Imaging of Aortic Atherosclerosis and Inflammation in the Metabolic Syndrome

尽管在识别和降低风险方面取得了进展，动脉粥样硬化性心血管疾病(CVD)仍然是美国发病率和死亡率的主要原因。动脉粥样硬化主要影响大中型血管，尸检数据表明腹主动脉为动脉粥样硬化的研究提供了一个有价值的早期窗口。冠心病的危险因素包括年龄、男性、早发冠心病家族史、高血压、吸烟、糖尿病、高密度脂蛋白胆固醇升高和低高密度脂蛋白胆固醇。代谢综合征(肥胖、胰岛素抵抗、高血压、糖耐量受损、高胰岛素血症和血脂异常)在美国非常普遍，与冠心病和炎症有关，越来越多地被认为是动脉粥样硬化和胰岛素抵抗的主要致病因素。非侵入性血管成像技术，包括心血管磁共振(CMR)和多探测器计算机断层扫描(MDCT)提供了识别、量化和表征动脉粥样硬化的机会。CMR和MDCT在提供有关斑块体积和特征的信息方面具有互补性，CMR在提供有关斑块成分的信息方面具有更高的敏感性，包括在非电离辐射环境中和在没有碘化造影剂的情况下的炎症。对比增强CMR(CE-CMR)是一种新的CMR应用，已被证明有助于评估主动脉斑块的纤维化和识别纤维帽的局灶性炎症。我们研究所最近资助了一个专门的临床导向研究中心(SCCOR)的血管损伤、修复和重塑项目，其中心主题是“代谢综合征、炎症和血管重塑”。这项母公司SCCOR将随机对720名患有冠心病和代谢综合征的患者进行30个月的1)常规护理，2)新的抗炎盐酸盐或3)强化生活方式改变，监测炎症标志物和基线/30个月冠状动脉MDCT以监测动脉粥样硬化。这一母公司SCCOR提供了及时和经济高效的机会来扩大我们对动脉粥样硬化过程的了解，包括这些新疗法对局部斑块炎症的影响，通过应用先进的CMR方法来表征代谢综合征中的动脉粥样硬化和炎症，它与生化炎症标志物的关系，以及斑块和斑块成分(包括炎症)对常规和新疗法的反应。我们还将有机会将这些发现与冠状动脉MDCT测量的软斑块和钙化斑块进行比较。我们建议从720名患有代谢综合征的父母SCCOR受试者中招募420名受试者(每个治疗组140人)。主要和次要目标包括将主动脉斑块体积、斑块成分、管壁面积、血管炎症的定量CMR测量与MDCT斑块测量和全身炎症的系统生化测量相关联，并表征这些CMR测量对30个月的常规和新型抗炎治疗的反应，并与全身炎症生化测量的变化相关联。PHS 398/2590(版本09/04,2006年4月再次发布)页面延续格式页面首席研究员/项目主管(最后、第一、中间)：Manning，Warren J.尽管动脉粥样硬化性心血管疾病(CVD)在识别和降低风险方面取得了进展，但仍是美国发病率和死亡率的主要原因。动脉粥样硬化主要影响大中型血管，尸检数据表明腹主动脉为动脉粥样硬化的研究提供了一个有价值的早期窗口。非侵入性血管成像技术，包括心血管磁共振(CMR)和多探测器计算机断层扫描(MDCT)提供了识别、量化和表征动脉粥样硬化的机会。我们研究所最近资助了一个专门的临床导向研究中心(SCCOR)的血管损伤、修复和重塑项目，其中心主题是“代谢综合征、炎症和血管重塑”。这项母公司SCCOR将随机对720名患有冠心病和代谢综合征的患者进行30个月的1)常规护理，2)新的抗炎盐酸盐或3)强化生活方式改变，监测炎症标志物和基线/30个月冠状动脉MDCT以监测动脉粥样硬化。在这项研究中，主要和次要目的包括将主动脉斑块体积、管壁面积、血管炎症的CMR指标与MDCT斑块指标和全身炎症的生化标志物指标联系起来，并通过与全身炎症生化标志物的相关性来表征这些CMR指标对常规和新型抗炎治疗30个月的反应。

Despite advances in both identification and risk reduction, atherosclerotic cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Atherosclerosis primarily affects large and medium sized vessels with autopsy data demonstrating that the abdominal aorta offers a valuable early window for the study of atherosclerosis. Coronary heart disease (CHD) risk factors include age, male gender, family history of premature CHD, hypertension, smoking, diabetes, elevated LDL-C, and low HDL-C. The Metabolic Syndrome [obesity, insulin resistance, hypertension, impaired glucose tolerance, hyperinsulinemia, and dyslipidemia), highly prevalent in the United States and implicated in CHD and inflammation, is increasingly accepted as a major contributor to the pathogenesis both of atherosclerosis and of insulin resistance. Non-invasive vascular imaging techniques, including cardiovascular magnetic resonance (CMR) and multidetector computed tomography (MDCT) offer the opportunity to identify, quantify, and characterize atherosclerosis. CMR and MDCT are complementary in providing information about plaque volume and characterization, with increased sensitivity of CMR for providing information regarding plaque components, including inflammation in a non-ionizing radiation environment and in the absence of iodinated contrast. Contrast-enhanced CMR (CE-CMR) is a new CMR application that has been shown to be useful for the evaluation of aortic plaque for fibrosis and for identification of focal inflammation in the fibrous cap. A Specialized Center of Clinically Oriented Research (SCCOR) program in Vascular Injury, Repair, and