseases (CVD) since several observations indicate a cardiovascular protective effect of PTX3 while others speculate that the increased plasma levels of PTX3 in subjects with CVD correlate with disease severity and with poor prognosis in elderly patients. In the present review, we discuss the multifaceted effects of PTX3 on the cardiovascular system focusing on its involvement in atherosclerosis, endothelial function, hypertension, myocardial infarction and angiogenesis. This may help to explain how the specific modulation of PTX3 such as the use of different dosing, time, and target organs could help to contain different vascular diseases. These opposite actions of PTX3 will be emphasized concerning the modulation of cardiovascular system where potential therapeutic implications of PTX3 in humans are discussed.
Insulin has direct effects on vascular walls which, depending on experimental models, can be either predominantly antiatherogenic or proatherogenic. In observational studies, insulin therapy is usually associated with an increase in the incidence of major cardiovascular events. However, this result is probably determined by the effect of confounders. In clinical trials performed in the acute phase of coronary syndromes, the benefits observed with insulin therapy are probably due to the improvement of glycemic control, rather than to direct effects of insulin on the cardiovascular system. In long-term trials for primary or secondary prevention such as UKPDS and ORIGIN insulin has no relevant effects on major cardiovascular events beyond those determined by the improvement of metabolic control. On the other hand, severe hypoglycemia, which is a possible side effect of insulin therapy, is associated with a worse prognosis of cardiovascular disease. The availability of new long-acting insulin analogs, which reduce the incidence of hypoglycemia for similar levels of glycemic control, makes insulin therapy easier and potentially safer for the cardiovascular system.
This article updates current knowledge about epidemiology, prognosis, and risk factors for major complications in mastocytosis. A prevalence of mastocytosis of 1 in 10000 inhabitants has been reported, but underdiagnosis is assumed. The prognosis for cutaneous and indolent systemic mastocytosis is excellent. For more advanced forms of disease, prognostic parameters have been identified. A high extent of skin involvement, increased basal serum tryptase values, and extensive blistering are risk factors for severe mast cell activation episodes in children, whereas these associations seem to be less strong or nonexistent for anaphylaxis and osteoporosis in adult patients with indolent systemic mastocytosis.
Vaquero Barrios, José Manuel; Redel Montero, Javier; Santos Luna, Francisco
The aim of this review is to give an overview of the clinical circumstances presenting before lung transplant that may have negative repercussions on the long and short-term prognosis of the transplant. Methods for screening and diagnosis of common comorbidities with negative impact on the prognosis of the transplant are proposed, both for pulmonary and extrapulmonary diseases, and measures aimed at correcting these factors are discussed. Coordination and information exchange between referral centers and transplant centers would allow these comorbidities to be detected and corrected, with the aim of minimizing the risks and improving the life expectancy of transplant receivers.
Heeger, C-H; Rillig, A; Ouyang, F; Kuck, K-H; Tilz, R R
Syncope is a common clinical issue. Around 40 % of the total population experience syncope during their lifetime. Serious injuries and reduced quality of life are often observed after syncope. Furthermore, in some cases syncope can be associated with an unfavorable prognosis. Due to the complex etiology and pathophysiology, syncope provides challenges for doctors both in private and in clinical practices. This review is based on the latest European guidelines for syncope which were formulated by internists, neurologists, emergency physicians and cardiologists and gives an overview of the current epidemiology, definition, classification, pathophysiology and prognosis of syncope.
As periodontics has progressed towards an understanding of the influences of risk factors such as genetics, smoking and stress in the occurrence and severity of periodontal disease, the question of prognosis, so essential to treatment planning, has become even more perplexing to the clinician. A survey of long term clinical practice gives insight into the outcome of therapy relative to initial severity, and modern concepts of bacteria versus host relationships provide directions for greater predictability. However, it is only with observation over time that a more accurate assessment of prognosis can be made, as response to initial therapeutic measures can be determined.
Cardiovascular Reactivity in Patients With Major Depressive Disorder With High- or Low-Level Depressive Symptoms: A Cross-Sectional Comparison of Cardiovascular Reactivity to Laboratory-Induced Mental Stress.
Wang, Mei-Yeh; Chiu, Chen-Huan; Lee, Hsin-Chien; Su, Chien-Tien; Tsai, Pei-Shan
Depression increases the risk of adverse cardiac events. Cardiovascular reactivity is defined as the pattern of cardiovascular responses to mental stress. An altered pattern of cardiovascular reactivity is an indicator of subsequent cardiovascular disease. Because depression and adverse cardiac events may have a dose-dependent association, this study examined the differences in cardiovascular reactivity to mental stress between patients with major depressive disorder (MDD) with high depression levels and those with low depression levels. Moreover, autonomic nervous system regulation is a highly plausible biological mechanism for the pattern of cardiovascular reactivity to mental stress. The association between cardiovascular reactivity and parameters of heart rate variability (HRV), an index for quantifying autonomic nervous system activity modulation, was thus examined. This study included 88 patients with MDD. HRV was measured before stress induction. The Stroop Color and Word Test and mirror star-tracing task were used to induce mental stress. We observed no significant association between depressive symptom level and any of the cardiovascular reactivity parameters. Cardiovascular reactivity to mental stress was comparable between patients with MDD with high-level depressive symptoms and those with low-level depressive symptoms. After adjusting for confounding variables, the high-frequency domain of HRV was found to be an independent predictor of the magnitude of heart rate reactivity (β = -.33, p = .002). In conclusion, the magnitude of cardiovascular reactivity may be independent of depression severity in patients with MDD. The autonomic regulation of cardiovascular responses to mental stress primarily influences heart rate reactivity in patients with MDD.
Zusman, R M; Morales, A; Glasser, D B; Osterloh, I H
Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is the first in a new class of orally effective treatments for erectile dysfunction. During sexual stimulation, the cavernous nerves release nitric oxide (NO), which induces cyclic guanosine monophosphate (cGMP) formation and smooth muscle relaxation in the corpus cavernosum. Sildenafil facilitates the erectile process during sexual stimulation by inhibiting PDE5 and thus blocking the breakdown of cGMP. Sildenafil alone can cause mean peak reductions in systolic/diastolic blood pressure of 10/7 mm Hg that are not dose related, whereas the heart rate is unchanged. Sildenafil and nitrates both increase cGMP levels in the systemic circulation but at different points along the NO-cGMP pathway. The combination is contraindicated because they synergistically potentiate vasodilation and may cause excessive reductions in blood pressure. Erectile dysfunction is a significant medical condition that shares numerous risk factors with ischemic heart disease, and hence a substantial overlap exists between these patient groups. From extensive clinical trials, the most commonly reported cardiovascular adverse events in patients treated with sildenafil were headache (16%), flushing (10%), and dizziness (2%). The incidences of hypotension, orthostatic hypotension, and syncope and the rate of discontinuation of treatment due to adverse events were <2% and were the same in patients taking sildenafil and those taking placebo. Retrospective analysis of the concomitant use of antihypertensive medications (beta blockers, alpha blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium antagonists) in patients taking sildenafil did not indicate an increase in the reports of adverse events or significant episodes of hypotension compared with patients treated with sildenafil alone. In clinical trials, the incidence of serious cardiovascular adverse events, including stroke and myocardial infarction, was the
Truskey, George A.
Cardiovascular tissue engineering offers the promise of biologically based repair of injured and damaged blood vessels, valves, and cardiac tissue. Major advances in cardiovascular tissue engineering over the past few years involve improved methods to promote the establishment and differentiation of induced pluripotent stem cells (iPSCs), scaffolds from decellularized tissue that may produce more highly differentiated tissues and advance clinical translation, improved methods to promote vascularization, and novel in vitro microphysiological systems to model normal and diseased tissue function. iPSC technology holds great promise, but robust methods are needed to further promote differentiation. Differentiation can be further enhanced with chemical, electrical, or mechanical stimuli. PMID:27303643
Kovacs, Richard; Baggish, Aaron L
Millions of athletes train for and participate in competitive athletics each year. Many of these athletes will present to a cardiovascular specialist with signs or symptoms that might indicate heart disease and these athletes/patients will ask for advice on their ability to continue to train and compete safely. By virtue of their training, athletes׳ hearts may undergo significant structural and electrical change, presenting a special challenge for the cardiovascular specialist. It is important to understand normal adaptive changes in order to separate normal physiology from pathology.
Gómez Morales, Luis; Beltrán Romero, Luis Matías; García Puig, Juan
Cardiovascular diseases are the leading cause of death in the Spanish population and may be a relationship between the prevalence of these and excessive sugar consumption. In recent years, researchers have focused on the properties of these nutrients. Although there are many studies examining this association, the results are not unanimous. In any case there is sufficient basis for designing public health strategies in order to reduce the consumption of sugary drinks as part of a healthy lifestyle. Therefore, the question we address is: sugar intake in abundant amounts, is associated with a higher risk of cardiovascular disease? We use as the focus of the discussion SAFO analysis model.
Nicholls, Stephen J; Hazen, Stanley L
Myeloperoxidase (MPO) is a leukocyte-derived enzyme that catalyzes the formation of a number of reactive oxidant species. In addition to being an integral component of the innate immune response, evidence has emerged that MPO-derived oxidants contribute to tissue damage during inflammation. MPO-catalyzed reactions have been attributed to potentially proatherogenic biological activities throughout the evolution of cardiovascular disease, including during initiation, propagation, and acute complication phases of the atherosclerotic process. As a result, MPO and its downstream inflammatory pathways represent attractive targets for both prognostication and therapeutic intervention in the prophylaxis of atherosclerotic cardiovascular disease.
McLoughlin, Sarah C.; Haines, Philip; FitzGerald, Garret A.
Circadian clocks in central and peripheral tissues enable the temporal synchronization and organization of molecular and physiological processes of rhythmic animals, allowing optimum functioning of cells and organisms at the most appropriate time of day. Disruption of circadian rhythms, from external or internal forces, leads to widespread biological disruption and is postulated to underlie many human conditions, such as the incidence and timing of cardiovascular disease. Here, we describe in vivo and in vitro methodology relevant to studying the role of circadian rhythms in cardiovascular function and dysfunction PMID:25707279
Bull, Joseph L
Gas bubbles can form in the cardiovascular system as a result of patho-physiological conditions or can be intentionally introduced for diagnostic or therapeutic reasons. The dynamic behavior of these bubbles is caused by a variety of mechanisms, such as inertia, pressure, interfacial tension, viscosity, and gravity. We review recent advances in the fundamental mechanics and applications of cardiovascular bubbles, including air embolism, ultrasound contrast agents, targeted microbubbles for drug delivery and molecular imaging, cavitation-induced tissue erosion for ultrasonic surgery, microbubble-induced angiogenesis and arteriogenesis, and gas embolotherapy.
Hossain, Mohammad B; Li, Huiqi; Hedmer, Maria; Tinnerberg, Håkan; Albin, Maria; Broberg, Karin
Background Welders are at risk for cardiovascular disease. Recent studies linked tobacco smoke exposure to hypomethylation of the F2RL3 (coagulation factor II (thrombin) receptor-like 3) gene, a marker for cardiovascular disease prognosis and mortality. However, whether welding fumes cause hypomethylation of F2RL3 remains unknown. Methods We investigated 101 welders (median span of working as a welder: 7 years) and 127 unexposed controls (non-welders with no obvious exposure to respirable dust at work), age range 23–60 years, all currently non-smoking, in Sweden. The participants were interviewed about their work history, lifestyle factors and diseases. Personal sampling of respirable dust was performed for the welders. DNA methylation of F2RL3 in blood was assessed by pyrosequencing of four CpG sites, CpG_2 (corresponds to cg03636183) to CpG_5, in F2RL3. Multivariable linear regression analysis was used to assess the association between exposure to welding fumes and F2RL3 methylation. Results Welders had 2.6% lower methylation of CpG_5 than controls (p<0.001). Higher concentrations of measured respirable dust among the welders were associated with hypomethylation of CpG_2, CpG_4 and CpG_5 (β=−0.49 to −1.4, p<0.012); p<0.029 adjusted for age, previous smoking, passive smoking, education, current residence and respirator use. Increasing the number of years working as a welder was associated with hypomethylation of CpG_4 (linear regression analysis, β=−0.11, p=0.039, adjusted for previous smoking). Previous tobacco smokers had 1.5–4.7% (p<0.014) lower methylation of 3 of the 4 CpG sites in F2RL3 (CpG_2, CpG_4 and CpG_5) compared to never-smokers. A non-significant lower risk of cardiovascular disease with more methylation was observed for all CpG sites. Conclusions Welding fumes exposure and previous smoking were associated with F2RL3 hypomethylation. This finding links low-to-moderate exposure to welding fumes to adverse effects on the cardiovascular
Osman, Faizel; Gammage, Michael D; Franklyn, Jayne A
Hyperthyroidism is a common disorder affecting multiple systems in the body. The cardiovascular effects are among the most striking. The availability of effective treatments for hyperthyroidism has led to the widespread perception that it is a reversible disorder without any long-term consequences. Recent evidence suggests, however, that there may be adverse outcomes. Long-term follow-up studies have revealed increased mortality from cardiovascular and cerebrovascular disease in those with a past history of overt hyperthyroidism treated with radioiodine, as well as those with subclinical hyperthyroidism. Thyroid hormones are known to exert direct effects on the myocardium, as well as the systemic vasculature and predispose to dysrhythmias, especially supraventricular. Atrial fibrillation (AF) is a recognized complication of overt hyperthyroidism, and subclinical hyperthyroidism is also known to be a risk factor for development of AF. Supraventricular dysrhythmias, particularly atrial fibrillation, in older patients may account for some of the excess cardiovascular and cerebrovascular mortality described, especially because AF is known to predispose to embolic phenomena.
Fisher, M M; Graham, R
Progressive challenge was used to investigate twenty-seven patients with a history of an adverse response to local anaesthesia. True allergy was detected in only one patient. The method does not exclude reactions to additives and preservatives in local anaesthetics. If preservative-free local anaesthetics are used for subsequent exposure in patients with no response to progressive challenge, subsequent exposure is safe. The possibility that some of these patients may be reacting to preservatives in the solutions cannot be excluded by such testing. Where possible preservative-free local anaesthetic preparations should be used for subsequent anaesthesia.
Roback, Howard B.
Group forms of therapy have been growing at a rapid rate, in part because of their documented effectiveness and economic considerations such as managed care. It is therefore becoming increasingly important to assess the psychological risks of these interventions. The author provides an overview of the published literature and conference presentations on negative effects in adult outpatient groups. Although much of the literature on adverse outcomes in group therapy focuses on single risk factors (e.g., negative leader, group process, or patient characteristics), the author argues that an interactional model should be encouraged. Means of reducing casualties are also discussed, as well as methodological issues and research directions. PMID:10896735
Yang, Fan; Wang, Qixia; Wang, Zhaoyue; Miao, Qi; Xiao, Xiao; Tang, Ruqi; Chen, Xiaoyu; Bian, Zhaolian; Zhang, Haiyan; Yang, Yue; Sheng, Li; Fang, Jingyuan; Qiu, Dekai; Krawitt, Edward L; Gershwin, M Eric; Ma, Xiong
Although a variant of primary biliary cirrhosis (PBC) characterized by features of autoimmune hepatitis (AIH) has been recognized for many years, few studies with ample numbers of patients have focused on its natural history. This study aimed to clarify the natural history, prognosis, and response to therapy in a cohort of patients with PBC with AIH features. We retrospectively analyzed 277 PBC patients without AIH features and 46 PBC patients with AIH features seen between September 2004 and April 2014. The 5-year adverse outcome-free survival of PBC patients with AIH features was 58% compared to 81% in PBC patients without AIH features. Multivariate analysis in the patients with AIH features indicated that total bilirubin ≥ 2.70× the upper limit of normal predicted a poor prognosis (p = 0.008, relative risk 8.39, 95% confidence interval (CI) 1.73, 40.73). Combination therapy with ursodeoxycholic acid (UDCA) and immunosuppression provided better short-term responses in PBC patients with AIH features, defined by multiple criteria. Higher aspartate aminotransferase (AST) level at accession suggested better prognosis for PBC patients with AIH features while worse prognosis for PBC patients without AIH features. PBC patients with AIH features differ from those without AIH features in terms of natural history, prognostic indicators, and response to therapy.
Mehta, Nehal N.; Yu, YiDing; Pinnelas, Rebecca; Krishnamoorthy, Parasuram; Shin, Daniel B.; Troxel, Andrea B.; Gelfand, Joel M.
Background Recent studies suggest that psoriasis, particularly if severe, may be a risk factor for major adverse cardiac events such as myocardial infarction, stroke, and mortality from cardiovascular disease. We compared the risk of major adverse cardiac events between patients with psoriasis and the general population and estimated the attributable risk of severe psoriasis. Methods We performed a cohort study in the General Practice Research Database. Severe psoriasis was defined as receiving a psoriasis diagnosis and systemic therapy (N=3,603). Up to 4 patients without psoriasis were selected from the same practices and start dates for each patient with psoriasis (N=14,330). Results Severe psoriasis was a risk factor for major adverse cardiac events (hazard ratio 1.53; 95% confidence interval 1.26, 1.85) after adjusting for age, gender, diabetes, hypertension, tobacco use and hyperlipidemia. After fully adjusted analysis, severe psoriasis conferred an additional 6.2% absolute risk of 10-year major adverse cardiac events. Conclusions Severe psoriasis confers an additional 6.2% absolute risk of 10-year rate of major adverse cardiac events compared to the general population. This potentially has important therapeutic implications for cardiovascular risk stratification and prevention in patients with severe psoriasis. Future prospective studies are needed to validate these findings. PMID:21787906
Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only...
van Soest, Gijs; Regar, Evelyn; van der Steen, Antonius F. W.
The use of photonics technology is bringing new capabilities and insights to cardiovascular medicine. Intracoronary imaging and sensing, laser ablation and optical pacing are just some of the functions being explored to help diagnose and treat conditions of the heart and arteries.
Johnson, Julie A; Humma, Larisa M
Pharmacogenetics is a field aimed at understanding the genetic contribution to inter-patient variability in drug efficacy and toxicity. Treatment of cardiovascular disease is, in most cases, guided by evidence from well-controlled clinical trials. Given the solid scientific basis for the treatment of most cardiovascular diseases, it is common for patients with a given disease to be treated in essentially the same manner. Thus, the clinical trials have been very informative about treating large groups of patients with a given disease, but are slightly less informative about the treatment of individual patients. Pharmacogenetics and pharmacogenomics have the potential of taking the information derived from large clinical trials and further refining it to select the drugs with the greatest likelihood for benefit, and least likelihood for harm, in individual patients, based on their genetic make-up. In this paper, the current literature on cardiovascular pharmacogenetics is emphasised, and how the use of pharmacogenetic/pharmacogenomic information may be particularly useful in the future in the treatment of cardiovascular diseases is also highlighted.
Jenkins, C. David
Reviews epidemiological studies of cardiovascular diseases especially coronary heart disease (CHD), to document their major public health importance, changes in mortality during this century, and international comparisons of trends. Finds major risk factors for CHD are determined in large part by psychosocial and behavioral mechanisms. Asserts…
Ganong, W F
Neuropeptides can affect cardiovascular function in various ways. They can serve as cotransmitters in the autonomic nervous system; for example, vasoactive intestinal peptide (VIP) is released with acetylcholine and neuropeptide Y with norepinephrine from postganglionic neurons. Substance P and, presumably, other peptides can can affect cardiovascular function when released near blood vessels by antidromically conducted impulses in branches of stimulated sensory neurons. In the central nervous system, many different neuropeptides appear to function as transmitters or contransmittes in the neural pathways that regulate the cardiovascular system. In addition neuropeptides such as vasopressin and angiotensin II also circulate as hormones that are involved in cardiovascular control. Large doses of exogenous vasopressin are required to increase blood pressure in normal animals because the increase in total peripheral resistance produced by the hormones is accompanied by a decrease in cardiac output. However, studies with synthetic peptides that selectively antagonize the vasopressor action of vasopressin indicate that circulating vasopressin is important in maintaining blood pressure when animals are hypovolemic due to dehydration, haemorrhage or adrenocortical insufficiency. VIP dilates blood vessels and stimulates renin secretion by a direct action on the juxtaglomerular cells. Renin secretion is stimulated when the concentration of VIP in plasma exceeds 75 pmol/litre, and higher values are seen in a number of conditions. Neostigmine, a drug which increases the secretion of endogenous VIP, also increases renin secretion, and this increase is not blocked by renal denervation or propranolol. Thus, VIP may be a physiologically significant renin stimulating hormone.(ABSTRACT TRUNCATED AT 250 WORDS)
Visseren, Frank L J
Atherosclerotic vascular disease is rare in the young. Nevertheless, the foundations for atherosclerotic disease in later life are laid early by a harmful lifestyle including overweight and smoking. Adolescents who are overweight or have the metabolic syndrome are at increased cardiovascular risk later in life.
Fassett, Robert G; Coombes, Jeff S
Astaxanthin is a xanthophyll carotenoid present in microalgae, fungi, complex plants, seafood, flamingos and quail. It is an antioxidant with anti-inflammatory properties and as such has potential as a therapeutic agent in atherosclerotic cardiovascular disease. Synthetic forms of astaxanthin have been manufactured. The safety, bioavailability and effects of astaxanthin on oxidative stress and inflammation that have relevance to the pathophysiology of atherosclerotic cardiovascular disease, have been assessed in a small number of clinical studies. No adverse events have been reported and there is evidence of a reduction in biomarkers of oxidative stress and inflammation with astaxanthin administration. Experimental studies in several species using an ischaemia-reperfusion myocardial model demonstrated that astaxanthin protects the myocardium when administered both orally or intravenously prior to the induction of the ischaemic event. At this stage we do not know whether astaxanthin is of benefit when administered after a cardiovascular event and no clinical cardiovascular studies in humans have been completed and/or reported. Cardiovascular clinical trials are warranted based on the physicochemical and antioxidant properties, the safety profile and preliminary experimental cardiovascular studies of astaxanthin.
Cavallari, Larisa H.; Mason, Darius L.
Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. Thus, patients with CKD often require treatment with cardiovascular drugs, such as antiplatelet, antihypertensive, anticoagulant, and lipid-lowering agents. There is significant inter-patient variability in response to cardiovascular therapies, which contributes to risk for treatment failure or adverse drug effects. Pharmacogenomics offers the potential to optimize cardiovascular pharmacotherapy and improve outcomes in patients with cardiovascular disease, though data in patients with concomitant CKD are limited. The drugs with the most pharmacogenomic evidence are warfarin, clopidogrel, and statins. There are also accumulating data for genetic contributions to β-blocker response. Guidelines are now available to assist with applying pharmacogenetic test results to optimize warfarin dosing, selection of antiplatelet therapy after percutaneous coronary intervention, and prediction of risk for statin-induced myopathy. Clinical data, such as age, body size, and kidney function have long been used to optimize drug prescribing. An increasing number of institutions are also implementing genetic testing to be considered in the context of important clinical factors to further personalize drug therapy for patients with cardiovascular disease. PMID:26979147
Kitzmiller, Joseph P; Mikulik, Eduard B; Dauki, Anees M; Murkherjee, Chandrama; Luzum, Jasmine A
Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes), statin efficacy (eg, drug targets and pathways), and end-organ toxicity (eg, myopathy pathways) highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy. PMID:27757045
Thase, Michael E; Larsen, Klaus G; Reines, Elin; Kennedy, Sidney H
The cardiovascular effects of escitalopram were examined in a large group of participants in double-blind, randomized, placebo-controlled studies. Escitalopram (n=3298) was administered at doses between 5 and 20mg/day. Patients were treated in acute (8-12 weeks) and long-term (24 weeks) studies. Assessment of cardiovascular safety included heart rate, blood pressure (BP), treatment-emergent adverse events (TEAEs) and electrocardiograms (ECGs). In the short-term, there was a small, but statistically significant 2 beats per minute decrease in heart rate with escitalopram compared with placebo. The difference compared to placebo in systolic or diastolic BP was not clinically or statistically significant. Valid ECG assessments at both baseline and last assessment were available for 2407 escitalopram patients and 1952 placebo patients. Escitalopram-placebo differences in mean changes in ECG values were not clinically meaningful. The mean difference to placebo in the corrected QT [Fridericia's (QTcF)] interval was 3.5 ms (all escitalopram doses); 1.3 ms (escitalopram 10mg) and 1.7 ms (escitalopram 20mg) (p=0.2836 for 10 versus 20 mg). One out of 2407 escitalopram patients had a QTcF interval >500 ms and a change from baseline >60 ms. The incidence and types of cardiac-associated adverse events were similar between patients treated for 8-12 weeks with placebo (2.2%) or escitalopram (1.9%) and for 24 weeks with placebo (2.7%) or escitalopram (2.3%). Analyses of data from long-term studies and studies of the elderly showed similar results. In conclusion, these data demonstrate that escitalopram, like other SSRIs, has a statistically significant effect on heart rate and no clinically meaningful effect on ECG values, BP, with a placebo-level incidence of cardiac-associated adverse events.
Aging is one of the most important cardiovascular risk factors. Age-related morphologic changes in large resistance vessels include an intima-media-thickening and increased deposition of matrix substance, ultimately leading to a reduced compliance and an increased stiffness of the vessels. Aging of the heart is mainly characterized by an increase of the left ventricular mass in relation to the chamber volume and a decrease of diastolic function. There is some controversy in regard to the question if these changes in the vessel wall are the consequence of aging or if a decrease in physical activity is a major contributor of this process. With age the cardiovascular profile is changing. Whereas smoking is less prominent, arterial hypertension and diabetes mellitus are more often encountered. Primary and secondary prevention through cardiovascular risk factor management is also very important in the aging population due to the increased risk of acute vascular complications with age. Preventive measures have to include life style factor interventions as well as optimized drug therapy. There is no scientific evidence that vascular aging can be prevented by administration of supplements such as antioxidant vitamins. Aspirin is effective for cardiovascular prevention up to a higher age. Betablockers and ACE-inhibitors are generally underused in older patients after myocardial infarctions. Statins are effective in reducing cardiovascular complications up to an age of 80 years. Myocardial infarction in elderly patients is often characterized by atypical symptoms and may be even silent. Interventional therapy in elderly patients is as successful as in younger patients but has an increased complication rate. Ambulatory cardiac rehabilitation in elderly patients leads to significant improvements of physical capacity, well-being and quality of life and may help to prevent social isolation.
Espinola-Klein, C; Savvidis, S; Kopp, H
Peripheral arterial disease (PAD) increases cardiovascular event rate in patients with coronary artery disease (CAD). Therefore PAD should be considered in patients with CAD with regard to diagnostic and therapeutic strategies. PAD may difficult diagnostic tests in CAD patients. Patients with PAD and CAD may be limited in stress testing by decreased leg perfusion. In addition, arterial puncture can be more difficult in sclerotic femoral arteries. Cardiovascular risk factors should be treated carefully in all manifestations of atherosclerosis. Target values from current guidelines are similar for PAD and CAD. Inhibitors of platelet aggregation are indication in both CAD and PAD. Exercise not only improves walking distance in patients with intermittent claudication but also improves cardiovascular prognosis in patients with atherosclerosis.
The general use of adversative conjunction in (primarily) English and U.S. poetry is outlined. The contention is that the adversative is not merely a grammatical convenience but sometimes a highly functional tool of rhetorical strategy. (36 references) (LB)
Holden, Arthur L; Contreras, Jorge L; John, Sally; Nelson, Matthew R
The International Serious Adverse Events Consortium is generating novel insights into the genetics and biology of drug-induced serious adverse events, and thereby improving pharmaceutical product development and decision-making.
Marr, Celia M
The neonatal foal is in a transitional state from prenatal to postnatal circulation. Healthy newborn foals often have cardiac murmurs and dysrhythmias, which are usually transient and of little clinical significance. The neonatal foal is prone to infection and cardiac trauma. Echocardiography is the main tool used for valuation of the cardiovascular system. With prompt identification and appropriate action, dysrhythmias and other sequel to cardiac trauma can be corrected. With infection, the management and prognosis are driven by concurrent sepsis. Congenital disease represents an interesting diagnostic challenge for the neonatologist, but surgical correction is not appropriate for most equids.
Klein, Stephanie K; Redfern, Will S
This is a report on a 2-day joint meeting between the British Society of Toxicological Pathology (BSTP) and the Safety Pharmacology Society (SPS) held in the UK in November 2013. Drug induced adverse effects on the cardiovascular system are associated with the attrition of more marketed and candidate drugs than any other safety issue. The objectives of this meeting were to foster inter-disciplinary approaches to address cardiovascular risk assessment, improve understanding of the respective disciplines, and increase awareness of new technologies. These aims were achieved. This well attended meeting covered both 'purely functional' cardiovascular adverse effects of drugs (e.g., electrophysiological and haemodynamic changes) as well as adverse effects encompassing both functional and pathological changes. Most of the presentations focused on nonclinical safety data, with information on translation to human where known. To reflect the content of the presentations we have cited key references and review articles.
Simon, R A
There is a long list of additives used by the pharmaceutical industry. Most of the agents used have not been implicated in hypersensitivity reactions. Among those that have, only reactions to parabens and sulfites have been well established. Parabens have been shown to be responsible for rare immunoglobulin E-mediated reactions that occur after the use of local anesthetics. Sulfites, which are present in many drugs, including agents commonly used to treat asthma, have been shown to provoke severe asthmatic attacks in sensitive individuals. Recent studies indicate that additives do not play a significant role in "hyperactivity." The role of additives in urticaria is not well established and therefore the incidence of adverse reactions in this patient population is simply not known. In double-blind, placebo-controlled studies, reactions to tartrazine or additives other than sulfites, if they occur at all, are indeed quite rare for the asthmatic population, even for the aspirin-sensitive subpopulation.
Wu, Audrey H; Gladden, James D; Ahmed, Mustafa; Ahmed, Ali; Filippatos, Gerasimos
This review summarizes recent published literature on the association between serum uric acid and cardiovascular disease, a relationship which is complex and not fully elucidated. Uric acid may be a marker for risk, a causative agent in cardiovascular disease, or both. Various biologic factors can influence serum uric acid levels, and serum uric acid level itself is closely related to conditions such as hypertension, dyslipidemia, obesity, and impaired glucose metabolism, that contribute to cardiovascular disease pathophysiology. Serum uric acid levels have been found to be associated with adverse outcomes, including mortality, in the general population. In addition, serum uric acid is associated with increased risk for incident coronary heart disease, heart failure, and atrial fibrillation. In the setting of established systolic heart failure, serum uric acid is positively associated with disease severity and mortality risk. Whether targeting treatment based on uric acid levels might affect clinical outcomes is still being studied.
