CAROTID PLAQUE COMPOSITION BY MRI DURING LIPID-LOWERING

基于动物实验的观察，人类冠脉斑块特征与不稳定临床发作的关系，以及降脂治疗的血管造影消退和临床事件减少，建立了斑块和临床稳定性的脂质耗竭假说。然而，到目前为止，降脂治疗对体内人类动脉粥样硬化斑块成分的影响还不可能。磁共振成像(MRI)是动脉粥样硬化纵向研究的理想选择，因为它是非侵入性的，在区分组织对比方面优于其他成像手段。我们的初步研究的令人鼓舞的结果表明，长时间的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大的因素。我们建议对60例有心血管疾病家族史且载脂蛋白B等于或大于125 mg/dl的冠心病患者进行颈动脉MRI研究。这些患者将被随机分为三联降脂治疗(阿托伐他汀10-40 mg/d，烟酸2-3gm/d，可乐醇20gm/d)或单用他汀类药物(阿托伐他汀20-80 mg/d)，并每年进行一次双侧颈动脉MRI检查，为期三年，共4次。我们将：1)验证强化降脂治疗可耗尽MRI确定的冠心病患者颈动脉斑块脂质成分的假说，并研究斑块脂质及其他斑块成分耗竭与斑块消退的关系；2)通过评估一系列颈动脉MRI检查来确定降脂过程中动脉粥样硬化斑块脂质耗竭的时程；3)继续发展这一非侵入性方法，通过MRI在体内表征人的颈动脉粥样硬化斑块成分。这项研究使用最先进的技术来评估降脂的益处的大小和机制。这将是第一批研究降脂治疗对体内人类动脉粥样硬化斑块影响的研究之一，并将为我们理解动脉粥样硬化斑块的病理机制和降脂治疗预防缺血事件的机制提供新的见解。

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.