As atherosclerotic plaques develop, so does the risk of thrombosis, particularly when plaques have a high macrophage inflammatory content, a large core of extracellular lipid, a thin cap, and a reduced smooth muscle content. As the proportion of plaques with these characteristics varies widely, it is important to identify subjects with large numbers of vulnerable plaques to target aggressive therapy to those most at risk. The initial inflammatory stimulus to plaque formation is modification and oxidation of low-density lipid having crossed into the intima. This causes monocyte migration into the intima followed by lipid uptake by macrophages to form foam cells, which then release their contents after death by apoptosis and necrosis to form the plaque core. Thrombus follows either endothelial erosion or plaque disruption—both processes are mediated by release of proteases and other mediators for macrophages, such as monocyte chemoattractant protein–1 (MCP-1), whose importance is being increasingly recognized. Lipid lowering by statins has significantly reduced the risk of acute events. Animal models confirm that lipid lowering will reduce the plaque inflammatory content and initiate collagen synthesis to form a stable plaque. Lipid lowering does not totally abolish risk—there are other nonlipid stimuli of plaque inflammation that may operate as enhancers, Chlamydia being an example...