The vulnerable atherosclerotic plaque

Abstract

Several major clinical trials reported over the past three years have shown that lowering of plasma cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, has led to a substantial reduction in clinical events such as heart attack, stroke or death. These striking and encouraging observations were not predicted from the morphological changes in atherosclerotic lesions measured in a number of trials reported a few years earlier. Concurrent with these experiences with drugs, pathologists were describing those atherosclerotic plaques from post-mortem examination that seemed to be responsible for the acute coronary events. These plaques were usually eccentric in cross-section and contained a fluid lipid core with a thinned fibrous cap. Such vulnerable plaques were believed to be particularly prone to rupture which led to thrombosis and to the acute coronary events. A combination of these concurrent paths of clinical and pathological research has led to the proposition that the statins, and some other drugs, may stabilise the vulnerable atherosclerotic plaques, perhaps as a downstream consequence of their primary mechanism of action. An explosion of interest in the biology of the vulnerable atherosclerotic plaque has resulted. Numerous factors have been identified that may contribute to stabilisation or destabilisation of plaques and many of these may be candidates for pharmacological intervention. However, the difficulty in assessing plaque stability non-invasively is a major technical barrier which must be overcome before these targets can be exploited.