What have we learned about the biology of atherosclerosis? The role of inflammation

In the past, we believed that atherosclerosis gradually and progressively l ed to the complete occlusion of an artery, thereby causing acute coronary e vents. However, we now understand that rupture of a nonstenotic, yet vulner able atherosclerotic plaque frequently leads to an acute coronary syndrome. Rupture-prone plaques typically have a thin fibrous cap, numerous inflamma tory cells, a substantial lipid core, and surprisingly few smooth muscle ce lls. Physical disruption of such a plaque allows circulating blood coagulat ion factors to meet with the highly thrombogenic material in the plaque's l ipid core, thereby instigating the formation of a potentially occluding and fatal thrombus. Much evidence implicates inflammation in the thinning of t he fibrous cap and the disruption of the vulnerable atherosclerotic plaque. Lipid lowering undisputedly reduces the incidence of acute coronary events . However, the hypothesis that the mechanism of event reduction involves re gression of fixed stenoses has proved untenable. In 14 angiographic studies , treatment of abnormal lipid levels increased luminal diameter only modest ly, in stark contrast to the resounding and consistent decrease in acute co ronary events produced by lipid lowering. Therefore, we now believe that li pid-lowering treatments, such as statins, modify plaques qualitatively as m uch as quantitatively, reducing inflammation and stabilizing noncritically stenotic, yet vulnerable plaques. Studies in rabbits with diet-induced athe rosclerosis have shown that bits reducing cholesterol consumption indeed de creases inflammation in atheroma and improves those features of plaques ass ociated with stability. (C) 2001 by Excerpta Medica, Inc.