HDL Increased Plaque Stablization in the Elderly

描述（由申请方提供）：本提案的总体目标是研究在患有心血管疾病的老年人中，高密度胆固醇（HDL）血清水平升高对动脉粥样硬化斑块结构和组成的额外益处，超过降脂他汀类药物治疗所实现的益处。 随着对降脂治疗基本机制的进一步了解，以及测量其对动脉粥样硬化有益作用的技术的发展，设计小型临床试验已成为可能，这些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。 这项临床试验将使用最先进的磁共振成像（MRI）技术，其灵敏度足以测量动脉粥样硬化斑块大小的减少以及直接在主动脉和颈动脉中斑块组成的改变。 此外，这项研究将进一步了解与降脂治疗相关的炎症减少作为斑块消退的潜在介质，通过MRI确定斑块结构和组成的改变。 我们将检验以下假设：NCEP指导的降脂治疗结合长效烟酸诱导的血清HDL升高20%或更高，可减少老年心血管疾病患者的斑块大小。 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治疗增强的辛伐他汀对斑块大小和组成的影响，2）确定降脂治疗诱导的动脉粥样硬化炎性标志物的改变是否与患有心血管疾病的老年患者中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。 拟议的试验结果将直接适用于制定老年人斑块稳定的策略，这些老年人最容易发生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.