Carotid plaque composition by MRI during lipid-lowering

描述（由申请人提供）：这是R01HL63895的续篇修订申请，题为“降脂期间颈动脉斑块组成MRI”，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例冠心病或颈动脉疾病患者，载脂蛋白B大于或等于120 mg/dl （LDL水平100-190 mg/dl）被随机分为三个治疗组：(1)单一治疗-阿托伐他汀单独治疗，niaspan和colesvelam安慰剂；(2)双重治疗-阿托伐他汀加尼亚斯潘（2g /天），和安慰剂治疗colesevelam；(3)三联治疗-阿托伐他汀，尼亚斯潘加colesevam （3.8 g/天）。低密度脂蛋白的治疗目标在单药和双药治疗中小于等于80 mg/dl，在三联治疗中小于等于60 mg/dl。两个烟酸治疗组的HDL目标是比基线增加10 mg/dl。患者招募已完成，患者临床/实验室随访正在进行中。所有患者均每年行双颈动脉MRI检查，为期三年，共4次检查。本研究是第一个在颈动脉粥样硬化患者体内通过磁共振造影增强检查强化脂质修饰过程中斑块脂质消耗、体积减小、增强降低的研究。最初拨款的假设和具体目的是：(1)验证强化降脂治疗降低颈动脉斑块脂质含量的假设，通过对比增强MRI评估。(2)验证二级和探索性假设，即强化脂质治疗与斑块消退和斑块增强减少有关，对比增强MRI评估。(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)研究与单纯降低ldl相比，高密度脂蛋白升高和高密度ldl降低对颈动脉脂质含量、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）或其变化是否能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。探索性终点是斑块增强，通过对比增强MRI评估。本研究采用了最先进的技术来检查降脂治疗对体内人类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和强化脂质修饰预防缺血性事件的机制的理解提供新的见解。

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.