Importance of endothelial function in mediating the benefits at lipid-lowering therapy

Trials of lipid lowering by various methods have clearly demonstrated the b enefits, clinically and angiographically. Evidence of slowed arterial disea se progression and even regression has been convincing but modest, at best. For example, among those treated intensively in the Familial Atheroscleros is Treatment Study (FATS), the mean improvement in proximal stenosis severi ty was <1% per patient, and only 12% of all lesions showed convincing regre ssion. Despite these modest arterial benefits, the associated reductions in major cardiovascular events have been surprisingly great (24-35% in 3 rece nt large trials and greater than or equal to 50% in angiographic trials usi ng combination therapies). The process of plaque disruption helps explain t his discrepancy. Disruption can be predicted by a large accumulation of cor e lipid in the plaque and a high density of lipid-laden macrophages in its thinned fibrous cap. Lesions with these characteristics comprise only 10-20 % of the overall lesion population but account for 60-90% of the acute clin ical events. Lipid-lowering therapy has beneficial effects on these "high-r isk" features of plaque morphology. The composite of data presented here su pports the hypothesis that lipid-lowering therapy selectively depletes lipi ds from this relatively small but dangerous subgroup of fatty lesions, effe ctively stabilizing them. (C) 1998 by Excerpta Medica, Inc.