Godinjak, Amina; Iglica, Amer; Burekovic, Azra; Jusufovic, Selma; Ajanovic, Anes; Tancica, Ira; Kukuljac, Adis
Introduction: Hyperglycemia is a common complication of critical illness. Patients in intensive care unit with stress hyperglycemia have significantly higher mortality (31%) compared to patients with previously confirmed diabetes (10%) or normoglycemia (11.3%). Stress hyperglycemia is associated with increased risk of critical illness polyneuropathy (CIP) and prolonged mechanical ventilation. Intensive monitoring and insulin therapy according to the protocol are an important part of the treatment of critically ill patients. Objective: To evaluate the incidence of stress hyperglycemia, complications and outcome in critically ill patients in our Medical intensive care unit. Materials and methods: This study included 100 patients hospitalized in Medical intensive care unit during the period January 2014–March 2015 which were divided into three groups: Diabetes mellitus, stress-hyperglycemia and normoglycemia. During the retrospective-prospective observational clinical investigation the following data was obtained: age, gender, SAPS, admission diagnosis, average daily blood glucose, highest blood glucose level, glycemic variability, vasopressor and corticosteroid therapy, days on mechanical ventilation, total days of hospitalization in Medical intensive care unit, and outcome. Results: Patients with DM treated with a continuous insulin infusion did not have significantly more complications than patients with normoglycemia, unlike patients with stress hyperglycemia, which had more severe prognosis. There was a significant difference between the maximum level of blood glucose in recovered and patients with adverse outcome (p = 0.0277). Glycemic variability (difference between max. and min. blood glucose) was the strongest predictor of adverse outcome. The difference in glycemic variability between the stress-hyperglycemia and normoglycemic group was statistically significant (p = 0.0066). There was no statistically significant difference in duration of mechanical
Fazio, Serafino; Palmieri, Emiliano A; Lombardi, Gaetano; Biondi, Bernadette
Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that overt hyperthyroidism induces a hyperdynamic cardiovascular state (high cardiac output with low systemic vascular resistance), which is associated with a faster heart rate, enhanced left ventricular (LV) systolic and diastolic function, and increased prevalence of supraventricular tachyarrhythmias - namely, atrial fibrillation - whereas overt hypothyroidism is characterized by the opposite changes. However, whether changes in cardiac performance associated with overt thyroid dysfunction are due mainly to alterations of myocardial contractility or to loading conditions remains unclear. Extensive evidence indicates that the cardiovascular system responds to the minimal but persistent changes in circulating thyroid hormone levels, which are typical of individuals with subclinical thyroid dysfunction. Subclinical hyperthyroidism is associated with increased heart rate, atrial arrhythmias, increased LV mass, impaired ventricular relaxation, reduced exercise performance, and increased risk of cardiovascular mortality. Subclinical hypothyroidism is associated with impaired LV diastolic function and subtle systolic dysfunction and an enhanced risk for atherosclerosis and myocardial infarction. Because all cardiovascular abnormalities are reversed by restoration of euthyroidism ("subclinical hypothyroidism") or blunted by beta-blockade and L-thyroxine (L-T4) dose tailoring ("subclinical hyperthyroidism"), timely treatment is advisable in an attempt to avoid adverse cardiovascular effects. Interestingly, some data indicate that patients with acute and chronic cardiovascular disorders and those undergoing cardiac surgery may have altered peripheral thyroid hormone metabolism that, in turn, may contribute to altered cardiac function. Preliminary clinical investigations suggest that administration of
Gen, Shikou; Inoue, Tsutomu; Nodaira, Yuka; Ikeda, Naofumi; Kobayashi, Kazuhiro; Watanabe, Yusuke; Kanno, Yoshihiko; Nakamoto, Hidetomo; Suzuki, Hiromichi
In the present study, we examined the association between vascular and valvular calcification and the prognosis of patients on continuous ambulatory peritoneal dialysis (CAPD). Data were collected from the records of patients introduced onto CAPD therapy during 1999 - 2006 at the Department of Nephrology, Saitama Medical University. At the start of CAPD, cardiac and vascular echography were used to examine 162 patients (average age: 56 +/- 5 years; 58 men, 104 women; 43 with and 119 without diabetes) for evaluation of vascular and valvular calcification. Both vascular and valvular calcification were found in 32 patients. Vascular calcification was found in 16, and valvular calcification in 11. Over 5 years, 11 patients suffered from cardiovascular disease (7 with stroke, 4 with myocardial infarction). All of these patients had vascular or valvular calcification at the start of CAPD therapy. We also used Cox hazard analysis to examine values for Ca, P, Ca x P, intact parathyroid hormone (iPTH), and lipids. None of these values were independent contributory factors for incidence of cardiovascular disease in patients on CAPD. These data suggest the importance of vascular and valvular echography to evaluate patients on CAPD, especially at the start of CAPD therapy. Vascular and valvular calcification are important factors for determining the prognosis of patients on CAPD.
Coelho, Maria Caroline Alves; Santos, Camila Vicente; Vieira Neto, Leonardo; Gadelha, Mônica R
Hypercortisolism is associated with various systemic manifestations, including central obesity, arterial hypertension, glucose intolerance/diabetes mellitus, dyslipidemia, nephrolithiasis, osteoporosis, gonadal dysfunction, susceptibility to infections, psychiatric disorders, and hypercoagulability. The activation of the hemostatic system contributes to the development of atherosclerosis and subsequent cardiovascular morbidity and mortality. Previous studies have identified an increased risk of both unprovoked and postoperative thromboembolic events in patients with endogenous and exogenous Cushing's syndrome (CS). The risk for postoperative venous thromboembolism in endogenous CS is comparable to the risk after total hip or knee replacement under short-term prophylaxis. The mechanisms that are involved in the thromboembolic complications in hypercortisolism include endothelial dysfunction, hypercoagulability, and stasis (Virchow's triad). It seems that at least two factors from Virchow's triad must be present for the occurrence of a thrombotic event in these patients. Most studies have demonstrated that this hypercoagulable state is explained by increased levels of procoagulant factors, mainly factors VIII, IX, and von Willebrand factor, and also by an impaired fibrinolytic capacity, which mainly results from an elevation in plasminogen activator inhibitor 1. Consequently, there is a shortening of activated partial thromboplastin time and increased thrombin generation. For these reasons, anticoagulant prophylaxis might be considered in patients with CS whenever they have concomitant prothrombotic risk factors. However, multicenter studies are needed to determine which patients will benefit from anticoagulant therapy and the dose and time of anticoagulation.
Hargens, A. R.; Watenpaugh, D. E.
This article reviews recent flight and ground-based studies of cardiovascular adaptation to spaceflight. Prominent features of microgravity exposure include loss of gravitational pressures, relatively low venous pressures, headward fluid shifts, plasma volume loss, and postflight orthostatic intolerance and reduced exercise capacity. Many of these short-term responses to microgravity extend themselves during long-duration microgravity exposure and may be explained by altered pressures (blood and tissue) and fluid balance in local tissues nourished by the cardiovascular system. In this regard, it is particularly noteworthy that tissues of the lower body (e.g., foot) are well adapted to local hypertension on Earth, whereas tissues of the upper body (e.g., head) are not as well adapted to increase in local blood pressure. For these and other reasons, countermeasures for long-duration flight should include reestablishment of higher, Earth-like blood pressures in the lower body.
Schappell, R. T.; Polhemus, J. T.; Ganiaris, N. J.
The observation mechanisms dealing with pressure, flow, morphology, temperature, etc. are discussed. The approach taken in the performance of this study was to (1) review ground and space-flight data on cardiovascular function, including earlier related ground-based and space-flight animal studies, Mercury, Gemini, Apollo, Skylab, and recent bed-rest studies, (2) review cardiovascular measurement parameters required to assess individual performance and physiological alternations during space flight, (3) perform an instrumentation survey including a literature search as well as personal contact with the applicable investigators, (4) assess instrumentation applicability with respect to the established criteria, and (5) recommend future research and development activity. It is concluded that, for the most part, the required instrumentation technology is available but that mission-peculiar criteria will require modifications to adapt the applicable instrumentation to a space-flight configuration.
Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine. PMID:26170595
Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine.
de Menezes Martins, Reinaldo; Fernandes Leal, Maria da Luz; Homma, Akira
Yellow fever vaccine was considered one of the safest vaccines, but in recent years it was found that it could rarely cause invasive and disseminated disease in some otherwise healthy individuals, with high lethality. After extensive studies, although some risk factors have been identified, the real cause of causes of this serious adverse event are largely unknown, but findings point to individual host factors. Meningoencephalitis, once considered to happen only in children less than 6 months of age, has also been identified in older children and adults, but with good prognosis. Efforts are being made to develop a safer yellow fever vaccine, and an inactivated vaccine or a vaccine prepared with the vaccine virus envelope produced in plants are being tested. Even with serious and rare adverse events, yellow fever vaccine is the best way to avoid yellow fever, a disease of high lethality and should be used routinely in endemic areas, and on people from non-endemic areas that could be exposed, according to a careful risk-benefit analysis.
Manzoli, Lamberto; Flacco, Maria Elena; Boccia, Stefania; D'Andrea, Elvira; Panic, Nikola; Marzuillo, Carolina; Siliquini, Roberta; Ricciardi, Walter; Villari, Paolo; Ioannidis, John P A
This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider
Phoon, Colin K.L.; Turnbull, Daniel H.
The mouse is the mammalian model of choice for investigating cardiovascular biology, given our ability to manipulate it by genetic, pharmacologic, mechanical, and environmental means. Imaging is an important approach to phenotyping both function and structure of cardiac and vascular components. This review details commonly used imaging approaches, with a focus on echocardiography and magnetic resonance imaging and brief overviews of other imaging modalities. We also briefly outline emerging imaging approaches but caution that reliability and validity data may be lacking. PMID:26928662
Faget, Julien; Sisirak, Vanja; Blay, Jean-Yves; Caux, Christophe; Bendriss-Vermare, Nathalie; Ménétrier-Caux, Christine
Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) that infiltrate primary breast tumors impair patient survival. The ICOS-mediated interaction between tumor-infiltrating CD4(+) T cells and pDCs leads to the amplification of Tregs and interleukin-10 secretion. Importantly, ICOS(+) cell infiltration correlates with adverse patient prognosis, identifying ICOS as a new target for cancer immunotherapy.
This article, derived from an invited Distinguished Scientist lecture presented at the American Heart Association Scientific Sessions in 2007, reviews 4 themes (adventures) in clinical cardiovascular research carried out over a period of 58 years. It begins with the author's introduction to cardiovascular hemodynamics during a medical school elective in 1951. The 4 adventures include valvular heart disease, hypertrophic cardiomyopathy, heart failure (HF), and myocardial ischemia. In each of these adventures, the author describes briefly what was known when he entered each field, followed by the author's contribution to the field (the adventure), and ends with comments about the current status of the field. Of particular interest are the changes in the technologies used in clinical cardiovascular research over the past half century, commencing with pressure tracings in left heart chambers with the use of needle puncture in the operating room to genetic technologies designed to understand differences between drugs that inhibit platelet activation. The article ends with some general comments on conducting research and the rewards that can come with this activity.
diagnosed at distant stage than whites (57 versus 45%; p = 0.03). In multivariable analyses adjusted for pack-years of smoking, age, body mass index, health ...cancer in under- served populations,14 understanding lung cancer prognosis in these populations is necessary for targeted public health interventions...Division of Epidemiology, Department of Medicine, ‡Institute for Medicine and Public Health , Department of Medicine, Vanderbilt University Medical
pathologists. In the end, the pathologists have resorted to scoring the slides either by directly reading the images scanned from the Leica scanner...stains. Regardless, the reading of 5304 cores requires a single pathologist on average approximately 70 hours to look at and score all of the cores...addition, we have proposed testing a series of biomarkers of prognosis and a set of biomarkers that correlate with Gleason Score . We have made
Antonov, V. A.; Grosmann, M. H.; Kartavenko, V. I.; Larkin, A. I.; Trukhanov, K. A.
The various methods of laser coherent photonic implementations of multiparametric classification are discussed in this paper. The holographic and optical data processing methods for medical application are considered. Inverse two-phase coding and analysis of light distribution in the correlation plane enables us to realize a number of algorithms: search for a precedent, Hamming distance measurement, Bayes probability algorithm, deterministic and ‘correspondence’ algorithms. The experimental holographic results for medicine prognosis are shown.
Rafter, N; Hickey, A; Condell, S; Conroy, R; O'Connor, P; Vaughan, D; Williams, D
Large national reviews of patient charts estimate that approximately 10% of hospital admissions are associated with an adverse event (defined as an injury resulting in prolonged hospitalization, disability or death, caused by healthcare management). Apart from having a significant impact on patient morbidity and mortality, adverse events also result in increased healthcare costs due to longer hospital stays. Furthermore, a substantial proportion of adverse events are preventable. Through identifying the nature and rate of adverse events, initiatives to improve care can be developed. A variety of methods exist to gather adverse event data both retrospectively and prospectively but these do not necessarily capture the same events and there is variability in the definition of an adverse event. For example, hospital incident reporting collects only a very small fraction of the adverse events found in retrospective chart reviews. Until there are systematic methods to identify adverse events, progress in patient safety cannot be reliably measured. This review aims to discuss the need for a safety culture that can learn from adverse events, describe ways to measure adverse events, and comment on why current adverse event monitoring is unable to demonstrate trends in patient safety.
Roy, G C; Sutradhar, S R; Barua, U K; Datta, N C; Debnath, C R; Hoque, M M; Hossain, A S; Haider, M S; Das, M
Chronic kidney disease (CKD) is a worldwide public health problem. Cardiovascular disease (CVD) is frequently associated with CKD, which is important because individuals with CKD are more likely to die from CVD than to develop kidney failure. CVD in CKD is treatable and potentially preventable and CKD appears to be a risk factor for CVD. In order of incidence and frequency systemic hypertension, left ventricular failure, congestive cardiac failure, ischemic heart disease, anaemic heart failure, rhythm disturbances, pericarditis with or without effusion, cardiac tamponade, uraemic cardiomyopathy are various cardiovascular complications encountered in patients with chronic renal failure. A patient may present with one or more complications of cardiovascular system. The survival rate and prognosis to a great extent depends on proper management of these complications. Use of regular dialysis and renal transplant has changed the death pattern in developed countries but it is still a major problem in developing country. The aim of this article is early detection of CKD and proper management of it thereby preventing the major cardiovascular complications.
Russell, J M; Blair, V; Hunter, R D
Retrospective analysis of 2870 patients with invasive carcinoma of the cervix treated by radiotherapy from 1971 to 1978 showed that the prognosis for younger patients (defined as either under 35 or under 40) was better than that for older age groups, but young patients presented with earlier disease. When the effect of stage on prognosis was also considered the improved survival of patients under 35 was confirmed, although the result was of only borderline significance. The better survival of younger patients was particularly noticeable for stage IB disease, the corrected five year survival of those under 35 being 93% compared with 79% for those over 35. On the basis of this analysis and a review of previous reports it is concluded that age alone is a poor indicator of prognosis and should not be used as an indication for adjuvant treatment. There is no evidence in this series of an aggressive form of cervical carcinoma in younger patients during the 1970s. PMID:3115418
Korhonen, Maarit Jaana; Halonen, Jaana I.; Brookhart, M. Alan; Kawachi, Ichiro; Pentti, Jaana; Karlsson, Hasse; Kivimäki, Mika; Vahtera, Jussi
Purpose To investigate whether adverse experiences in childhood predict non-adherence to statin therapy in adulthood. Methods A cohort of 1378 women and 538 men who initiated statin therapy during 2008–2010 after responding to a survey on childhood adversities, was followed for non-adherence during the first treatment year. Log-binomial regression was used to estimate predictors of non-adherence, defined as the proportion of days covered by dispensed statin tablets <80%. In fully adjusted models including age, education, marital status, current smoking, heavy alcohol use, physical inactivity, obesity, presence of depression and cardiovascular comorbidity, the number of women ranged from 1172 to 1299 and that of men from 473 to 516, because of missing data on specific adversities and covariates. Results Two in three respondents reported at least one of the following six adversities in the family: divorce/separation of the parents, long-term financial difficulties, severe conflicts, frequent fear, severe illness, or alcohol problem of a family member. 51% of women and 44% of men were non-adherent. In men, the number of childhood adversities predicted an increased risk of non-adherence (risk ratio [RR] per adversity 1.11, 95% confidence interval [CI] 1.01–1.21], P for linear trend 0.013). Compared with those reporting no adversities, men reporting 3–6 adversities had a 1.44-fold risk of non-adherence (95% CI 1.12–1.85). Experiencing severe conflicts in the family (RR 1.27, 95% CI 1.03–1.57]) and frequent fear of a family member (RR 1.27, 95% CI 1.00–1.62]) in particular, predicted an increased risk of non-adherence. In women, neither the number of adversities nor any specific type of adversity predicted non-adherence. Conclusions Exposure to childhood adversity may predict non-adherence to preventive cardiovascular medication in men. Usefulness of information on childhood adversities in identification of adults at high risk of non-adherence deserves
Itani, Nozomi; Skeffington, Katie L; Beck, Christian; Niu, Youguo; Giussani, Dino A
There is a search for rescue therapy against fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia, particularly following clinical diagnosis of fetal growth restriction (FGR). Melatonin protects the placenta in adverse pregnancy; however, whether melatonin protects the fetal heart and vasculature in hypoxic pregnancy independent of effects on the placenta is unknown. Whether melatonin can rescue fetal cardiovascular dysfunction when treatment commences following FGR diagnosis is also unknown. We isolated the effects of melatonin on the developing cardiovascular system of the chick embryo during hypoxic incubation. We tested the hypothesis that melatonin directly protects the fetal cardiovascular system in adverse development and that it can rescue dysfunction following FGR diagnosis. Chick embryos were incubated under normoxia or hypoxia (14% O2) from day 1 ± melatonin treatment (1 mg/kg/day) from day 13 of incubation (term ~21 days). Melatonin in hypoxic chick embryos rescued cardiac systolic dysfunction, impaired cardiac contractility and relaxability, increased cardiac sympathetic dominance, and endothelial dysfunction in peripheral circulations. The mechanisms involved included reduced oxidative stress, enhanced antioxidant capacity and restored vascular endothelial growth factor expression, and NO bioavailability. Melatonin treatment of the chick embryo starting at day 13 of incubation, equivalent to ca. 25 wk of gestation in human pregnancy, rescues early origins of cardiovascular dysfunction during hypoxic development. Melatonin may be a suitable antioxidant candidate for translation to human therapy to protect the fetal cardiovascular system in adverse pregnancy.
The experience of poverty during childhood is a potent predictor of a variety of adverse health outcomes during middle and late adulthood. Children who live in poverty are more likely as adults than their peers to develop and die earlier from a range of diseases. These effects are especially strong for cardiovascular disease and type II diabetes. Most disturbingly, these effects appear in large part to be biologically embedded such that later improved life circumstances have only a modest ameliorative effect. Considering these findings and the relatively high rates of child poverty in nations such as Canada, UK, and USA, those concerned with improving the health of citizens should focus their attention on advocating for public policy that will reduce the incidence of child poverty.
Moazzam, Md Shahnawaz; Nasreen, Farah; Bano, Shahjahan; Amir, Syed Hussain
Ondansetron is a serotonin receptor antagonist which has been used frequently to reduce the incidence of post-operative nausea and vomiting in laparoscopic surgery. It has become very popular drug for the prevention of post-operative nausea and vomiting due to its superiority in-terms of efficacy as well as lack of side effects and drug interactions. Although cardiovascular adverse effects of this drug are rare, we found a case of symptomatic sinus bradycardia in a 43-year-old female patient, going for laparoscopic cholecystectomy, who developed the same after she was given intravenous ondansetron in operation theater during premedication. Hence, we report this case, as the rare possibility of encountering bradycardia effect after intravenous administration of ondansetron should be born in mind. PMID:21655029
Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen
Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043
Sasidharanpillai, Sarita; Riyaz, Najeeba; Khader, Anza; Rajan, Uma; Binitha, Manikoth P; Sureshan, Deepthi N
Background: Drug eruptions range from transient erythema to the life threatening severe cutaneous adverse reactions (SCAR) that encompass Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms complex (DRESS). Aims and Objectives: To study the clinical and epidemiological aspects of cutaneous adverse drug reactions (CADR). Materials and Methods: Ethical clearance was obtained from the institutional ethics committee. All patients admitted in the Dermatology ward of our tertiary care hospital with CADR (those who fit in the category of probable or possible drug reaction as per WHO casuality assessment) from first September 2011 to 31st August 2012 were included in this cross sectional study after obtaining written informed consent. The drug reaction patterns observed in the study population were determined and the common offending drugs were identified. Results: In the study, population of males outnumbered females and the majority were between 46 and 60 years of age. The commonest reaction pattern observed was SJS- TEN spectrum of illness and aromatic anticonvulsants were the common offending drugs. Prompt withdrawal of the culprit drug and administration of systemic steroids with or without I/V Ig reverted the adverse reaction in all except one. Conclusion: Severe drug reactions predominated as the study population was comprised of inpatients of a tertiary referral centre. Though; previous authors had reported a mortality rate of up to 20% in DRESS, all our patients with this reaction pattern, responded well to treatment. The mortality rate among TEN cases was much lower than the previous reports. Early diagnosis, prompt withdrawal of the suspected drug, careful monitoring for development of complications and immediate intervention can improve the prognosis of CADR. PMID:25657416
Husserl, F E; Messerli, F H
Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.
Mersky, Joshua P; Janczewski, Colleen E; Topitzes, James
Research on adverse childhood experiences (ACEs) has unified the study of interrelated risks and generated insights into the origins of disorder and disease. Ten indicators of child maltreatment and household dysfunction are widely accepted as ACEs, but further progress requires a more systematic approach to conceptualizing and measuring ACEs. Using data from a diverse, low-income sample of women who received home visiting services in Wisconsin ( N = 1,241), this study assessed the prevalence of and interrelations among 10 conventional ACEs and 7 potential ACEs: family financial problems, food insecurity, homelessness, parental absence, parent/sibling death, bullying, and violent crime. Associations between ACEs and two outcomes, perceived stress and smoking, were examined. The factor structure and test-retest reliability of ACEs was also explored. As expected, prevalence rates were high compared to studies of more representative samples. Except for parent/sibling death, all ACEs were intercorrelated and associated at the bivariate level with perceived stress and smoking. Exploratory factor analysis confirmed that conventional ACEs loaded on two factors, child maltreatment and household dysfunction, though a more complex four-factor solution emerged once new ACEs were introduced. All ACEs demonstrated acceptable test-retest reliability. Implications and future directions toward a second generation of ACE research are discussed.
BACKGROUND: Approximately 200 000 kidney transplant recipients are living in the United States; they are at increased risk for cardiovascular and other adverse outcomes. Biomarkers predicting these outcomes are needed. Using specimens collected during the Folic Acid for Vascular Outcome Reduction in...
Background A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. Description The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term ‘adverse event’ denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. Conclusion OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of
Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad
Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490
Mooser, V; Waterworth, D M; Isenhour, T; Middleton, L
In the past pharmacological agents have contributed to a significant reduction in age-adjusted incidence of cardiovascular events. However, not all patients treated with these agents respond favorably, and some individuals may develop side-effects. With aging of the population and the growing prevalence of cardiovascular risk factors worldwide, it is expected that the demand for cardiovascular drugs will increase in the future. Accordingly, there is a growing need to identify the 'good' responders as well as the persons at risk for developing adverse events. Evidence is accumulating to indicate that responses to drugs are at least partly under genetic control. As such, pharmacogenetics - the study of variability in drug responses attributed to hereditary factors in different populations - may significantly assist in providing answers toward meeting this challenge. Pharmacogenetics mostly relies on associations between a specific genetic marker like single nucleotide polymorphisms (SNPs), either alone or arranged in a specific linear order on a certain chromosomal region (haplotypes), and a particular response to drugs. Numerous associations have been reported between selected genotypes and specific responses to cardiovascular drugs. Recently, for instance, associations have been reported between specific alleles of the apoE gene and the lipid-lowering response to statins, or the lipid-elevating effect of isotretinoin. Thus far, these types of studies have been mostly limited to a priori selected candidate genes due to restricted genotyping and analytical capacities. Thanks to the large number of SNPs now available in the public domain through the SNP Consortium and the newly developed technologies (high throughput genotyping, bioinformatics software), it is now possible to interrogate more than 200,000 SNPs distributed over the entire human genome. One pharmacogenetic study using this approach has been launched by GlaxoSmithKline to identify the approximately 4% of
Rationale: Ambient particulate matter (PM) exposure has been associated with adverse cardiovascular effects. A recent epidemiology study reported that omega-3 polyunsaturated fatty acid (fish oil) supplementation blunted the response of study participants to PM. Our study was des...
Cordes, J; Lange-Asschenfeldt, C; Hiemke, C; Kahl, K G
Increased cardiometabolic morbidity and increased overall mortality has been observed in patients with severe mental disorders. Therefore, cardiometabolic safety is an important issue in the treatment of patients with psychiatric disorders, in particular in patients with comorbid cardiometabolic diseases. Frequent adverse side effects include disturbances of lipid and glucose metabolism, body weight changes and alterations of the QTc interval. Dependent on the particular substance used and on factors concerning individual vulnerability, these side effects vary in relative frequency. Therefore, regular monitoring is recommended including ECG. Furthermore, interactions between different medicaments may occur, either leading to enhanced or decreased drug concentrations. Prior to psychopharmacological treatment, proper cardiological treatment is recommended. The management of cardiovascular risks under psychopharmacology requires interdisciplinary cooperation between the cardiologist, general practitioner and psychiatrist.
Driazhenko, I V
Cardiovascular system involvement with early development of atherosclerosis is characteristic for rheumatic diseases. Among causes of death in various rheumatic diseases cardiovascular pathology also prevails. This paper contains a review of most important studies of impairment of the heart, arterial and venous parts of cardiovascular system in patients with diffuse diseases of connective tissue, rheumatoid arthritis and systemic vasculitides. The role of immune mechanisms, endothelial dysfunction, dyslipidemia in pathogenesis of cardiovascular disturbances with development of myocardial and vascular remodeling in rheumatic diseases is also discussed. Major risk factors of cardiovascular pathology in rheumatic patients are presented. Treatment of a cardiovascular pathology in these patients presumes the use of angiotensin converting enzyme inhibitors, aldosterone antagonists and statins.
Recent studies indicate that deficient vitamin D status may increase risk of both ischemic and nonischemic cardiovascular diseases independently of established cardiovascular risk factors. The role of vitamin D in potentially regulating many functions in the cardiovascular system is just beginning to be understood. Among the potentially relevant mechanisms for cardiovascular diseases, vitamin D may influence blood pressure through the renin-angiotensin system, parathyroid hormone levels, myocardial function, inflammation, and vascular calcification. Cardiovascular risk appears especially elevated at 25-hydroxy-vitamin D levels below 10 or 15 ng/mL, and optimal levels may be at least 30 ng/mL. Among individuals who are not receiving substantial exposure to sun, intakes of 1000 to 2000 IU may be needed to achieve levels of at least 30 ng/mL. Further study, including properly designed randomized control trials, is required to further establish the role of vitamin D on cardiovascular diseases.
Wang, Xi-Xu; Dong, Bo; Hong, Biao; Gong, Yi-Qun; Wang, Wei; Wang, Jue; Zhou, Zhen-Yu; Jiang, Wei-Jun
AIM To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. METHODS All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t- or χ2-test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the difference was compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. RESULTS A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups (70.8 ± 11.4 vs 62.4 ± 12.0, P < 0.001; 8 (8.2%) vs 15 (21.7%), P < 0.05; 65 (66.3%) vs 13 (18.8%), P < 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant (P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients
Abboud, François M; Benson, Christopher J
In this review we address primarily the role of ASICs in determining sensory signals from arterial baroreceptors, peripheral chemoreceptors, and cardiopulmonary and somatic afferents. Alterations in these sensory signals during acute cardiovascular stresses result in changes in sympathetic and parasympathetic activities that restore cardiovascular homeostasis. In pathological states, however, chronic dysfunctions of these afferents result in serious sympatho-vagal imbalances with significant increases in mortality and morbidity. We identified a role for ASIC2 in the mechano-sensitivity of aortic baroreceptors and of ASIC3 in the pH sensitivity of carotid bodies. In spontaneously hypertensive rats, we reported decreased expression of ASIC2 in nodose ganglia neurons and overexpression of ASIC3 in carotid bodies. This reciprocal expression of ASIC2 and ASIC3 results in reciprocal changes in sensory sensitivity of baro- and chemoreceptors and a consequential synergistic exaggeration sympathetic nerve activity. A similar reciprocal sensory dysautonomia prevails in heart failure and increases the risk of mortality. There is also evidence that ASIC heteromers in skeletal muscle afferents contribute significantly to the exercise pressor reflex. In cardiac muscle afferents of the dorsal root ganglia, they contribute to nociception and to the detrimental sympathetic activation during ischemia. Finally, we report that an inhibitory influence of ASIC2-mediated baroreceptor activity suppresses the sympatho-excitatory reflexes of the chemoreceptors and skeletal muscle afferents, as well as the ASIC1a-mediated excitation of central neurons during fear, threat, or panic. The translational potential of activation of ASIC2 in cardiovascular disease states may be a beneficial sympatho-inhibition and parasympathetic activation. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'.
Scheid, Carl C.
The detection of a cardiovascular stenosis involves the complex interaction of technique selection, system performance and anatomy. Technique selection for instance involves choosing the correct focal spot, pulse width, KVp, and frame rate for a given patient and projection angle. In order to provide guidance in this selection process, these variables were investigated in terms of their impact on image quality. Conclusions which were confirmed clinically are summarized in terms of recommended techniques for a range of patient sizes. The confirmation includes clinical films which demonstrates the effects of parameter changes.
McCullough, Peter A; Chan, Christopher T; Weinhandl, Eric D; Burkart, John M; Bakris, George L
with lower risk for cardiovascular hospitalization. In conclusion, intensive HD likely reduces left ventricular mass and may lead to lower risks for adverse cardiac events.
