Carotid plaque characteristics by MRI in AIM-HIGH

AIM-HIGH 中 MRI 的颈动脉斑块特征

• 批准号: 7682623
• 负责人: XUE-QIAO ZHAO
• 金额: $ 28.7万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7682623
• 关键词: Abbreviations; Apolipoproteins; Appendix; Arterial Fatty Streak; Atherosclerosis; Bile fluid; Biological; Blinded; Blood Vessels; Calcium; Cardiovascular system; Carotid Arteries; Carotid Artery Plaques; Cause of Death; Cells; Cessation of life; Characteristics; Cholesterol; Clinical; Combined Modality Therapy; Condition; Data; Development; Effectiveness; End Point; Enrollment; Event; Excision; Excretory function; Fatty acid glycerol esters; Future; Goals; Health; Hemorrhage; Heterogeneity; High Density Lipoproteins; Hospitalization; Human; Hypertriglyceridemia; Imaging Techniques; Inflammatory; Intervention; Laboratories; Lipids; Lipoproteins; Liver; Low-Density Lipoproteins; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Metabolic syndrome; Morphology; Myocardial Infarction; Nicotinic Acids; Outcome; Pathology; Patients; Peripheral; Randomized; Research; Risk; Risk Factors; Series; Stroke; Study Subject; Testing; Thick; Time; Tissues; United States; Vascular Diseases; acute coronary syndrome; atherothrombosis; base; cardiovascular risk factor; clinical efficacy; design; in vivo; indexing; insight; novel; prevent; response

DESCRIPTION (provided by applicant): This is a resubmission application of our research application (1 R01 HL088214- 01) entitled 'Carotid plaque characteristics by MRI in AIM-HIGH.' Although studies have suggested that plaque morphology and composition are important determinants of plaque stability, however, our understanding on plaque tissue components is mainly from histological studies until recent development in MRI technique. A low level of HDL is associated with higher risk of cardiovascular events and increased amount of lipid content in the carotid plaques. Treatment with LDL-lowering plus HDL-raising compared with LDL-lowering alone more effectively protects against atherosclerosis progression. It is widely believed that HDL or its apolipoproteins mediate the removal of excess free cholesterol from peripheral cells and the cholesterol is delivered via either LDL or HDL to the liver for excretion into the bile. However, it has not been tested and approved in human atherosclerotic condition in vivo. The NIH/KOS-supported multi-center AIM-HIGH trial is designed to compare the clinical efficacy of LDL-lowering alone with statin versus LDL-lowering plus HDL-raising with statin plus nicotinic acid combination therapy in patients with established vascular disease and high triglycerides and low HDL. We propose to conduct a carotid MRI sub-study in 300 subjects enrolled in AIM-HIGH to investigate the important vascular biological mechanisms of HDL-raising therapy. The hypotheses and specific aims are: (1) To test the primary hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the mean plaque lipid composition in carotid arteries assessed by MRI. (2) To test the hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the plaque burden including volume and wall thickness. (3) To test the hypothesis that increased plaque lipid composition or vessel wall thickness by MRI is associated with increased risk of cardiovascular events. (4) To examine the association of clinical risk factors, lipids, lipoprotein heterogeneity, inflammatory markers and carotid plaque characteristics. This proposed MRI sub-study offers a unique opportunity to investigate the effectiveness of LDL-lowering plus HDL-raising therapy on human atherosclerotic plaque in vivo, to examine the association of plaque characteristics both lipid composition and volume assessed by MRI and cardiovascular outcome, and to gain novel insights in our understanding of atherosclerotic plaque pathology and the mechanisms of intensive lipid management in preventing cardiovascular events. Heart attacks and strokes caused by the unstable atherosclerotic plaques remain the leading cause of death in the United States. Unstable plaques often have more fat than stable plaques. The proposed study will investigate if a treatment with LDL-lowering plus HDL-raising compared with LDL-lowering alone would more effectively reduce the plaque fat content assessed by magnetic resonance imaging (MRI), therefore, further reducing heart attacks and strokes.

描述(申请人提供)：这是我们的研究申请(1 R01 HL088214-01)的重新提交申请，标题为‘AIM-HIGH中的颈动脉斑块特征通过MRI。’虽然研究表明斑块的形态和组成是斑块稳定性的重要决定因素，但我们对斑块组织成分的了解主要来自组织学研究，直到MRI技术的最新发展。低密度脂蛋白水平与较高的心血管事件风险和颈动脉斑块中脂质含量的增加有关。与单独降低低密度脂蛋白相比，降低低密度脂蛋白加升高高密度脂蛋白的治疗更有效地防止动脉粥样硬化的进展。人们普遍认为，高密度脂蛋白或其载脂蛋白介导外周细胞清除多余的游离胆固醇，胆固醇通过低密度脂蛋白或高密度脂蛋白输送到肝脏，然后排泄到胆汁中。然而，它还没有在人体动脉粥样硬化的情况下进行测试和批准。这项由NIH/KOS支持的多中心AIM-HIGH试验旨在比较单独使用他汀类药物降低低密度脂蛋白与降低低密度脂蛋白加升高高密度脂蛋白加他汀加烟酸联合治疗在已有血管疾病、高甘油三酯和低高密度脂蛋白患者中的临床疗效。我们建议在300名参加AIM-HIGH的受试者中进行颈动脉MRI亚研究，以探讨升高高密度脂蛋白治疗的重要血管生物学机制。研究的假说和具体目的是：(1)验证最初的假说，即与单纯降低低密度脂蛋白相比，强化降低低密度脂蛋白加高密度脂蛋白治疗可降低MRI评估的颈动脉平均斑块脂质成分。(2)与单纯降低低密度脂蛋白相比，强化低密度脂蛋白加高密度脂蛋白治疗可降低斑块负荷，包括斑块体积和管壁厚度。(3)验证MRI斑块脂质成分或血管壁厚度增加与心血管事件风险增加相关的假说。(4)探讨临床危险因素、血脂、脂蛋白异质性、炎性标志物与颈动脉斑块特征的关系。这项拟议的MRI亚研究提供了一个独特的机会，可以在活体内研究降低低密度脂蛋白和升高高密度脂蛋白治疗对人类动脉粥样硬化斑块的有效性，检查MRI评估的斑块特征和脂质成分和体积与心血管结局的关系，并对我们理解动脉粥样硬化斑块的病理学和强化血脂管理预防心血管事件的机制提供新的见解。在美国，由不稳定的动脉粥样硬化斑块引起的心脏病发作和中风仍然是主要的死亡原因。不稳定斑块通常比稳定斑块含有更多的脂肪。这项拟议的研究将调查，与单独降低低密度脂蛋白相比，降低低密度脂蛋白加升高高密度脂蛋白的治疗是否会更有效地减少磁共振成像(MRI)评估的斑块脂肪含量，从而进一步减少心脏病发作和中风。