Current Atherosclerosis Reports

Olsson, Anders

doi: 10.1007/s11883-004-0108-4pmid: 14662101

Several recent observations support the notion of an independent role of psychosocial factors in the pathophysiology of CHD. More has to be learned about the mechanisms whereby these factors mediate its deleterious effects. Hopefully, more knowledge of this relationship may help us to discover new treatments for this ubiquitous disease.

doi: 10.1007/s11883-004-0109-3pmid: N/A

Hennekens, Charles

doi: 10.1007/s11883-004-0110-xpmid: 14662102

During the past decade, numerous landmark trials of statins in secondary and primary prevention and their meta-analyses have demonstrated statistically significant and clinically important reductions in myocardial infarction, stroke, and vascular death (by about one third), as well as total mortality (by about one fifth). In the past year, two trials of statins have been reported among hypertensive subjects enrolled in blood pressure-lowering trials, one in the United States and the other in Europe. The US trial, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial—Lipid Lowering Trial (ALLHAT-LLT), was reported as showing no significant benefit. In contrast, the European trial, the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA), was terminated early based on the unanimous recommendation of the Data and Safety Monitoring Board, due principally to the emergence of a statistically extreme 36% reduction in the primary endpoint of nonfatal myocardial infarction and death from coronary heart disease (P<0.0005). These trial results have been viewed as discrepant, but methodologic issues of inadequate power of ALLHAT due to lower than projected sample size and poor compliance due to an open design render these discrepancies more apparent than real. The ALLHAT-LLT trial should be viewed not as null, but as uninformative, as the 95% confidence limits around the point estimate include the most plausible small to moderate benefit of statins. The totality of evidence on statins continues to strongly support their benefits in a wide range of patients on a large number of cardiovascular disease endpoints.

LaRosa, John

doi: 10.1007/s11883-004-0111-9pmid: 14662103

Recent clinical trials of statins have clearly demonstrated the benefit of statin therapy in preventing both coronary and cerebral vascular events. These benefits have been demonstrated to be present without reference to older age, sex, or comorbid conditions, including hypertension and diabetes. Future trials will test the value of more aggressive low-density lipoprotein cholesterol lowering, the value of immediate statin intervention during acute coronary syndromes, the role of cholesterol lowering with or without angioplasty, and the role of cholesterol lowering in stroke prevention.

Jacoby, Douglas; Mohler, Emile; Rader, Daniel

doi: 10.1007/s11883-004-0112-8pmid: 14662104

Noninvasive assessment of atherosclerosis offers an opportunity to provide individual cardiovascular risk management and an opportunity to monitor the efficacy of therapy targeted toward atherosclerosis. The three imaging modalities that currently hold the most promise at the clinical and research levels are ultrasound for carotid intima-media thickness, computed tomography for coronary artery calcification, and magnetic resonance imaging for carotid and aortic plaque imaging. The following review describes the evidence that validates each technique as a surrogate marker of atherosclerosis, with an emphasis on cardiovascular events and the progression of disease. Both the particular strengths and limitations of each imaging modality are discussed.

Davignon, Jean

doi: 10.1007/s11883-004-0113-7pmid: 14662105

In addition to their lipid-modulating properties, statins have a large number of beneficial cardiovascular effects that have emerged over time and that were not anticipated during drug development. The lipid and nonlipid effects act in a concerted way to reduce the ischemic burden of the myocardium and to protect it against injury. By acting on the vessel wall, statins may prevent lesion initiation and repair injuries, enhance myocardial perfusion, slow lesion progression, and prevent coronary occlusion. They may also directly reduce myocardial damage, favor myocardial repair, and protect against immune injury. This review focuses on properties of statins that contribute to their cardioprotective effect. The first section includes information on modulation of vascular tone, endothelial permeability and function, inhibition of complement injury, curbing of foam cell formation, antioxidant and anti-inflammatory properties, and profibrinolytic and anticoagulant activities. The second section relates to reduction of myocardial necrosis, myocardial hypertrophy, blood pressure, and heart failure, as well as mobilization of endothelial progenitor cells for repair, angiogenic effects, and immunomodulation. In many instances, results of in vitro and animal studies have raised expectations and prompted studies in humans. Several clinical trials have confirmed these expectations and have strengthened the value of statins as valuable antiatherosclerotic and cardioprotective agents.

Calabro, Paolo; Yeh, Edward

doi: 10.1007/s11883-004-0114-6pmid: 14662106

Statins can profoundly affect cellular metabolism by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is the rate-limiting enzyme responsible for cholesterol synthesis. Many physicians prescribe statins to lower plasma cholesterol levels, which has beneficial effects in both the primary and secondary prevention of coronary artery disease. However, in vitro, in vivo, animal, and clinical studies have all shown that statins may also have important pleiotropic properties. In fact, a number of clinical studies have suggested that statins are involved in modulating diseases such as cancer, osteoporosis, and dementia (including Alzheimer’s disease). However, because these studies have been only preliminary and observational in nature, large randomized, placebo-controlled studies are needed to confirm the modulatory role of statins in these important diseases.

Maki, Kevin

doi: 10.1007/s11883-004-0115-5pmid: 14662107

The National Cholesterol Education Program Adult Treatment Panel III has provided a clinical definition for the metabolic syndrome that is practical for use in an office setting. Identification and treatment of the metabolic syndrome is of enormous public health importance because it is associated with a marked elevation in coronary heart disease risk and affects nearly 25% of adults in the United States. First-line therapy is lifestyle modification, which includes body weight reduction, increased physical activity, and moderation of the dietary glycemic load. Drug treatments focusing on the major components of the syndrome (atherogenic dyslipidemia, hypertension, and a prothrombotic state) have demonstrated efficacy for reducing coronary heart disease events. Fibrates seem to be particularly effective in patients for whom a disturbance of the triglyceride-high-density lipoprotein axis is the primary lipid disorder. Fibrates also appear to influence a number of emerging risk factors, including hemostatic and inflammatory markers and indicators of improved vascular wall biology, which may contribute to their cardioprotective effects.

Ballantyne, Christie

doi: 10.1007/s11883-004-0116-4pmid: 14662108

Ezetimibe, a cholesterol absorption inhibitor, lowered low-density lipoprotein cholesterol levels and improved high-density lipoprotein cholesterol and triglyceride levels when used as monotherapy or when coadministered with a statin in clinical trials, and its safety profile is similar to placebo or statin plus placebo. Addition of ezetimibe to ongoing statin therapy increased the proportion of patients reaching recommended low-density lipoprotein cholesterol treatment goals. Ezetimibe is an effective treatment option that may enable more patients with hypercholesterolemia to achieve optimal cholesterol levels and reduce their risk for coronary heart disease.

Patel, Samir; Rajaram, Venkataraman; Pandya, Sanjay; Fiedler, Benjamin; Bai, Charlotte; Neems, Rachel; Feinstein, Matt; Goldin, Marshall; Feinstein, Steven

doi: 10.1007/s11883-004-0117-3pmid: 14662109

Noninvasive surrogate markers of atherosclerosis allow the physician to identify subclinical disease before the occurrence of adverse cardiovascular events, thereby limiting the need to perform invasive diagnostic procedures. Imaging modalities, such as carotid artery ultrasound, two-dimensional echocardiography, coronary artery calcium imaging, cardiac magnetic resonance imaging, ankle-brachial indices, brachial artery reactivity testing, and epicardial coronary flow reserve measurements, provide information that may improve the predictive value of a person’s risk of developing clinically significant atherosclerotic disease. Newer imaging modalities have also emerged to bring insight into the pathophysiology and treatment of atherosclerosis.