Background Adverse events are considered a major international problem related to the performance of health systems. Evaluating the occurrence of adverse events involves, as any other outcome measure, determining the extent to which the observed differences can be attributed to the patient's risk factors or to variations in the treatment process, and this in turn highlights the importance of measuring differences in the severity of the cases. The current study aims to evaluate the association between deaths and adverse events, adjusted according to patient risk factors. Methods The study is based on a random sample of 1103 patient charts from hospitalizations in the year 2003 in 3 teaching hospitals in the state of Rio de Janeiro, Brazil. The methodology involved a retrospective review of patient charts in two stages - screening phase and evaluation phase. Logistic regression was used to evaluate the relationship between hospital deaths and adverse events. Results The overall mortality rate was 8.5%, while the rate related to the occurrence of an adverse event was 2.9% (32/1103) and that related to preventable adverse events was 2.3% (25/1103). Among the 94 deaths analyzed, 34% were related to cases involving adverse events, and 26.6% of deaths occurred in cases whose adverse events were considered preventable. The models tested showed good discriminatory capacity. The unadjusted odds ratio (OR 11.43) and the odds ratio adjusted for patient risk factors (OR 8.23) between death and preventable adverse event were high. Conclusions Despite discussions in the literature regarding the limitations of evaluating preventable adverse events based on peer review, the results presented here emphasize that adverse events are not only prevalent, but are associated with serious harm and even death. These results also highlight the importance of risk adjustment and multivariate models in the study of adverse events. PMID:21929810
Chiodini, Paolo; Zoccali, Carmine; Borrelli, Silvio; Cianciaruso, Bruno; Di Iorio, Biagio; Santoro, Domenico; Giancaspro, Vincenzo; Abaterusso, Cataldo; Gallo, Ciro; Conte, Giuseppe; Minutolo, Roberto
Summary Background and objectives Prognosis in nondialysis chronic kidney disease (CKD) patients under regular nephrology care is rarely investigated. Design, setting, participants, & measurements We prospectively followed from 2003 to death or June 2010 a cohort of 1248 patients with CKD stages 3 to 5 and previous nephrology care ≥1 year in 25 Italian outpatient nephrology clinics. Cumulative incidence of ESRD or death before ESRD were estimated using the competing-risk approach. Results Estimated rates (per 100 patient-years) of ESRD and death 8.3 (95% confidence interval [CI], 7.4 to 9.2) and 5.9 (95% CI 5.2 to 6.6), respectively. Risk of ESRD and death increased progressively from stages 3 to 5. ESRD was more frequent than death in stage 4 and 5 CKD, whereas the opposite was true in stage 3 CKD. Younger age, lower body mass index, proteinuria, and high phosphate predicted ESRD, whereas older age, diabetes, previous cardiovascular disease, ESRD, proteinuria, high uric acid, and anemia predicted death (P < 0.05 for all). Among modifiable risk factors, proteinuria accounted for the greatest contribution to the model fit for either outcome. Conclusions In patients receiving continuity of care in Italian nephrology clinics, ESRD was a more frequent outcome than death in stage 4 and 5 CKD, but the opposite was true in stage 3. Outcomes were predicted by modifiable risk factors specific to CKD. Proteinuria used in conjunction with estimated GFR refined risk stratification. These findings provide information, specific to CKD patients under regular outpatient nephrology care, for risk stratification that complement recent observations in the general population. PMID:21817127
Newberry, Kate J.; Naqvi, Kiran; Nguyen, Khanh T.; Cardenas-Turanzas, Marylou; Tanaka, Maria Florencia; Pierce, Sherry; Verstovsek, Srdan
Background Comorbidities have been shown to play an important role in prognostic assessment of several hematologic conditions; however, the role of comorbidities in primary myelofibrosis has not been studied. The aim of our study was to evaluate the prevalence and impact of comorbidities in patients with primary myelofibrosis (PMF) using the Adult Comorbidity Evaluation-27 (ACE-27). Methods In this retrospective observational cohort study, we evaluated 349 consecutive patients with a confirmed diagnosis of PMF who presented to our institution from 2000 to 2008. We evaluated the frequency and severity of comorbidities in these patients and assessed their impact on survival in a bivariable model that included the ACE-27 and Dynamic International Prognostic Scoring System (DIPSS) scores as covariates. Results Sixty-four percent of patients had at least one comorbid condition, and diseases of the cardiovascular system (63%) were most common. Comorbidities had a significant negative impact on survival (P < 0.001). Patients with severe comorbidities had twice the risk of death as those with no comorbidities. When stratified by demographic and clinical characteristics, comorbidities were significantly associated with worse survival in patients younger than 65 years (P < 0.001) and those with performance status < 1 (P < 0.001). In a multivariable model that included the ACE-27 and Dynamic-International Prognostic Scoring System scores, comorbidities retained a significant association with shorter survival (P ≤ 0.001). Conclusions Assessment of comorbid conditions in patients with PMF, particularly those who are younger and with good performance status, has important implications for overall prognosis and treatment planning. PMID:24917509
Mortensen, Kristian H; Andersen, Niels H; Gravholt, Claus H
Cardiovascular disease is emerging as a cardinal trait of Turner syndrome, being responsible for half of the 3-fold excess mortality. Turner syndrome has been proposed as an independent risk marker for cardiovascular disease that manifests as congenital heart disease, aortic dilation and dissection, valvular heart disease, hypertension, thromboembolism, myocardial infarction, and stroke. Risk stratification is unfortunately not straightforward because risk markers derived from the general population inadequately identify the subset of females with Turner syndrome who will suffer events. A high prevalence of endocrine disorders adds to the complexity, exacerbating cardiovascular prognosis. Mounting knowledge about the prevalence and interplay of cardiovascular and endocrine disease in Turner syndrome is paralleled by improved understanding of the genetics of the X-chromosome in both normal health and disease. At present in Turner syndrome, this is most advanced for the SHOX gene, which partly explains the growth deficit. This review provides an up-to-date condensation of current state-of-the-art knowledge in Turner syndrome, the main focus being cardiovascular morbidity and mortality. The aim is to provide insight into pathogenesis of Turner syndrome with perspectives to advances in the understanding of genetics of the X-chromosome. The review also incorporates important endocrine features, in order to comprehensively explain the cardiovascular phenotype and to highlight how raised attention to endocrinology and genetics is important in the identification and modification of cardiovascular risk.
Mavrogeni, Sophie; Markousis-Mavrogenis, George; Kolovou, Genovefa
Immunoglobulin 4-related disease (IgG4-related disease) is a systemic inflammatory disease that presents with increases of serum IgG4. It may affect various systems, including the cardiovascular (CV) system. Assessment of serum IgG4 levels and involved organ biopsy are necessary for diagnosis. IgG4-related disease is characterized by fibrosclerosis, lymphocytic infiltration and presence of IgG4-positive plasma cells. The disease usually responds to treatment with corticosteroids and/or immunosuppressive medication. CV involvement may manifest as cardiac pseudotumors, inflammatory periaortitis, coronary arteritis and/or pericarditis. IgG4-related cardiovascular disorders can severely affect patient prognosis. Various imaging techniques, including echocardiography, Computed Tomography (CT), 18FDG-PET, Cardiovascular Magnetic Resonance (CMR) and cardiac catheterisation, have been successfully used for early disease detection and follow-up. Echocardiography and vascular ultrasound are the most commonly used non-invasive, non-radiating imaging techniques for the evaluation of IgG4-related CV disease. Periaortitis/periarteritis can be also assessed by CT, showing a soft tissue thickening around arteries. Coronary artery aneurysms can be easily diagnosed by coronary CT. In case of active periarterial or coronary artery inflammation, 18FDG-PET will show FDG uptake at the area of the lesion. CMR, due to its capability to perform function and tissue characterisation, can offer an integrated imaging of aorta, coronary arteries and the heart, assessment of disease acuity, extent of fibrosis and guide further treatment. However, multimodality imaging may be necessary for assessment of disease activity and fibrosis extent in those cases with multifocal CV involvement.
Sleep disturbance is a common problem in general adult population. Recent evidence suggests the link between the occurrence of cardiovascular events and several sleep disturbances including sleep apnea syndrome, insomnia and periodic limb movements during sleep. Sleep duration may affect the cardiovascular outcome. Shift work also may increase the risk of ischemic heart disease. Normalization of sleep rhythm has a potential to be a therapeutic target of ischemic heart diseases, although further study is required to evaluate the preventive effect on cardiovascular events. Here we describe the current understandings regarding the roles of sleep disorders during the pathogenesis of cardiovascular events.
Kim, Yoon Ho; Jeong, Tae Min; Pang, Kang Mi
Objectives The purpose of this article is to evaluate factors influencing prognosis of arthrocentesis in patients with temporomandibular joint (TMJ) disorder. Materials and Methods The subjects included 145 patients treated with arthrocentesis at the Dental Center of Ajou University Hospital from 2011 to 2013 for the purpose of recovering mouth opening limitation (MOL) and pain relief. Prognosis of arthrocentesis was evaluated 1 month after the operation. Improvement on MOL was defined as an increase from below 30 mm (MOL ≤30 mm) to above 40 mm (MOL ≥40 mm), and pain relief was defined as when a group with TMJ pain with a visual analog scale (VAS) score of 4 or more (VAS ≥4) decreased to a score of 3 or more. The success of arthrocentesis was determined when either mouth opening improved or pain relief was fulfilled. To determine the factors influencing the success of arthrocentesis, the patients were classified by age, gender, diagnosis group (the anterior disc displacement without reduction group, the anterior disc displacement with reduction group, or other TMJ disorders group), time of onset and oral habits (clenching, bruxism) to investigate the correlations between these factors and prognosis. Results One hundred twenty out of 145 patients who underwent arthrocentesis (83.4%) were found to be successful. Among the influencing factors mentioned above, age, diagnosis and time of onset had no statistically significant correlation with the success of arthrocentesis. However, a group of patients in their fifties showed a lower success rate (ANOVA P=0.053) and the success rate of the group with oral habits was 71% (Pearson's chi-square test P=0.035). Conclusion From this study, we find that factors influencing the success of arthrocentesis include age and oral habits. We also conclude that arthrocentesis is effective in treating mouth opening symptoms and for pain relief. PMID:25247144
The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment in the toxicologic pathology community regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop in June 2015 to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports. The international group of expert pathologists and toxicologists emphasized that a holistic, weight-of-evidence, case-specific approach should be followed for each adversity assessment. It was recommended that nonclinical adversity should typically be determined at a morphological level (most often the organ) in the pathology report and should refer specifically to the test species. Final adversity calls, integration of target pharmacology/pathway information, and consideration of human translation should generally be made in toxicology overview reports. Differences in interpretation and implications of adversity calls between (agro)chemical and pharmaceutical industries and among world regions were highlighted. The results of this workshop should serve a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP. This
Hooper, Stuart B; Te Pas, Arjan B; Lang, Justin; van Vonderen, Jeroen J; Roehr, Charles Christoph; Kluckow, Martin; Gill, Andrew W; Wallace, Euan M; Polglase, Graeme R
The transition to newborn life at birth involves major cardiovascular changes that are triggered by lung aeration. These include a large increase in pulmonary blood flow (PBF), which is required for pulmonary gas exchange and to replace umbilical venous return as the source of preload for the left heart. Clamping the umbilical cord before PBF increases reduces venous return and preload for the left heart and thereby reduces cardiac output. Thus, if ventilation onset is delayed following cord clamping, the infant is at risk of superimposing an ischemic insult, due to low cardiac output, on top of an asphyxic insult. Much debate has centered on the timing of cord clamping at birth, focusing mainly on the potential for a time-dependent placental to infant blood transfusion. This has prompted recommendations for delayed cord clamping for a set time after birth in infants not requiring resuscitation. However, recent evidence indicates that ventilation onset before cord clamping mitigates the adverse cardiovascular consequences caused by immediate cord clamping. This indicates that the timing of cord clamping should be based on the infant's physiology rather than an arbitrary period of time and that delayed cord clamping may be of greatest benefit to apneic infants.
Ganz, Melanie; de Bruijne, Marleen; Nielsen, Mads
Despite general acceptance that a healthy lifestyle and the treatment of risk factors can prevent the development of cardiovascular diseases (CVD), CVD are the most common cause of death in Europe and the United States. It has been shown that abdominal aortic calcifications (AAC) correlate strongly with coronary artery calcifications. Hence an early detection of aortic calcified plaques helps to predict the risk of related coronary diseases. Also since two thirds of the adverse events have no prior symptoms, possibilities to screen for risk in low cost imaging are important. To this end the Morphological Atherosclerotic Calcification Distribution (MACD) index was developed. In the following several potential severity scores relating to the geometrical outline of the calcified deposits in the lumbar aortic region are introduced. Their individual as well as their combined predictive power is examined and a combined marker, MACD, is constructed. This is done using a Cox regression analysis, also known as survival analysis. Furthermore we show how a Cox regression yields MACD to be the most efficient marker. We also demonstrate that MACD has a larger individual predictive power than any of the other individual imaging markers described. Finally we present that the MACD index predicts cardiovascular death with a hazard ratio of approximately four.
von Schacky, Clemens
Recent large trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the cardiovascular field did not demonstrate a beneficial effect in terms of reductions of clinical endpoints like total mortality, sudden cardiac arrest or other major adverse cardiac events. Pertinent guidelines do not uniformly recommend EPA + DHA for cardiac patients. In contrast, in epidemiologic findings, higher blood levels of EPA + DHA were consistently associated with a lower risk for the endpoints mentioned. Because of low biological and analytical variability, a standardized analytical procedure, a large database and for other reasons, blood levels of EPA + DHA are frequently assessed in erythrocytes, using the HS-Omega-3 Index® methodology. A low Omega-3 Index fulfills the current criteria for a novel cardiovascular risk factor. Neutral results of intervention trials can be explained by issues of bioavailability and trial design that surfaced after the trials were initiated. In the future, incorporating the Omega-3 Index into trial designs by recruiting participants with a low Omega-3 Index and treating them within a pre-specified target range (e.g., 8%–11%), will make more efficient trials possible and provide clearer answers to the questions asked than previously possible. PMID:24566438
Latrech, Hanane; Polak, Michel
Laron syndrome is a rare cause of short stature due to an abnormality of growth hormone receptor (GHR). It is characterized by poor phenotype-genotype correlation and geographic predilection essentially in the Mediterranean rim, the Middle East and Indian subcontinent. This syndrome corresponds to an endogenous and exogenous complete insensitivity of GH and manifests by early hypoglycemia, an extremely severe short stature and dysmorphic features contrasting with high levels of circulating GH. To date, treatment with recombinant IGF1 is the only treatment option that has improved the terrible prognosis in these patients but does not actually realize the conditions for genuine replacement therapy.
van Amsterdam, Jan; Opperhuizen, Antoon; Hartgens, Fred
Anabolic-androgenic steroids (AAS) are synthetic drugs derived from testosterone. Illegally, these drugs are regularly self-administered by body builders and power lifters to enhance their sportive performance. Adverse side effects of AAS include sexual dysfunction, alterations of the cardiovascular system, psyche and behavior, and liver toxicity. However, severe side effects appear only following prolonged use of AAS at high dose and their occurrence is limited. Occasionally, AAS abuse may be linked to certain social and psychological traits of the user, like low self-esteem, low self-confidence, suffered hostility, childhood conduct disorder, and tendency to high-risk behavior. The overwhelming stereotype about AAS is that these compounds cause aggressive behavior in males. However, the underlying personality traits of a specific subgroup of the AAS abusers, who show aggression and hostility, may be relevant, as well. Use of AAS in combination with alcohol largely increases the risk of violence and aggression. The dependence liability of AAS is very low, and withdrawal effects are relatively mild. Based on the scores for acute and chronic adverse health effects, the prevalence of use, social harm and criminality, AAS were ranked among 19 illicit drugs as a group of drugs with a relatively low harm.
Goffinet, F; Kayem, G
Diagnosis. Preterm labor is defined by cervical changes associated with regular painful uterine contractions (UC) between 22 and 36 weeks + 6 days. Tocometry does not improve diagnosis or prognosis, despite the identification of more UC (NP 4). Electromyography and cervical distensibility (cervicotonometer) are promising techniques but are still in the research field. Clinical markers for prognosis. Clinical markers associated with clinical cervical examination tested in scoring systems are not validated and can't be recommended in clinical practise (NP 4). Ultrasonographic examination of the cervix. Technical evaluation of ultrasonographic examination of the cervix is satisfactory (NP 3); the transvaginal technical have to be used (NP 3). This method has a better accuracy and reproducibility than clinical examination provided a good apprenticeship (NP 3). Three ultrasound abnormal criteria are defined: a short length, a large internal cervical os and the presence of a funnel in the cervical canal. The best cut-off of cervical length to predict preterm delivery lies between 18 and 30 mm (NP 3). The choice of the cutt-off level depends on the prectitioner: high sensitivity but with many false-positives (cut-off close to 30 mm) or lower sensitivity with few false-positives (close to 20 mm). Cervical length seems to be more accurate that internal os or presence of a funnel which should be used with caution in clinical decisions (NP 3). There is no comparative study about the use of ultrasonographic examination of the cervix in women with preterm labor to evaluate benefits and adverse effects in clinical practice. However, ultrasonographic examination of the cervix supply a progress identifying women at risk of preterm delivery and this technique has a better predictive value than clinical cervical examination (NP 3). It seems reasonable to recommend utilisation of ultrasonographic examination of the cervic in preterm labor. It would not seem reasonable to replace the
Marso, Steven P; Bain, Stephen C; Consoli, Agostino; Eliaschewitz, Freddy G; Jódar, Esteban; Leiter, Lawrence A; Lingvay, Ildiko; Rosenstock, Julio; Seufert, Jochen; Warren, Mark L; Woo, Vincent; Hansen, Oluf; Holst, Anders G; Pettersson, Jonas; Vilsbøll, Tina
Background Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown. Methods We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio. Results At baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.58 to 0.95; P<0.001 for noninferiority). Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74; 95% CI, 0.51 to 1.08; P=0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P=0.04). Rates of death from cardiovascular causes were similar in the two groups. Rates of new or worsening nephropathy were lower in the semaglutide group, but rates of retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation) were significantly higher (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P=0.02). Fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment
Huang, Yi; Liu, Dan; Chen, Bojiang; Zeng, Jing; Wang, Lei; Zhang, Shangfu; Mo, Xianming; Li, Weimin
Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P < 0.05). Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P < 0.05). Overall survival time was also drastically shortened for Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P < 0.05). In conclusion, this study provided clinical evidence that loss of Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.
The increased incidence of cardiovascular diseases (CVDs) has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES), a polyphenolic compound notably present in grapes and red wine, has been involved in the “French paradox”. RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS). RES was able to scavenge •OH/O2•− and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC) under glucose-induced oxidative stress, RES restored the activity of dimethylargininedimethylaminohydrolase (DDAH), an enzyme that degrades an endogenous inhibitor of eNOS named asymmetric dimethylarginine (ADMA). Thus, RES could improve •NO availability and decrease the endothelial dysfunction observed in diabetes. Preclinical studies have made it possible to identify molecular targets (SIRT-1, AMPK, Nrf2, NFκB…); however, there are limited human clinical trials, and difficulties in the interpretation of results arise from the use of high-dose RES supplements in research studies, whereas low RES concentrations are present in red wine. The discussions on potential beneficial effects of RES in CVDs (atherosclerosis, hypertension, stroke, myocardial infarction, heart failure) should compare the results of preclinical studies with those of clinical trials. PMID:27144581
Burgess, Adriane; Founds, Sandra
Cardiovascular disease (CVD) is the leading cause of death of women in the United States. Many healthcare providers are unaware of sex-specific factors that affect the development of CVD. Nursing care for women with a history of preeclampsia and their children is presented. Preeclampsia affects 4% to 8% of all pregnancies. Rates have increased by 25% over the past 2 decades. Research supports the link between preeclampsia and risk of future CVD in women and the children of affected pregnancies. Appropriate preconception, prenatal and postpartum education, and surveillance are necessary to improve the long-term health of both mother and infant. Currently, there are no evidence-based interventions specific to the prevention of CVD for women and their children who have been affected by preeclampsia. However, women who have had preeclampsia may require yearly risk factor assessment and education regarding cardiovascular prevention strategies such as smoking cessation, increased physical activity, importance of a healthy diet, and maintenance of a healthy weight. Preeclampsia should be acknowledged by healthcare providers as a CVD risk factor. Appropriate monitoring, education, and CVD preventive strategies need to be implemented with this population and their children.
Cecanho, Rodrigo; De Luca, Laurival Antonio; Ranali, José
Cardiovascular effects of felypressin (FEL) were studied in Wistar rats. Heart rate and mean arterial pressure measurements were taken in awake rats treated with vasopressin (AVP), FEL, or epinephrine (EPI). Each group received either an intravenous (IV) or an intracerebroventricular V1 receptor antagonist, saline, area postrema removal, or sham surgery. Analysis of variance and Student-Newman-Keuls (P < .05) were applied. Felypressin and AVP induced a pressor effect, and bradycardia was inhibited by IV V1 antagonist. Intracerebroventricular V1 antagonist and area postrema removal enhanced their pressor effects. Epinephrine induced a higher pressor effect and a similar bradycardia that was not affected by the treatments. It was concluded that FEL depends on V1 receptors to induce pressor and bradycardic effects, and that it produces a high relationship between bradycardia and mean arterial pressure variation depending on area postrema and central V1 receptors. These effects are potentially less harmful to the cardiovascular system than the effects of EPI. PMID:17177590
Marsden, Alison L.
Fluid mechanics plays a key role in the development, progression, and treatment of cardiovascular disease. Advances in imaging methods and patient-specific modeling now reveal increasingly detailed information about blood flow patterns in health and disease. Building on these tools, there is now an opportunity to couple blood flow simulation with optimization algorithms to improve the design of surgeries and devices, incorporating more information about the flow physics in the design process to augment current medical knowledge. In doing so, a major challenge is the need for efficient optimization tools that are appropriate for unsteady fluid mechanics problems, particularly for the optimization of complex patient-specific models in the presence of uncertainty. This article reviews the state of the art in optimization tools for virtual surgery, device design, and model parameter identification in cardiovascular flow and mechanobiology applications. In particular, it reviews trade-offs between traditional gradient-based methods and derivative-free approaches, as well as the need to incorporate uncertainties. Key future challenges are outlined, which extend to the incorporation of biological response and the customization of surgeries and devices for individual patients.
Gongora, Maria Carolina; Wenger, Nanette K.
Pregnancy causes significant metabolic and hemodynamic changes in a woman’s physiology to allow for fetal growth. The inability to adapt to these changes might result in the development of hypertensive disorders of pregnancy (hypertension, preeclampsia or eclampsia), gestational diabetes and preterm birth. Contrary to previous beliefs these complications are not limited to the pregnancy period and may leave permanent vascular and metabolic damage. There is in addition, a direct association between these disorders and increased risk of future cardiovascular disease (CVD, including hypertension, ischemic heart disease, heart failure and stroke) and diabetes mellitus. Despite abundant evidence of this association, women who present with these complications of pregnancy do not receive adequate postpartum follow up and counseling regarding their increased risk of future CVD. The postpartum period in these women represents a unique opportunity to intervene with lifestyle modifications designed to reduce the development of premature cardiovascular complications. In some cases it allows early diagnosis and treatment of chronic hypertension or diabetes mellitus. The awareness of this relationship is growing in the medical community, especially among obstetricians and primary care physicians, who play a pivotal role in detecting these complications and assuring appropriate follow up. PMID:26473833
Gongora, Maria Carolina; Wenger, Nanette K
Pregnancy causes significant metabolic and hemodynamic changes in a woman's physiology to allow for fetal growth. The inability to adapt to these changes might result in the development of hypertensive disorders of pregnancy (hypertension, preeclampsia or eclampsia), gestational diabetes and preterm birth. Contrary to previous beliefs these complications are not limited to the pregnancy period and may leave permanent vascular and metabolic damage. There is in addition, a direct association between these disorders and increased risk of future cardiovascular disease (CVD, including hypertension, ischemic heart disease, heart failure and stroke) and diabetes mellitus. Despite abundant evidence of this association, women who present with these complications of pregnancy do not receive adequate postpartum follow up and counseling regarding their increased risk of future CVD. The postpartum period in these women represents a unique opportunity to intervene with lifestyle modifications designed to reduce the development of premature cardiovascular complications. In some cases it allows early diagnosis and treatment of chronic hypertension or diabetes mellitus. The awareness of this relationship is growing in the medical community, especially among obstetricians and primary care physicians, who play a pivotal role in detecting these complications and assuring appropriate follow up.
Sakai, Takamasa; Ohtsu, Fumiko; Sekiya, Yasuaki; Mori, Chiyo; Sakata, Hiroshi; Goto, Nobuyuki
Safety information regarding drug use during pregnancy is insufficient. The present study aimed to establish an optimal signal detection method to identify adverse drug reactions in pregnant women and to evaluate information in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and November 2014. We identified reports on pregnant women using the Standardised MedDRA Queries. We calculated the proportional reporting ratio (PRR) and reporting odds ratio (ROR) of the risk factors for the two known risks of antithyroid drugs and methimazole (MMI) embryopathy, and ritodrine and fetal/infant cardiovascular events. The PRR and ROR values differed between all reports in the JADER database and those on pregnant women, affecting whether signal detection criteria were met. Therefore we considered that reports on pregnant women should be used when risks associated with pregnancy were determined using signal detection. Analyses of MMI embryopathy revealed MMI signals [PRR, 159.7; ROR, 669.9; 95% confidence interval (CI), 282.4-1588.7] but no propylthiouracil signals (PRR, 1.98; ROR, 2.0; 95%CI, 0.3-15.4). These findings were consistent with those of reported risks. Analyses of fetal/infant cardiovascular events revealed ritodrine signals (PRR, 2.1; ROR, 2.1; 95%CI, 1.4-3.3). These findings were also consistent with reported risks. Mining the JADER database was helpful for analyzing adverse drug reactions in pregnant women.
Siracuse, Jeffrey J; Huang, Zhen S; Gill, Heather L; Parrack, Inkyong; Schneider, Darren B; Connolly, Peter H; Meltzer, Andrew J
Successful treatment of patients with critical limb ischemia (CLI), hinges on the adequacy of revascularization. However, CLI is associated with a severe burden of systemic atherosclerosis, and patients often suffer from multiple cardiovascular comorbidities. Therefore, CLI patients in general represent a cohort at increased risk for procedural complications and adverse events. Although endovascular therapy represents a minimally invasive alternative to open surgical bypass, the durability of surgical reconstruction is superior, and it remains the “gold standard” approach to revascularization in CLI. Therefore, selection of the optimal treatment modality for individual patients requires careful consideration of the procedural risks and likelihood of adverse events associated with surgery. Individualized decision-making with regard to revascularization strategy requires a comprehensive understanding of the likelihood of adverse outcomes after major surgery. Here we review the risks of surgical bypass in patients with CLI, with particular emphasis on the identification of preoperative variables that predict poor outcome. PMID:25018636
Weiss, Sarah A; Hanniford, Douglas; Hernando, Eva; Osman, Iman
The American Joint Committee on Cancer staging system for cutaneous melanoma is based on primary tumor thickness and the presence of ulceration, mitoses, lymph node spread, and distant metastases as determinants of prognosis. Although this cutaneous melanoma staging system has evolved over time to more accurately reflect patient prognosis, improvements are still needed, because current understanding of the particular factors (genetic mutation, expression alteration, host response, etc) that are critical for predicting patient outcomes is incomplete. Given the clinical and biologic heterogeneity of primary melanomas, new prognostic tools are needed to more precisely identify patients who are most likely to develop advanced disease. Such tools would affect clinical surveillance strategies and aid in patient selection for adjuvant therapy. The authors reviewed the literature on prognostic molecular and immunologic markers in primary cutaneous melanoma, their associations with clinicopathologic and survival outcomes, and their potential for incorporation into current staging models. Overall, the studies considered in this review did not define prognostic markers that could be readily incorporated into the current staging system. Therefore, efforts should be continued in these and other directions to maximize the likelihood of identifying clinically useful prognostic biomarkers for cutaneous melanoma.
Zamora-Ros, Raul; Guinó, Elisabeth; Henar Alonso, M.; Vidal, Carmen; Barenys, Mercè; Soriano, Antonio; Moreno, Victor
Flavonoids and lignans are polyphenol classes with anticarcinogenic activities against colorectal cancer (CRC). However, very limited epidemiological evidence exists on their effects on CRC prognosis. This study aimed to evaluate the association between flavonoid and lignan intakes with the risk of CRC recurrence and overall survival in CRC patients. The study followed incident histologically confirmed CRC cases in Barcelona (Spain). Validated dietary questionnaires and lifestyle information were collected at recruitment. An ad hoc food composition database on flavonoids and lignans was compiled by using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted hazards ratios (HR) and 95% confidence intervals (CIs) were estimated using multivariable Cox models. After 8.6 years of mean follow-up, 133 of 409 (32.5%) participants died and 77 of 319 (24.1%) had a CRC recurrence. Total flavonoids were associated neither with CRC recurrence (HR comparing extreme tertiles 1.13, 95% CI 0.64–2.02; P-trend 0.67) nor with overall survival (HRT3vsT1 1.06, 95% CI 0.69–1.65; P-trend 0.78) in the multivariable models. No associations were also observed with either total lignans or any flavonoid subclass intake. In conclusion, the results of the current study do not support a role of flavonoid and lignan intake in the CRC prognosis. PMID:26369380
Gbaguidi, Audrey; Kim, Daewon
Among the essential steps to be taken in structural health monitoring systems, damage prognosis would be the field that is least investigated due to the complexity of the uncertainties. This paper presents the possibility of using Affine Arithmetic for uncertainty propagation of crack damage in damage prognosis. The structures examined are thin rectangular plates made of titanium alloys with central mode I cracks and a composite plate with an internal delamination caused by mixed mode I and II fracture modes, under a harmonic uniaxial loading condition. The model-based method for crack growth rates are considered using the Paris Erdogan law model for the isotropic plates and the delamination growth law model proposed by Kardomateas for the composite plate. The parameters for both models are randomly taken and their uncertainties are considered as defined by an interval instead of a probability distribution. A Monte Carlo method is also applied to check whether Affine Arithmetic (AA) leads to tight bounds on the lifetime of the structure.
