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.
The health-related importance and significance of this project revolves around the increasing prevalence of fatty liver disease, which can lead to liver failure and cirrhosis. Fatty liver disease is the most common cause of chronic liver disease, with a prevalence of 34% among adults in the United States. Furthermore, there is a relationship between obesity, diabetes and fatty liver, and with increasing prevalence of these disorders, and better understanding of the associated factors and prevalence of fatty liver in a population based study is critical to understanding and potentially treating this disorder. 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. The primary long-term objective of this proposal is to determine the epidemiology, genetics and associations of non-alcoholic fatty liver (NAFLD). 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.
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