Subclinical atherosclerosis: what it is, what it means and what we can do about it.

Atherosclerosis is a chronic, progressive, inflammatory disease with a long asymptomatic phase. Disease progression can lead eventually to the occurrence of acute cardiovascular events such as myocardial infarction, unstable angina pectoris and sudden cardiac death. While the disease is still in a subclinical stage, however, the presence of atherosclerosis can be identified by several methods, including coronary angiography, intravascular ultrasonography, B-mode ultrasonography, computed tomography and magnetic resonance imaging.

SPARCL: the glimmer of statins for stroke risk reduction.

Stroke is the third leading cause of mortality in the United States and is associated with grave morbidity and disability. Although dyslipidemias are not as well established as risk factors for stroke, clinical trial data suggest that the incidence of stroke is reduced significantly by the administration of statins. As these risk reductions surpass those expected solely via cholesterol reduction, this has fed the notion of another so-called "pleiotropic" effect of statins.

Making a case for quantitative assessment of cardiovascular risk.

Cardiovascular disease (CVD) causes nearly one third of all deaths worldwide. Estimates of the cumulative effects of the most common cardiovascular risk factors indicate that >30% of the chronic care burden of CVD and >50% of deaths from CVD are attributable to modifiable risk factors, such as cigarette smoking, elevated low-density lipoprotein cholesterol, low levels of high-density lipoprotein cholesterol, diabetes mellitus, and hypertension. While a significant percentage of patients present with one or more of these risk factors, health care practitioners encounter great difficulty in achieving long-term patient adherence to risk-factor modification interventions.

Implications of recent statin trials for primary care practice.

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are the first-line treatment for dyslipidemia and the results of large statin trials have a significant impact on guidelines for cardiovascular disease (CVD) management, such as those set by the National Cholesterol Education Program Adult Treatment Panel. The benefit of statin therapy in CVD prevention has traditionally been demonstrated in clinical trials by the superior efficacy of statins vs placebo in lowering low-density lipoprotein cholesterol (LDL-C) and preventing hard coronary heart disease (CHD) outcomes including myocardial infarction and CHD death. However, due to earlier and improved treatment of CVD, the clinical manifestations of atherosclerosis are changing and other forms of CVD are now thought to predominate (such as revascularization and stroke).

Reducing cardiovascular risk by targeting high-density lipoprotein cholesterol.

Although lowering low-density lipoprotein (LDL) cholesterol with statins can substantially reduce cardiovascular morbidity and mortality, many treated patients retain a residual risk for cardiovascular events. Low levels of high-density lipoprotein (HDL) cholesterol may underpin this residual risk and may represent an additional target for intervention. Several new therapies for substantially increasing HDL cholesterol levels are under investigation, including cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I mimetics and recombinant HDL, liver X receptor (LXR) agonists, and peroxisome proliferator-activated receptor (PPAR) agonists.

The CARDS trial: diabetic patients dealt a winning hand.

Until recently, the role of statin therapy in diabetic patients without clinical signs or symptoms of coronary heart disease had been inadequately defined. The Collaborative Atorvastatin Diabetes Study (CARDS) is a prospective, randomized, placebo-controlled trial designed to compare the effects of atorvastatin with placebo in preventing primary coronary events in diabetic patients. After a median of only 3.

Cholesterol absorption blockade with ezetimibe.

The reduction of circulating atherogenic lipoproteins through lifestyle modification and pharmacologic intervention is an important therapeutic goal in patients at risk for acute cardiovascular events. A large number of clinical trials have demonstrated that the reduction of low-density lipoprotein cholesterol (LDL-C) is associated with significant decreases in the incidence of all cause mortality, stroke, fatal and nonfatal myocardial infarction, and the need for revascularization with coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. Therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (i.

High-density lipoprotein as a therapeutic target: clinical evidence and treatment strategies.

The clinical importance of low serum levels of high-density lipoprotein (HDL) cholesterol is often under-recognized and underappreciated as a risk factor for premature atherosclerosis as well as for cardiovascular morbidity and mortality. Low serum levels of HDL are frequently encountered, especially in patients who are obese or have the metabolic syndrome. In prospective epidemiologic studies, every 1-mg/dL increase in HDL is associated with a 2% to 3% decrease in coronary artery disease risk, independent of low-density lipoprotein (LDL) cholesterol and triglyceride (TG) levels.

New insights in the treatment of dyslipidemia: a focus on cardiovascular event reduction and the anti-atherosclerotic effects of atorvastatin.

The identification and treatment of dyslipidemia is a critical component of ongoing efforts to reduce the incidence of atherosclerotic disease in both men and women. Several recent large-scale atorvastatin trials provide a plethora of information that expands the current body of literature describing the pathophysiology of cardiovascular disease and the prevention of acute cardiovascular events. These trials demonstrate the benefit of statin therapy in a broad variety of patient populations, explore the clinical efficacy of more intensive statin regimens, and suggest that the pleiotropic effects of statins may contribute to cardiovascular endpoint reduction.

Simvastatin plus ezetimibe: combination therapy for the management of dyslipidaemia.

Hyperlipidaemia is a pivotal risk factor for the development of atherosclerotic disease. A large number of studies have demonstrated that the treatment of abnormalities in lipoprotein levels reduces the risk for myocardial infarction, peripheral vascular disease, carotid artery disease, stroke, and cardiovascular mortality. Despite the development of multiple drug classes to treat dyslipidaemias and the promulgation of clearly defined guidelines for the management of lipid disorders, dyslipidaemia tends to be undertreated in the majority of patients at risk for cardiovascular disease.

Low-density lipoprotein reduction in high-risk patients: how low do you go?

Cardiovascular disease and its clinical sequelae remain the leading causes of morbidity and mortality in many regions of the world. Dyslipidemia is a critical risk factor to intercept in both the primary and secondary prevention of acute cardiovascular events. The prospective, placebo-controlled clinical trials conducted with statins over the course of the past 15 years have conclusively demonstrated that these drugs significantly reduce risk for fatal and nonfatal myocardial infarction, ischemic stroke, unstable angina, and frequency of myocardial ischemia, as well as cardiovascular and all-cause mortality.

Therapeutic interventions targeted at the augmentation of reverse cholesterol transport.

Purpose Of Review: Serum high-density lipoproteins (HDLs) and reverse cholesterol transport (RCT) are important therapeutic targets in the management of atherosclerotic disease. This review summarizes the pathway of RCT and the currently available means by which investigators are attempting to modulate HDL levels and increase rates of RCT.

Recent Findings: Low levels of HDL are commonly encountered in patients with atherosclerotic disease.