Liao, J P; Hu, Y; Qiu, J X; Jin, Z; Zhang, H; Ma, J; Wang, G F
Objective: To investigate the clinical characteristics and prognosis of mediastinal fibrosis. Methods: Twelve patients with mediastinal fibrosis diagnosed between 2008 and 2015 in our hospital were studied retrospectively. Clinical manifestations, radiological characteristics, endoscopic features, treatment and prognosis were analyzed. Results: There were 3 males and 9 females, with a mean age of 68.8 years.Six patients had previous tuberculosis infection. The most common clinical symptoms were dyspnea on exertion (11 cases), cough (7 cases), and wheezing (6 cases). Chest CT scans revealed an infiltrative mediastinal process, with a discrete mass, enlargement of mediastinal lymph nodes, mediastinal lymph node calcification (9 case). Twelve patients had bronchial and pulmonary artery compression at lobar or segmental levels, 7 cases had localized pulmonary edema, and 6 cases had pulmonary atelectasis. The principal findings of bronchoscopy were distortion of bronchus with stenosis, multiple pigmentation of bronchial mucosa, and bronchial mucosal edema. Pulmonary hypertension (PH) was the main severe complication. One patients suffered from sudden death after bronchoscopy. Eleven patients were followed for 3 month to 7 years, and 5 patients got progression. Anti-tuberculosis therapy with or without corticosteroid was not beneficial. Conclusion: Tuberculosis was the leading cause of mediastinal fibrosis in our study, which was characterized with diffuse bronchial and pulmonary artery compression at lobar or segmental levels, and multiple pigmentation of bronchial mucosa.Anti-tuberculosis therapy with or without corticosteroids was not beneficial.
that was selectively blocked by DPCPX. The protection induced by A3 receptor agonist was completely abrogated in phospholipase C β2/β3-null mice while...completely abrogated in phospholipase C β2/ β3-null mice while that caused by A1 agonist remained unaffected in these animals. The protection by A1 and...β2/ β 3 (PLC β2/ β3) -null mice . Cl-IBMECA-induced protection was completely abrogated in PLC β2/ β3-null mice while that induced by CCPA remained
Lillie, M A; Piscitelli, M A; Vogl, A W; Gosline, J M; Shadwick, R E
Fin whales have an incompliant aorta, which, we hypothesize, represents an adaptation to large, depth-induced variations in arterial transmural pressures. We hypothesize these variations arise from a limited ability of tissues to respond to rapid changes in ambient ocean pressures during a dive. We tested this hypothesis by measuring arterial mechanics experimentally and modelling arterial transmural pressures mathematically. The mechanical properties of mammalian arteries reflect the physiological loads they experience, so we examined a wide range of fin whale arteries. All arteries had abundant adventitial collagen that was usually recruited at very low stretches and inflation pressures (2-3 kPa), making arterial diameter largely independent of transmural pressure. Arteries withstood significant negative transmural pressures (-7 to -50 kPa) before collapsing. Collapse was resisted by recruitment of adventitial collagen at very low stretches. These findings are compatible with the hypothesis of depth-induced variation of arterial transmural pressure. Because transmural pressures depend on thoracic pressures, we modelled the thorax of a diving fin whale to assess the likelihood of significant variation in transmural pressures. The model predicted that deformation of the thorax body wall and diaphragm could not always equalize thoracic and ambient pressures because of asymmetrical conditions on dive descent and ascent. Redistribution of blood could partially compensate for asymmetrical conditions, but inertial and viscoelastic lag necessarily limits tissue response rates. Without pressure equilibrium, particularly when ambient pressures change rapidly, internal pressure gradients will develop and expose arteries to transient pressure fluctuations, but with minimal hemodynamic consequence due to their low compliance.
(1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with
Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...
White, R. C.; And Others
The National Heart and Blood Vessel Research and Demonstration Center has developed a program called the Cardiovascular Curriculum Education Project, designed for secondary school students, which consists of self-instructional education units on cardiovascular disease and associated risk factors. Describes its three major components and method of…
Lymperopoulos, Anastasios; Bathgate, Ashley
Of the four mammalian arrestins, only the β-arrestins (βarrs; Arrestin2 and -3) are expressed throughout the cardiovascular system, where they regulate, as either desensitizers/internalizers or signal transducers, several G-protein-coupled receptors (GPCRs) critical for cardiovascular homeostasis. The cardiovascular roles of βarrs have been delineated at an accelerated pace via a variety of techniques and tools, such as knockout mice, siRNA knockdown, artificial or naturally occurring polymorphic GPCRs, and availability of new βarr "biased" GPCR ligands. This chapter summarizes the current knowledge of cardiovascular arrestin physiology and pharmacology, addressing the individual cardiovascular receptors affected by βarrs in vivo, as well as the individual cell types, tissues, and organs of the cardiovascular system in which βarr effects are exerted; for example, cardiac myocyte or fibroblast, vascular smooth muscle, adrenal gland and platelet. In the broader scope of cardiovascular βarr pharmacology, a discussion of the βarr "bias" of certain cardiovascular GPCR ligands is also included.
Soubrier, Martin; Barber Chamoux, Nicolas; Tatar, Zuzana; Couderc, Marion; Dubost, Jean-Jacques; Mathieu, Sylvain
The objectives of this review are to discuss data on the cardiovascular risk increase associated with rheumatoid arthritis (RA), the effects of RA treatments on the cardiovascular risk level, and the management of cardiovascular risk factors in patients with RA. Overall, the risk of cardiovascular disease is increased 2-fold in RA patients compared to the general population, due to the combined effects of RA and conventional risk factors. There is some evidence that the cardiovascular risk increase associated with nonsteroidal anti-inflammatory drug therapy may be smaller in RA patients than in the general population. Glucocorticoid therapy increases the cardiovascular risk in proportion to both the current dose and the cumulative dose. Methotrexate and TNFα antagonists diminish cardiovascular morbidity and mortality rates. The management of dyslipidemia remains suboptimal. Risk equations may perform poorly in RA patients even when corrected using the multiplication factors suggested by the EUropean League Against Rheumatism (EULAR) (multiply the score by 1.5 when two of the following three criteria are met: disease duration longer than 10 years, presence of rheumatoid factor or anti-cyclic citrullinated peptide (CCP) antibodies, and extraarticular manifestations). Doppler ultrasonography of the carotid arteries in patients at moderate cardiovascular risk may allow a more aggressive approach to dyslipidemia management via reclassification into the high-risk category of patients with an intima-media thickness greater than 0.9 mm or atheroma plaque.
Gospodarowicz, Mary; O'Sullivan, Brian
The depiction of prognosis is one of the main activities and a mainstay in medical practice. In cancer, as in other diseases, the prognosis differs for a variety of situations and evolves with time and with medical interventions. Although most commonly described at diagnosis, prognosis may be defined at any time during the course of the disease and for any endpoint including response to therapy, failure of treatment, survival, or preservation of function, and so forth. To facilitate the accurate portrayal of the future, the prognosis should be defined within a specific setting, referred to as a 'management scenario'. In the concept of a management scenario, the prognosis is defined using systematically considered prognostic factors, interventions and the outcome of interest. A deliberate and careful determination of prognosis is essential to clinical decision making and patient care. We illustrate the use of the concept of management scenario in several clinical examples.
Chang, Chin-Yao; Tulpule, Punit; Rizzoni, Giorgio; Zhang, Wei; Du, Xinyu
A probabilistic framework is developed for the prognosis of battery packs. It is demonstrated using aging campaign data, that aging models alone may not be sufficient for aging prognosis, and aging model parameter estimation may further improve the accuracy of prognosis. A systematic framework that extends the aging models to battery pack aging and prognosis still remains challenging. We propose a framework that bridges the gap in cell and pack aging prognosis in a probabilistic sense, and further improves the prognosis by estimating the aging model parameters for the pack. The framework is versatile for various applications because it is not restricted to a specific cell chemistry, or a type of aging model. In addition, the proposed framework could distinguish more aged cells as compared to other cells in the pack. Numerical examples are provided to demonstrate the effectiveness of the proposed framework.
Han, Seung Hwan; Nicholls, Stephen J; Sakuma, Ichiro; Zhao, Dong
Residual cardiovascular risk and failure of high density lipoprotein cholesterol raising treatment have refocused interest on targeting hypertriglyceridemia. Hypertriglyceridemia, triglyceride-rich lipoproteins, and remnant cholesterol have demonstrated to be important risk factors for cardiovascular disease; this has been demonstrated in experimental, genetic, and epidemiological studies. Fibrates can reduce cardiovascular event rates with or without statins. High dose omega-3 fatty acids continue to be evaluated and new specialized targeting treatment modulating triglyceride pathways, such as inhibition of apolipoprotein C-III and angiopoietin-like proteins, are being tested with regard to their effects on lipid profiles and cardiovascular outcomes. In this review, we will discuss the role of hypertriglyceridemia, triglyceride-rich lipoproteins and remnant cholesterol on cardiovascular disease, and the potential implications for treatment stargeting hypertriglyceridemia. PMID:27014342
Ramaraj, Radhakrishnan; Alpert, Joseph Stephen
Cardiovascular disease is among the world's leading causes of death, and nearly 80% of deaths occur in developing countries. Cardiovascular disease is becoming a major health problem in India, where life expectancy has increased with decreases in infectious disease and childhood mortality. It is well established that this population experiences coronary artery disease at a younger age than other populations. With infectious diseases still endemic, noncommunicable diseases are a lower priority for the governments of developing countries. There is a clear progression to degenerative and lifestyle-related diseases such as cardiovascular disease as a result of current social and economic change. The lack of a public response to the increasing risk for cardiovascular disease thus far is due mostly to a perception among policy makers and the public that cardiovascular disease is largely a problem of the urban rich. In conclusion, this review addresses the imminent threats and ways to tackle the epidemic in India.
Heida, Karst Y; Franx, Arie; Bots, Michiel L
Cardiovascular diseases (CVD) are the primary cause of death in women. Guidelines for identifying high-risk individuals have been developed, e.g. the Dutch Guideline on Cardiovascular Risk Management. In the most recent version of this guideline, diabetes mellitus (DM) and rheumatoid arthritis (RA) are cited as cardiovascular risk factors; therefore, individuals with these conditions are identified as being at high risk. As with DM and RA, there is strong evidence that the experience of having a hypertensive disorder during pregnancy is a cardiovascular risk factor. This is particularly the case for early preeclampsia, which constitutes a 7-fold increased risk of ischemic heart disease. However, in the Netherlands, there are no guidelines and there is no consensus on how to screen or treat these women. Trial evidence is therefore urgently needed to substantiate the value of cardiovascular risk management for those women with a history of hypertension during pregnancy.
The multitude of applications offered by CMR make it an increasing popular modality to study the heart and the surrounding vessels. Nevertheless the anatomical complexity of the chest, together with cardiac and respiratory motion, and the fast flowing blood, present many challenges which can possibly translate into imaging artefacts. The literature is wide in terms of papers describing specific MR artefacts in great technical detail. In this review we attempt to summarise, in a language accessible to a clinical readership, some of the most common artefacts found in CMR applications. It begins with an introduction of the most common pulse sequences, and imaging techniques, followed by a brief section on typical cardiovascular applications. This leads to the main section on common CMR artefacts with examples, a short description of the mechanisms behind them, and possible solutions. PMID:23697969
Nekolla, Stephan G; Rischpler, Christoph; Paschali, Anna; Anagnostopoulos, Constantinos
Non-invasive imaging in the form of single-photon emission-computed tomography (SPECT), positron-emission tomography (PET), computed tomography (CT), echocardiography or magnetic resonance imaging (MRI) is a very useful tool for cardiovascular research as it allows assessment of biological processes in vivo. Nuclear imaging with SPECT and PET offers the advantage of high sensitivity, the potential for serial imaging, and reliable quantification. Currently a wide range of established as well as innovative agents is available and can be imaged with dedicated preclinical and clinical SPECT and PET imaging systems. These scanners can be equipped with CT and MRI components to form hybrid imaging systems. This review provides an outline on SPECT and PET as capable tools for translational research in cardiology as part of a workflow similar to the one used in clinical imaging illustrating the concept "from bench to bedside".
Shirodkar, Apurva V.; Marsden, Philip A.
Purpose of review To provide an overview of the biological processes implicated in chromatin-based pathways that control endothelial gene expression patterns in both health and disease and highlight how these processes are relevant to cardiovascular disease. Recent findings Epigenetics refers to chromatin-based pathways important in the regulation of gene expression and includes three distinct, but highly interrelated, mechanisms: DNA methylation, histone density and posttranslational modifications, and RNA-based mechanisms. It is of great interest that epigenetic regulation of genes enriched in the vascular endothelium is a prominent regulatory pathway. How environmental cues within the vasculature, such as hemodynamic forces or hypoxia, influence these epigenetic mechanisms will be reviewed. Summary Although a newer area for study, exciting new evidence identifies that epigenetic processes are highly dynamic and respond to a myriad of environmental stimuli. Integrating chromatin-based pathways into our understanding of gene expression offers newer insight into disease processes. PMID:21415727
Chen, Edith; Lee, William K.; Cavey, Lisa; Ho, Amanda
Little is understood about why some youth from low-socioeconomic-status (SES) environments exhibit good health despite adversity. This study tested whether role models and "shift-and-persist" approaches (reframing stressors more benignly while persisting with future optimism) protect low-SES youth from cardiovascular risk. A total of 163…
The cardiovascular system, at all its various developmental and life stages, represents a critical target organ system that can be adversely affected by a variety of chemicals and routes of exposure. A World Health Organization report estimated the impact of environmental chemica...
BACKGROUND: Millions of people are at risk from the adverse effects of arsenic exposure through drinking water. Increasingly, non-cancer effects such as cardiovascular disease have been associated with drinking water arsenic exposures. However, most studies have been conducted in...
Diesel exhaust (DE) has been associated with adverse cardiovascular and pulmonary health effects. The relative contributions of the gas-phase and particulate (PM) components of DE are less well understood. We exposed WKY rats with or without implanted radiotransmitters to air or ...
Background: Many studies have reported associations between PM2.5 and adverse cardiovascular effects. However there is increased concern that ultrafine PM (aerodynamic diameter less than 0.1 micron) may be disproportionately toxic relative to the 0.1 to 2.5 micron fraction of PM2...
Cardiovascular diseases are a major source of morbidity and mortality in the United States. Early detection of disease can often be used to improved outcomes, either through direct interventions (e.g. surgical corrections) or by causing the patient to modify his or her behavior (e.g. smoking cessation or dietary changes). Ideally, the detection process should be noninvasive (i.e. it should not be associated with significant risk). Magnetic Resonance Imaging (MRI) refers to the formation of images by localizing NMR signals, typically from protons in the body. As in other applications of NMR, a homogeneous static magnetic field ( ~0.5 to 4 T) is used to create ``longitudinal" magnetization. A magnetic field rotating at the Larmor frequency (proportional to the static field) excites spins, converting longitudinal magnetization to ``transverse" magnetization and generating a signal. Localization is performed using pulsed gradients in the static field. MRI can produce images of 2-D slices, 3-D volumes, time-resolved images of pseudo-periodic phenomena such as heart function, and even real-time imaging. It is also possible to acquire spatially localized NMR spectra. MRI has a number of advantages, but perhaps the most fundamental is the richness of the contrast mechanisms. Tissues can be differentiated by differences in proton density, NMR properties, and even flow or motion. We also have the ability to introduce substances that alter NMR signals. These contrast agents can be used to enhance vascular structures and measure perfusion. Cardiovascular MRI allows the reliable diagnosis of important conditions. It is possible to image the blood vessel tree, quantitate flow and perfusion, and image cardiac contraction. Fundamentally, the power of MRI as a diagnostic tool stems from the richness of the contrast mechanisms and the flexibility in control of imaging parameters.
Wu, Wei; Zhu, Huayuan; Fu, Yuan; Shen, Wenyi; Miao, Kourong; Hong, Min; Xu, Wei; Fan, Lei; Young, Ken H; Liu, Peng; Li, Jianyong
Aberrant activation of lymphoid enhancer-binding factor-1 (LEF1) has been identified in several cancers, including chronic lymphocytic leukemia (CLL). As a key transcription factor of the Wnt/β-catenin pathway, LEF1 helps to regulate important genes involved in tumor cell death mechanisms. In this study, we determined LEF1 gene expression levels in CLL (n = 197) and monoclonal B-cell lymphocytosis (MBL) (n = 6) patients through real-time RT-PCR. LEF1 was significantly up-regulated in both MBL and CLL patients compared with normal B cells. Treatment-free survival (TFS) time and overall survival (OS) time were much longer in CLL patients with low LEF1 expression than in those with high LEF1 levels. Furthermore, Wnt inhibitor ethacrynic acid (EA) induced both apoptosis and necroptosis in primary CLL cells. EA also enhanced the cytotoxicity of both fludarabine and cyclophosphamide against CLL cells in vitro. Finally, we demonstrated that EA functions by inhibiting the recruitment of LEF1 to DNA promoters and restoring cylindromatosis (CYLD) expression in CLL cells. Our results showed, for the first time, that high LEF1 expression is associated with poor survival for CLL patients. Combined with other chemotherapeutic drugs, EA may be a promising therapeutic agent for CLL.
Wu, Wei; Zhu, Huayuan; Fu, Yuan; Shen, Wenyi; Miao, Kourong; Hong, Min; Xu, Wei; Fan, Lei; Young, Ken H.; Liu, Peng; Li, Jianyong
Aberrant activation of lymphoid enhancer-binding factor-1 (LEF1) has been identified in several cancers, including chronic lymphocytic leukemia (CLL). As a key transcription factor of the Wnt/β-catenin pathway, LEF1 helps to regulate important genes involved in tumor cell death mechanisms. In this study, we determined LEF1 gene expression levels in CLL (n = 197) and monoclonal B-cell lymphocytosis (MBL) (n = 6) patients through real-time RT-PCR. LEF1 was significantly up-regulated in both MBL and CLL patients compared with normal B cells. Treatment-free survival (TFS) time and overall survival (OS) time were much longer in CLL patients with low LEF1 expression than in those with high LEF1 levels. Furthermore, Wnt inhibitor ethacrynic acid (EA) induced both apoptosis and necroptosis in primary CLL cells. EA also enhanced the cytotoxicity of both fludarabine and cyclophosphamide against CLL cells in vitro. Finally, we demonstrated that EA functions by inhibiting the recruitment of LEF1 to DNA promoters and restoring cylindromatosis (CYLD) expression in CLL cells. Our results showed, for the first time, that high LEF1 expression is associated with poor survival for CLL patients. Combined with other chemotherapeutic drugs, EA may be a promising therapeutic agent for CLL. PMID:26950276
Almagro, Pere; Lapuente, Anna; Pareja, Julia; Yun, Sergi; Garcia, Maria Estela; Padilla, Ferrán; Heredia, Josep Ll; De la Sierra, Alex; Soriano, Joan B
Background Retrospective studies based on clinical data and without spirometric confirmation suggest a poorer prognosis of patients with ischemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) following percutaneous coronary intervention (PCI). The impact of undiagnosed COPD in these patients is unknown. We aimed to evaluate the prognostic impact of COPD – previously or newly diagnosed – in patients with IHD treated with PCI. Methods Patients with IHD confirmed by PCI were consecutively included. After PCI they underwent forced spirometry and evaluation for cardiovascular risk factors. All-cause mortality, new cardiovascular events, and their combined endpoint were analyzed. Results A total of 133 patients (78%) male, with a mean (SD) age of 63 (10.12) years were included. Of these, 33 (24.8%) met the spirometric criteria for COPD, of whom 81.8% were undiagnosed. IHD patients with COPD were older, had more coronary vessels affected, and a greater history of previous myocardial infarction. Median follow-up was 934 days (interquartile range [25%–75%]: 546–1,160). COPD patients had greater mortality (P=0.008; hazard ratio [HR]: 8.85; 95% confidence interval [CI]: 1.76–44.47) and number of cardiovascular events (P=0.024; HR: 1.87; 95% CI: 1.04–3.33), even those without a previous diagnosis of COPD (P=0.01; HR: 1.78; 95% CI: 1.12–2.83). These differences remained after adjustment for sex, age, number of coronary vessels affected, and previous myocardial infarction (P=0.025; HR: 1.83; 95% CI: 1.08–3.1). Conclusion Prevalence and underdiagnosis of COPD in patients with IHD who undergo PCI are both high. These patients have an independent greater mortality and a higher number of cardiovascular events during follow-up. PMID:26213464
Fuchs, Felipe C.; Ribeiro, Jorge P.; Fuchs, Flávio D.; Wainstein, Marco V.; Bergoli, Luis C.; Wainstein, Rodrigo V.; Zen, Vanessa; Kerkhoff, Alessandra C.; Moreira, Leila B.; Fuchs, Sandra C.
Background: The importance of coronary anatomy in predicting cardiovascular events is well known. The use of traditional anatomical scores in routine angiography, however, has not been incorporated to clinical practice. SYNTAX score (SXscore) is a scoring system that estimates the anatomical extent of coronary artery disease (CAD). Its ability to predict outcomes based on a baseline diagnostic angiography has not been tested to date. Objective: To evaluate the performance of the SXscore in predicting major adverse cardiac events (MACE) in patients referred for diagnostic angiography. Methods: Prospective cohort of 895 patients with suspected CAD referred for elective diagnostic coronary angiography from 2008 to 2011, at a university-affiliated hospital in Brazil. They had their SXscores calculated and were stratified in three categories: no significant CAD (n = 495), SXscoreLOW-INTERMEDIATE: < 23 (n = 346), and SXscoreHIGH: ≥ 23 (n = 54). Primary outcome was a composite of cardiac death, myocardial infarction, and late revascularization. Secondary endpoints were the components of MACE and death from any cause. Results: On average, patients were followed up for 1.8 ± 1.4 years. The primary outcome occurred in 2.2%, 15.3%, and 20.4% in groups with no significant CAD, SXscoreLOW-INTERMEDIATE, and SXscoreHIGH, respectively (p < 0.001). All-cause death was significantly higher in the SXscoreHIGH compared with the 'no significant CAD' group, 16.7% and 3.8% (p < 0.001), respectively. After adjustment for confounding factors, all outcomes remained associated with the SXscore. Conclusions: SXscore independently predicts MACE in patients submitted to diagnostic coronary angiography. Its routine use in this setting could identify patients with worse prognosis. PMID:27509092
Nguyen, Maria U; Wallace, Megan J; Pepe, Salvatore; Menheniott, Trevelyan R; Moss, Timothy J; Burgner, David
Cardiovascular disease continues to be the leading cause of global morbidity and mortality. Traditional risk factors account for only part of the attributable risk. The origins of atherosclerosis are in early life, a potential albeit largely unrecognized window of opportunity for early detection and treatment of subclinical cardiovascular disease. There are robust epidemiological data indicating that poor intrauterine growth and/or prematurity, and perinatal factors such as maternal hypercholesterolaemia, smoking, diabetes and obesity, are associated with adverse cardiovascular intermediate phenotypes in childhood and adulthood. Many of these early-life risk factors result in a heightened inflammatory state. Inflammation is a central mechanism in the development of atherosclerosis and cardiovascular disease, but few studies have investigated the role of overt perinatal infection and inflammation (chorioamnionitis) as a potential contributor to cardiovascular risk. Limited evidence from human and experimental models suggests an association between chorioamnionitis and cardiac and vascular dysfunction. Early life inflammatory events may be an important mechanism in the early development of cardiovascular risk and may provide insights into the associations between perinatal factors and adult cardiovascular disease. This review aims to summarise current data on the early life origins of atherosclerosis and cardiovascular disease, with particular focus on perinatal inflammation.
Maeder, Micha T; Schoch, Otto D; Rickli, Hans
Obstructive sleep apnea (OSA) is associated with cardiovascular risk factors, cardiovascular diseases, and increased mortality. Epidemiological studies have established these associations, and there are now numerous experimental and clinical studies which have provided information on the possible underlying mechanisms. Mechanistic proof-of-concept studies with surrogate endpoints have been performed to demonstrate that treatment of OSA by continuous positive airway pressure (CPAP) has the potential to reverse or at least to attenuate not only OSA but also the adverse cardiovascular effects associated with OSA. However, no randomized studies have been performed to demonstrate that treatment of OSA by CPAP improves clinical outcomes in patients with cardiovascular risk factors and/or established cardiovascular disease and concomitant OSA. In the present review, we summarize the current knowledge on the role of OSA as a potential cardiovascular risk factor, the impact of OSA on cardiac function, the role of OSA as a modifier of the course of cardiovascular diseases such as coronary artery disease, atrial fibrillation, and heart failure, and the insights from studies evaluating the impact of CPAP therapy on the cardiovascular features associated with OSA. PMID:27051291
Since endogenous estrogen shows some preventative benefits against cardiovascular risk factors in premenopausal women, cardiovascular disease (CVD) is often considered a male disease. However, CVD is the biggest cause of death in women, especially after menopause when endogenous estrogen withdrawal has detrimental effects on cardiovascular physiology and whole-body metabolism. Despite this, awareness of the risk of CVD is low in both women and in doctors; this needs rectifying. Women are under-represented in most clinical studies of CVD. Following diagnosis of CVD, the prognosis for women is not systematically similar to that for men. Furthermore, from the few comparisons conducted, gender differences in response to pharmacological interventions are evident, so that results obtained in wholly or largely male-based studies cannot be systematically extrapolated to women. Women with CVD should be afforded equivalent investigations and treatment to men, and it is vital that women be included in clinical trials in sufficient numbers to allow sub-group analyses and subsequent development of appropriate therapies. Since CVD is usually advanced by the time symptoms appear, prevention is the key; health management advice might include smoking cessation, adoption of a healthy diet, and incorporation of physical activity into the lifestyle.
Chao, Tze-Fan; Lu, Tse-Min; Lin, Yenn-Jiang; Tsao, Hsuan-Ming; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Hsieh, Ming-Hsiung; Chen, Shih-Ann
Objectives Elevated plasma levels of asymmetric dimethylarginine (ADMA) have been reported to be associated with endothelial dysfunction, inflammation, and oxidative stress in multiple cardiovascular diseases. This study aimed to investigate whether ADMA was a predictor of clinical outcomes in atrial fibrillation (AF). Methods and Results From 2006-2009, 990 individuals were referred to our institution for coronary angiography. Among these patients, 141 subjects with a diagnosis of AF, including 52 paroxysmal AF (PAF) and 89 non-paroxysmal AF (non-PAF) patients, were identified as the study population. Plasma ADMA levels were measured. An adverse event was defined as the occurrence of ischemic stroke or cardiovascular death. The ADMA levels were higher in AF than non-AF patients (0.50±0.13 versus 0.45±0.07 µmol/L; p<0.001). Besides, non-PAF patients had higher ADMA levels than PAF patients (0.52±0.15 versus 0.48±0.08 µmol/L; p<0.001). During the follow-up of 30.7±14.4 months, 21 patients (14.9%) experienced adverse events, including cardiovascular death in 7 patients and ischemic stroke in 14. ADMA level, CHA2DS2-VASc score, and left atrial diameter were independent predictors of adverse events in the multivariate analysis. At a cutoff-value of 0.55 µmol/L, the Kaplan-Meier survival analysis showed that patients with a high ADMA level had a higher event rate during the follow-up period. Conclusions A higher level of ADMA was a risk factor of adverse events in AF patients, which was independent from the CHA2DS2-VASc score. It deserves to further study whether ADMA could potentially refine the clinical risk stratification in AF. PMID:23951217
Putnam, Karen T; Harris, William W; Putnam, Frank W
Numerous studies find a cumulative effect of different types of childhood adversities on increasing risk for serious adult mental and medical outcomes. This study uses the National Comorbidity Survey-Replication sample to investigate the cumulative impact of 8 childhood adversities on complex adult psychopathology as indexed by (a) number of lifetime diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994); (b) number of 4 DSM-IV disorder categories (mood, anxiety, impulse control, and substance abuse disorders); and (c) coexistence of internalizing and externalizing disorders. Seven of the 8 childhood adversities were significantly associated with complex adult psychopathology. Individuals with 4 or more childhood adversities had an odds ratio of 7.3, 95% confidence interval [4.7, 11.7] for 4 disorder categories. Additive and multiplicative synergistic effects increasing adult psychopathology were found for specific pairwise combinations of childhood adversities. Synergistic patterns differed by gender suggesting that women are more impacted by sexual abuse and men by economic hardship. The absence of childhood adversities was protective, in that it significantly decreased an individual's risk for subsequent adult mental illness. The results support the clinical impression that increased childhood adversity is associated with more complex adult psychopathology.
Fujimoto, Hajime; Kobayashi, Tetsu; Azuma, Arata
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a prognosis that can be worse than for many cancers. The initial stages of the condition were thought to mainly involve chronic inflammation; therefore, corticosteroids and other drugs that have anti-inflammatory and immunosuppressive actions were used. However, recently, agents targeting persistent fibrosis resulting from aberrant repair of alveolar epithelial injury have been in the spotlight. There has also been an increase in the number of available antifibrotic treatment options, starting with pirfenidone and nintedanib. These drugs prevent deterioration but do not improve IPF. Therefore, nonpharmacologic approaches such as long-term oxygen therapy, pulmonary rehabilitation, and lung transplantation must be considered as additional treatment modalities. PMID:27980445
Dignan, F; Symon, D; AbuArafeh, I; Russell, G
AIMS—The medium term prognosis of cyclical vomiting syndrome (CVS) was studied to determine the proportion of affected individuals who had gone on to develop headaches fulfilling the International Headache Society criteria for migraine. METHODS—Twenty six (76%) of 34 CVS sufferers identified from the authors' clinical records were traced, and all agreed to participate. Each child was matched to a control, and telephone interviews were conducted using a standardised questionnaire. RESULTS—Thirteen (50%) of the subjects had continuing CVS and/or migraine headaches while the remainder were currently asymptomatic. The prevalence of past or present migraine headaches in subjects (46%) was significantly higher than in the control population (12%). CONCLUSION—Results support the concept that CVS is closely related to migraine. PMID:11124785
Berta, E; Harangi, M; Zsíros, N; Nagy, E V; Paragh, G; Bodor, M
Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP
Hidalgo, A; Pons-Lladó, G
Cardiac magnetic resonance imaging (MRI) is an important tool that makes it possible to evaluate patients with cardiovascular disease; in addition to infarction and alterations in myocardial perfusion, cardiac MRI is useful for evaluating other phenomena such as microvascular obstruction and ischemia. The main prognostic factors in cardiac MRI are ventricular dysfunction, necrosis in late enhancement sequences, and ischemia in stress sequences. In acute myocardial infarction, cardiac MRI can evaluate the peri-infarct zone and quantify the size of the infarct. Furthermore, cardiac MRI's ability to detect and evaluate microvascular obstruction makes it a fundamental tool for establishing the prognosis of ischemic heart disease. In patients with chronic ischemic heart disease, cardiac MRI can detect ischemia induced by pharmacological stress and can diagnose infarcts that can be missed on other techniques.
Gonzalez, Jorge A.; Kramer, Christopher M.
