Mechanisms of plaque stabilization

Numerous angiographic control regression studies have demonstrated that agg ressive reduction of plasma cholesterol significantly reduces the incidence of clinical overt cardiovascular complications, but has almost no effect o n 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 mai nly determined by the extent of a single stenosis but by the number and bio logical nature of atherosclerotic plaque. Accordingly, stable plaques can b e differentiated from instable or vulnerable plaques. The vulnerable or ins table plaque is characterized by a large lipid-rich core with surrounding i nflammation and a thin friable overlying fibrous cap susceptible to rupture or fissuring and thereby a high risk of thrombus formation. Rupture and th rombus formation can cause an acute coronary syndrome, such as unstable ang ina 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 vasocons triction of cardiac vessels, a phenomenon indicating endothelial dysfunctio n, In addition, lipid lowering therapy can result in a diminution of the li pid-rich core, a reduction of inflammatory cells within the plaques, decrea sed macrophage activation as well as foam cell formation and events related to thickening of the fibrous cap. A clinical prospective should be to bett er clinically morphologically characterize the vulnerability of plaques in order to therapeutically and preventively reduced specific events leading t o acute coronary syndromes, such as unstable angina or myocardial infarctio n.