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: 7626448
• 负责人: XUE-QIAO ZHAO
• 金额: $ 28.93万
• 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/7626448
• 关键词: Aftercare; Apolipoproteins B; Arterial Fatty Streak; Arts; Blinded; Cardiovascular system; Carotid Arteries; Carotid Artery Plaques; Carotid Atherosclerotic Disease; Characteristics; Clinical; Disease; Double-Blind Method; Enrollment; Event; Future; Goals; Grant; Heterogeneity; High Density Lipoprotein therapy; High Density Lipoproteins; Hospitalization; Human; Inflammation; Ischemia; Laboratories; Lipids; Lipoproteins; Low-Density Lipoproteins; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Modification; Monitor; Nicotinic Acids; Oxidative Stress; Pathology; Patient Recruitments; Patients; Placebo Control; Placebos; Protocols documentation; Randomized; Research; Research Personnel; Risk; Risk Factors; Stroke; Study Subject; Techniques; Testing; Time; Tissues; atorvastatin; colesevelam; follow-up; improved; in vivo; inflammatory marker; insight; mortality; neovasculature; novel; patient safety; placebo controlled study; prevent; programs; treatment effect

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）：这是一份标题为“通过MRI在降脂期间观察颈动脉斑块组成”的R 01 HL 63895的修订后延续申请，该研究是一项随机、双盲和部分安慰剂对照研究。在这项研究中，123例CAD或颈动脉疾病患者，载脂蛋白B ≥ 120 mg/dl，（LDL水平100-190 mg/dl）被随机分配到三个治疗组中的一个：（1）单一疗法-单独的阿托伐他汀，用于niaspan和考来维仑的安慰剂;（2）双重疗法-阿托伐他汀加niaspan（2 g/天），和用于考来维仑的安慰剂;（3）三联疗法-阿托伐他汀、niaspan加考来维仑（3.8g/天）。LDL的治疗目标是单药和双联治疗小于或等于80 mg/dl，三联治疗小于或等于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。所有患者均接受双侧颈动脉的MRI检查，每年一次，共4次，共3年。这项研究是第一项研究，以检查斑块脂质耗竭，体积减少，增强减少对比增强MRI在体内强化脂质修饰的颈动脉粥样硬化患者。最初的资助加上这次提议的延续的假设和具体目的是：（1）检验强化降脂治疗降低对比增强MRI评估的颈动脉斑块脂质含量的假设。(2)检验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降低相关的次要和探索性假设。(3)探讨临床危险因素、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)研究3年来，与单纯降低LDL相比，升高HDL和非常密集的降低LDL对颈动脉脂质含量、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、其他组织内容物。探索性终点是通过对比增强MRI评估斑块增强。这项研究采用了最先进的技术，以检查降脂治疗对人体动脉粥样硬化斑块特征在体内的影响，并将提供新的见解，我们了解动脉粥样硬化斑块的病理学和机制，密集的脂质修饰，以防止缺血事件。