Cardiac Magnetic Resonance (CMR) has evolved into a major tool for the diagnosis and assessment of prognosis of patients suffering from heart failure. Anatomical and structural imaging, functional assessment, T1 and T2 mapping tissue characterization and late gadolinium enhancement (LGE) have provided clinicians with tools to distinguish between non-ischemic and ischemic cardiomyopathies and to identify the etiology of non-ischemic cardiomyopathies. LGE is a useful tool to predict the likelihood of functional recovery after revascularization in patients with CAD and to guide the LV lead placement in those who qualify for cardiac resynchronization (CRT) therapy. In addition, the presence of LGE and its extent in myocardial tissue relates to overall cardiovascular outcomes. Emerging roles for cardiac imaging in Heart Failure with Preserved Ejection Fraction (HFpEF) are being studied and CMR continues to be among the most promising noninvasive imaging alternatives in the diagnosis of this disease. PMID:26041670
Iodice, Valeria; Low, David A; Vichayanrat, Ekawat; Mathias, Christopher J
In Parkinsons disease and multiple system atrophy (MSA), cardiovascular dysfunction may occur for a variety of reasons and may manifest itself through inappropriate changes and/or levels in blood pressure, heart rate and/or regional vascular perfusion in a range of situations. The early occurrence of orthostatic hypotension often leads to consideration of MSA, especially in the presence of other features of autonomic failure. Orthostatic hypotension, however, is increasingly recognised in PD, and especially with increasing age, severity of disease and as a result of drug therapy, sometimes for associated disorders. Investigation of cardiovascular autonomic dysfunction in Parkinsonism is therefore important for a variety of reasons, that include determining the precise diagnosis and in predicting prognosis. In Parkinsonian disorders, understanding the pathophysiological basis of the cardiovascular autonomic dysfunction aids targeting of therapy, improves management strategies and provides benefit for such patients.
Stapleton, Phoebe A; Abukabda, Alaeddin B; Hardy, Steven L; Nurkiewicz, Timothy R
The cardiovascular response to xenobiotic particle exposure has been increasingly studied over the last two decades, producing an extraordinary scope and depth of research findings. With the flourishing of nanotechnology, the term "xenobiotic particles" has expanded to encompass not only air pollution particulate matter (PM) but also anthropogenic particles, such as engineered nanomaterials (ENMs). Historically, the majority of research in these fields has focused on pulmonary exposure and the adverse physiological effects associated with a host inflammatory response or direct particle-tissue interactions. Because these hypotheses can neither account entirely for the deleterious cardiovascular effects of xenobiotic particle exposure nor their time course, the case for substantial neurological involvement is apparent. Indeed, considerable evidence suggests that not only is neural involvement a significant contributor but also a reality that needs to be investigated more thoroughly when assessing xenobiotic particle toxicities. Therefore, the scope of this review is several-fold. First, we provide a brief overview of the major anatomical components of the central and peripheral nervous systems, giving consideration to the potential biologic targets affected by inhaled particles. Second, the autonomic arcs and mechanisms that may be involved are reviewed. Third, the cardiovascular outcomes following neurological responses are discussed. Lastly, unique problems, future risks, and hurdles associated with xenobiotic particle exposure are discussed. A better understanding of these neural issues may facilitate research that in conjunction with existing research, will ultimately prevent the untoward cardiovascular outcomes associated with PM exposures and/or identify safe ENMs for the advancement of human health.
Palmeiro, Christopher; Davila, Maria I; Bhat, Mallika; Frishman, William H; Weiss, Irene A
Subclinical hyperthyroidism (SHy), the mildest form of hyperthyroidism, is diagnosed in patients having a persistently low or undetectable serum concentration of thyroid-stimulating hormone (TSH) with normal free T4 and T3 concentrations. Although overt hyperthyroidism is associated with an increased risk of adverse cardiovascular outcomes, the cardiovascular risk of SHy is controversial. Multiple studies have demonstrated an increased risk of atrial fibrillation, especially in older individuals with TSH levels <0.1 mU/L. The effects of SHy on all-cause and cardiovascular mortality are not clear, but recent meta-analyses suggest a modest increase in mortality, with the risk increasing with age and associated with the lowest TSH levels. The long-term consequences of SHy in young- and middle-aged adults, and in those with TSH levels are mildly low, are uncertain. For these reasons, guidelines for treatment are based on patient age, the degree of TSH suppression, symptoms consistent with hyperthyroidism, and overall cardiovascular and osteoporotic fracture risks.
Vangelova, Katia; Deyanov, Christo; Israel, Mishel
The aim of the study was to assess the long-term effects of radiofrequency electromagnetic radiation (EMR) on the cardiovascular system. Two groups of exposed operators (49 broadcasting (BC) station and 61 TV station operators) and a control group of 110 radiorelay station operators, matched by sex and age, with similar job characteristics except for the radiofrequency EMR were studied. The EMR exposure was assessed and the time-weighted average (TWA) was calculated. The cardiovascular risk factors arterial pressure, lipid profile, body mass index, waist/hip ratio, smoking, and family history of cardiovascular disease were followed. The systolic and diastolic blood pressure (SBP and DBP), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly higher in the two exposed groups. It was found that the radiofrequency EMR exposure was associated with greater chance of becoming hypertensive and dyslipidemic. The stepwise multiple regression equations showed that the SBP and TWA predicted the high TC and high LDL-C, while the TC, age and abdominal obesity were predictors for high SBP and DBP. In conclusion, our data show that the radiofrequency EMR contributes to adverse effects on the cardiovascular system.
Lavie, Carl J; Arena, Ross; Swift, Damon L; Johannsen, Neil M; Sui, Xuemei; Lee, Duck-Chul; Earnest, Conrad P; Church, Timothy S; O'Keefe, James H; Milani, Richard V; Blair, Steven N
Substantial evidence has established the value of high levels of physical activity, exercise training (ET), and overall cardiorespiratory fitness in the prevention and treatment of cardiovascular diseases. This article reviews some basics of exercise physiology and the acute and chronic responses of ET, as well as the effect of physical activity and cardiorespiratory fitness on cardiovascular diseases. This review also surveys data from epidemiological and ET studies in the primary and secondary prevention of cardiovascular diseases, particularly coronary heart disease and heart failure. These data strongly support the routine prescription of ET to all patients and referrals for patients with cardiovascular diseases, especially coronary heart disease and heart failure, to specific cardiac rehabilitation and ET programs.
The neutrophil-to-lymphocyte ratio (NLR) is a novel simple biomarker of inflammation. It has emerged as a predictor of poor prognosis in cancer and cardiovascular disease in general population. But little was known of its prognostic value in chronic hemodialysis (HD) patients. Here we investigated the association between NLR and cardiovascular risk markers, including increased pulse pressure (PP), left ventricular mass index (LVMI) and intima-media thickness (IMT), and mortality in HD patients. Two hundred and sixty-eight HD patients were enrolled in this study and were followed for 36 months. The primary end point was all-cause mortality and cardiovascular mortality. Multivariable Cox regression was used to calculate the adjusted hazard ratios for NLR on all-cause and cardiovascular survival. We pinpointed that higher NLR in HD patients was a predictor of increased PP, LVMI, and IMT; HD patients with higher NLR had a lower survival at the end of the study; furthermore, high NLR was an independent predictor of all-cause and cardiovascular mortality when adjusted for other risk factors. In conclusion, higher NLR in HD patients was associated with cardiovascular risk factors and mortality. PMID:28316378
Błaszczyk, Barbara; Lasoń, Władysław; Czuczwar, Stanisław Jerzy
This paper summarizes current views on clinical manifestation, pathogenesis, prognosis and management of antiepileptic drug (AED)-induced adverse skin reactions. Cochrane Central Register of Controlled Trials, MEDLINE (PubMed) and ISI Web of Knowledge were searched. The recent classification, among drug-induced skin injuries, points to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis and hypersensitivity syndrome (HSS), which may be also recognized as a drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS). The use of aromatic AEDs, e.g. phenytoin, carbamazepine, oxcarbazepine, phenobarbital, primidone, zonisamide, and lamotrigine is more frequently associated with cutaneous eruption and other signs or symptoms of drug hypersensitivity. There is a high degree of cross-reactivity (40-80%) in patients with hypersensitivity or allergic reactions to AEDs. Pharmacogenetic variations in drug biotransformation may also play a role in inducing these undesired effects. It is suggested that avoidance of specific AEDs in populations at special risk, cautious dose titration and careful monitoring of clinical response and, if applicable, laboratory parameters can minimize the serious consequences of idiosyncratic reactions.
Michael, Joel A; Wenderoth, Mary Pat; Modell, Harold I; Cliff, William; Horwitz, Barbara; McHale, Philip; Richardson, Daniel; Silverthorn, Dee; Williams, Stephen; Whitescarver, Shirley
Undergraduates students in 12 courses at 8 different institutions were surveyed to determine the prevalence of 13 different misconceptions (conceptual difficulties) about cardiovascular function. The prevalence of these misconceptions ranged from 20 to 81% and, for each misconception, was consistent across the different student populations. We also obtained explanations for the students' answers either as free responses or with follow-up multiple-choice questions. These results suggest that students have a number of underlying conceptual difficulties about cardiovascular phenomena. One possible source of some misconceptions is the students' inability to apply simple general models to specific cardiovascular phenomena. Some implications of these results for teachers of physiology are discussed.
Li, Yan Chun
Vitamin D deficiency is a global health problem that has various adverse consequences. Vitamin D is mainly synthesized in the skin by sunlight (UV light) irradiation; therefore, vitamin D status is influenced by geographic locations, seasonal changes, and skin pigmentations. The kidney is involved in the biosynthesis of 1,25-dihydroxyvitamin D and the reuptake of filtered 25-hydroxyvitamin D from the proximal tubules, thus, vitamin D deficiency is highly prevalent in patients with kidney disease who have renal insufficiency. There is a growing body of epidemiological and clinical evidence in the literature that links vitamin D deficiency to cardiovascular disease. The discovery of the vitamin D hormone functioning as an endocrine inhibitor of the renin-angiotensin system provides an explanation for this association. This review will discuss the mechanism underlying the connection between vitamin D and cardiovascular disease and its physiological and therapeutic implications.
Morgan, Craig; Gayer‐Anderson, Charlotte
There is a substantial body of research reporting evidence of associations between various forms of childhood adversity and psychosis, across the spectrum from experiences to disorder. This has been extended, more recently, to include studies of cumulative effects, of interactions with other factors, of specific effects, and of putative biological and psychological mechanisms. In this paper we evaluate this research and highlight the remaining methodological issues and gaps that temper, but do not dismiss, conclusions about the causal role of childhood adversity. We also consider the emerging work on cumulative, synergistic, and specific effects and on mechanisms; and discuss the broader implications of this line of research for our understanding of psychosis. We conclude that the current balance of evidence is that childhood adversities – particularly exposure to multiple adversities involving hostility and threat – do, in some people, contribute to the onset of psychotic experiences and psychotic disorders. PMID:27265690
Measurement instruments are needed to stimulate research on the long-term outcomes of childhood adversity. Therefore, the purpose of this review was to locate, describe, and assess instruments to measure retrospective perceptions of childhood adversity. An electronic search of instruments was conducted using a combination of keywords that included child maltreatment, child trauma, and childhood stressful events. Nine instruments were located and described according to format, definition of childhood adversity as measured by the instrument, characteristics of the sample used in development and testing, reliability and validity evidence, and feasibility for use. Six out of the nine instruments were suitable for investigators who require a comprehensive measure of childhood adversity. Corroboration with independent sources and use of randomized samples are needed to improve upon reports of validity.
INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences, including racial residential segr...
A challenge for both human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. The adverse outcome pathway (AOP) is a conceptual framework designed to meet this need. Specifical...
Farley, T M; Collins, J; Schlesselman, J J
The most frequent major adverse effect of hormonal contraception is an increased risk of cardiovascular disease. The effect on the risk of venous thromboembolism (VTE), ischemic and hemorrhagic stroke, and myocardial infarction (MI) differs and is strongly influenced by smoking and the presence of other cardiovascular risks factors, such as hypertension and diabetes mellitus. The incidence of each disease rises with age and there are differences in risk among hormonal contraceptive preparations. This article provides a framework within which to assess the balance of risks among types of hormonal contraceptives according to individual circumstances. Data on cardiovascular disease mortality rates in women of reproductive age in different countries of the world were compiled from nationally reported statistics and supplemented where possible with reported disease incidence rates. Risks associated with current use of hormonal contraception were compiled from the most recent publications on the cardiovascular effects of steroid hormone contraception. These were combined to estimate the total cardiovascular incidence and mortality according to baseline cardiovascular risk and individual characteristics. Mortality rates for cardiovascular diseases are very low in women of reproductive age. Myocardial infarction mortality rates rise from < 0.4 per 100,000 woman-years at age 15-24 years to the range 2 to 7 per 100,000 woman-years at age 35-44 years. Stroke mortality rates similarly rise steeply with age and are between 3 and 5 times higher than those for MI. VTE mortality rates rise less steeply with age and are approximately one-tenth the MI mortality rates at age 35-44 years. The adverse effect of oral contraceptives (OC) on the risk of VTE is the most important contributor to the total number of cardiovascular cases attributable to OC use. The increased risk of stroke and MI dominate the patterns of mortality in OC users and smokers. The additional risks attributable to
Marcilly, Romaric; Chazard, Emmanuel; Beuscart-Zéphir, Marie-Catherine; Hackl, Werner; Băceanu, Adrian; Kushniruk, Andre; Borycki, Elizabeth M
This paper presents the design of Adverse Drug Event-Scorecards. The scorecards described are innovative and novel, not having previously been reported in the literature. The Scorecards provide organizations (e.g. hospitals) with summary information about Adverse Drug Events (ADEs) using a Web-based platform. The data used in the Scorecards are routinely updated and report on ADEs detected through data mining processes. The development of the ADE Scorecards is ongoing and they are currently undergoing clinical testing.
Muller, Y; Andrey, D; Emonet, S; Harr, T; Spoerl, D
The prescription ot fluoroquinolones has been constantly increasing over the past decade. consequently, an increasing number of hyper-sensitivity reactions and adverse events have been reported. The aim of the review is to discuss the incidence of hypersensitivity reactions either IgE (immediate) or T cells mediated (delayed). We will make an overview ofthe diagnostic tools available to detect such hypersensitivity reactions. Finally, the specific adverse events associated with fluoroquinolones, including tendinopathy, chondrotoxicity, peripheral neuropathy or retinal detachment will be discussed.
Fiddler, Maggie; Jackson, Judy; Kapur, Navneet; Wells, Adrian; Creed, Francis
We assessed possible psychological mediators of the relationship between childhood adversity and frequent medical consultations among new outpatients at neurology, cardiology, and gastroenterology clinics. We assessed whether these differed in patients with and without organic disease that explained their symptoms. At first clinic visit we recorded Hospital Anxiety and Depression scale (HADS--anxiety and depression subscale scores), Illness Perception Questionnaire (IPQ--four subscales: consequences, cure, identity, timeline), Health Anxiety Questionnaire (total score), and Symptom Amplification Scale (total score). Subjects were divided into two groups according to whether they had experienced any type of childhood adversity using the Childhood Experience of Care and Abuse Schedule. Outcome was the (log) number of medical consultations for 12 months before and 6 months after the index clinic visits. Multiple regression analysis was used to determine mediators; this was performed separately for patients with symptoms explained and not explained by organic disease. One-hundred and twenty-nine patients (61% response) were interviewed. Fifty-two (40.3%) had experienced childhood adversity; they made a median of 16 doctor visits compared with 10 for those without adversity (adjusted P=.026). IPQ identity score (number of symptoms attributed to the illness) and HAD depression scores were significantly associated with both childhood adversity and number of medical consultations and these variables acted as mediators between childhood adversity and frequency of consultation in the multiple regression analyses. This association was limited to patients with medically unexplained symptoms and was mediated by IPQ Identity Score (number of symptoms attributed to the patient's illness) and HAD depression score. Sexual abuse and overt neglect were the adversities most closely associated with frequent consultations. In patients with medically unexplained symptoms the association
Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa
Introduction: The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. Objective: To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. Methods: A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Results: Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p= 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p= 0.005). Conclusions: Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics. PMID:27821893
The cardiocirculatory changes in hyperthyroidism seem to be an accommodation to the increased metabolic demands and lead to an increased perfusion of the peripheral tissues. Due to the influence of elevated thyroid hormone levels, contractility, stroke volume, resting heart rate, and contraction and relaxation velocity of the left ventricle increase. Caused by direct effect on the smooth vascular muscle, systemic vascular resistance is decreased with the consequence of a diminished afterload and an increased cardiac efficiency. The activation of the renin-angiotensin-aldosteron system and the increased production of erythropoietin additionally lead to an increased blood volume, which increases cardiac preload together with the increased venous backflow. Manifest hypothyroidism is characterized by bradycardia and diastolic dysfunction in rest and systolic dysfunction at stress. Despite a slight increase of diastolic blood pressure due to an increased systemic vascular resistance, blood pressure remains nearly stable because of diminished cardiac output. Hypercholesterinaemia and diastolic hypertension in hypothyroid patients can lead to the development of arteriosclerosis and coronary heart disease (CHD). Also subclinical hypothyroidism is associated with a significantly higher risk for arteriosclerosis and CHD, whereas subclinical hyperthyroidism seems to be associated with an increased mortality for all reasons, especially for cardiovascular diseases.
Sartori, Claudio; Rimoldi, Stefano F; Rexhaj, Emrush; Allemann, Yves; Scherrer, Urs
Epidemiological studies have shown an association between pathologic events occurring during early life and the development of cardiovascular and metabolic disease in adulthood. These observations have led to the so-called fetal programming of adult disease hypothesis. In line with this hypothesis, short-term exposure to hypoxia after birth predisposes to exaggerated hypoxic pulmonary vasoconstriction later in life in rats, and transient perinatal hypoxia predisposes to exaggerated pulmonary hypertension during short-term exposure to high altitude in humans. Along the same lines, in recent studies in Bolivian high-altitude dwellers, we found that preeclampsia predisposes the offspring to pulmonary and systemic endothelial dysfunction possibly related to impaired NO bioavailability and augmented oxidative stress. Very recent data from our lab suggest that assisted reproductive technologies may represent another important example consistent with this hypothesis. The mechanisms underpinning the developmental origin of this vascular dysfunction are poorly understood. Increasing evidence suggests that epigenetic alterations, such as DNA methylation or histone acetylation may play a role.
Elderon, Larkin; Whooley, Mary A
Approximately one out of every five patients with cardiovascular disease (CVD) suffers from major depressive disorder (MDD). Both MDD and depressive symptoms are risk factors for CVD incidence, severity and outcomes. Great progress has been made in understanding potential mediators between MDD and CVD, particularly focusing on health behaviors. Investigators have also made considerable strides in the diagnosis and treatment of depression among patients with CVD. At the same time, many research questions remain. In what settings is depression screening most effective for patients with CVD? What is the optimal screening frequency? Which therapies are safe and effective? How can we better integrate the care of mental health conditions with that of CVD? How do we motivate depressed patients to change health behaviors? What technological tools can we use to improve care for depression? Gaining a more thorough understanding of the links between MDD and heart disease, and how best to diagnose and treat depression among these patients, has the potential to substantially reduce morbidity and mortality from CVD.
Voutilainen, Sari; Nurmi, Tarja; Mursu, Jaakko; Rissanen, Tiina H
Cardiovascular disease (CVD) is the main cause of death in Western countries. Nutrition has a significant role in the prevention of many chronic diseases such as CVD, cancers, and degenerative brain diseases. The major risk and protective factors in the diet are well recognized, but interesting new candidates continue to appear. It is well known that a greater intake of fruit and vegetables can help prevent heart diseases and mortality. Because fruit, berries, and vegetables are chemically complex foods, it is difficult to pinpoint any single nutrient that contributes the most to the cardioprotective effects. Several potential components that are found in fruit, berries, and vegetables are probably involved in the protective effects against CVD. Potential beneficial substances include antioxidant vitamins, folate, fiber, and potassium. Antioxidant compounds found in fruit and vegetables, such as vitamin C, carotenoids, and flavonoids, may influence the risk of CVD by preventing the oxidation of cholesterol in arteries. In this review, the role of main dietary carotenoids, ie, lycopene, beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein, and zeaxanthin, in the prevention of heart diseases is discussed. Although it is clear that a higher intake of fruit and vegetables can help prevent the morbidity and mortality associated with heart diseases, more information is needed to ascertain the association between the intake of single nutrients, such as carotenoids, and the risk of CVD. Currently, the consumption of carotenoids in pharmaceutical forms for the treatment or prevention of heart diseases cannot be recommended.
Lucas, L. M.; Colley, C. A.
Although physicians in practice are most likely to see patients with adverse drug reactions, they may fail to recognize an adverse effect or to attribute it to a drug effect and, when recognized, they may fail to report serious reactions to the US Food and Drug Administration (FDA). To recognize and attribute an adverse event to a drug effect, physicians should review the patient's clinical course, looking at patient risk factors, the known adverse reactions to the suspected drug, and the likelihood of a causal relationship between the drug and the adverse event-based on the temporal relationship, response to stopping or restarting the drug, and whether other factors could explain the reaction. Once an adverse drug reaction has been identified, the patient should be informed and appropriate documentation made in the patient's medical record. Serious known reactions and all reactions to newly released drugs or those not previously known to occur (even if the certainty is low) should be reported to the FDA. PMID:1536067
Zhou, Chu; Wang, Fang; Wang, Jin-Wei; Zhang, Lu-Xia; Zhao, Ming-Hui
Background: Mineral and bone disorder (MBD), especially hyperphosphatemia, is an independently risk factor for adverse prognosis in patients with chronic kidney disease (CKD). However, CKD-MBD among Chinese population was poorly studied. This study aimed to investigate the status of MBD and its association with cardiovascular parameters in Chinese patients with predialysis CKD. Methods: Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) is a prospective multicenter cohort study involving predialysis CKD patients in China. Markers of MBD, including serum phosphorus, calcium, and intact parathyroid hormone, were measured in baseline samples at the patients’ entry. The association between serum phosphorus and abdominal aortic calcification (AAC), left ventricular hypertrophy (LVH) were examined by logistic regression models. Results: Altogether 3194 predialysis patients with mean estimated glomerular filtration of 51.8 ± 33.1 ml·min−1.1.73 m−2 were included. The proportion of patients with hyperphosphatemia were 2.6%, 2.9%, 6.8%, and 27.1% in CKD Stages 3a, 3b, 4, and 5, respectively. Moreover, 71.6% of the patients with hyperphosphatemia did not receive any phosphate-binder (PB). Lateral abdominal X-rays were obtained in 2280 patients, 9.8% of the patients were diagnosed as having AAC. Altogether 2219 patients had data of echocardiography, and 13.2% of them were diagnosed with LVH. Multivariate logistic regression analysis showed that serum phosphorus was independently associated with the presence of AAC and LVH. Conclusions: In Chinese patients with CKD, the percentage of hyperphosphatemia is comparable to that of other countries while the usage of PBs is suboptimal. The prevalence of vascular calcification in Chinese patients is relatively lower compared with the Caucasian population. PMID:27647184
There is a significant prevalence (20%–80% depending on the population and the study) of lipid disorders and other cardiovascular risk factors in people living with HIV infection. This review focuses on HIV and HIV treatment–associated metabolic and cardiovascular concerns, including dyslipidemias, lipodystrophy syndromes, endothelial dysfunctions, and associated metabolic events such as insulin resistance. Emerging hypotheses of the underlying pathophysiology of these issues, with impact on selection of specific antiretroviral treatment (ART) strategies, therapy, and preventive approaches to decreasing cardiovascular risk and other problems associated with these syndromes are discussed. Screening for cardiovascular risk as part of the decision of starting antiretroviral therapy, and during care of patients with HIV regardless of ART therapy status, is suggested with particular areas of focus. Statins, other hyperlipidemic therapies, treatment for specific problems arising due to lipodystrophy, and implications on ART selection to avoid drug interactions and adverse effects are also discussed. PMID:21181310
Troll, J Gregory
There is a significant prevalence (20%-80% depending on the population and the study) of lipid disorders and other cardiovascular risk factors in people living with HIV infection. This review focuses on HIV and HIV treatment-associated metabolic and cardiovascular concerns, including dyslipidemias, lipodystrophy syndromes, endothelial dysfunctions, and associated metabolic events such as insulin resistance. Emerging hypotheses of the underlying pathophysiology of these issues, with impact on selection of specific antiretroviral treatment (ART) strategies, therapy, and preventive approaches to decreasing cardiovascular risk and other problems associated with these syndromes are discussed. Screening for cardiovascular risk as part of the decision of starting antiretroviral therapy, and during care of patients with HIV regardless of ART therapy status, is suggested with particular areas of focus. Statins, other hyperlipidemic therapies, treatment for specific problems arising due to lipodystrophy, and implications on ART selection to avoid drug interactions and adverse effects are also discussed.
Derman, R J
Although a prospective, longitudinal study on the long-term cardiovascular effects of oral contraceptives has yet to be performed, available data are useful in determining a safe course of action while physicians await definitive answers. Exogenous sex steroids produce important effects on lipid metabolism. Early intervention against cholesterol is important in reducing cardiovascular risk. Current users of high-dose formulations, particularly older women who smoke, are at greatest risk for cardiovascular complications, especially myocardial infarction. Low-dose oral contraceptives have more modest effects on lipid metabolism, but important differences in the potency of progestins remain. Fortunately, recent studies among users of lower-dose oral contraceptive formulations fail to show an increase in cardiovascular morbidity and mortality. Nonetheless, prudent physicians will avoid oral contraceptives that may adversely affect lipoprotein metabolism, such as those containing progestins with high androgenic and antiestrogenic potency.
Pires da Rosa, Gilberto; Libânio, Diogo; Filipe Azevedo, Luís
The influence of fibrates on cardiovascular risk has been the focus of several clinical trials. This Cochrane Collaboration Systematic Review evaluated the efficacy of fibrates for secondary prevention of cardiovascular events and stroke, analyzing 13 randomized controlled trials, in a total of 16 112 participants with a history of cardiovascular disease. Fibrates showed a protective effect for the composite outcome of non-fatal stroke, non-fatal myocardial infarction (MI) and vascular death, mainly due to reduction in the risk of non-fatal or fatal MI. Nonetheless, these results largely relied on studies including clofibrate, a drug withdrawn from the market in 2002. No statistically significant differences regarding adverse events were found between fibrates and placebo. Although insufficient to support the routine prescription of fibrates in this setting, this evidence should be taken into account when deciding on lipid-modifying therapy in dyslipidemic patients with a history of cardiovascular disease.
Shang, Hongcai; Gao, Xiumei; Ernst, Edzard
Abstract Objective To systematically review the Chinese-language literature on acupuncture-related adverse events. Methods We searched three Chinese databases (the Chinese Biomedical Literature Database, 1980–2009; the Chinese Journal Full-Text Database, 1980–2009; and the Weipu Journal Database, 1989–2009) to identify Chinese-language articles about the safety of traditional needle acupuncture. Case reports, case series, surveys and other observational studies were included if they reported factual data, but review articles, translations and clinical trials were excluded. Findings The inclusion criteria were met by 115 articles (98 case reports and 17 case series) that in total reported on 479 cases of adverse events after acupuncture. Fourteen patients died. Acupuncture-related adverse events were classified into three categories: traumatic, infectious and “other”. The most frequent adverse events were pneumothorax, fainting, subarachnoid haemorrhage and infection, while the most serious ones were cardiovascular injuries, subarachnoid haemorrhage, pneumothorax and recurrent cerebral haemorrhage. Conclusion Many acupuncture-related adverse events, most of them owing to improper technique, have been described in the published Chinese literature. Efforts should be made to find effective ways of monitoring and minimizing the risks related to acupuncture. PMID:21124716
Fifty five years after the first finding relating mood disturbances and cardiovascular diseases, there is still debate on the formation of a cogent conception embracing all the fragments of insight within the various aspects relating psychosocial stress to cardiovascular diseases. The clinical comorbidity is empirically evident, but there are ambiguous research results limiting the value of the proposed pathophysiological mechanisms. Psychosocial stress represents here any event that relates psychological phenomena to the social environment and to the associated pathophysiological changes. Stress denotes the external or environmental factors to which people are exposed, as well as the behavioural or biological reaction to it (response that some authors call "distress"). Cardiovascular diseases will be considered here only when being the consequence of chronic inflammatory disease of arteries (atherosclerosis).The question is: Are there pathophysiological reliable mechanisms relating psychosocial stress to the development of cardiovascular diseases? PMID:15998817
López Rubio, María Antonia; Tárraga López, Pedro Juan; Rodríguez Montes, José Antonio; Frías López, María del Carmen; Solera Albero, Juan; Bermejo López, Pablo
Objetivos: Valorar si el hipotiroidismo subclínico puede comportarse como un factor de riesgo cardiovascular o un modificador del mismo, identificando variables epidemiológicas y riesgo cardiovascular estimado en una muestra de sujetos diagnosticados en la provincia de Albacete. Método: Estudio observacional, descriptivo y transversal realizado en Albacete durante la primera quincena de enero de 2012 en pacientes de ambos géneros con hipotiroidismo subclínico. Se analizaron las siguientes variables: glucemia basal, colesterol total, colesterol HDL, colesterol LDL, triglicéridos, TSH, T4, peso, talla, I.M.C., tensión arterial, antecedentes de patología cardiovascular, factores de riesgo cardiovascular y riesgo cardiovascular estimado. Resultados: Se obtuvieron 326 pacientes, con predominio femenino (79,2 %), menores de 65 años en el 78% y sin factores de riesgo cardiovascular en el 48,61%. La prevalencia de los factores de riesgo cardiovascular identificados fué: tabaquismo (33,2%), diabetes mellitus (24,9%), hipertensión arterial (23,4%), alteraciones lipídicas (28,9%) y fibrilación auricular (4,9 %). No se encontró asociación entre hipotiroidismo subclínico y la mayoría de los parámetros del perfil lipídico que condicionan un perfil pro-aterogénico, salvo con la hipertrigliceridemia. Asimismo, tampoco se constató asociación con riesgo cardiovascular aumentado. Conclusiones: El perfil del paciente con hipotiroidismo subclínico es una mujer de mediana edad sin factores de riesgo cardiovascular en la mitad de casos. Se ha encontrado relación entre hipotiroidismo subclínico e hipertrigliceridemia, pero no con el resto de parámetros del perfil lipídico, otros factores de riesgo cardiovascular o con aumento de dicho riesgo. Sin embargo, un 25% de diabéticos y un 22% de no diabéticos están en situación de riesgo cardiovascular moderado-alto.
