TOWARD THE QUIESCENT CORONARY PLAQUE

The treatment of coronary atherosclerosis requires an understanding of the pathophysiology of plaque rupture. The rupture of lipid-laden, ma crophage-rich plaques initiates unstable angina, acute myocardial infa rction and sudden cardiac death. Plaque rupture occurs when the circum ferential tension on a plaque exceeds its tensile strength, an event t hat cannot be predicted by coronary angiography. The incidence of plaq ue rupture appears to be reduced in patients receiving cholesterol-low ering therapy, beta-adrenergic blocking agents and, possibly, angioten sin-converting enzyme inhibitors and antioxidants. Not all ruptured co ronary plaques produce an acute coronary syndrome. The consequences of plaque rupture depend on the extent of thrombus formation over the fi ssured plaque. This is determined by flow characteristics within the v essel as well as the activity of the thrombotic and fibrinolytic syste ms. Recent advances in cardiovascular molecular biology, coronary diag nostic techniques and cardiac therapeutics have opened windows of oppo rtunity to study and modify the factors leading to plaque rupture. The local modification of gene expression to alter plaque composition and to elucidate and subsequently inhibit the prothrombotic and fibrinoly tic defects that promote coronary thrombosis may, in future, prevent p laque rupture and its consequences. The application of such a concerte d interdisciplinary approach promises a paradigm shift in the manageme nt of coronary artery disease toward the prevention of plaque rupture and its sequelae.