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 延续的修订申请，题为“CAROTID PLAQUE COMPOSITION BY MRI DURING LIPID-LOWERING”，这是一项随机、双盲和部分安慰剂对照研究。在这项研究中，123 名患有 CAD 或颈动脉疾病且载脂蛋白 B 大于或等于 120 mg/dl（LDL 水平 100-190 mg/dl）的患者被随机分入三个治疗组之一：(1) 单一疗法 - 阿托伐他汀单独使用 niaspan 和考来维仑的安慰剂； (2)双重疗法——阿托伐他汀加niaspan(2g/天)，以及考来维仑安慰剂； (3)三联疗法——阿托伐他汀、niaspan加考来维仑(3.8g/天)。单次和双联治疗的 LDL 治疗目标为小于或等于 80 mg/dl，三联治疗的 LDL 治疗目标为小于或等于 60 mg/dl。两个烟酸治疗组的 HDL 目标是从基线增加 10 mg/dl。患者招募已完成，患者临床/实验室随访正在进行中。所有患者均每年接受双侧颈动脉MRI检查，连续三年，共4次检查。这项拟议的研究是第一项在颈动脉粥样硬化患者的强化调脂过程中通过体内对比增强 MRI 检查斑块脂质消耗、体积减少、增强减少的研究。原始资助加上此提议的延续的假设和具体目标是：（1）检验强化降脂治疗可降低通过对比增强 MRI 评估的颈动脉斑块脂质含量的假设。 (2) 检验次要和探索性假设，即强化脂质治疗与通过对比增强 MRI 评估的斑块消退和斑块增强减少相关。 (3)考察临床危险因素、血脂、脂蛋白异质性、炎症标志物、氧化应激标志物与颈动脉斑块特征的关系。 (4) 调查与单独降低 LDL 相比，HDL 升高和非常强烈的 LDL 降低对 3 年内颈动脉脂质含量、体积和增强的影响。 (5) 确定颈动脉斑块特征（脂质含量、体积和增强）或其变化是否可以预测未来的主要心血管事件。主要 MRI 终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增强 MRI 评估斑块增强情况。这项研究采用最先进的技术来检查降脂疗法对人体内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和强化脂质修饰预防缺血事件的机制的理解提供新的见解。 。