Coronary heart disease prevention and the infarctogenic plaque

The characteristics of a subset of atherosclerotic plaques that is responsible for myocardial infarction (infarctogenic plaques) are increasingly well defined. They include moderate size, a thin fibrous cap, and a large lipid pool. Fissuring of the cap leads to thrombotic occlusion and often to an acute coronary event. Physical stresses on, and proteolytic weakening of, the cap--both related to effects of hyperlipidemia on the plaque--increase the risk of fissuring. Treatment of hyperlipidemia leads to regression of experimental atherosclerosis, promotes regression and reduces progression of human coronary artery disease. The arterial changes in humans are predictive of reduced incidence of coronary events. This sequence of events may reflect gradual depletion of plaque lipids, and also a more rapid depletion of chronic inflammatory cells in the plaque cap that are the source of collagenase and other proteases. The primary objective of lipid-lowering therapy appears to be the induction of these changes in infarctogenic plaques, and vigorous treatment should be targeted on patients likely to harbor such plaques.