CAROTID PLAQUE COMPOSITION BY MRI DURING LIPID-LOWERING

基于动物研究的观察结果、人类冠状动脉斑块特征与不稳定临床发作之间的关系以及血管造影消退和降脂治疗的临床事件减少，已经建立了斑块和临床稳定性的脂质耗竭假设。 然而，迄今为止，降脂治疗对体内人动脉粥样硬化斑块组成的影响尚不可能。磁共振成像（MRI）是理想的纵向研究动脉粥样硬化动脉，因为它是无创性的，是上级优于其他成像方式在区分组织对比。 我们的初步研究令人鼓舞的结果表明，长期强化降脂治疗似乎与斑块中脂质成分的减少有关，这被认为是预测斑块稳定性更高的因素。我们建议对60例有心血管疾病家族史且ApoB ≥ 125 mg/dl的CAD患者进行颈动脉MRI研究。 这些患者将随机接受三联降脂治疗（阿托伐他汀10-40 mg/天、烟酸2-3 gm/天和考来替泊20 gm/天）或单他汀类药物治疗（阿托伐他汀20-80 mg/天），并将每年接受双侧颈动脉MRI检查，持续3年，共4次检查。 我们将：1）检验强化降脂治疗耗尽CAD患者颈动脉中通过MRI鉴定的斑块脂质组成的假设，并检查斑块脂质和其它斑块组分的耗尽与斑块消退之间的关系; 2）通过评估连续颈动脉MRI检查来确定降脂期间动脉粥样硬化斑块脂质耗尽的时间过程; 3）继续发展这种无创方法，通过MRI在体内表征人类颈动脉粥样硬化斑块的组成。 本研究采用最先进的技术来评估降脂获益的程度和机制。 这将是第一个研究降脂治疗对人体动脉粥样硬化斑块在体内的影响，并将提供新的见解，我们了解动脉粥样硬化斑块的病理和降脂治疗预防缺血事件的机制。

The hypothesis of lipid depletion for plaque and clinical stability has been established based on observations from animal studies, the relation between human coronary plaque features and unstable clinical episodes, and angiographic regression and clinical event reduction with lipid-lowering therapy. However, the effect of lipid-lowering therapy on human atherosclerotic plaque composition in vivo has not been possible, to date. Magnetic resonance imaging (MRI) is ideal for longitudinal studies of atherosclerotic arteries because it is noninvasive and is superior to other imaging modalities in discriminating tissue contrast. Encouraging results from our pilot study show that prolonged intensive lipid-lowering therapy appears to be associated with a decreased lipid composition in the plaque, which is considered to predict greater plaque stability. We propose to perform carotid MRI studies in 60 CAD patients with a family history of cardiovascular disease and ApoB equal to or greater than 125 mg/dl. These patients will be randomized to triple lipid-lowering therapy (atorvastatin 10-40 mg/day, niacin 2-3 gm/day, and colestipol 20 gm/day) or to mono-statin therapy (atorvastatin 20-80 mg/day), and will undergo MRI examination of both carotid arteries annually for three years, a total of 4 examinations. We will: 1) test the hypothesis that intensive lipid-lowering therapy depletes plaque lipid composition identified by MRI in carotid arteries in CAD patients and examine the relationship between depletion of plaque lipid and other plaque components and plaque regression; 2) determine the time- course of atherosclerotic plaque lipid depletion during lipid- lowering by assessing serial carotid MRI examinations; 3) continue the development of this noninvasive approach to characterize human carotid atherosclerotic plaque composition in vivo by MRI. This study employs a state-of-the art technique to assess both the magnitude and mechanisms of benefit of lipid- lowering. It will be one of the first studies to examine the effects of lipid-lowering therapy on human atherosclerotic plaques in vivo and will provide novel insights into our understanding of atherosclerotic plaque pathology and the mechanisms of lipid-lowering therapy preventing ischemic events.