HDL Increased Plaque Stablization in the Elderly

这项提案的总体目标是调查增加高密度胆固醇的额外好处 (HDL)血清水平对动脉粥样硬化斑块结构和组成的影响 通过降脂他汀类药物治疗，在患有心血管疾病的老年人中实现。具有改进 了解降脂治疗的基本机制，以及 技术来衡量其对动脉粥样硬化的有益影响，已经有可能设计更小的 使用替代终点确定治疗策略有效性的临床试验， 特殊患者群体。这项临床试验将使用最先进的磁共振成像（MRI） 足够灵敏的技术来测量动脉粥样硬化斑块大小的减少以及 斑块组成直接在主动脉和颈动脉。此外，这项研究将进一步促进我们的 了解与降脂治疗相关的炎症减少作为 斑块消退，通过MRI确定为斑块结构和组成的改变。我们将测试 假设NCEP指导的降脂治疗与20%或更高的血清 长效烟酸诱导的高密度脂蛋白降低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 辛伐他汀增加烟酸治疗对斑块大小和组成的影响，2）确定是否 降脂治疗诱导的动脉粥样硬化炎症标志物的变化 老年心血管疾病患者斑块结构和组成的改变，3） 确定这些干预措施对心血管和脑血管疾病发生率的影响 事件拟议试验的结果将直接适用于制定牙菌斑治疗策略 稳定的老年人谁遭受最严重的并发症，先进的心血管 ] therapy.

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% 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 ]therosclerosis.