Carotid plaque composition by MRI during lipid-lowering

说明(申请人提供)：这是一项随机、双盲、部分安慰剂对照的随机、双盲、部分安慰剂对照研究，是R01HL63895题为《降脂期间颈动脉斑块成分的MRI》的修订申请。在这项研究中，123名冠心病或颈动脉疾病且载脂蛋白B大于或等于120 mg/dl(低密度脂蛋白水平为100-190 mg/dl)的患者被随机分成三组：(1)单一治疗--阿托伐他汀，NIASPAN和科莱维仑的安慰剂；(2)双重治疗--阿托伐他汀加NIASPAN(2g/天)，以及安慰剂(科莱维仑)；(3)三联治疗--阿托伐他汀，NIASPAN+科莱维仑(3.8g/天)。低密度脂蛋白的治疗目标对于单次和双重治疗小于或等于80 mg/dl，对于三联治疗小于或等于60 mg/dl。两个烟酸治疗组的高密度脂蛋白目标是在基线的基础上增加10 mg/dl。病人招募工作已经完成，病人的临床/实验室跟进工作正在进行中。所有患者均接受为期3年的双侧颈动脉MRI检查，共4次。这项研究是首次通过增强MRI检查颈动脉粥样硬化患者强化调脂过程中的斑块脂质耗竭、体积缩小、强化减少的情况。最初的拨款加上这项拟议的继续拨款的假设和具体目标是：(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)验证强化脂肪治疗与斑块消退和斑块增强程度降低相关的二级和探索性假说。(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)与单纯降低低密度脂蛋白比较，观察3年内高密度脂蛋白升高和低密度脂蛋白高强度降低对颈动脉脂质含量、体积和强化的影响。(5)确定颈动脉斑块特征(脂质含量、体积和强化)或其变化是否预测未来的重大心血管事件。MRI的主要终点是颈动脉斑块中的脂质含量。次要终点为斑块体积、其他组织内容物。探查终点是通过对比增强MRI评估的斑块强化。本研究采用最先进的技术，在活体内检测了降脂治疗对人类动脉粥样硬化斑块特征的影响，将为我们理解动脉粥样硬化斑块的病理学和强化脂质修饰预防缺血事件的机制提供新的见解。

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.