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：
7563275
负责人：
XUE-QIAO ZHAO
金额：
$ 70.82万
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/7563275
关键词：
Apolipoproteins Arterial Fatty Streak Atherosclerosis Authorship Bile fluid Biological Biology Blinded Blood Vessels Blood specimen Calcium Cardiovascular system Carotid Arteries Carotid Artery Plaques Cause of Death Cells Cessation of life Characteristics Cholesterol Clinical Clinical Research Clinical Trials Data Monitoring Committees Code Combined Modality Therapy Critiques Data Development Effectiveness Enrollment Event Excision Excretory function Fatty acid glycerol esters Funding Future Goals Health Hemorrhage Heterogeneity High Density Lipoproteins Hospitalization Human Hypertriglyceridemia Image Imaging Techniques Individual Intervention Knowledge Laboratories Link Lipids Lipoproteins Liver Low-Density Lipoproteins Magnetic Resonance Imaging Measurement Measures Mediating Medicine Metabolic syndrome Monitor Morphology Myocardial Infarction Nicotinic Acids Outcome Paper Pathology Patients Peer Review Peripheral Principal Investigator Procedures Publications Qualifying Randomized Reader Reproducibility Research Research Personnel Research Project Grants Risk Risk Factors Safety Scanning Series Stroke Study Subject Testing Thick Time Tissues Translating United States Vascular Diseases acute coronary syndrome atherothrombosis base cardiovascular risk factor clinical efficacy data management design experience high risk human subject protection in vivo indexing inflammatory marker innovation insight novel prevent programs response skills sound statistical service statistics success

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的重新提交申请（1 R01 HL088214-01），标题为“ MRI在AIM-HIGH中由MRI进行的carotid斑块特性”。尽管研究表明，斑块形态和组成是斑块稳定性的重要决定因素，但是，我们对斑块组织成分的理解主要来自组织学研究，直到MRI技术的最新发展。低水平的HDL与颈动脉斑块中心血管事件的较高风险和增加的脂质含量有关。与单独使用LDL的降低相比，使用LDL降低加和HDL升高的治疗可以更有效地防止动脉粥样硬化的进展。人们普遍认为，HDL或其载脂蛋白介导了从外围细胞中去除过量的游离胆固醇，并且胆固醇通过LDL或HDL递送到肝脏中，以排出胆汁。但是，尚未在人体动脉粥样硬化状态下对其进行测试和批准。 NIH/KOS支持的多中心AIM-HIGH试验旨在将单独使用LDL降低的临床功效与他汀类药物与降低LDL的抗LDL和毒素降低的HDL-RASIS与他汀类药物加HDL-Rising在患有既定血管疾病和高triglycerides和High Triglycerides和低HDL的患者中使用他汀类药物和烟酸组合疗法。我们建议在300名参与AIM-HIGH的受试者中进行颈动脉MRI子研究，以研究HDL促进疗法的重要血管生物学机制。假设和特定目的是：（1）测试主要假设，即与单独降低LDL的降低LDL降低和HDL促进疗法相比，在MRI评估的颈动脉中，降低了平均斑块脂质组成。（2）为了测试与单独降低LDL的假设相比，密集的LDL降低加和HDL-RAISIS疗法会减少牙菌斑负担，包括体积和壁厚。（3）测试假说，即MRI增加的斑块脂质组成或血管壁厚与心血管事件的风险增加有关。（4）检查临床危险因素，脂质，脂蛋白异质性，炎症标记和颈动脉斑块特征的关联。这项提出的MRI子研究提供了一个独特的机会，可以调查降低LDL的效果以及体内对人动脉粥样硬化斑块上的HDL-RISIS疗法的有效性，以研究斑块特征和通过MRI和心血管疾病的新颖性，并在我们的理解中获得新颖的理解，并在本机构中获得了新的理解，并在本体内评估了斑块组合和体积的相关性。心血管事件。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美国的主要死亡原因。不稳定的斑块通常比稳定的斑块更多。拟议的研究将调查与单独使用LDL降低LDL的处理以及单独使用LDL降低的治疗方法是否会更有效地减少通过磁共振成像（MRI）评估的斑块脂肪含量（MRI），因此，进一步降低了心脏病发作和中风。