The overall goal of this proposal is to investigate the added benefit of increased high-density cholesterol (HDL) serum levels on atherosclerotic plaque architecture and composition over and above those achieved by lipid lowering statin therapy, in older individuals with cardiovascular disease. With improved understanding of the basic mechanisms underlying lipid lowering therapy, as well as the development of technology to measure its beneficial effects on atherosclerosis, it has become possible to design smaller clinical trials that use surrogate endpoints to determine the efficacy of treatment strategies taylored to specific patient groups. This clinical trial will use state-of-the-art magnetic resonance imaging (MRI) technology sensitive enough to measure reduction of atherosclerotic plaque size as well as alterations of plaque composition directly in the aorta and carotid arteries. In addition, this study will further our understanding of reduced inflammation associated with lipid lowering therapy as potential mediators of plaque regression, determined by MRI as alterations of plaque architecture and composition. We will test the hypothesis that NCEP guided lipid lowering therapy combined with 20 percent or greater increase in serum HDL induced by long-acting niacin reduces plaque size in older individuals with cardiovascular disease. To test our hypothesis, we have the following specific aims: 1) to determine the effects of simvastatin vs. simvastatin augmented by niacin therapy on plaque size and composition, 2) to determine whether alterations of inflammatory markers of atherosclerosis induced by lipid lowering therapy parallel alterations of plaque architecture and composition in older patients with cardiovascular disease, 3) to determine the effects of these interventions on the incidence of cardiovascular and cerebrovascular events. The results of the proposed trial will be directly applicable to developing strategies for plaque stabilization in the elderly who suffer the most from the severe complications of advanced cardiovascular atherosclerosis. ? ?
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