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(Circulation. 2004;109:II-1.)
© 2004 American Heart Association, Inc.

Vascular Effects of Statins

Introduction

Peter Libby, MD; James T. Willerson, MD, Editor-in-Chief, Circulation

Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass., University of Texas Health Science Center and Texas Heart Institute Houston, Tex.

An extract of the first 250 words of the full text is provided, because this article has no abstract.

All agree that the introduction of the 3-hydroxy 3-methylglutaryl coenzyme A inhibitors (HMG-CoA reductase inhibitors, statins) has revolutionized the practice of cardiovascular medicine. A series of well-known, well-designed, conclusive, and concordant studies has shown that statin therapy can reduce "hard" end points, including myocardial infarction, stroke, and cardiovascular, and all-cause mortality in a broad variety of populations. This victory of therapeutics has raised questions about the mechanisms by which this class of drugs produces these profound clinical benefits. Designed as interventions to reduce low-density lipoprotein (LDL), the statins certainly provide at least some of their benefit by targeting this trigger of lipid overload and altering arterial biology at the heart of atherosclerosis.

However, the statins have a panoply of effects unrelated to their LDL-lowering ability. Indeed, the biosynthetic pathway of cholesterol is a long one, encompassing more than 20 steps on the way from mevalonate to cholesterol. Many of the smaller lipid intermediates play important roles in biologic control, as explained in detail in the various contributions to this supplement. Yet the clinical relevance of many of these effects, often referred to as pleiotropic, remains uncertain.

In view of the central role of the statin class of drugs in contemporary cardiovascular therapeutics and the controversial nature of their pleiotropic effects, we believed that it was timely to gather a panel of experts to explore these mechanisms and weigh the evidence favoring their operation in the clinic. This exercise has clear scholarly and intellectual interest, but it may also have practical . . . [Full Text of this Article]