Secondary Cardiovascular Events Research Articles

Sex Steroids, Cardiovascular Disease, and Hypertension

The roles that both male and female sex steroids play in mediating or protecting against cardiovascular disease (CVD) and hypertension are controversial. For example, whereas animal studies have strongly implicated androgens as being mediators of CVD and hypertension, human epidemiological studies have shown that with chronic disease, including hypertension, serum testosterone levels are actually reduced.1 Thus, whether androgens are truly causative of CVD is not clear. However, premenopausal women are typically protected from CVD and hypertension compared with men, and this has been hypothesized to be because of the protective effects of estrogens. The negative findings of Heart and Estrogen/progestin Replacement Study (HERS) I and II2,3 and Women’s Health Initiative (WHI)4,5 studies on hormone replacement therapy (HRT) in postmenopausal women have shaken our previous ideas that HRT was protective against CVD. In this short review, the latest findings regarding the roles of sex steroids in hypertension and CVD are discussed, questions yet to be answered are suggested, and some speculations are made. In both males and females, the hypothalamus secretes gonadotropin-releasing hormone, which stimulates the anterior pituitary to release both luteinizing hormone and follicular-stimulating hormone. Luteinizing hormone binds to receptors on thecal cells in ovaries of females and Leydig cells in testes of males to cause testosterone to be synthesized. Follicular-stimulating hormone, however, binds to receptors on granulosa cells in females or Sertoli cells in males and stimulates the synthesis of aromatase, which converts testosterone to estradiol. There are 2 main types of estrogen receptors, ERα and ERβ, but several variants of both have also been identified. ERβ is present in a greater number of tissues than is ERα, but both isoforms are present in kidneys and the vasculature. ERβ has been found to be the predominant isoform in human vascular smooth muscle cells. The androgen receptor …

Short-term benefit of smoking cessation in patients with coronary heart disease: estimates based on self-reported smoking data and serum cotinine measurements

To assess the short-term impact of smoking and smoking cessation measured by self-report and by serum cotinine on the risk of secondary cardiovascular disease events (CVD events). Cohort study among participants of an in-patient 3-week rehabilitation programme following an acute coronary syndrome or coronary artery revascularization. Smoking status at baseline was assessed by self-report (beginning of the rehabilitation programme, rehab) and serum cotinine (end of rehab). Active follow-up was conducted one year later. Subsequent CVD events were observed in 139 of the 967 patients. Both self-reported smoking status (odds ratio (OR) compared to continued smokers: recent quitters 0.96, former smokers 0.83, never smokers 0.54, p for trend 0.04) and serum cotinine (OR 0.59 (95% confidence interval (CI) 0.36-0.97) for cotinine-negative compared to cotinine-positive subjects) were associated with the occurrence of a secondary CVD event. After reclassification of all cotinine-positive subjects to continued smokers and cotinine-negative self-reported smokers to recent quitters, this association became even stronger. The OR now reached 0.71 (95% CI interval 0.38-1.33) for recent quitters, 0.64 (0.36-1.11) for former smokers and 0.44 (0.24-0.81) for never smokers (p-value for trend=0.009). The benefits of non-smoking and smoking cessation in cardiac patients are beyond controversy and might even be larger than suggested by previous studies which exclusively relied on self-reported smoking status.

Vitamin E Modulation of Cardiovascular Disease

Endothelium in the vascular system is an important modulator of vasomotor tone and coagulation, and it plays a crucial role in the inhibition of adhesion and activation of platelets and leukocytes. Evidence indicates that dietary antioxidants may modulate these endothelium-dependent vascular functions through several mechanisms and may contribute to the prevention of vascular diseases such as atherosclerosis. Several cell cultures as well as animal and human clinical and observational studies have tested the efficacy of vitamin E on vascular function and the prevention of atherosclerosis. Our cell culture studies have indicated that vitamin E (alpha-tocopherol) inhibits the activation of endothelial cells stimulated by high levels of low-density lipoprotein cholesterol and pro-inflammatory cytokines. This inhibition is associated with the suppression of chemokines, the expression of cell surface adhesion molecules, and the adhesion of leukocytes to endothelial cells, all of which contribute to the development of lesions in the arterial wall. The molecular mechanisms by which alpha-tocopherol and other tocopherols modulate endothelial cells and smooth muscle functions have been delineated. We, and others, have also demonstrated a positive effect of dietary vitamin E on endothelium and vascular function in animal models of atherosclerosis. Several human clinical trials have also shown an improvement in the surrogate markers of atherosclerosis and vascular function by vitamin E supplementation. However, these findings have been contradicted by several vitamin E supplementation trials for the prevention of secondary cardiovascular events showing null effect. Intervention at a relatively late stage of disease and the single use of vitamin E rather than in combination with other antioxidants might have contributed to these contradictory findings. Evidence from cell cultures, as well as animal and human clinical and observational studies, strongly supports the contribution of dietary vitamin E to the maintenance of vascular function and health, in particular when it is used in combination with other dietary antioxidants, which are found in fruits, vegetables, and nuts.

