Carotid plaque composition by MRI during lipid-lowering

降脂期间颈动脉斑块组成的MRI分析

• 批准号: 7148228
• 负责人: XUE-QIAO ZHAO
• 金额: $ 29.38万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148228
• 关键词: antihypercholesterolemic agent; antihyperlipoproteinemic agent; atherosclerotic plaque; atorvastatin; bioimaging /biomedical imaging; biomarker; blood lipid; cardiovascular disorder chemotherapy; cardiovascular disorder risk; cardiovascular imaging /visualization; carotid artery; clinical research; contrast media; coronary disorder; high density lipoproteins; human subject; human therapy evaluation; inflammation; longitudinal human study; low density lipoprotein; magnetic resonance imaging; oxidative stress; patient oriented research; prognosis

DESCRIPTION (provided by applicant): This is a revised application of continuation of R01HL63895 entitled CAROTID PLAQUE COMPOSITION BY MRI DURING LIPID-LOWERING, which is a randomized, double blind, and partial placebo controlled study. In this study, 123 patients with CAD or carotid disease and with apolipoprotein B greater to or equal to 120 mg/dl (LDL levels 100-190 mg/dl) were randomized to one of three treatment groups: (1) single therapy - atorvastatin alone, placebos for niaspan and colesevelam; (2) double therapy - atorvastatin plus niaspan (2 g/day), and placebo for colesevelam; (3) triple therapy - atorvastatin, niaspan plus colesevelam (3.8 g/day). The treatment target for LDL is less than or equal to 80 mg/dl for the single and double therapy and less than or equal to 60 mg/dl for the triple therapy. The HDL target for the two niacin-treated groups is to increase 10 mg/dl from baseline. The patient recruitment is completed, and patient clinical/laboratory follow-up is on-going. All patients are undergoing MRI examination of both carotid arteries annually for three years, a total of 4 examinations. This proposed research is the first study to examine plaque lipid depletion, volume reduction, enhancement decrease by contrast-enhanced MRI in vivo during intensive lipid modification among patients with carotid atherosclerosis. The hypotheses and specific aims of the original grant plus this proposed continuation are: (1) to test the hypothesis that intensive lipid-lowering therapy decreases carotid plaque lipid content assessed by contrast-enhanced MRI. (2) To test the secondary and exploratory hypotheses that intensive lipid therapy is associated with plaque regression and decreased plaque enhancement assessed by contrast-enhanced MRI. (3) To examine the association of clinical risk factors, lipids, lipoprotein heterogeneity, inflammatory markers, oxidative stress markers with carotid plaque characteristics. (4) To investigate the effects of HDL-raising and very intensive LDL-lowering, comparing to LDL-lowering alone, on carotid lipid content, volume, and enhancement over 3 years. (5) To determine if carotid plaque characteristics (lipid content, volume, and enhancement) or its change predicts future major cardiovascular events. The primary MRI endpoint is carotid plaque lipid content. The secondary endpoints are plaque volume, other tissue contents. The exploratory endpoint is plaque enhancement assessed by contrast- enhanced MRI. This study employs a state-of-the art technique to examine the effects of lipid-lowering therapy on human atherosclerotic plaque characteristics in vivo and will provide novel insights into our understanding of atherosclerotic plaque pathology and the mechanisms of intensive lipid modification in preventing ischemic events.

描述（由申请人提供）：这是R01HL63895延续的修订应用，标题为MRI在脂质降低过程中由MRI组成，这是一项随机，双盲和部分安慰剂对照研究。在这项研究中，将123例CAD或颈动脉疾病患者和载脂蛋白B的患者更大至或等于120 mg/dl（LDL水平100-190 mg/dl）被随机分为三个治疗组之一：（1）单一治疗 - 单疗疗法 - 单独的atorvastatin，niaspan和colesevelam plentbos； （2）双重治疗 - atorvastatin加niaspan（2 g/day），安慰剂为Colesevelam； （3）三重疗法 - 阿托伐他汀，Niaspan加Colesevelam（3.8 g/天）。对于单疗法和双重治疗，LDL的治疗靶标小于或等于80 mg/dl，对于三重治疗，小于或小于或等于60 mg/dl。两个烟酸蛋白处理组的HDL靶标是从基线增加10 mg/dl。患者招募已完成，并且患者临床/实验室随访正在进行中。所有患者每年三年对两种颈动脉进行MRI检查，共4例检查。这项拟议的研究是第一项研究，在颈动脉粥样硬化患者的强化脂质修饰过程中，在体内进行对比增强的MRI在体内通过对比增强的MRI进行了检查斑块脂质耗竭，增强，增强降低。原始赠款的假设和具体目的加上此拟议的延续是：（1）检验以下假设：强化降低脂质的疗法降低了通过对比增强MRI评估的颈动脉斑块脂质含量。 （2）测试次要和探索性假设，即强化脂质疗法与斑块回归有关，并通过对比增强的MRI评估的牙菌斑增强量减少。 （3）检查临床危险因素，脂质，脂蛋白异质性，炎症标记，氧化应激标志物与颈动脉斑块特征的关联。 （4）研究HDL升高和非常密集的LDL降低的影响，与单独降低LDL的含量对颈动脉脂质含量，体积和增强相比，在3年内。 （5）确定颈动脉斑块特征（脂质含量，体积和增强）是否会预测未来的主要心血管事件。主要MRI端点是颈动脉斑块脂质含量。次要终点是斑块体积，其他组织含量。探索性终点是通过对比度增强MRI评估的牙菌斑增强。这项研究采用了一种最先进的技术来检查体内降低脂质疗法对人动脉粥样硬化斑块特征的影响，并将为我们对动脉粥样硬化斑块病理学的理解提供新颖的见解，以及在预防缺血性事件中进行强化脂质修饰的机制。