Subclinical CVD in African American Type 2 Diabetics

描述（由申请人提供）：相对于欧洲裔美国人（EAs），非洲裔美国人（aa）有更高的心肌梗死率，可能反映了较差的医疗保健机会。相比之下，当提供平等的医疗保健机会时，AAs的心肌梗死发生率比ea低50%。一个相关的观察结果是，以冠状动脉钙化斑块（CAC）衡量，AAs明显较少发生亚临床心血管疾病（CVD）。尽管在AAs中存在更严重的传统心血管疾病危险因素，但仍会发生这种情况。CAC可预测未来心肌梗死的风险。基于我们早期的发现，AAs发生CAC（及相关心肌梗死）的生物学风险低于ea，这一范式发生了转变。在人群中表现出不同频率的遗传多态性可能导致CAC的种族差异，以及存在新的cvd相关因素，包括骨矿化和血清维生素D水平。

DESCRIPTION (provided by applicant): Relative to European Americans (EAs), African Americans (AAs) have higher rates of myocardial infarction, possibly reflecting poorer access to healthcare. In contrast, when provided equal access to healthcare, AAs have 50% lower myocardial infarction rates than EAs. A related observation is that AAs have markedly less subclinical cardiovascular disease (CVD) measured as coronary artery calcified plaque (CAC). This occurs despite the presence of more severe conventional CVD risk factors in AAs. CAC predicts future risk of myocardial infarction. A paradigm shift developed based on our earlier finding that AAs are at lower biologic risk for developing CAC (and associated myocardial infarction) than EAs. Genetic polymorphisms exhibiting different frequencies between population groups likely contribute to the racial difference in CAC, as well as presence of novel CVD-associated factors including bone mineralization and serum vitamin D levels, both associated with CAC. This project targets the pathogenesis of CAC by focusing on racial differences in subclinical CVD with emphasis on the understudied relationship between bone health, vitamin D, and CAC. AAs also manifest lower rates of osteoporosis despite lower vitamin D levels and ingestion of less dietary calcium than EAs. There remains a critical need to collect longitudinal data tracking changes in CAC and bone mineral density in relation to vitamin D and assess the importance of these factors in AAs who are at high CVD risk. This renewal application proposes to: (1) longitudinally measure CAC and bone mineral density, and their relative association with novel CVD-associated factors including serum vitamin D and bone metabolism in African American-Diabetes Heart Study (AA-DHS) participants, among the most extensively phenotyped AA cohort with type 2 diabetes~ (2) explore the roles of novel CVD risk factors on development and progression of CAC~ and (3) identify the genetic variation that contributes to lower rates of CAC in AAs. The presence of diabetes in our unique AA-DHS cohort likely contributed to their higher CAC scores. Follow-up exams in the well phenotyped and genotyped AA-DHS cohort will provide critically important data which will increase our understanding of CVD risk in AAs. Our diabetes-duration matched sample of 1,200 EAs recruited in the Wake Forest Diabetes Heart Study with genome-wide association data will allow for rapid replication of genetic associations with CAC in AAs. The roles of vitamin D and bone metabolism on development and progression of CAC are of intense interest, as controversy surrounds supplemental vitamin D in AAs due to potential injury to coronary arteries and bone. Exploring links between genetic risk, bone health and vitamin D will improve our understanding of subclinical atherosclerosis in AAs and aid in development of novel treatment and prevention strategies.