Charles, John B.; Bungo, Michael W.
The effects of space flight on the cardiovascular system have been studied since the first manned flights. In several instances, the results from these investigations have directly contradicted the predictions based on established models. Results suggest associations between space flight's effects on other organ systems and those on the cardiovascular system. Such findings provide new insights into normal human physiology. They must also be considered when planning for the safety and efficiency of space flight crewmembers.
Goodwin, Julie E
Glucocorticoids affect the developing and mature cardiovascular system in profound and, at times, contradictory ways. The glucocorticoid receptor is ubiquitous in most cell types and conserved across species, highlighting its importance in development and homeostasis. Despite the fact that the glucocorticoid receptor is widely expressed, tissue-specific effects of glucocorticoids may have pronounced effects on whole organism phenotypes. Here we will review the interactions between glucocorticoids and the cardiovascular system.
Sansone, Randy A.; Sansone, Lori A.
For years, there has been speculation among clinicians about possible relationships between (a) depression and the development of cardiovascular disease (CVD) and (b) comorbid depression and adverse CVD outcomes. In a review of the recent literature, we noted that there are data to support both of these clinical urban legends. In addition, while data are preliminary, several studies indicate modest medical benefits with antidepressant treatment among individuals with comorbid depression and CVD. Clearly, additional studies are warranted in this intriguing area of the mind/body interface. This ongoing column is dedicated to the challenging clinical interface between psychiatry and primary care—two fields that are inexorably linked. PMID:19724717
Lee, Hyun-Ha; Jeong, Seung-Young; Park, Sang-Hyun; Lee, Kwan-Hee
This paper reviews the status of assessment and prognosis system for nuclear emergency response in Korea, especially atmospheric dispersion model. The Korea Institute of Nuclear Safety (KINS) performs the regulation and radiological emergency preparedness of the nuclear facilities and radiation utilizations. Also, KINS has set up the "Radiological Emergency Technical Advisory Plan" and the associated procedures such as an emergency response manual in consideration of the IAEA Safety Standards GS-R-2, GS-G-2.0, and GS-G-2.1. The Radiological Emergency Technical Advisory Center (RETAC) organized in an emergency situation provides the technical advice on radiological emergency response. The "Atomic Computerized Technical Advisory System for nuclear emergency" (AtomCARE) has been developed to implement assessment and prognosis by RETAC. KINS developed Accident Dose Assessment and Monitoring (ADAMO) system in 2015 to reflect the lessons learned from Fukushima accident. It incorporates (1) the dose assessment on the entire Korean peninsula, Asia region, and global region, (2) multi-units accident assessment (3) applying new methodology of dose rate assessment and the source term estimation with inverse modeling, (4) dose assessment and monitoring with the environmental measurements result. The ADAMO is the renovated version of current FADAS of AtomCARE. The ADAMO increases the accuracy of the radioactive material dispersion with applying the LDAPS(Local Data Assimilation Prediction System, Spatial resolution: 1.5 km) and RDAPS(Regional Data Assimilation Prediction System, Spatial resolution: 12km) of weather prediction data, and performing the data assimilation of automatic weather system (AWS) data from Korea Meteorological Administration (KMA) and data from the weather observation tower at NPP site. The prediction model of the radiological material dispersion is based on the set of the Lagrangian Particle model and Lagrangian Puff model. The dose estimation methodology
Zhu, K Y; Ang, Alvin; Acharya U, Rajendra; Lim, C M
Cardiovascular diseases (CVDs) can be known as a class of diseases which affect different parts of the cardiovascular system such as the heart or blood vessels. Hemodynamic signals are an important tool used by doctors to diagnose the type of CVD occurred in a patient. Diagnosing the correct type of CVD in a patient early will allow the patient to have the suitable medical treatment. Some examples of CVDs include coronary heart disease, cerebrovascular disease and peripheral arterial disease. A human cardiovascular model is developed in order to simulate different hemodynamic signals of the cardiovascular system. The hemodynamic signals include the blood pressures, flow rates and volumes in various part of the cardiovascular system. This paper presents a model which is able to simulate hemodynamic signals and they are able to represent the human arterial blood pressure accurately. Hence this model can also be used to simulate hypertensive patients in order to design control systems for regulation of blood pressure. Signal verification has been performed and the stability of the model is being investigated. Applications of the human cardiovascular model are also presented.
Norman, P E; Powell, J T
Vitamin D plays a classical hormonal role in skeletal health by regulating calcium and phosphorus metabolism. Vitamin D metabolites also have physiological functions in nonskeletal tissues, where local synthesis influences regulatory pathways via paracrine and autocrine mechanisms. The active metabolite of vitamin D, 1α,25-dihydroxyvitamin D, binds to the vitamin D receptor that regulates numerous genes involved in fundamental processes of potential relevance to cardiovascular disease, including cell proliferation and differentiation, apoptosis, oxidative stress, membrane transport, matrix homeostasis, and cell adhesion. Vitamin D receptors have been found in all the major cardiovascular cell types including cardiomyocytes, arterial wall cells, and immune cells. Experimental studies have established a role for vitamin D metabolites in pathways that are integral to cardiovascular function and disease, including inflammation, thrombosis, and the renin-angiotensin system. Clinical studies have generally demonstrated an independent association between vitamin D deficiency and various manifestations of degenerative cardiovascular disease including vascular calcification. However, the role of vitamin D supplementation in the management of cardiovascular disease remains to be established. This review summarizes the clinical studies showing associations between vitamin D status and cardiovascular disease and the experimental studies that explore the mechanistic basis for these associations.
Laroche, Michel; Pécourneau, Virginie; Blain, Hubert; Breuil, Véronique; Chapurlat, Roland; Cortet, Bernard; Sutter, Bruno; Degboe, Yannick
Osteoporosis and cardiovascular disease were long viewed as independent of each other. However, numerous epidemiological studies, which are discussed in the first part of this review, have provided incontrovertible evidence of a link. Thus, the risk of coronary artery disease and stroke is higher in patients with a history of osteoporotic fracture or low bone mineral density than in non-osteoporotic patients. In the other direction, patients with cardiovascular disease are at higher risk for bone loss and osteoporotic fracture. The link between osteoporosis and cardiovascular disease is due in part to shared conventional risk factors such as estrogen deprivation in women, smoking, low physical activity, and diabetes. In addition, atheroma plaque calcification involves cytokines and growth factors that also play a role in bone turnover, including proinflammatory cytokines (IL-6 and TNFα), osteoprotegerin, sclerostin, matrix GLA protein, and FGF-23. Several recent studies have provided support for these pathophysiological hypotheses. Thus, elevation of osteoprotegerin, sclerostin, or FGF-23 levels may explain and predict the occurrence of both osteoporotic fractures and cardiovascular events. The association between osteoporosis and cardiovascular disease found in most epidemiological and pathophysiological studies suggests a need for evaluating potential benefits from routine bone absorptiometry and osteoporotic fracture detection in patients with cardiovascular disease and from exercise testing and arterial Doppler imaging in patients with osteoporosis.
Dhutia, Harshil; Sharma, Sanjay
Regular physical activity controls acquired cardiovascular risk factors such as obesity, diabetes mellitus, hypertension and hyperlipidaemia. Exercise is generally associated with a 50% reduction in adverse events from coronary artery disease (CAD). The benefits of exercise extend well beyond the cardiovascular system. Recent evidence suggests that exercise prevents cell senescence, and active individuals are at lower risk of developing certain malignancies including cancer of the prostate and the colon, osteoporosis, depression and dementia. Individuals who exercise regularly extend their life expectancy by three to seven years. Healthy individuals should engage in 150 minutes of moderate-intensity, aerobic exercise per week. Recent studies have demonstrated that even lower volumes of exercise below these recommendations confer health benefits, which is highly relevant to individuals with established cardiac disease including heart failure. Sudden cardiac death in athletes under 35 is rare with.estimates ranging from 1 in 50,000 to 1 in 200,000. Hereditary and congenital abnormalities of the heart are the most common cause of nontraumatic death during sport in young athletes. In middle-aged recreational athletes more than 90% of sudden cardiac deaths occur in males and more than 90% are caused by atherosclerotic CAD. The AHA and the ESC advocate pre-participation screening of young athletes. The ECG has the ability to detect congenital accessory pathways and ion channelopathies, and is frequently abnormal in individuals with cardiomyopathy. Screening with a 12-lead ECG in older athletes is of limited value given the overwhelming contribution of atherosclerotic CAD to sudden cardiac death.
Bedi, Updesh Singh; Arora, Rohit
Posttraumatic stress disorder (PTSD) involves the onset of psychiatric symptoms after exposure to a traumatic event. PTSD has an estimated lifetime prevalence of 7.8% among adult Americans, and about 15.2% of the men and 8.5% of the women who served in Vietnam suffered from posttraumatic stress disorder (PTSD) > or =15 years after their military service. Physiological responses (increase in heart rate, blood pressure, tremor and other symptoms of autonomic arousal) to reminders of the trauma are a part of the DSM-IV definition of PTSD. Multiple studies have shown that patients suffering from PTSD have increased resting heart rate, increased startle reaction, and increased heart rate and blood pressure as responses to traumatic slides, sounds and scripts. Some researchers have studied the sympathetic nervous system even further by looking at plasma norepinephrine and 24-hour urinary norepinephrine and found them to be elevated in veterans with PTSD as compared to those without PTSD. PTSD is associated with hyperfunctioning of the central noradrenergic system. Hyperactivity of the sympathoadrenal axis might contribute to cardiovascular disease through the effects of the catecholamines on the heart, the vasculature and platelet function. A psychobiological model based on allostatic load has also been proposed and states that chronic stressors over long durations of time lead to increased neuroendocrine responses, which have adverse effects on the body. PTSD has also been shown to be associated with an increased prevalence of substance abuse. With this review, we have discussed the effects of PTSD on the cardiovascular system. PMID:17595933
Fox, P. L.; Mazumder, B.; Ehrenwald, E.; Mukhopadhyay, C. K.
Transition metal ion-mediated oxidation is a commonly used model system for studies of the chemical, structural, and functional modifications of low-density lipoprotein (LDL). The physiological relevance of studies using free metal ions is unclear and has led to an exploration of free metal ion-independent mechanisms of oxidation. We and others have investigated the role of human ceruloplasmin (Cp) in oxidative processes because it the principal copper-containing protein in serum. There is an abundance of epidemiological data that suggests that serum Cp may be an important risk factor predicting myocardial infarction and cardiovascular disease. Biochemical studies have shown that Cp is a potent catalyst of LDL oxidation in vitro. The pro-oxidant activity of Cp requires an intact structure, and a single copper atom at the surface of the protein, near His(426), is required for LDL oxidation. Under conditions where inhibitory protein (such as albumin) is present, LDL oxidation by Cp is optimal in the presence of superoxide, which reduces the surface copper atom of Cp. Cultured vascular endothelial and smooth muscle cells also oxidize LDL in the presence of Cp. Superoxide release by these cells is a critical factor regulating the rate of oxidation. Cultured monocytic cells, when activated by zymosan, can oxidize LDL, but these cells are unique in their secretion of Cp. Inhibitor studies using Cp-specific antibodies and antisense oligonucleotides show that Cp is a major contributor to LDL oxidation by these cells. The role of Cp in lipoprotein oxidation and atherosclerotic lesion progression in vivo has not been directly assessed and is an important area for future studies.
Tuñón, José; Cristóbal, Carmen; Tarín, Nieves; Aceña, Álvaro; González-Casaus, María Luisa; Huelmos, Ana; Alonso, Joaquín; Lorenzo, Óscar; González-Parra, Emilio; Mahíllo-Fernández, Ignacio; Pello, Ana María; Carda, Rocío; Farré, Jerónimo; Rodríguez-Artalejo, Fernando
Objective Vitamin D and fibroblast growth factor-23 (FGF-23) are related with cardiovascular disorders. We have investigated the relationship of calcidiol (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse outcomes in patients with coronary artery disease. Methods Prospective follow-up study of 704 outpatients, attending the departments of Cardiology of four hospitals in Spain, 6–12 months after an acute coronary event. Baseline calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The outcome was the development of acute ischemic events (any acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox regression adjusted for the main confounders was performed. Results Calcidiol levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23, and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients, respectively. Only 22.4% of patients had glomerular filtration rate<60 ml/min1.73 m2. After a mean follow-up was 2.15±0.99 years, 77 patients developed the outcome. Calcidiol (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.48–0.94; p = 0.021) and FGF-23 (HR = 1.13; 95% CI = 1.04–1.23; p = 0.005) plasma levels predicted independently the outcome. There was a significant interaction between calcidiol and FGF-23 levels (p = 0.025). When the population was divided according to FGF-23 levels, calcidiol still predicted the outcome independently in patients with FGF-23 levels higher than the median (HR = 0.50; 95% CI = 0.31–0.80; p = 0.003) but not in those with FGF-23 levels below this value (HR = 1.03; 95% CI = 0.62–1.71; p = 0.904). Conclusions Abnormalities in mineral metabolism are frequent in patients with stable coronary artery disease. In this population, low calcidiol plasma levels predict an adverse prognosis in the presence of high FGF-23 levels. PMID:24748388
Johnson, B. Delia; Rutledge, Thomas; Bittner, Vera; Whittaker, Kerry S.; Krantz, David S.; Cornell, Carol E.; Eteiba, Wafia; Handberg, Eileen; Vido, Diane; Bairey Merz, C. Noel
Abstract Background Black women are less likely to be evaluated and treated for anginal symptoms, despite a higher premature cardiac mortality rate compared to white women. Our objective was to compare angina symptoms in black versus white women regarding (1) angina symptoms characterization; (2) relationship with obstructive coronary artery disease (CAD); and (3) relationship with subsequent mortality. Methods A cohort of 466 women (69 black and 397 white) undergoing coronary angiography for suspected ischemia and without prior history of CAD completed symptom checklists. Four symptom clusters (CHEST, UPPER, STOMACH, and TYPICAL TRIGGERS) were derived by factor analysis. All angiograms were analyzed by core lab. Mortality data over 10 years were obtained from National Death Index. Results (1) Black women had lower mean CHEST cluster scores (0.60±0.30 vs. 0.73±30, p=0.002), but higher STOMACH scores (0.41±0.25 vs. 0.30±0.25, p=0.011) than white women. (2) Prevalence and severity of CAD did not differ in black and white women and was not predicted by symptom cluster scores. (3) All-cause mortality rates were 24.9% in blacks versus 14.5% in whites, p=0.007; and cardiovascular mortality 22.5% vs.8.8%, p=0.001. Symptom clusters were not predictive of adverse events in white women. However, black women with a low TYPICAL score had significantly higher mortality compared to those with a high TYPICAL score (43% vs. 10%, p=0.006). Conclusions Among women undergoing coronary angiography, black women report fewer chest-related and more stomach-related symptoms, regardless of presence or severity of CAD, and these racial symptom presentation differences are linked with the more adverse prognosis observed in the black women. Atypical symptom presentation may be a barrier to appropriate and timely diagnosis and treatment and contribute to poorer outcomes for black women. PMID:23992103
Issa, Mohamad R.; Samuels, Stuart E.; Bellile, Emily; Shalabi, Firas L.; Eisbruch, Avraham; Wolf, Gregory
Tumor staging systems for laryngeal cancer (LC) have been developed to assist in estimating prognosis after treatment and comparing treatment results across institutions. While the laryngeal TNM system has been shown to have prognostic information, varying cure rates in the literature have suggested concern about the accuracy and effectiveness of the T-classification in particular. To test the hypothesis that tumor volumes are more useful than T classification, we conducted a retrospective review of 78 patients with laryngeal cancer treated with radiation therapy at our institution. Using multivariable analysis, we demonstrate the significant prognostic value of anatomic volumes in patients with previously untreated laryngeal cancer. In this cohort, primary tumor volume (GTVP), composite nodal volumes (GTVN) and composite total volume (GTVP + GTVN = GTVC) had prognostic value in both univariate and multivariate cox model analysis. Interestingly, when anatomic volumes were measured from CT scans after a single cycle of induction chemotherapy, all significant prognosticating value for measured anatomic volumes was lost. Given the literature findings and the results of this study, the authors advocate the use of tumor anatomic volumes calculated from pretreatment scans to supplement the TNM staging system in subjects with untreated laryngeal cancer. The study found that tumor volume assessment after induction chemotherapy is not of prognostic significance. PMID:26569309
Nishikawa, Hiroki; Osaki, Yukio
The liver is the major organ for the metabolism of three major nutrients: protein, fat, and carbohydrate. Chronic hepatitis C virus infection is the major cause of chronic liver disease. Liver cirrhosis (LC) results from different mechanisms of liver injury that lead to necroinflammation and fibrosis. LC has been seen to be not a single disease entity but one that can be graded into distinct clinical stages related to clinical outcome. Several noninvasive methods have been developed for assessing liver fibrosis and these methods have been used for predicting prognosis in patients with LC. On the other hand, subjects with LC often have protein-energy malnutrition (PEM) and poor physical activity. These conditions often result in sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictive factors for poorer survival in patients with LC. Based on these backgrounds, several methods for evaluating nutritional status in patients with chronic liver disease have been developed and they have been preferably used in the clinical field practice. In this review, we will summarize the current knowledge in the field of LC from the viewpoints of diagnostic method, nutritional status, and clinical outcomes.
Nolan, Mary; Catania, Rebecca; deMare, Gregory
The Prognostics Framework is a set of software tools with an open architecture that affords a capability to integrate various prognostic software mechanisms and to provide information for operational and battlefield decision-making and logistical planning pertaining to weapon systems. The Prognostics NASA Tech Briefs, February 2005 17 Framework is also a system-level health -management software system that (1) receives data from performance- monitoring and built-in-test sensors and from other prognostic software and (2) processes the received data to derive a diagnosis and a prognosis for a weapon system. This software relates the diagnostic and prognostic information to the overall health of the system, to the ability of the system to perform specific missions, and to needed maintenance actions and maintenance resources. In the development of the Prognostics Framework, effort was focused primarily on extending previously developed model-based diagnostic-reasoning software to add prognostic reasoning capabilities, including capabilities to perform statistical analyses and to utilize information pertaining to deterioration of parts, failure modes, time sensitivity of measured values, mission criticality, historical data, and trends in measurement data. As thus extended, the software offers an overall health-monitoring capability.
Hemminki, E.; McPherson, K.
OBJECTIVE: To examine the incidence of cardiovascular diseases and cancer from published clinical trials that studied other outcomes of postmenopausal hormone therapy as some surveys have suggested that it may decrease the incidence of cardiovascular diseases and increase the incidence of hormone dependent cancers. DESIGN: Trials that compared hormone therapy with placebo, no therapy, or vitamins and minerals in comparable groups of postmenopausal women and reported cardiovascular or cancer outcomes were searched from the literature. SUBJECTS: 22 trials with 4124 women were identified. In each group, the numbers of women with cardiovascular and cancer events were summed and divided by the numbers of women originally allocated to the groups. RESULTS: Data on cardiovascular events and cancer were usually given incidentally, either as a reason for dropping out of a study or in a list of adverse effects. The calculated odds ratios for women taking hormones versus those not taking hormones was 1.39 (95% confidence interval 0.48 to 3.95) for cardiovascular events without pulmonary embolus and deep vein thrombosis and 1.64 (0.55 to 4.18) with them. It is unlikely that such results would have occurred if the true odds ratio were 0.7 or less. For cancers, the numbers of reported events were too low for a useful conclusion. CONCLUSIONS: The results of these pooled data do not support the notion that postmenopausal hormone therapy prevents cardiovascular events. PMID:9251544
Murphy, Margaret O.; Petriello, Michael C.; Han, Sung Gu; Sunkara, Manjula; Morris, Andrew J; Esser, Karyn; Hennig, Bernhard
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that contribute to the initiation of cardiovascular disease. Exercise has been shown to reduce the risk of cardiovascular disease; however, whether exercise can modulate PCB-induced vascular endothelial dysfunction and associated cardiovascular risk factors is unknown. We examined the effects of exercise on coplanar PCB- induced cardiovascular risk factors including oxidative stress, inflammation, impaired glucose tolerance, hypercholesteremia, and endothelium-dependent relaxation. Male ApoE−/− mice were divided into sedentary and exercise groups (voluntary wheel running) over a 12 week period. Half of each group was exposed to vehicle or PCB 77 at weeks 1, 2, 9, and 10. For ex vivo studies, male C57BL/6 mice exercised via voluntary wheel training for 5 weeks and then were administered with vehicle or PCB 77 24 hours before vascular reactivity studies were performed. Exposure to coplanar PCB increased risk factors associated with cardiovascular disease, including oxidative stress and systemic inflammation, glucose intolerance, and hypercholesteremia. The 12 week exercise intervention significantly reduced these pro-atherogenic parameters. Exercise also upregulated antioxidant enzymes including phase II detoxification enzymes. Sedentary animals exposed to PCB 77 exhibited endothelial dysfunction as demonstrated by significant impairment of endothelium-dependent relaxation, which was prevented by exercise. Lifestyle modifications such as aerobic exercise could be utilized as a therapeutic approach for the prevention of adverse cardiovascular health effects induced by environmental pollutants such as PCBs. Keywords: exercise, polychlorinated biphenyl, endothelial function, antioxidant response, cardiovascular disease, inflammation, oxidative stress PMID:25586614
Uzoigwe, Jacinta C.; Prum, Thavaleak; Bresnahan, Eric; Garelnabi, Mahdi
Outdoor and indoor air pollution poses a significant cardiovascular risk, and has been associated with atherosclerosis, the main underlying pathology in many cardiovascular diseases. Although, it is well known that exposure to air pollution causes pulmonary disease, recent studies have shown that cardiovascular health consequences of air pollution generally equal or exceed those due to pulmonary diseases. The objective of this article is to evaluate the current evidence on the emerging role of environmental air pollutions in cardiovascular disease, with specific focus on the types of air pollutants and mechanisms of air pollution-induced cardiotoxicity. Published literature on pollution was systematically reviewed and cited in this article. It is hoped that this review will provide a better understanding of the harmful cardiovascular effects induced by air pollution exposure. This will help to bring a better understanding on the possible preventive health measures and will also serve regulatory agencies and researchers. In addition, elucidating the biological mechanisms underlying the link between air pollution and cardiovascular disease is an essential target in developing novel pharmacological strategies aimed at decreasing adverse effects of air pollution on cardiovascular system. PMID:24083218
Liu, Yonggang; Goodson, Jamie M.; Zhang, Bo; Chin, Michael T.
Exposure to air pollution has long been known to trigger cardiovascular events, primarily through activation of local and systemic inflammatory pathways that affect the vasculature. Detrimental effects of air pollution exposure on heart failure and cardiac remodeling have also been described in human populations. Recent studies in both human subjects and animal models have provided insights into the basic physiological, cellular and molecular mechanisms that play a role in adverse cardiac remodeling. This review will give a brief overview of the relationship between air pollution and cardiovascular disease, describe the clinical effects of air pollution exposure on cardiac remodeling, describe the basic mechanisms that affect remodeling as described in human and animal systems and will discuss future areas of investigation. PMID:26042051
Yergeau, A; Alain, L; Pless, R; Robert, Y
OBJECTIVE: To determine the incidence of severe adverse events temporally associated with meningococcal vaccines administered as part of a mass vaccination program. DESIGN: Retrospective descriptive study of events reported to a passive provincial surveillance system. SETTING: The province of Quebec. PARTICIPANTS: The 1,198,751 individuals aged 6 months to 20 years who were vaccinated against meningococcal disease between Dec. 27, 1992, and Mar. 31, 1993. OUTCOME MEASURES: Total numbers and rates of severe adverse events, including allergic reactions, anaphylactic reactions, neurological events (other than abnormal crying and screaming) and other serious or unusual events. RESULTS: A total of 118 reports of severe adverse events were selected from the surveillance system. The most frequent were allergic reactions (9.2 per 100,000 doses). Few anaphylactic or neurologic reactions were reported (0.1 and 0.5 per 100,000 doses respectively). There were no reports of sequelae or of encephalopathy, meningitis or encephalitis. CONCLUSION: Meningococcal vaccines seem to be associated with fewer adverse events than have previously been reported. Existing surveillance programs are useful for determining the incidence of adverse events temporally associated with vaccines. PMID:8630839
Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen
The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028
Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.
Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092
Pandiri, Arun R; Kerlin, Roy L; Mann, Peter C; Everds, Nancy E; Sharma, Alok K; Myers, L Peyton; Steinbach, Thomas J
One of the principal challenges facing a toxicologic pathologist is to determine and differentiate a true adverse effect from a nonadverse or an adaptive response. Recent publications from the Society of Toxicologic Pathology (STP) and the European STP provide guidance for determining and communicating adversity in nonclinical toxicology studies. In order to provide a forum to inform and engage in a discussion on this important topic, a continuing education (CE) course was held during the 2016 STP Annual meeting in San Diego, CA. The lectures at this course provided guidance on determining and communicating adversity using case studies involving both clinical pathology and anatomic pathology. In addition, one talk also focused on data quality, study design, and interpretation of artifacts that could hinder the determination of adversity. The CE course ended with a talk on understanding adversity in preclinical studies and engaging the regulatory agencies in the decision-making process. This manuscript is designed to provide brief summaries of all the talks in this well-received CE course.
Andras, Peter; Lazarus, John; Roberts, Gilbert
Background A major cornerstone of evolutionary biology theory is the explanation of the emergence of cooperation in communities of selfish individuals. There is an unexplained tendency in the plant and animal world – with examples from alpine plants, worms, fish, mole-rats, monkeys and humans – for cooperation to flourish where the environment is more adverse (harsher) or more unpredictable. Results Using mathematical arguments and computer simulations we show that in more adverse environments individuals perceive their resources to be more unpredictable, and that this unpredictability favours cooperation. First we show analytically that in a more adverse environment the individual experiences greater perceived uncertainty. Second we show through a simulation study that more perceived uncertainty implies higher level of cooperation in communities of selfish individuals. Conclusion This study captures the essential features of the natural examples: the positive impact of resource adversity or uncertainty on cooperation. These newly discovered connections between environmental adversity, uncertainty and cooperation help to explain the emergence and evolution of cooperation in animal and human societies. PMID:18053138
Over the last two decades, several invasive and non-invasive coronary atherosclerosis imaging modalities have emerged as predictors of cardiovascular outcomes in at-risk population. These modalities have demonstrated independent or incremental prognostic information over existing/standard risk stratification schemes, such as the Framingham risk score (FRS), by identifying characteristics of coronary artery diseases (CADs). In this review, we begin with discussing the importance of pre-test probability and quality of outcome measure, followed by specific findings of each modality in relation to prognosis. We focused on both short and long term prognostic aspects of coronary computed tomography (CT) (including coronary calcium score and coronary angiography) and magnetic resonance imaging as non-invasive tools, as well as invasive modalities including intravascular ultrasound (IVUS), optical coherence tomography (OCT), near infrared spectroscopy and Angioscopy. PMID:27500091
Grasser, Erik Konrad; Miles-Chan, Jennifer Lynn; Charrière, Nathalie; Loonam, Cathríona R; Dulloo, Abdul G; Montani, Jean-Pierre
Globally, the popularity of energy drinks is steadily increasing. Scientific interest in their effects on cardiovascular and cerebrovascular systems in humans is also expanding and with it comes a growing number of case reports of adverse events associated with energy drinks. The vast majority of studies carried out in the general population report effects on blood pressure and heart rate. However, inconsistencies in the current literature render it difficult to draw firm conclusions with regard to the effects of energy drinks on cardiovascular and cerebrovascular variables. These inconsistencies are due, in part, to differences in methodologies, volume of drink ingested, and duration of postconsumption measurements, as well as subject variables during the test. Recent well-controlled, randomized crossover studies that used continuous beat-to-beat measurements provide evidence that cardiovascular responses to the ingestion of energy drinks are best explained by the actions of caffeine and sugar, with little influence from other ingredients. However, a role for other active constituents, such as taurine and glucuronolactone, cannot be ruled out. This article reviews the potentially adverse hemodynamic effects of energy drinks, particularly on blood pressure and heart rate, and discusses the mechanisms by which their active ingredients may interact to adversely affect the cardiovascular system. Research areas and gaps in the literature are discussed with particular reference to the use of energy drinks among high-risk individuals.
Zannad, Faiez; Stough, Wendy Gattis; Piña, Ileana L; Mehran, Roxana; Abraham, William T; Anker, Stefan D; De Ferrari, Gaetano M; Farb, Andrew; Geller, Nancy L; Kieval, Robert S; Linde, Cecilia; Redberg, Rita F; Stein, Kenneth; Vincent, Alphons; Woehrle, Holger; Pocock, Stuart J
Several features of cardiovascular devices raise considerations for clinical trial conduct. Prospective, randomized, controlled trials remain the highest quality evidence for safety and effectiveness assessments, but, for instance, blinding may be challenging. In order to avoid bias and not confound data interpretation, the use of objective endpoints and blinding patients, study staff, core labs, and clinical endpoint committees to treatment assignment are helpful approaches. Anticipation of potential bias should be considered and planned for prospectively in a cardiovascular device trial. Prospective, single-arm studies (often referred to as registry studies) can provide additional data in some cases. They are subject to selection bias even when carefully designed; thus, they are generally not acceptable as the sole basis for pre-market approval of high risk cardiovascular devices. However, they complement the evidence base and fill the gaps unanswered by randomized trials. Registry studies present device safety and effectiveness in day-to-day clinical practice settings and detect rare adverse events in the post-market period. No single research design will be appropriate for every cardiovascular device or target patient population. The type of trial, appropriate control group, and optimal length of follow-up will depend on the specific device, its potential clinical benefits, the target patient population and the existence (or lack) of effective therapies, and its anticipated risks. Continued efforts on the part of investigators, the device industry, and government regulators are needed to reach the optimal approach for evaluating the safety and performance of innovative devices for the treatment of cardiovascular disease.
Carver, Alissa R; Tamayo, Esther; Perez-Polo, J Regino; Saade, George R; Hankins, Gary D V; Costantine, Maged M
Animal and human studies show that in-utero exposure to preeclampsia alters fetal programming and results in long-term adverse cardiovascular outcomes in the offspring. Human epidemiologic data also suggest that offspring born to preeclamptic mothers are also at risk of adverse long term neurodevelopmental outcomes. Pravastatin, a hydrophilic lipid-lowering drug with pleiotropic properties, was found to prevent the altered cardiovascular phenotype of preeclampsia and restore fetal growth in animal models, providing biological plausibility for its use as a preventive agent for preeclampsia. In this study, we used a murine model of preeclampsia based on adenovirus over-expression of the anti-angiogenic factor soluble Fms-like tyrosine kinase 1, and demonstrated that adult offspring born to preeclamptic dams perform poorly on assays testing vestibular function, balance, and coordination, and that prenatal pravastatin treatment prevents impairment of fetal programming.
