Longitudinal Changes in Pericardial Adiposity and Subclinical Atherosclerosis

描述(由申请人提供)：肥胖症的流行威胁着最近在美国人口中减轻冠心病(CHD)健康负担的努力。虽然关于肥胖和心脏代谢风险因素如何影响冠状动脉和心脏已知很多，但仍有许多不确定之处。除了相当丰富的关于内脏脂肪组织(VAT)的CT测量的文献外，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测量精炼肥胖症的表型，以精确的器官特异性测量。该项目是NHLBI的青年冠状动脉风险发展(CARDIA)的辅助研究，CARDIA是一项基于人群的研究，拥有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)在一个年龄在33岁到55岁的混血人群中，通过心脏CT在三个时间点(2000-2010年)确定冠状动脉钙化(CAC)斑块负荷的发展和自然历史、斑块病变的形态以及这两个过程的相互关系。2)测量同一受试者在3个时间点的PAT和PATEPI，并进行纵向分析，调整体脂测量(BMI和腰围)和其他危险因素，以CT测量的CAC评分和斑块的发展、数量和特征为因变量，超声心动图测量不利的心脏结构和功能。3)用25年高分辨率CT扫描测量43~55岁人群的冠状动脉重塑指数(RI)，确定RI与PAT、PATEPI、VAT(主要研究测量)、CAC评分和斑点状病变之间的关系，并调整体脂测量(BMI和腰围)和其他危险因素。到2015-2020年，对目标1-3进行冠心病事件预测的未来分析将成为可能。心脏CT图像将从一次曝光中以标准和高分辨率获得，没有对比度，从资助的腹部CT额外扫描14秒，测量PAT、PATEPI、CAC评分、斑点形态和RI。后两种“高危”表型与冠状动脉内超声或尸检确定的急性冠脉综合征的元凶病变有关。这项建议通过增加与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平衡对CARDIA的投资。该项目将把CARDIA 25年的纵向数据(人体测量、生物标记物、行为、心理社会、营养、遗传、CT增值税和心脏超声心动图)与新的表型联系起来。在2010-11年前瞻性地测量这些表型，将使到2015-20年预测临床CHD事件的未来分析成为可能，从而进一步加强影响。

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.