Remodeling with the central theme "Metabolic Syndrome, Inflammation and Vascular Remodeling" was recently funded by the NHLBI at our insitution. This parent SCCOR will randomize 720 subjects with CHD and Metabolic Syndrome to 30 months of 1) usual care 2) novel anti-inflammatory salsalates or 3) intensive lifestyle modification with monitoring inflammatory markers and baseline/30 month coronary MDCT to monitor atherosclerosis. This parent SCCOR offers the timely and cost-effective opportunity to expand our knowledge regarding the atherosclerotic process including the impact of these novel therapies on focal plaque inflammation by applying advanced CMR methods to characterize aortic atherosclerosis and inflammation in the Metabolic Syndrome, its relationship to biochemical inflammatory markers, and the response of the plaque and plaque components (including inflammation) to usual and novel treatment. We will also have the opportunity to compare these findings with coronary MDCT measures of soft and calcified plaque. We propose to recruit a subset of 420 subjects (n=140 in each treatment group) of the 720 parent SCCOR subjects with Metabolic Syndrome. The primary and secondary aims include relating quantitative CMR measures of aortic plaque volume, plaque components, vessel wall area, vessel inflammation with MDCT plaque measures and systemic biochemical measures of systemic inflammation and to characterize the response of these CMR measures to 30 months of conventional and novel antiinflammatory therapies with correlation with changes in systemic biochemical measures of inflammation. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): Manning, Warren J. Despite advances in both identification and risk reduction, atherosclerotic cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Atherosclerosis primarily affects large and medium sized vessels with autopsy data demonstrating that the abdominal aorta offers a valuable early window for the study of atherosclerosis. Non-invasive vascular imaging techniques, including cardiovascular magnetic resonance (CMR) and multidetector computed tomography (MDCT) offer the opportunity to identify, quantify, and characterize atherosclerosis. A Specialized Center of Clinically Oriented Research (SCCOR) program in Vascular Injury, Repair, and Remodeling with the central theme "Metabolic Syndrome, Inflammation and Vascular Remodeling" was recently funded by the NHLBI at our insitution. This parent SCCOR will randomize 720 subjects with CHD and Metabolic Syndrome to 30 months of 1) usual care 2) novel anti-inflammatory salsalates or 3) intensive lifestyle modification with monitoring inflammatory markers and baseline/30 month coronary MDCT to monitor atherosclerosis. In this study, the primary and secondary aims include relating CMR measures of aortic plaque volume, vessel wall area, vessel inflammation with MDCT plaque measures and measures of biochemical markers of systemic inflammation and to characterize the response of these CMR measures to 30 months of conventional and novel antiinflammatory therapies with correlation with systemic biochemical markers of inflammation.