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

In the past, we believed that atherosclerosis gradually and progressively led to the complete occlusion of an artery, thereby causing acute coronary events. However, we now understand that rupture of a nonstenotic, yet vulnerable atherosclerotic plaque frequently leads to an acute coronary syndrome. Rupture-prone plaques typically have a thin fibrous cap, numerous inflammatory cells, a substantial lipid core, and surprisingly few smooth muscle cells. Physical disruption of such a plaque allows circulating blood coagulation factors to meet with the highly thrombogenic material in the plaque’s lipid core, thereby instigating the formation of a potentially occluding and fatal thrombus. Much evidence implicates inflammation in the thinning of the 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 regression of fixed stenoses has proved untenable. In 14 angiographic studies, treatment of abnormal lipid levels increased luminal diameter only modestly, in stark contrast to the resounding and consistent decrease in acute coronary events produced by lipid lowering. Therefore, we now believe that lipid-lowering treatments, such as statins, modify plaques qualitatively as much as quantitatively, reducing inflammation and stabilizing noncritically stenotic, yet vulnerable plaques. Studies in rabbits with diet-induced atherosclerosis have shown that reducing cholesterol consumption indeed decreases inflammation in atheroma and improves those features of plaques associated with stability.