Pathophysiology of plaque rupture and the concept of plaque stabilization.

Atherosclerosis complicated by plaque rupture or disruption and thrombosis is primarily responsible for the potentially lethal acute coronary syndromes. Plaques with a large extracellular lipid-rich core, thin fibrous cap with reduced collagen content and smooth muscle density, and increased numbers of activated macrophages and mast cells appear to be most vulnerable to rupture. Plaque disruption tends to occur at points at which the plaque surface is weakest and most vulnerable, which coincide with points at which stresses, resulting from biomechanical and hemodynamic forces acting on plaques, are concentrated. Reduced matrix synthesis as well as increased matrix degradation may predispose fibrous caps to rupture spontaneously or in response to extrinsic mechanical or hemodynamic stresses. Modification of endothelial dysfunction and reduction of vulnerability to plaque rupture and thrombosis may lead to plaque stabilization resulting in reduction of the frequency of acute coronary syndromes. This putative concept of plaque stabilization, although attractive, has not yet been rigorously validated in humans. Indirect data from clinical trials involving lipid lowering/modification and lifestyle/risk factor modification, however, provide strong support for this new paradigm. Thus, plaque stabilization may prove to be an important modality for reduction of lethal consequences of coronary atherosclerosis.