Levy, Barry S; Sidel, Victor W
The adverse health consequences of the Iraq War (2003-11) were profound. We conclude that at least 116,903 Iraqi non-combatants and more than 4800 coalition military personnel died over the 8-year course. Many Iraqi civilians were injured or became ill because of damage to the health-supporting infrastructure of the country, and about 5 million were displaced. More than 31,000 US military personnel were injured and a substantial percentage of those deployed suffered post-traumatic stress disorder, traumatic brain injury, and other neuropsychological disorders and their concomitant psychosocial problems. Many family members of military personnel had psychological problems. Further review of the adverse health consequences of this war could help to minimise the adverse health consequences of, and help to prevent, future wars.
Wang, Liwei; Jiang, Guoqian; Li, Dingcheng; Liu, Hongfang
Normalizing data in the Adverse Event Reporting System (AERS), an FDA database, would improve the mining capacity of AERS for drug safety signal detection. In this study, we aim to normalize AERS and build a publicly available normalized Adverse drug events (ADE) data source.he drug information in AERS is normalized to RxNorm, a standard terminology source for medication. Drug class information is then obtained from the National Drug File - Reference Terminology (NDF-RT). Adverse drug events (ADE) are aggregated through mapping with the PT (Preferred Term) and SOC (System Organ Class) codes of MedDRA. Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). The AERS-DM could provide more perspectives to mine AERS database for drug safety signal detection and could be used by research community in the data mining field.
Skora, Daniel; Frankfurter, David
Since the advent of ART, much research has focused on the potential adverse for resultant harm. Prematurity, low birth-weight, PIH, congenital malformations, and CP are closely tied to multiple gestation. With the increase in elective single embryo transfer, there will be a reduction in adversity related to multiple birth. It is understood that underlying causes of infertility, including advanced maternal age, PCOS, thyroid disease, and uterine fibroids, predispose to adverse outcomes. However, imprinting abnormalities do not appear to stem from multiple births, and thus the need to consider the association between fertility treatment and methylation disorders remains essential. These, as well as risks of multi-fetal gestation, must be discussed with patients when considering using assisted reproduction.
Bick, Johanna; Nelson, Charles A
Children exposed to various forms of adversity early in life are at increased risk for a broad range of developmental difficulties, affecting both cognitive and emotional adjustment. We review a growing body of evidence suggesting that exposure to adverse circumstances affects the developing brain in ways that increase risk for a myriad of problems. We focus on two forms of adversity, one in which children are exposed to childhood maltreatment in family environments, and another in which children are exposed to extreme psychosocial deprivation in contexts of institutional rearing. We discuss ways in which each of these experiences represent violations of species-expected caregiving conditions, thereby imposing challenges to the developing brain. We also review emerging data pointing to the effectiveness of early intervention in remediating neurodevelopmental consequences associated with maltreatment or institutional rearing. We conclude by discussing implications of this work for public health efforts and highlight important directions for the field. PMID:26334107
Kamphuis, Vivian P; Westenberg, Jos J M; van der Palen, Roel L F; Blom, Nico A; de Roos, Albert; van der Geest, Rob; Elbaz, Mohammed S M; Roest, Arno A W
Knowledge of normal and abnormal flow patterns in the human cardiovascular system increases our understanding of normal physiology and may help unravel the complex pathophysiological mechanisms leading to cardiovascular disease. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has emerged as a suitable technique that enables visualization of in vivo blood flow patterns and quantification of parameters that could potentially be of prognostic value in the disease process. In this review, current image processing tools that are used for comprehensive visualization and quantification of blood flow and energy distribution in the heart and great vessels will be discussed. Also, imaging biomarkers extracted from 4D flow CMR will be reviewed that have been shown to distinguish between normal and abnormal flow patterns. Furthermore, current applications of 4D flow CMR in the heart and great vessels will be discussed, showing its potential as an additional diagnostic modality which could aid in disease management and timing of surgical intervention.
Faget, Julien; Sisirak, Vanja; Blay, Jean-Yves; Caux, Christophe; Bendriss-Vermare, Nathalie; Ménétrier-Caux, Christine
Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) that infiltrate primary breast tumors impair patient survival. The ICOS-mediated interaction between tumor-infiltrating CD4+ T cells and pDCs leads to the amplification of Tregs and interleukin-10 secretion. Importantly, ICOS+ cell infiltration correlates with adverse patient prognosis, identifying ICOS as a new target for cancer immunotherapy. PMID:23802069
Campos, Maria; Batista, C; Jesus, N R; Silva, C M; Silva, T P
Cardiovascular patients frequently use herbal medicinal products, in order to contribute to the improvement of their chronic condition without medical intervention. However, they are likely to suffer from adverse effects from natural products and herb-drug interactions. This work aimed to alert cardiovascular patients and healthcare providers of the potential of occurrence of herb-drug interactions with cardiovascular therapy. Information obtained from the campaign "Aprender Saúde Entre as Plantas e os Medicamentos", carried out by the Observatory of Herb-Drug Interactions (www.oipm.uc.pt), was accessed in order to exemplify some selected interactions. From data received during the campaign, it was highlighted the prevalence of certain natural products particularly goji berries, green tea, mangosteen and rooibos that have significant cardiovascular effects. For this reason their intake should be carefully monitored in cardiovascular patients. This prevalence of use suggests a pattern in their use in Portugal. The ending results also indicate that there is still a lack of knowledge about the possible risks of herbal products, which may adversely affect the health of any patient. Thus becomes clear the value of the role of health professionals in the screening of such interactions.
Stitham, J; Vanichakarn, P; Ying, L; Hwa, J
The use of antithrombotic agents, particularly antiplatelet drugs like aspirin and clopidogrel, has been instrumental in decreasing the risk for adverse cardiovascular events across a wide range of patients. However, despite the established benefits, the use of these medications remains suboptimal. There is a high degree of inter-individual variation in response to these treatments, whereby patients experience occlusive thromboembolic events, in spite of maintaining an appropriate treatment regimen. This has lead to the notion of antithrombotic "resistance" or "poor responders", which has been a growing concern amongst clinicians and other healthcare providers. Compounding this matter even further, reports of increased cardiovascular risk associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, have revealed additional and unforeseen contributors to myocardial infarction and stroke. With all medications, striking a balance between the potential risks and benefits seems more art than science at times. However, given their widespread use and critical cardiovascular implications, further emphasis has been placed on understanding factors influencing antithrombotic and NSAID therapies. A major aim in cardiovascular pharmacogenetics is the discovery of genetic biomarkers that will allow for prospective screening and individualized prediction of drug efficacy and adverse reactions for these medications (both alone and together) within the context of cardiovascular disease.
Adrenocortical carticnoma (ACC) is a rare malignancy with an incidence of 0.7–2.0 cases/million habitants/year. The diagnosis of malignancy relies on careful investigations of clinical, biological, and imaging features before surgery and pathological examination after tumor removal. Most patients present with steroid hormone excess or abdominal mass effects, but 15% of patients with ACC is initially diagnosed incidentally. After the diagnosis, in order to assess the ACC prognosis and establish an adequate basis for treatment decisions different tools are proposed. The stage classification proposed by the European Network for the Study of Adrenal Tumors (ENSAT) is recommended. Pathology reports define the Weiss score, the resection status and the proliferative index, including the mitotic count and the Ki67 index. As far as the treatment is concerned, in case of tumor limited to the adrenal gland, the complete resection of the tumor is the first option. Most patients benefit from adjuvant mitotane treatment. In metastatic disease, mitotane is the cornerstone of initial treatment, and cytotoxic drugs should be added in case of progression. Recently, the First International Randomized (FIRM-ACT) Trial in metastatic ACC reported the association between mitotane and etoposide/doxorubicin/cisplatin (EDP) as the new standard in first line treatment of ACC. In last years, new targeted therapies, including the IGF-1 receptor inhibitors, have been investigated, but their efficacy remains limited. Thus, new treatment concepts are urgently needed. The ongoing “omic approaches” and next-generation sequencing will improve our understanding of the pathogenesis and hopefully will lead to better therapies. PMID:26191527
Moreno-Acosta, Pablo; Carrillo, Schyrly; Gamboa, Oscar; Romero-Rojas, Alfredo; Acosta, Jinneth; Molano, Monica; Balart-Serra, Joseph; Cotes, Martha; Rancoule, Chloé; Magné, Nicolas
High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored. A total of 53 patients (80.3%) presented a complete response. For these patients, the protein expression levels of GLUT1, CAIX and HKII were overexpressed. A significant difference was observed (P=0.0127) for hemoglobin levels (≤11 g/dl) in responsive compared with non-responsive patients. The expression of GLUT1 is associated with a lower rate of both overall and disease-free survival, with a trend of decreased risk of 1.1x and 1.5x, respectively. Co-expression of GLUT1 and HKII is associated with a decreased trend risk of 1.6x for overall survival. Patients with hemoglobin levels ≤11 g/dl had a 4.3-fold risk (P=0.02) in decreasing both to the rate of overall and disease-free survival. The presence of anemic hypoxia (hemoglobin ≤11 g/dl) and the expression of GLUT1 and/or HKII influence treatment response and are associated with a lower overall and disease-free survival. The present results demonstrated that these biomarkers may be used as predictive markers and suggested that these metabolic pathways can be used as potential novel therapeutic targets. PMID:28101358
Thinggaard, Mikael; McGue, Matt; Jeune, Bernard; Osler, Merete; Vaupel, James W.; Christensen, Kaare
OBJECTIVES To determine whether simple functional indicators are predictors of survival prognosis in very old adults. DESIGN In-person survey conducted over a 3-month period in 1998; assessment of survival over a 15-year follow-up period. SETTING Denmark. PARTICIPANTS All 3,600 Danes born in 1905 and living in Denmark in 1998, were invited to participate regardless of residence and health; 2,262 (63%) participated in the survey: 1,814 (80.2%) in person and 448 (19.8%) through a proxy. MEASUREMENTS Socioeconomic factors, medications and diseases, activities of daily living, physical performance, cognition, depression symptomatology, self-rated health, and all-cause mortality, evaluated as average remaining lifespan and chance of surviving to 100 years. RESULTS Men aged 92 to 93 had an overall 6.0% chance of surviving to 100 years, whereas the chance for women was 11.4%. Being able to rise without use of hands increased the chance for men to 11.2% (95% confidence interval (CI) = 7.7–14.7) and for women to 22.0% (95% CI = 18.9–25.1). When combining this with a Mini-Mental State Examination (MMSE) scores from 28 to 30, the chances were 21.7% (95% CI = 11.5–31.9) for men and 34.2% (95% CI = 24.8–43.5) for women. CONCLUSION Chair stand score combined with MMSE score is a quick and easy way to estimate overall chance of survival in very old adults, which is particularly relevant when treatment with potential side effects for nonacute diseases is considered. J Am Geriatr Soc 64:81–88, 2016. PMID:26782855
Heart failure (HF) is a major and growing health problem in western communities. Recent data indicate that more than 50% of patients with the clinical syndrome of HF have a preserved left ventricular ejection fraction (HF with preserved ejection fraction, HFpEF). In contrast to the calculated expectations, the observed incidence of HF is rising. Despite the fact that the relative proportion of patients with preserved left ventricular function is also increasing, other factors, such as ageing of the population and the concomitant change of compound risk factors may also contribute to the actual rise in the incidence of HF. Patients with HF suffer from reduced exercise capacity, impaired quality of life and also from recurrent hospitalization due to HF. Over the past decades, an increase of recurrent HF events has been documented. In contrast to earlier reports in which HFpEF was considered to be more benign than HF with reduced ejection fraction (HFrEF), recent data suggest that once hospitalized for HF, patients with HFpEF and those with HFrEF have a comparable prognosis in terms of morbidity and mortality. Despite increasing clinical and economic relevance, no treatment has yet been shown to convincingly reduce mortality in HFpEF. In contrast, strategies for improving survival have now been established for HFrEF. The problem of HF will continue to be major challenge for the healthcare systems in western communities; therefore, consolidated clinical research is necessary to further improve therapeutic strategies for HFrEF and to generally establish treatment options for HFpEF.
Bang, Woo-Dae; Kim, Kiwoong; Lee, Yong-Ho; Kwon, Hyukchan; Park, Yongki; Pak, Hui-Nam; Ko, Young-Guk; Lee, Moonhyoung
Purpose Magnetocardiography (MCG) has been proposed as a noninvasive, diagnostic tool for risk-stratifying patients with acute myocardial infarction (AMI). This study evaluated whether MCG predicts long-term prognosis in AMI. Materials and Methods In 124 AMI patients (95 males, mean age 60±11 years), including 39 with ST-elevation myocardial infarction, a 64-channel MCG was performed within 2 days after AMI. During a mean follow-up period of 6.1 years, major adverse cardiac events (MACE) were evaluated. Results MACE occurred in 31 (25%) patients, including 20 revascularizations, 8 deaths, and 3 re-infarctions. Non-dipole patterns were observed at the end of the T wave in every patients. However, they were observed at T-peak in 77% (24/31) and 54% (50/93) of patients with and without MACE, respectively (p=0.03). Maximum current, field map angles, and distance dynamics were not different between groups. In the multivariate analysis, patients with non-dipole patterns at T-peak had increased age- and gender-adjusted hazard ratios for MACE (hazard ratio 2.89, 95% confidence interval 1.20–6.97, p=0.02) and lower cumulative MACE-free survival than those with dipole patterns (p=0.02). Conclusion Non-dipole patterns at T-peak were more frequently observed in patients with MACE and were related to poor long-term prognosis. Thus, repolarization heterogeneity measured by MCG may be a useful predictor for AMI prognosis. PMID:27593860
Chorro, Francisco J; Such-Belenguer, Luis; López-Merino, Vicente
The use of animal models to study cardiovascular disease has made a substantial contribution to increasing our understanding of disease pathogenesis, has led to the development of diagnostic techniques, and has made it possible to verify the effectiveness of different preventative and therapeutic approaches, whether pharmacological or interventional. The main limitations stem from differences between human and experimentally induced pathology, in terms of both genetic regulatory mechanisms and factors that influence cardiovascular function. The experimental models and preparations used in cardiovascular research include those based on isolated cells or tissues or structures immersed in organ baths. The Langendorff system enables isolated perfused hearts to be studied directly under conditions of either no load or controlled loading. In small mammals, a number of models have been developed of cardiovascular conditions that result from spontaneous genetic mutations or, alternatively, that may be induced by specific genomic modification. One of the techniques employed is gene transfer, which can involve the controlled induction of mutations that result in the expression of abnormalities associated with the development of a broad range of different types of cardiovascular disease. Larger animals are used in experimental models in which it is important that physiological regulatory and homeostatic mechanisms are present.
Hamblin, Milton; Chang, Lin; Fan, Yanbo; Zhang, Jifeng; Chen, Y Eugene
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone-receptor superfamily. Originally cloned in 1990, PPARs were found to be mediators of pharmacologic agents that induce hepatocyte peroxisome proliferation. PPARs also are expressed in cells of the cardiovascular system. PPAR gamma appears to be highly expressed during atherosclerotic lesion formation, suggesting that increased PPAR gamma expression may be a vascular compensatory response. Also, ligand-activated PPAR gamma decreases the inflammatory response in cardiovascular cells, particularly in endothelial cells. PPAR alpha, similar to PPAR gamma, also has pleiotropic effects in the cardiovascular system, including antiinflammatory and antiatherosclerotic properties. PPAR alpha activation inhibits vascular smooth muscle proinflammatory responses, attenuating the development of atherosclerosis. However, PPAR delta overexpression may lead to elevated macrophage inflammation and atherosclerosis. Conversely, PPAR delta ligands are shown to attenuate the pathogenesis of atherosclerosis by improving endothelial cell proliferation and survival while decreasing endothelial cell inflammation and vascular smooth muscle cell proliferation. Furthermore, the administration of PPAR ligands in the form of TZDs and fibrates has been disappointing in terms of markedly reducing cardiovascular events in the clinical setting. Therefore, a better understanding of PPAR-dependent and -independent signaling will provide the foundation for future research on the role of PPARs in human cardiovascular biology.
Safaei, Soroush; Bradley, Christopher P; Suresh, Vinod; Mithraratne, Kumar; Muller, Alexandre; Ho, Harvey; Ladd, David; Hellevik, Leif R; Omholt, Stig W; Chase, J Geoffrey; Müller, Lucas O; Watanabe, Sansuke M; Blanco, Pablo J; de Bono, Bernard; Hunter, Peter J
Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well-established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers. In this paper we propose a roadmap for developing an open source cardiovascular circulation model. The model should be registered to the musculo-skeletal system. The computational infrastructure for the cardiovascular model should provide for near real-time computation of blood flow and pressure in all parts of the body. The model should deal with vascular beds in all tissues, and the computational infrastructure for the model should provide links into CellML models of cell function and tissue function. In this work we review the literature associated with 1D blood flow modelling in the cardiovascular system, discuss model encoding standards, software and a model repository. We then describe the coordinate systems used to define the vascular geometry, derive the equations and discuss the implementation of these coupled equations in the open source computational software OpenCMISS. Finally, some preliminary results are presented and plans outlined for the next steps in the development of the model, the computational software and the graphical user interface for accessing the model.
Smith, D F; Hutton, J L; Sandemann, D; Foy, P M; Shaw, M D; Williams, I R; Chadwick, D W
It is not known whether conservative or early aggressive (resective surgery with or without radiotherapy) management is better for tumours presenting with epilepsy. The prognosis of 560 patients with a clinical and CT diagnosis of intrinsic supratentorial tumour was examined retrospectively. Epilepsy was the first symptom in 164 patients. Histological confirmation of diagnosis was available in 391 (70%) of cases. Median survival was 37 months in the group presenting with epilepsy and six months in those presenting with other symptoms (p less than 0.0001). Patients presenting with epilepsy were more likely to have a normal clinical examination, a non-enhancing low density lesion on CT scan and a low grade tumour. From Cox's stepwise proportional hazards model, significant independent variables adversely affecting prognosis were increasing age, focal neurological signs and enhancing CT lesions at diagnosis, non-resective surgery and male sex. Of those presenting with epilepsy 80 patients had surgical treatment within two months of CT diagnosis. The Cox's model failed to identify any beneficial effects for either early resective surgery or radiotherapy. In primary intracerebral tumours with presentations other than epilepsy, resective surgery and radiotherapy were amongst the important factors associated with prolonged survival. Primary intracerebral tumours presenting with epilepsy are relatively benign and their outcome appears to be chiefly determined by clinical factors. PMID:1744647
Taskinen, Minna; Louhimo, Riku; Koivula, Satu; Chen, Ping; Rantanen, Ville; Holte, Harald; Delabie, Jan; Karjalainen-Lindsberg, Marja-Liisa; Björkholm, Magnus; Fluge, Øystein; Pedersen, Lars Møller; Fjordén, Karin; Jerkeman, Mats; Eriksson, Mikael; Hautaniemi, Sampsa; Leppä, Sirpa
Background Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods We analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients. Results We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. Conclusion COMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL. Trial Registration ClinicalTrials.gov NCT01502982 PMID:24625556
Xin, Xiaoyan; Zeng, Xianqin; Gu, Huajian; Li, Min; Tan, Huaming; Jin, Zhishan; Hua, Teng; Shi, Rui; Wang, Hongbo
CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) plays an important role in tumor progression and a number of studies have suggested that it is an indicator of tumor prognosis. This current meta-analysis systematically reevaluated the predictive potential of CD147/EMMPRIN in various cancers. We searched PubMed and Embase databases to screen the literature. Fixed-effect and random-effect meta-analytical techniques were used to correlate CD147 expression with outcome measures. A total of 53 studies that included 68 datasets were eligible for inclusion in the final analysis. We found a significant association between CD147/EMMPRIN overexpression and adverse tumor outcomes, such as overall survival, disease-specific survival, progression-free survival, metastasis-free survival or recurrence-free survival, irrespective of the model analysis. In addition, CD147/EMMPRIN overexpression predicted a high risk for chemotherapy drugs resistance. CD147/EMMPRIN is a central player in tumor progression and predicts a poor prognosis, including in patients who have received chemo-radiotherapy. Our results provide the evidence that CD147/EMMPRIN could be a potential therapeutic target for cancers. PMID:27608940
Sweeney, Shaun; Air, Tracy; Zannettino, Lana; Shah, Sonal S.; Galletly, Cherrie
The link between childhood trauma and/or adversity and risk of psychosis is well known. Our aim was to determine the prevalence of childhood trauma and/or adversity in people who have psychotic disorders and to investigate the association between childhood trauma and/or adversity and a range of social and health measures. Participants (n = 391, 42% male) were specifically asked about any experience of childhood trauma and/or adversity. Respondents provided information about education, employment, physical health, and health service utilization. Univariate analyses revealed that childhood trauma and/or adversity was associated with poorer levels of self-reported physical health and social problems. This includes the experience of chronic pain, headaches, arthritis, asthma, and victimization/stigma in men. Participants with a childhood trauma and/or adversity history indicated higher rates of lifetime suicide attempts with women reporting more lifetime depressive symptoms. Multivariate analyses revealed differing profiles in relation to physical and psychological health variable between males and females. Males with the experience of childhood trauma and/or adversity were significantly more likely to report cardiovascular/stroke issues, migraines and anhedonia. Females with the experience of childhood trauma and/or adversity were more likely to report a lifetime history of elevated mood and to be married or in a de facto relationship. There has been very little research into the assessment and treatment of the effects of childhood trauma and/or adversity in adults with psychosis. Childhood trauma and/or adversity may contribute to higher rates of self-reported poor health in men and is associated with increased depression in women. Our findings suggest that interventions to address the effects of past trauma are urgently needed. PMID:26635676
Sweeney, Shaun; Air, Tracy; Zannettino, Lana; Galletly, Cherrie
The link between childhood trauma and/or adversity and risk of psychosis is well known. Our aim was to determine the prevalence of childhood trauma and/or adversity in people who have psychotic disorders and to investigate the association between childhood trauma and/or adversity and a range of social and health measures. Participants (n = 391, 42% male) were specifically asked about any experience of childhood trauma and/or adversity. Respondents provided information about education, employment, physical health, and health service utilization. Univariate analyses revealed that childhood trauma and/or adversity was associated with poorer levels of self-reported physical health and social problems. This includes the experience of chronic pain, headaches, arthritis, asthma, and victimization/stigma in men. Participants with a childhood trauma and/or adversity history indicated higher rates of lifetime suicide attempts with women reporting more lifetime depressive symptoms. Multivariate analyses revealed differing profiles in relation to physical and psychological health variable between males and females. Males with the experience of childhood trauma and/or adversity were significantly more likely to report cardiovascular/stroke issues, migraines and anhedonia. Females with the experience of childhood trauma and/or adversity were more likely to report a lifetime history of elevated mood and to be married or in a de facto relationship. There has been very little research into the assessment and treatment of the effects of childhood trauma and/or adversity in adults with psychosis. Childhood trauma and/or adversity may contribute to higher rates of self-reported poor health in men and is associated with increased depression in women. Our findings suggest that interventions to address the effects of past trauma are urgently needed.
Slopen, Natalie; Loucks, Eric B.; Appleton, Allison A.; Kawachi, Ichiro; Kubzansky, Laura D.; Non, Amy L.; Buka, Stephen; Gilman, Stephen E.
Background Children exposed to social adversity carry a greater risk of poor physical and mental health into adulthood. This increased risk is thought to be due, in part, to inflammatory processes associated with early adversity that contribute to the etiology of many adult illnesses. The current study asks whether aspects of the prenatal social environment are associated with levels of inflammation in adulthood, and whether prenatal and childhood adversity both contribute to adult inflammation. Methods We examined associations of prenatal and childhood adversity assessed through direct interviews of participants in the Collaborative Perinatal Project between 1959–1974 with blood levels of C-reactive protein in 355 offspring interviewed in adulthood (mean age=42.2 years). Linear and quantile regression models were used to estimate the effects of prenatal adversity and childhood adversity on adult inflammation, adjusting for age, sex, and race and other potential confounders. Results In separate linear regression models, high levels of prenatal and childhood adversity were associated with higher CRP in adulthood. When prenatal and childhood adversity were analyzed together, our results support the presence of an effect of prenatal adversity on (log) CRP level in adulthood (β=0.73, 95% CI: 0.26, 1.20) that is independent of childhood adversity and potential confounding factors including maternal health conditions reported during pregnancy. Supplemental analyses revealed similar findings using quantile regression models and logistic regression models that used a clinically-relevant CRP threshold (>3 mg/L). In a fully-adjusted model that included childhood adversity, high prenatal adversity was associated with a 3-fold elevated odds (95% CI: 1.15, 8.02) of having a CRP level in adulthood that indicates high risk of cardiovascular disease. Conclusions Social adversity during the prenatal period is a risk factor for elevated inflammation in adulthood independent of
Ho, Edwin; Karimi Galougahi, Keyvan; Liu, Chia-Chi; Bhindi, Ravi; Figtree, Gemma A
Oxidative stress is a common mediator in pathogenicity of established cardiovascular risk factors. Furthermore, it likely mediates effects of emerging, less well-defined variables that contribute to residual risk not explained by traditional factors. Functional oxidative modifications of cellular proteins, both reversible and irreversible, are a causal step in cellular dysfunction. Identifying markers of oxidative stress has been the focus of many researchers as they have the potential to act as an "integrator" of a multitude of processes that drive cardiovascular pathobiology. One of the major challenges is the accurate quantification of reactive oxygen species with very short half-life. Redox-sensitive proteins with important cellular functions are confined to signalling microdomains in cardiovascular cells and are not readily available for quantification. A popular approach is the measurement of stable by-products modified under conditions of oxidative stress that have entered the circulation. However, these may not accurately reflect redox stress at the cell/tissue level. Many of these modifications are "functionally silent". Functional significance of the oxidative modifications enhances their validity as a proposed biological marker of cardiovascular disease, and is the strength of the redox cysteine modifications such as glutathionylation. We review selected biomarkers of oxidative stress that show promise in cardiovascular medicine, as well as new methodologies for high-throughput measurement in research and clinical settings. Although associated with disease severity, further studies are required to examine the utility of the most promising oxidative biomarkers to predict prognosis or response to treatment.
Sasaki, Nobuo; Ozono, Ryoji; Edahiro, Yoshinobu; Ishii, Kiyomi; Seto, Ayako; Okita, Tomomi; Teramen, Kazushi; Fujiwara, Saeko; Kihara, Yasuki
Obstructive sleep apnea syndrome (OSAS) is a risk factor for cardiovascular events. However, it is unclear how OSAS contributes to the events. We investigated the impact of non-dipping on the incidence of cardiovascular events in a retrospective cohort study comprising 251 patients with OSAS. OSAS was diagnosed by overnight polysomnography and all patients underwent 24-h ambulatory blood pressure monitoring. Non-dipping was diagnosed when reduction in sleep blood pressure was <10% of awake blood pressure. Over a mean 43-month follow-up period, 15 patients (6.0%) developed cardiovascular events including stroke, heart failure, and ischemic heart disease. Significantly higher cardiovascular events were observed in the non-dipping group than those without it by Kaplan-Meier analyses. Cox regression analysis revealed that the presence of non-dipping was significantly and independently associated with the incidence of cardiovascular events (hazard ratio, 3.88; 95% confidence interval, 1.19-17.41; p < 0.05), after adjusting for severity of OSAS, and CPAP therapy. Thus, non-dipping was a marker for a poor prognosis in patients with OSAS.
White, Ronald J.; Leonard, Joel I.; Srinivasan, R. Srini; Charles, John B.
The purpose of NASA's Extended Duration Orbiter program is a gradual extension of the capabilities of the Space Shuttle Orbiter beyond its current 7-10 day limit on mission duration, as warranted by deepening understanding of the long-term physiological effects of weightlessness. Attention is being given to the cardiovascular problem of orthostatic tolerance loss due to its adverse effects on crew performance and health during reentry and initial readaptation to earth gravity. An account is given of the results of the application of proven mathematical models of circulatory and cardiovascular systems under microgravity conditions.
Zou, Cong; Hu, Honglin
Pioglitazone and other thiazolidinediones (TZDs) initially showed great promise as unique receptor-mediated oral therapy for type 2 diabetes, but a host of serious side effects, primarily cardiovascular, have limited their utility. It is crucial at this point to perform a risk- benefit analysis to determine what role pioglitazone should play in our current treatment of type 2 diabetes and where the future of this class of drugs is headed. This review provides a comprehensive overview of the present literature. Clinical data currently available indicate that pioglitazone is an effective and generally well-tolerated treatment option for use in patients with type 2 diabetes. Pioglitazone can still reduce adverse cardiovascular risk.
Visca, Dina; Aiello, Marina; Chetta, Alfredo
Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them. On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well. Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage. We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema. Patients with emphysema may differ among COPD population even in terms of cardiovascular function. PMID:24369007
Although ghrelin was initially associated with regulation of appetite, the cardiovascular system has also been recognized as a potentially important target for its effects. Moreover, experimental and a limited number of clinical studies suggest a potential role for ghrelin in the treatment of congestive heart failure. So far, reported cardiovascular effects of growth hormone secretagogues and/or ghrelin include lowering of peripheral resistance, either direct at the vascular level and/or by modulating sympathetic nervous activity. Other observed effects indicate possible improvement of contractility and cardioprotective and anti-inflammatory effects both in vivo and in vitro. Taken together, these results offer an interesting perspective on the future where further studies aiming at evaluating a role of growth hormone secretagogues and ghrelin in the treatment of cardiovascular disease are warranted.
Aspelund, Aleksanteri; Robciuc, Marius R; Karaman, Sinem; Makinen, Taija; Alitalo, Kari
The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease.
Mulder, Willem J M; Cormode, David P; Hak, Sjoerd; Lobatto, Mark E; Silvera, Stephane; Fayad, Zahi A
Targeted imaging and therapeutics is becoming a field of prime importance in the study and treatment of cardiovascular disease; it promises to enable early diagnosis, promote improved understanding of pathology, and offer a way to improve therapeutic efficacy. Agents, particularly for cardiovascular disease, have been reported to permit the in vivo imaging, by multiple modalities, of macrophages, vascular targets such as vascular cell adhesion molecule 1, and markers for angiogenesis such as alpha(v)beta(3) integrin. In this Article, we first discuss the general concept of multimodality nanoparticles and then focus in greater depth on their clinical application for molecular imaging and therapy. Lastly, several examples of cardiovascular applications are discussed, including combined imaging and therapy approaches.
