Ventricular Size and Valve Calcification Measures by CT

这一建议与动脉粥样硬化多种族研究(MESA)相一致，MESA是一项大型前瞻性流行病学研究，调查多种亚临床心血管措施和心血管疾病危险因素。MESA的亚临床测量包括冠脉钙化、颈动脉超声、心脏磁共振成像和踝关节/臂部血压指数。广泛的心血管危险因素评估既包括传统的危险因素，也包括新的指标，如炎症和内皮功能指标。这项建议的主要长期目标是确定非酒精性脂肪肝(NAFLD)的流行病学和遗传学。越来越多的数据表明，NAFLD与代谢综合征/糖尿病、亚临床动脉粥样硬化和心血管结果之间存在因果联系。通过比较肝脏密度和脾脏密度，CT可以很好地评价肝脏脂肪含量。在MESA进行的心脏研究允许在所有研究中显示高达93%的肝脏和脾，并应提供足够的能量，使用已经获得的非增强心脏CT扫描，在没有参与者负担的情况下，评估这种疾病以及随时间的时间变化。该项目的这一部分有三个主要的具体目标：1)在动脉粥样硬化的多种族研究中确定脂肪肝的患病率和临床相关性，包括糖尿病、胰岛素抵抗和炎症标记物；2)确定脂肪肝与血管和瓣膜钙化以及亚临床动脉粥样硬化(包括冠状动脉钙化和颈动脉内中膜厚度)的横向和纵向关联；3)确定脂肪肝与心血管事件的关联。目前提出的这项研究应该可以在多种族人群中首次大规模评估CT测量的NAFLD与亚临床动脉粥样硬化(踝臂指数、冠状动脉钙化、颈动脉内膜中层厚度、炎症、主动脉粥样硬化--包括胸主动脉和主动脉)和后续事件的关系。MESA研究是一项非常好的表型和基因分型的多民族队列研究--确实是世界上最有价值的流行病学资源之一。该应用建议NAFLD-检查与风险因素、亚临床疾病、炎性标记物以及与事件的关系的横断面关系。如果成功，与病理生理学相关的新信息，以及与心血管危险因素和亚临床动脉粥样硬化的关系，可能成为开发新的诊断或治疗策略的基础，以改进NAFLD和相关的心血管疾病的检测或减轻负担。

This proposal is coordinated with the Multi-Ethnic Study of Atherosclerosis (MESA), a large prospective epidemioloigic study investigating multiple subclinical CVD measures and CVD risk factors. Subclinical measures in MESA include coronary calcium, carotid ultrasound, cardiac magnetic resonance imaging, and the ankle/brachial blood pressure index. The extensive CVD risk factor assessement includes both traditional risk factors and newer measures such as inflammatory and endothelial function measures. The primary long-term objective of this proposal is to determine the epidemiology and genetics of non-alcoholic fatty liver (NAFLD). Increasing data suggests a causal link between NAFLD and metabolic syndrome/diabetes, subclinical atherosclerosis and cardiovascular outcomes. CT has been well validated to evaluate liver fat, by comparing the liver attenuation and spleen. The cardiac studies performed in MESA allow for visualization of the liver and spleen in up to 93% of all studies, and should provide ample power to allow assessment of this disease, as well as temporal changes over time, using the non-enhanced cardiac CT scans already obtained, with no participant burden. This portion of the project has three primary specific aims: 1) Determine the prevalence and clinical correlates of fatty liver in the Multi-Ethnic Study of Atherosclerosis, including diabetes, insulin resistance and inflammatory markers; 2) Determine the cross-sectional and longitudinal associations of fatty liver with vascular and valvular calcification and subclinical atherosclerosis (including coronary calcium and carotid intimalmedia thickness); 3) Determine the association of fatty liver with incident cardiovascular events. This current proposed study should allow the first large assessment of the relationship of NAFLD, as measured by CT, to subclinical atherosclerosis (ankle brachial index, coronary artery calcium, carotid intimal media thickness, inflammation, aortic atherosclerosis-both thoracic and aortic) and subsequent events in a multi-ethnic population. The MESA study is an exceptionally well phenotyped and genotyped multiethnic cohort – and truly among the most valuable epidemiological resources in the world. The application proposes NAFLD – examining the cross-sectional relations with risk factors, subclinical disease, inflammatory markers and the relation to incident events. If successful the new information related to the pathophysiology, as well as relationships to cardiovascular risk factors and subclinical atherosclerosis, may form the basis for the development of new diagnostic or therapeutic strategies that improve detection or reduce the burden of NAFLD and associated CV disease.