HDL Increased Plaque Stablization in the Elderly

HDL 增强老年人斑块稳定性

• 批准号: 6874326
• 负责人: Joao A C Lima
• 金额: $ 54.04万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6874326
• 关键词: aorta; atherosclerosis; atherosclerotic plaque; carotid artery; clinical chemistry; clinical research; clinical trials; combination chemotherapy; data collection methodology /evaluation; drug screening /evaluation; enzyme linked immunosorbent assay; heart disorder chemotherapy; high density lipoproteins; human old age (65+); human subject; human therapy evaluation; interview; longitudinal human study; magnetic resonance imaging; niacin; outcomes research; simvastatin

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.

描述（由申请人提供）：该提案的总体目标是研究在老年人中，除了降脂他汀类药物治疗所实现的效果之外，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成分的额外益处患有心血管疾病。 随着对降脂治疗基本机制的了解的加深，以及测量其对动脉粥样硬化有益影响的技术的发展，设计更小型的临床试验，使用替代终点来确定针对特定治疗策略的疗效已成为可能。患者群体。 该临床试验将使用最先进的磁共振成像（MRI）技术，该技术的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成分的变化。 此外，这项研究将进一步加深我们对降脂治疗相关炎症减轻的理解，作为斑块消退的潜在介质，通过 MRI 确定斑块结构和成分的改变。 我们将检验以下假设：NCEP 指导的降脂治疗与长效烟酸诱导的血清 HDL 增加 20% 或更多相结合，可减少老年心血管疾病患者的斑块大小。 为了检验我们的假设，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成分的影响，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平行老年心血管疾病患者斑块结构和成分的改变，3) 确定这些干预措施对心脑血管事件发生率的影响。 拟议试验的结果将直接适用于制定针对患有晚期心血管动脉粥样硬化严重并发症最严重的老年人的斑块稳定策略。