Capili, Bernadette; Anastasi, Joyce K.; Ogedegbe, Olugbenga
The incidence of cardiovascular disease (CVD) is increasing in HIV-infected people. Risk factors such as hyperlipidemia, impaired glucose tolerance, and insulin resistance have become common. CVD in HIV may also be related to non-traditional risk factors including accumulation of visceral fat, inflammation secondary to HIV, and effects of some antiretroviral drugs. This cross-sectional study described the CVD risk factors of 123 adults living with HIV and calculated the 10-year estimate for general cardiovascular risk score. Results showed that approximately 25% of the participants were considered to be at high risk for developing CVD in the next 10 years. Increased waist circumference and longer duration of smoking habit were associated with elevated general cardiovascular risk scores. Similar to the general population, most of the identified risks could be modified through lifestyle management. PMID:21277230
Mozos, Ioana; Caraba, Alexandru
Cardiovascular diseases are the main causes of mortality. Sudden cardiac death may also appear in athletes, due to underlying congenital or inherited cardiac abnormalities. The electrocardiogram is used in clinical practice and clinical trials, as a valid, reliable, accessible, inexpensive method. The aim of the present paper was to review electrocardiographic (ECG) signs associated with cardiovascular mortality and the mechanisms underlying those associations, providing a brief description of the main studies in this area, and consider their implication for clinical practice in the general population and athletes. The main ECG parameters associated with cardiovascular mortality in the present paper are the P wave (duration, interatrial block, and deep terminal negativity of the P wave in V1), prolonged QT and Tpeak-Tend intervals, QRS duration and fragmentation, bundle branch block, ST segment depression and elevation, T waves (inverted, T wave axes), spatial angles between QRS and T vectors, premature ventricular contractions, and ECG hypertrophy criteria. PMID:26257460
Dominic, Elizabeth A; Ramezani, Ali; Anker, Stefan D; Verma, Mukesh; Mehta, Nehal; Rao, Madhumathi
The global epidemic of cardiovascular disease remains the leading cause of death in the USA and across the world. Functional and structural integrity of mitochondria are essential for the physiological function of the cardiovascular system. The metabolic adaptation observed in normal heart is lost in the failing myocardium, which becomes progressively energy depleted leading to impaired myocardial contraction and relaxation. Uncoupling of electron transfer from ATP synthesis leads to excess generation of reactive species, leading to widespread cellular injury and cardiovascular disease. Accumulation of mitochondrial DNA mutation has been linked to ischaemic heart disease, cardiomyopathy and atherosclerotic vascular disease. Mitochondria are known to regulate apoptotic and autophagic pathways that have been shown to play an important role in the development of cardiomyopathy and atherosclerosis. A number of pharmacological and non-pharmacological treatment options have been explored in the management of mitochondrial diseases with variable success.
Varna, Mariana; Xuan, Hoa V; Fort, Emmanuel
Although originally applied in the field of oncology, recent results have illustrated the considerable potential of gold nanoparticles (GNPs) in the imaging of cardiovascular diseases (CVDs). CVDs represent the leading cause of mortality and disability in the world. The principal cause underpinning CVDs is atherosclerosis, which develops into mid and large blood vessels, often leading to severe complications. Thanks to their unique physicochemical properties, GNPs have drawn much attention from the research community in cardiovascular imaging. Thus, the optical properties of GNPs have led to their utilization as contrast agents for optical or X-ray imaging modalities allowing the detection of atherosclerotic plaques, intravascular thrombus, or fibrotic tissue. In this study, we detail the most promising preclinical scientific progresses based on the use of GNPs for imaging in cardiovascular field and their improvements for a potential clinical application. For further resources related to this article, please visit the WIREs website.
Visca, Dina; Aiello, Marina; Chetta, Alfredo
Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them. On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well. Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage. We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema. Patients with emphysema may differ among COPD population even in terms of cardiovascular function.
Bolívar-Mejía, Adrián; Rodríguez-Morales, Alfonso J; Paniz-Mondolfi, Alberto E; Delgado, Olinda
Toxocariasis is a parasitic infection produced by helminths that cannot reach their adult stage in humans. For their etiological species (Toxocara canis and Toxocara cati), man is a paratenic host. Infection by such helminths can produce a variety of clinical manifestations, such as: visceral larvae migrans syndrome, ocular larvae migrans syndrome and covert toxocariasis. In the visceral larvae migrans syndrome, the organs that are mainly involved include liver, lungs, skin, nervous system, muscles, kidneys and the heart. Regarding the latter, the importance of cardiovascular manifestations in toxocariasis, as well as its clinical relevance, has increasingly begun to be recognized. The current article is based on a systematic information search, focused mainly on the clinical and pathological aspects of cardiovascular manifestations in toxocariasis, including its pathophysiology, laboratory findings, diagnosis and therapeutical options, with the objective of highlighting its importance as a zoonosis and its relevance to the fields of cardiovascular medicine in adults and children.
Mondy, Kristin; Tebas, Pablo
The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.
Raven, Peter; Schneider, Sue
It was apparent that the bed-rest and spaceflight data indicated that decreases in plasma volume and cardiac atrophy along with cardiac remodeling were fundamental changes which predisposed many astronauts to post flight orthostatic intolerance. Despite the recently acquired in-flight and post-flight muscle sympathetic nerve activity findings suggesting that the sympathetic nerve responses were appropriate there remains significant contrary data from bed-rest studies, post- flight stand tests and hind-limb unweighted rat studies that suggest that the vasoconstrictive responses were compromised at least insufficient in susceptible individuals. The key issues raised is whether a diminished increase in sympathetic activity from baseline without changes in 254 First Biennial Space Biomedical Investigators'Workshop Cardiovascular peak response or receptor adaptations is an abnormal response or is an individual variance of response to the accentuated decrease in stroke volume. Data relating autonomic neural control of heart rate were presented to suggest that the vagal and sympathetic control of heart rate was attenuated. Also, bed-rest and space flight induced attenuated baroreflex control of heart rate was shown to be restored to pre-bedrest function by one bout of maximal dynamic exercise. However, these data were confounded by relying on the use of R-R interval as a measure of efferent responses of the baroreflex during a condition in which the baseline heart rate was changed. Clearly the idea that the autonomic control of heart rate may be changed by microgravity needs further investigation. This direction is suggested despite the fact that in the triple product (HR x SV x TPR = MAP) assessment of the regulation of arterial blood pressure during orthostasis the role of the HR reflex may be less influential than that associated. with cardiac atrophy (SV changes) and aberrant sympathetic vasoconstriction (resistance) changes. Although sympathetic nerve activity
The presence of cardiovascular disease (CVD) in Type 1 diabetes largely impairs life expectancy. Hyperglycemia leading to an increase in oxidative stress is considered to be the key pathophysiological factor of both micro- and macrovascular complications. In Type 1 diabetes, the presence of coronary calcifications is also related to coronary artery disease. Cardiac autonomic neuropathy, which significantly impairs myocardial function and blood flow, also enhances cardiac abnormalities. Also hypoglycemic episodes are considered to adversely influence cardiac performance. Intensive insulin therapy has been demonstrated to reduce the occurrence and progression of both micro- and macrovascular complications. This has been evidenced by the Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC) study. The concept of a metabolic memory emerged based on the results of the study, which established that intensified insulin therapy is the standard of treatment of Type 1 diabetes. Future therapies may also include glucagon-like peptide (GLP)-based treatment therapies. Pilot studies with GLP-1-analogues have been shown to reduce insulin requirements. PMID:24165454
Menon, Madhav C; Ix, Joachim H
Recent epidemiologic studies have linked higher serum phosphorus concentrations to cardiovascular disease (CVD) events and mortality. This association has been identified in the general population and in those with chronic kidney disease (CKD). The risk of adverse outcomes appears to begin with phosphorus concentrations within the upper limit of the normal reference range. Multiple experimental studies have suggested pathogenetic mechanisms that involve direct and indirect effects of high phosphorus concentrations to explain these associations. Drawing from these observations, guideline-forming agencies have recommended that serum phosphorus concentrations be maintained within the normal reference range in patients with CKD and that dietary phosphorus restriction or use of intestinal phosphate binders should be considered to achieve this goal. However, outside the dialysis population, the links between dietary phosphorus intake and serum phosphorus concentrations, and dietary phosphorus intake and CVD events, are uncertain. With specific reference to the nondialysis populations, this review discusses the available data linking dietary phosphorus intake with serum phosphorus concentrations and CVD events.
Kanjanarat, Penkarn; Winterstein, Almut G; Johns, Thomas E; Hatton, Randy C; Gonzalez-Rothi, Ricardo; Segal, Richard
A literature review was conducted to identify the drug classes, types of errors, and types of adverse outcomes related to preventable adverse drug events (pADEs). Studies were identified by keyword search of MEDLINE and International Pharmaceutical Abstracts and by a manual search. The search was limited to peer-reviewed literature reporting pADEs in hospitalized patients and the frequencies of at least one pADE characteristic. The frequencies of pADEs and their characteristics were summarized using median and range. Ten studies published between 1994 and 2001 were included in the review. The reported median frequency of pADEs was 1.8% (range, 1.3-7.8%), and the median preventability rate of ADEs in the hospitals was 35.2% (range, 18.7-73.2%). Cardiovascular drugs were implicated for 17.9% of pADEs (range, 4.3-28.1%). Most pADEs occurred in the prescribing stage of the medication-use process and were dose related. Inappropriate prescribing decisions and patient monitoring were the most frequently identified causes of pADEs. The most common adverse outcomes were allergic reactions, hepatic or renal problems, cardiovascular problems, hematologic problems and bleeding, and central nervous system problems. Frequently reported examples of pADEs included antihypertensive overdose associated with bradycardia or hypotension, antiinfectives prescribed despite a history of allergy, warfarin overdose and inappropriate monitoring resulting in hemorrhage, and opioid overdose or underdose associated with respiratory depression or poor pain control, respectively. Despite the heterogeneity of pADEs, the results of this literature review suggest that a few types of drugs, errors, and adverse outcomes constitute a substantial proportion of pADEs. Targeting these high-priority areas could significantly reduce the overall frequency of pADEs.
This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence.
Following a workshop on "Innovations in Employment Testing that Improve Validity and Reduce Adverse Impact," the City of Louisville (Kentucky) implemented a strategy to develop a comprehensive testing and recruiting program for police recruits. To improve candidate expectations and preparation, the following activities were undertaken:…
Skepticism about the power of education challenges the educational administrator to (1) attain a better understanding of the sources of dissatisfaction and their implications for change, (2) learn to cope with adversity and make constructive use of it, and (3) define the leadership requirements needed to address education's problems. (MB)
The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...
Tartrazine, a common additive in foods and drugs, often causes adverse reactions such as recurrent urticaria, angioedema, and asthma and is frequently implicated in hyperkinesis. This paper summarizes the recent literature on the subject and outlines a practical approach for the practicing physician to diagnose and treat these patients in an optimal manner.
Schlueter, Lisa J.; Watamura, Sarah Enos
Severe and chronic stress in early childhood has enormous physical and mental health costs across an individual's lifespan. Unfortunately, exposure to early life adversity is common, and costs accrue to individuals and society. This article highlights several promising approaches to buffer children from the negative health consequences associated…
Observational study is necessary for the evaluation of drug effectiveness in clinical practice. In recent years, the use of spontaneous reporting systems (SRS) for adverse drug reactions has increased and they have become an important resource for regulatory science. SRS, being the largest and most well-known databases worldwide, are one of the primary tools used for postmarketing surveillance and pharmacovigilance. To analyze SRS, the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report Database (JADER) are reviewed. Authorized pharmacovigilance algorithms were used for signal detection, including the reporting odds ratio. An SRS is a passive reporting database and is therefore subject to numerous sources of selection bias, including overreporting, underreporting, and a lack of a denominator. Despite the inherent limitations of spontaneous reporting, SRS databases are a rich resource and data mining index that provide powerful means of identifying potential associations between drugs and their adverse effects. Our results, which are based on the evaluation of SRS databases, provide essential knowledge that could improve our understanding of clinical issues.
Ameen, S; Entabi, M; Lee, N; Stavrakoglou, A
The authors describe two separate cases of skin eruption following intravitreal bevacizumab injection with evidence to suggest that these were adverse drug reactions to bevacizumab. The authors also discuss how each case was treated and report on the final outcome. PMID:22715260
A detailed checklist and timeline for ensuring due process are provided for adverse personnel actions, and the need to supplement this with expert, same-jurisdiction legal advice is stressed. This approach emphasizes the importance of treating due process as an ethical as well as a legal requirement. (SLD)
The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be mea...
Wacker, T; Eckert, S
Laser trabeculoplasty is a simple method for treating glaucoma and ocular hypertension and has few adverse effects. There are different laser systems for reducing the intraocular pressure of patients with glaucoma and ocular hypertension. Complications include transient intraocular pressure elevation, iritis, and anterior synechiae.
"Resilience" is the capacity for moving ahead under adverse circumstances. School superintendents are advised to stay upbeat and mindful of "both-and" opportunities; stay focused on what they care about; remain flexible and tolerant of ambiguity; be proactive, not reactive; and apply resilience-conserving strategies during…
Jiang, Yu; Shi, Xingjie; Zhao, Qing; Krauthammer, Michael; Rothberg, Bonnie E Gould; Ma, Shuangge
Multiple types of genetic, epigenetic, and genomic changes have been implicated in cutaneous melanoma prognosis. Many of the existing studies are limited in analyzing a single type of omics measurement and cannot comprehensively describe the biological processes underlying prognosis. As a result, the obtained prognostic models may be less satisfactory, and the identified prognostic markers may be less informative. The recently collected TCGA (The Cancer Genome Atlas) data have a high quality and comprehensive omics measurements, making it possible to more comprehensively and more accurately model prognosis. In this study, we first describe the statistical approaches that can integrate multiple types of omics measurements with the assistance of variable selection and dimension reduction techniques. Data analysis suggests that, for cutaneous melanoma, integrating multiple types of measurements leads to prognostic models with an improved prediction performance. Informative individual markers and pathways are identified, which can provide valuable insights into melanoma prognosis.
Bode, H J
The qualification of a person to drive a motor vehicle is the presupposition for the required permission. The prognosis on future human behaviour, which is indispensible for a judgement on such a qualification, is difficult. Only in a few of these cases a clear "good"-prognosis or "bad"-prognosis can be found out. Frequently only an "uncertain"-prognosis is to be justified as a matter of fact. It is only to be said by the regulations of law, whether in cases of uncertain qualification prognosis the driver's licence should be given or denied or whether a driver's licence already given should be withdrawn or not. Starting points for theory and dogmatics on prognosis-decisions due to law and orientated in the knowledge of empiric sciences are to be found in administrative law as well as in criminal law. For example: penal regulations which call for prognosis should be interpreted in the manner that as a sanction (only to be imposed in cases of "bad"-prognosis) the milder measure is to be used at first. Only after an unsuccessful attempt with this milder measure it is allowed to take a more incisive measure (Frisch). In planning law the dilemma with prognosis should be overcome by reflexive feedback within the scope of a new type of procedural law, which would make a process of learning and evaluation possible and enforcable. From these starting points common legal principles on a "test-method" can be developed, which may be used in cases of "uncertain"-prognosis. Such a test-method may help for example to decide on execution relaxations due to the Law on Execution of the Sentence (OLG Celle). The decree on driver's licences on probation (valid since 1.11.1986) contains the most extensive regulations concerning the application of test-methods within driver's licences law. The solution of the problem shown there should be extended: Not only the first driver's licence should only be given on probation but also a renewed one. Even motorists coming conspicuous after the
Saikus, Christina E.; Lederman, Robert J.
Cardiovascular magnetic resonance (CMR) combines excellent soft-tissue contrast, multiplanar views, and dynamic imaging of cardiac function without ionizing radiation exposure. Interventional cardiovascular magnetic resonance (iCMR) leverages these features to enhance conventional interventional procedures or to enable novel ones. Although still awaiting clinical deployment, this young field has tremendous potential. We survey promising clinical applications for iCMR. Next, we discuss the technologies that allow CMR-guided interventions and, finally, what still needs to be done to bring them to the clinic. PMID:19909937
Cengel, Atiye; Sahinarslan, Asife
Endothelium has many important functions including the control of blood-tissue permeability and vascular tonus, regulation of vascular surface properties for homeostasis and inflammation. Nitric oxide is the chief molecule in regulation of endothelial functions. Nitric oxide deficiency, which is also known as endothelial dysfunction, is the first step for the occurrence of many disease states in cardiovascular system including heart failure, hypertension, dyslipidemia, insulin resistance, diabetes mellitus, hyperhomocysteinemia and smoking. This review deals with the importance of nitric oxide for cardiovascular system. It also includes the latest improvements in the diagnosis and treatment of endothelial dysfunction.
Vazquez-Prieto, Marcela A; Miatello, Roberto M
Epidemiological studies have shown an inverse relationship between consumption of fruits and vegetables and the risk of cardiovascular disease. Phytochemicals are non-nutritional chemical compounds found in small quantities in fruits and vegetables with known health benefits. Among them, organosulfides are present mainly in garlic and onion characterized by their antioxidant and anti-inflammatory properties, and isothiocyanates in cruciferous vegetables have anticarcinogenic effects in experimental models. In this review, we are focusing on the main biological studies regarding the beneficial effect of organosulfur compounds on their protection against cardiovascular disease.
Epstein, Jonathan A; Aghajanian, Haig; Singh, Manvendra K
Semaphorins were originally identified as neuronal guidance molecules mediating their attractive or repulsive signals by forming complexes with plexin and neuropilin receptors. Subsequent research has identified functions for semaphorin signaling in many organs and tissues outside of the nervous system. Vital roles for semaphorin signaling in vascular patterning and cardiac morphogenesis have been demonstrated, and impaired semaphorin signaling has been associated with various human cardiovascular disorders, including persistent truncus arteriosus, sinus bradycardia and anomalous pulmonary venous connections. Here, we review the functions of semaphorins and their receptors in cardiovascular development and disease and highlight important recent discoveries in the field.
Barker, D J
Low birthweight, thinness and short body length at birth are now known to be associated with increased rates of cardiovascular disease and non-insulin dependent diabetes in adult life. The fetal origins hypothesis proposes that these diseases originate through adaptations which the fetus makes when it is undernourished. These adaptations may be cardiovascular, metabolic or endocrine. They permanently change the structure and function of the body. Prevention of the diseases may depend on prevention of imbalances in fetal growth or imbalances between prenatal and postnatal growth, or imbalances in nutrient supply to the fetus.
Pacher, Pal; Kecskemeti, Valeria
The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na+, Ca2+ and K+ channels often leading to life-threatening arrhythmia. To overcome the toxicity of old generation of antidepressants and antipsychotics, selective serotonin reuptake inhibitor antidepressants (SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxin) and several new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) were introduced during the past decade. Although these new compounds are not more effective in treating psychiatric disorders than older medications, they gained incredible popularity since they have been reported to have fewer and more benign side effect profile (including cardiovascular) than predecessors. Surprisingly, an increasing number of case reports have demonstrated that the use of SSRIs and new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) is associated with cases of arrhythmias, prolonged QTc interval on electrocardiogram (ECG) and orthostatic hypotension in patients lacking cardiovascular disorders, raising new concerns about the putative cardiovascular safety of these compounds. In agreement with these clinical reports these new compounds indeed show marked cardiovascular depressant effects in different mammalian and human cardiovascular preparations by inhibiting cardiac and vascular Na+, Ca2+ and K+ channels. Taken together, these results suggest that the new generation of antidepressants and antipsychotics also have clinically important cardiac as well as vascular effects. Clinicians should be more vigilant about these potential adverse reactions and ECG control may be suggested during therapy, especially in patients with
Dalton, Lori A.; Yousefi, Mohammadmahdi R.
Cancer prognosis prediction is typically carried out without integrating scientific knowledge available on genomic pathways, the effect of drugs on cell dynamics, or modeling mutations in the population. Recent work addresses some of these problems by formulating an uncertainty class of Boolean regulatory models for abnormal gene regulation, assigning prognosis scores to each network based on intervention outcomes, and partitioning networks in the uncertainty class into prognosis classes based on these scores. For a new patient, the probability distribution of the prognosis class was evaluated using optimal Bayesian classification, given patient data. It was assumed that (1) disease is the result of several mutations of a known healthy network and that these mutations and their probability distribution in the population are known and (2) only a single snapshot of the patient’s gene activity profile is observed. It was shown that, even in ideal settings where cancer in the population and the effect of a drug are fully modeled, a single static measurement is typically not sufficient. Here, we study what measurements are sufficient to predict prognosis. In particular, we relax assumption (1) by addressing how population data may be used to estimate network probabilities, and extend assumption (2) to include static and time-series measurements of both population and patient data. Furthermore, we extend the prediction of prognosis classes to optimal Bayesian regression of prognosis metrics. Even when time-series data is preferable to infer a stochastic dynamical network, we show that static data can be superior for prognosis prediction when constrained to small samples. Furthermore, although population data is helpful, performance is not sensitive to inaccuracies in the estimated network probabilities. PMID:27127404
Añón, Ramón; Boscá, Marta Maia; Sanchiz, Vicente; Tosca, Joan; Almela, Pedro; Amorós, Cirilo; Benages, Adolfo
). Stenosis was the only endoscopic finding that appeared more frequently in seriously ill patients than in slightly ill patients (66.6% vs 17.3%, P = 0.017). CONCLUSION: The factors that can predict poor prognosis of IC are the absence of hematochezia, tachycardia and peritonism, anemia and hyponatremia and stenosis. PMID:16937472
Flattet, Yves; Garin, Nicolas; Serratrice, Jacques; Perrier, Arnaud; Stirnemann, Jérome; Carballo, Sebastian
Background Acute exacerbations are the leading causes of hospitalization and mortality in patients with COPD. Prognostic tools for patients with chronic COPD exist, but there are scarce data regarding acute exacerbations. We aimed to identify the prognostic factors of death and readmission after exacerbation of COPD. Methods This was a retrospective study conducted in the Department of Internal Medicine of Geneva University Hospitals. All patients admitted to the hospital with a diagnosis of exacerbation of COPD between 2008 and 2011 were included. The studied variables included comorbidities, Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity classification, and biological and clinical parameters. The main outcome was death or readmission during a 5-year follow-up. The secondary outcome was death. Survival analysis was performed (log-rank and Cox). Results We identified a total of 359 patients (195 men and 164 women, average age 72 years). During 5-year follow-up, 242 patients died or were hospitalized for the exacerbation of COPD. In multivariate analysis, age (hazard ratio [HR] 1.03, 95% CI 1.02–1.05; P<0.0001), severity of airflow obstruction (forced expiratory volume in 1 s <30%; HR 4.65, 95% CI 1.42–15.1; P=0.01), diabetes (HR 1.47, 95% CI 1.003–2.16; P=0.048), cancer (HR 2.79, 95% CI 1.68–4.64; P<0.0001), creatinine (HR 1.003, 95% CI 1.0004–1.006; P=0.02), and respiratory rate (HR 1.03, 95% CI 1.003–1.05; P=0.028) on admission were significantly associated with the primary outcome. Age, cancer, and procalcitonin were significantly associated with the secondary outcome. Conclusion COPD remains of ominous prognosis, especially after exacerbation requiring hospitalization. Baseline pulmonary function remains the strongest predictor of mortality and new admission. Demographic factors, such as age and comorbidities and notably diabetes and cancer, are closely associated with the outcome of the patient. Respiratory rate at admission
Nussinovitch, Udi; de Carvalho, Jozélio Freire; Pereira, Rosa Maria R; Shoenfeld, Yehuda
Glucocorticoids (GC) are drugs commonly used, by approximately 1% of the total adult population as anti-inflammatory and immunosuppressive therapies for asthma, inflammatory bowel disease, dermatological, ophthalmic, neurological, and rheumatic autoimmune diseases. Supporting evidence exists of GC use in both immune mediated and non-immune mediated heart disease. The molecular mechanisms by which GC induces immune-modulation and direct cardioprotection, are complex and not fully understood. We review herein, the current knowledge of GC use in various immune-mediated or non-immune mediated cardiovascular conditions. GC have been investigated in autoimmune, inflammatory and idiopathic heart diseases such as atrio-ventricular conduction abnormalities, rheumatic fever, myocarditis, dilated cardiomyopathy, Churg-Strauss syndrome, Kawasaki disease and sarcoidosis. GC therapy has been studied in non-autoimmune and non-inflammatory indications such as acute myocardial infarction, angina, postpericardiotomy syndrome and other pericardial diseases, endocarditis and cardiac amyloidosis, as well as in invasive cardiology, coronary interventions, and cardiopulmonary-bypass surgery. Despite GC's role as natural, physiologic regulators of the immune system, cardiovascular adverse outcomes may occur. Some of the well-known side effects of GC therapy involve bone, metabolic, and cardiovascular systems and include osteoporosis, fractures, dyslipidemia, diabetes, obesity, and hypertension.
Eyres, Michael F.; Chisholm, Alexandra; Brown, Rachel C.
Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined. Observational evidence suggests that consumption of coconut flesh or squeezed coconut in the context of traditional dietary patterns does not lead to adverse cardiovascular outcomes. However, due to large differences in dietary and lifestyle patterns, these findings cannot be applied to a typical Western diet. Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease. PMID:26946252
Latimer, James; Batty, Jonathan A; Neely, R Dermot G; Kunadian, Vijay
Reducing plasma levels of low-density lipoprotein cholesterol (LDL-C) remains the cornerstone in the primary and secondary prevention of cardiovascular disease. However, lack of efficacy and adverse effects mean that a substantial proportion of patients fail to achieve acceptable LDL-C levels with currently available lipid-lowering drugs. Over the last decade, inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic strategy to reduce residual cardiovascular disease risk. Binding of PCSK9 to the LDL receptor targets the receptor for lysosomal degradation. The recognition that inhibition of PCSK9 increases LDL receptor activity has led to the development of a number of approaches to directly target PCSK9. Numerous monoclonal antibodies against PCSK9 are currently being evaluated in phase 3 trials, involving various patient categories on different background lipid-lowering therapies. Current evidence shows reductions in LDL-C levels of up to 70 % may be achieved with PCSK9 inhibition, independent of background statin therapy. This review examines the most recent evidence and future prospects for the use of PCSK9 inhibitors in the prevention of cardiovascular disease.
Rao, Ajay D; Bonyhay, Istvan; Dankwa, Joel; Baimas-George, Maria; Kneen, Lindsay; Ballatori, Sarah; Freeman, Roy; Adler, Gail K
Studies have shown associations between exposure to hypoglycemia and increased mortality, raising the possibility that hypoglycemia has adverse cardiovascular effects. In this study, we determined the acute effects of hypoglycemia on cardiovascular autonomic control. Seventeen healthy volunteers were exposed to experimental hypoglycemia (2.8 mmol/L) for 120 min. Cardiac vagal baroreflex function was assessed using the modified Oxford method before the initiation of the hypoglycemic-hyperinsulinemic clamp protocol and during the last 30 min of hypoglycemia. During hypoglycemia, compared with baseline euglycemic conditions, 1) baroreflex sensitivity decreases significantly (19.2 ± 7.5 vs. 32.9 ± 16.6 ms/mmHg, P < 0.005), 2) the systolic blood pressure threshold for baroreflex activation increases significantly (the baroreflex function shifts to the right; 120 ± 14 vs. 112 ± 12 mmHg, P < 0.005), and 3) the maximum R-R interval response (1,088 ± 132 vs. 1,496 ± 194 ms, P < 0.001) and maximal range of the R-R interval response (414 ± 128 vs. 817 ± 183 ms, P < 0.001) decrease significantly. These findings indicate reduced vagal control and impaired cardiovascular homeostasis during hypoglycemia.
Pieper, Petronella G
One-third of women with heart disease use medication for the treatment of cardiovascular disease (CVD) during pregnancy. Increased plasma volume, renal clearance, and liver enzyme activity in pregnant women change the pharmacokinetics of these drugs, often resulting in the need for an increased dose. Fetal well-being is a major concern among pregnant women. Fortunately, many drugs used to treat CVD can be used safely during pregnancy, with the exception of high-dose warfarin in the first trimester, angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, amiodarone, and spironolactone. A timely and thorough discussion between the cardiologist and the pregnant patient about the potential benefits and adverse effects of medication for CVD is important. Noncompliance with necessary treatment for cardiovascular disorders endangers not only the mother, but also the fetus. This Review is an overview of the pharmacokinetic changes in medications for CVD during pregnancy and the safety of these drugs for the fetus. The implications for maternal treatment are discussed. The Review also includes a short section on the cardiovascular effects of medication used for obstetric indications.
Eyres, Laurence; Eyres, Michael F; Chisholm, Alexandra; Brown, Rachel C
Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined. Observational evidence suggests that consumption of coconut flesh or squeezed coconut in the context of traditional dietary patterns does not lead to adverse cardiovascular outcomes. However, due to large differences in dietary and lifestyle patterns, these findings cannot be applied to a typical Western diet. Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease.
Bolland, Mark J; Grey, Andrew; Reid, Ian R
Calcium supplements have been widely used by older men and women. However, in little more than a decade, authoritative recommendations have changed from encouraging the widespread use of calcium supplements to stating that they should not be used for primary prevention of fractures. This substantial shift in recommendations has occurred as a result of accumulated evidence of marginal antifracture efficacy, and important adverse effects from large randomized controlled trials of calcium or coadministered calcium and vitamin D supplements. In this review, we discuss this evidence, with a particular focus on increased cardiovascular risk with calcium supplements, which we first described 5 years ago. Calcium supplements with or without vitamin D marginally reduce total fractures but do not prevent hip fractures in community-dwelling individuals. They also cause kidney stones, acute gastrointestinal events, and increase the risk of myocardial infarction and stroke. Any benefit of calcium supplements on preventing fracture is outweighed by increased cardiovascular events. While there is little evidence to suggest that dietary calcium intake is associated with cardiovascular risk, there is also little evidence that it is associated with fracture risk. Therefore, for the majority of people, dietary calcium intake does not require close scrutiny. Because of the unfavorable risk/benefit profile, widespread prescribing of calcium supplements to prevent fractures should be abandoned. Patients at high risk of fracture should be encouraged to take agents with proven efficacy in preventing vertebral and nonvertebral fractures.