Longitudinal Changes in Pericardial Adiposity and Subclinical Atherosclerosis

描述（由申请人提供）：肥胖的流行威胁着最近在美国人群中减少冠心病（CHD）健康负担的进展。关于肥胖和心脏代谢危险因素如何影响冠状动脉和心脏，我们已经知道了很多，但仍有很多不确定的地方。除了关于内脏脂肪组织（VAT）的计算机断层扫描（CT）测量的相当丰富的文献外，越来越多的证据表明，心包脂肪组织（PAT）和心外膜亚室（PATepi）与冠状动脉粥样硬化和心脏结构功能有关。与体重和体重指数相比，PAT、PATepi和VAT的CT测量将肥胖表型细化为精确的器官特异性测量。该项目是NHLBI的年轻人冠状动脉风险发展（CARDIA）的辅助研究，这是一项基于人群的研究，有25年的纵向数据。这项建议的长期目标是通过更好地了解肥胖和冠心病来减少死亡和疾病。我们的具体目标是：1)通过心脏CT在10年（2000-2010年）的三个时间点确定33至55岁的双种族社区居住人群中冠状动脉钙化（CAC）斑块负担、斑点状病变形态的发展和自然史，以及这两个过程的相互关系。2)在三个时间点测量同一受试者的PAT和PATepi，并进行纵向分析，校正体脂指标（BMI和腰围）等危险因素，因变量为CT CAC评分和点状斑块的发展、数量和特征，以及超声心动图测量的不良心脏结构和功能。3)利用高分辨率的25年CT扫描测量43-55岁人群的冠状动脉重构指数（RI），确定RI与PAT、PATepi、VAT（主要研究测量）、CAC评分和点状病变之间的关系，并校正体脂测量（BMI和腰围）等危险因素。针对目标1-3，在2015-2020年将有可能对冠心病事件进行预测分析。心脏CT图像，无需对比，将获得标准和高分辨率的单次暴露，以测量PAT， PATepi， CAC评分，斑点形态和RI，从14秒的额外扫描到资助的腹部CT。后两种“高风险”表型与冠状动脉内超声或尸检发现的急性冠状动脉综合征的罪魁祸首病变有关。该提案通过增加与PAT及其在冠状动脉粥样硬化和心脏结构功能中的作用相关的新科学来利用对CARDIA的投资。该项目将把25年的CARDIA纵向数据（人体测量、生物标志物、行为、社会心理、营养、遗传、CT VAT和心脏超声心动图）与新的表型联系起来。在2010- 2011年对这些表型进行前瞻性测量，将有助于在2015- 2020年对临床冠心病事件进行预测分析，进一步加强其影响。

DESCRIPTION (provided by applicant): The epidemic of obesity threatens recent rogress towards reducing the health burden of coronary heart disease (CHD) in the U.S. population. While much is known regarding how obesity and cardio- metabolic risk factors affect the coronary arteries and heart, much remains uncertain. In addition to the fairly rich literature on computed tomography (CT) measures of visceral adipose tissue (VAT), there is mounting evidence that pericardial adipose tissue (PAT), and the epicardial subcompartment (PATepi), is associated with coronary atherosclerosis and cardiac structure-function. CT measures of PAT, PATepi and VAT refine the adiposity phenotype to precise organ-specific measures, compared to weight and body mass index. This project is an ancillary study to NHLBI's Coronary Artery Risk Development in Young Adults (CARDIA), a population-based study that has 25 years of longitudinal data. The long-term objectives of this proposal are to reduce death and disease through a better understanding of obesity and CHD. Our Specific Aims are: 1) To define the development and natural history of coronary artery calcified (CAC) plaque burden, spotty lesion morphology, and the interrelatedness of the two processes by cardiac CT at three time points over 10 years (2000-2010) in a bi-racial community dwelling population ages 33 to 55 years. 2) To measure PAT and PATepi in the same participants at three time points and perform longitudinal analysis, adjusted for body fatness measures (BMI and waist circumference) and other risk factors, with dependent variables the development, amount, and character of CAC score and spotty plaques by CT and adverse cardiac structure and function measured by echocardiogram. 3) To measure coronary artery remodeling index (RI) in individuals aged 43-55 years with the high-resolution year 25 CT scans and determine the association between RI and PAT, PATepi, VAT (measured by main study), CAC score and spotty lesions, adjusted for body fatness measures (BMI and waist circumference) and other risk factors. Future analysis for prediction of CHD events will be possible by 2015-2020 for aims 1-3. Cardiac CT images, without contrast, will be obtained at standard and high-resolution from a single exposure to measure PAT, PATepi, CAC score, spotty morphology and RI from a 14 second additional scan to the funded abdominal CT. The latter two "high-risk" phenotypes are associated with culprit lesions of the acute coronary syndrome identified by intracoronary ultrasound or at autopsy. This proposal leverages the investment in CARDIA by adding new science related to PAT and its role in coronary atherosclerosis and cardiac structure-function. This project will link 25 years of CARDIA longitudinal data (anthropometric, biomarker, behavioral, psychosocial, nutritional, genetic, CT VAT and cardiac echocardiography) to new phenotypes. Prospectively measuring these phenotypes in 2010-11 will enable future analysis for prediction of clinical CHD events by 2015-20, further strengthening the impact.