Carotid plaque characteristics by MRI in AIM-HIGH

AIM-HIGH 中 MRI 的颈动脉斑块特征

基本信息

批准号：
7383537
负责人：
XUE-QIAO ZHAO
金额：
$ 72.14万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
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/7383537
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

项目摘要

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（由申请人提供）：这是我们的研究申请（1 R01 HL088214-01）的重新提交申请，题为“AIM-HIGH 中 MRI 的颈动脉斑块特征”。尽管研究表明斑块形态和成分是斑块稳定性的重要决定因素，然而，我们对斑块组织成分的理解主要来自组织学研究，直到最近MRI技术的发展。低水平的高密度脂蛋白与心血管事件的较高风险和颈动脉斑块中脂质含量的增加有关。与单独降低 LDL 相比，降低 LDL 联合升高 HDL 治疗可以更有效地防止动脉粥样硬化进展。人们普遍认为，HDL 或其载脂蛋白介导从外周细胞去除过量的游离胆固醇，并且胆固醇通过 LDL 或 HDL 输送到肝脏，然后排泄到胆汁中。然而，它尚未在人体动脉粥样硬化条件下进行体内测试和批准。 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 LDL 与使用他汀类药物联合烟酸联合治疗降低 LDL 和升高 HDL 对已患有血管疾病和高血压的患者的临床疗效。甘油三酯和低 HDL。我们建议对 AIM-HIGH 中登记的 300 名受试者进行颈动脉 MRI 子研究，以研究 HDL 升高治疗的重要血管生物学机制。假设和具体目标是：（1）检验主要假设，即与单独降低 LDL 相比，强化 LDL 降低加 HDL 升高治疗可降低 MRI 评估的颈动脉中平均斑块脂质成分。 (2) 检验以下假设：与单独降低 LDL 相比，强化 LDL 降低加 HDL 升高治疗可降低斑块负荷，包括体积和壁厚度。 (3) 通过 MRI 检验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设。 (4)检查临床危险因素、血脂、脂蛋白异质性、炎症标志物和颈动脉斑块特征的关联。这项拟议的 MRI 子研究提供了一个独特的机会来研究降低 LDL 和升高 HDL 疗法对体内人动脉粥样硬化斑块的有效性，检查通过 MRI 评估的斑块特征（脂质成分和体积）与心血管结果之间的关联，以及获得对动脉粥样硬化斑块病理学和强化脂质管理预防心血管事件机制的新见解。由不稳定的动脉粥样硬化斑块引起的心脏病和中风仍然是美国的主要原因。不稳定的斑块通常比稳定的斑块含有更多的脂肪。拟议的研究将调查与单独降低 LDL 相比，降低 LDL 加上提高 HDL 的治疗是否能更有效地降低磁共振成像 (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。