The relative importance of cardiovascular risk factors in type 2 diabetes

Summary Coronary artery disease (CAD) is the cause of death of many patients with type 2 diabetes (T2D). Type 2 diabetes intensifies the risk associated with cardiovascular events, especially coronary heart disease. Major risk factors for CAD in patients with T2D are dyslipidaemia (high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, high total triglycerides), elevated blood pressure, smoking, hyperglycaemia, and insulin resistance. Treating these conditions (dyslipidaemia, elevated blood pressure, and hyperglycaemia) as single cardiovascular risk factors is beneficial, but multifactorial intervention may be more clinically beneficial in preventing cardiovascular complications or secondary cardiovascular events.

Risk assessment in cardiovascular disease: from traditional risk factors to genomics

In addition to the traditional Framingham risk factors, candidate markers for cardiovascular disease are being proposed and their number continues to grow. High-sensitivity C-reactive protein has been validated as a risk factor for both primary and secondary cardiovascular events. Most other protein markers, however, remain incompletely validated. Molecular analysis of the genetic loci associated with monogenic disorders may help to identify polymorphisms that underlie major polygenic disorders, such as essential hypertension. Genomics and proteomics have accelerated the discovery of novel genes, gene expression patterns, proteins and single nucleotide polymorphisms as predictors of disease outcome and drug response, but their validation and characterization in clinical studies remain a challenge. Studies such as The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) Trial Programme are addressing this issue by collecting large numbers of samples for mass pharmacogenomic analysis. In conclusion, novel disease markers and risk factors promise to have a radical impact on cardiovascular medicine in the long term, but their adoption into clinical practice is dependent on widespread validation in patient populations, ease of measurement and extensive physician education.

Undertreatment of dyslipidemia in peripheral arterial disease and other high-risk populations: an opportunity for cardiovascular disease reduction.

Atherosclerosis is a form of arterial disease that manifests in the coronary circulation as coronary artery disease (CAD), in the carotid arteries as cerebrovascular disease, and in the aorta and lower extremity arteries as peripheral arterial disease (PAD). The systemic nature of the disease is reflected in the fact that individuals with PAD or carotid artery disease are more likely to have CAD than those without. Since individuals with PAD are at markedly increased risk of cardiovascular ischemic events, early identification of this population and more aggressive medical interventions could substantially improve both morbidity and survival. The incidence of PAD in the general population is high, and currently affects 8-10 million Americans. The risk of developing PAD is predicted by both age and common atherosclerosis risk factors (e.g., smoking and diabetes). Efficient office-based PAD detection depends on the application of objective techniques to establish this diagnosis. Objective noninvasive tests, such as measurement of the ankle-brachial index (ABI), are known to be more sensitive than traditional clinical assessments. Since the major threat to patients with PAD is from secondary cardiovascular ischemic events, a primary therapeutic goal is to modify atherosclerotic risk factors. While national recommendations mandate aggressive lowering of serum low-density lipoprotein cholesterol (LDL-C) levels as a primary treatment goal in all patients with overt atherosclerosis, as 'coronary heart disease risk equivalent' syndromes, individuals with PAD are less intensively treated than those with CAD. Statins are the most effective of current treatments in lowering LDL-C, and have proven efficacy in secondary prevention among patients with established CAD. The use of statin medications in high-risk groups such as PAD patients could prove particularly beneficial in reducing cardiovascular morbidity and mortality and therefore merits prospective clinical investigation.

Cardiovascular Outcomes During 6.8 Years of Hormone Therapy: Heart and Estrogen/Progestin Replacement Study Follow-Up (HERS II)

Grady, Deborah; Herrington, David; Bittner, Vera; Blumenthal, Roger; Davidson, Michael; Hlatky, Mark; Hsia, Judith; Hulley, Stephen; Herd, Alan; Khan, Steven; Newby, L. Kristin; Waters, David; Vittinghoff, Eric; Wenger, Nanette for the HERS Research Group

Vitamin E reduced secondary cardiovascular disease events in patients receiving long-term hemodialysis

Source Citation Boaz M, Smetana S, Weinstein T, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lance...