HDL Increased Plaque Stablization in the Elderly

描述（由申请人提供）：本提案的总体目标是研究在患有心血管疾病的老年人中，增加高密度胆固醇（HDL）血清水平对动脉粥样硬化斑块结构和组成的额外益处，而不是通过降脂他汀类药物治疗获得的益处。随着对降脂疗法的基本机制的进一步了解，以及测量其对动脉粥样硬化有益效果的技术的发展，设计更小的临床试验，使用替代终点来确定针对特定患者群体的治疗策略的疗效已经成为可能。这项临床试验将使用最先进的磁共振成像（MRI）技术，该技术足够敏感，可以测量动脉粥样硬化斑块大小的减少以及主动脉和颈动脉斑块组成的改变。此外，这项研究将进一步加深我们对与降脂治疗相关的炎症减少作为斑块消退的潜在介质的理解，通过MRI确定斑块结构和组成的改变。我们将验证NCEP指导的降脂治疗结合20%或以上的血清HDL增加的假说，长效烟酸诱导降低老年心血管疾病患者斑块大小。为了验证我们的假设，我们有以下具体目标：1)确定辛伐他汀与烟酸强化辛伐他汀治疗对斑块大小和组成的影响，2)确定降脂治疗引起的动脉粥样硬化炎症标志物的改变是否与老年心血管疾病患者斑块结构和组成的改变平行，3)确定这些干预措施对心脑血管事件发生率的影响。该试验的结果将直接适用于老年人斑块稳定策略的制定，老年人最容易遭受晚期心血管动脉粥样硬化的严重并发症。

DESCRIPTION (provided by applicant): 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.