[Mechanisms of plaque stabilization]

Numerous angiographic control regression studies have demonstrated that aggressive reduction of plasma cholesterol significantly reduces the incidence of clinical overt cardiovascular complications, but has almost no effect on the angiographically determined luminal diameter of the coronary arteries. These, as well as other morphological and molecular studies have led to a new paradigm of coronary heart disease, i.e. clinical prognosis is not mainly determined by the extent of a single stenosis but by the number and biological nature of atherosclerotic plaque. Accordingly, stable plaques can be differentiated from instable or vulnerable plaques. The vulnerable or instable plaque is characterized by a large lipid-rich core with surrounding inflammation and a thin friable overlying fibrous cap susceptible to rupture or fissuring and thereby a high risk of thrombus formation. Rupture and thrombus formation can cause an acute coronary syndrome, such as unstable angina or myocardial infarction. There is increasing clinical and experimental evidence that statins do not only lower plasma cholesterol, but might also have direct effects on the vessel wall, possibly explaining early benefits in cardiovascular complications. Reduction of plasma cholesterol by lipid lowering therapy has been shown to significantly improve paradoxic vasoconstriction of cardiac vessels, a phenomenon indicating endothelial dysfunction. In addition, lipid lowering therapy can result in a diminution of the lipid-rich core, a reduction of inflammatory cells within the plaques, decreased macrophage activation as well as foam cell formation and events related to thickening of the fibrous cap. A clinical prospective should be to better clinically morphologically characterize the vulnerability of plaques in order to therapeutically and preventively reduced specific events leading to acute coronary syndromes, such as unstable angina or myocardial infarction.