The evolving role of statins in the management of atherosclerosis

Abstract

Significant advances in the management of cardiovascular disease have been made possible by the development of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors--"statins." Initial studies explored the impact of statin therapy on coronary artery disease (CAD) progression and regression. Although the angiographic changes were small, associated clinical responses appeared significant. Subsequent large prospective placebo-controlled clinical trials with statins demonstrated benefit in the secondary and primary prevention of CAD in subjects with elevated cholesterol levels. More recently, the efficacy of statins has been extended to the primary prevention of CAD in subjects with average cholesterol levels. Recent studies also suggest that statins have benefits beyond the coronary vascular bed and are capable of reducing ischemic stroke risk by approximately one-third in patients with evidence of vascular disease. In addition to lowering low-density lipoprotein (LDL) cholesterol, statin therapy appears to exhibit pleiotropic effects on many components of atherosclerosis including plaque thrombogenicity, cellular migration, endothelial function and thrombotic tendency. Growing clinical and experimental evidence indicates that the beneficial actions of statins occur rapidly and yield potentially clinically important anti-ischemic effects as early as one month after commencement of therapy. Future investigations are warranted to determine threshold LDL values in primary prevention studies, and to elucidate effects of statins other than LDL lowering. Finally, given the rapid and protean effects of statins on determinants of platelet reactivity, coagulation, and endothelial function, further research may establish a role for statin therapy in acute coronary syndromes.

Effects of simvastatin on apolipoprotein M in vivo and in vitro

“…They are the most efficient agents for reducing plasma cholesterol, being also appreciated for their good tolerance. Angiographic studies have demonstrated that these compounds reduce the progression and may induce the regression of atherosclerotic lesion in cardiovascular vessels, which could lead to a significant decreases of cardiovascular morbidity and mortality [15]. Statins have been shown to inhibit hepatic production of apoA-IV apoB, apoCIII and apoE-containing lipoproteins both in vitro and in vivo [13,16].…”

Determinants of variable response to simvastatin treatment: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes

“…Data from clinical trials have demonstrated that statin treatment appears to be the most effective and well-tolerated means of lowering cholesterol levels, [1][2][3] but it is also clear that large interindividual variations in plasma cholesterol response are common and explained, in part, by genetic factors that affect drug pharmacodynamics and/or pharmacokinetics. In recent years, one of the focus of genetic investigation in cardiology has been to identify the genetic factors associated with variable response to statin treatment.…”

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy

“…CETP transfers cholesteryl esters associated with HDL to triglyceride-rich lipoproteins, facilitating the clearance of cholesteryl esters from plasma. 1 Although the potential contribution of CETP to reverse cholesterol transport suggests an antiatherogenic mode of action, knowledge of the physiologic role of CETP in lipoprotein metabolism remains incomplete. The overall effect of CETP on atherogenesis may vary depending on both metabolic context and molecular variation in the CETP gene.…”