Subclinical CVD in African American Type 2 Diabetics

非裔美国人 2 型糖尿病患者的亚临床 CVD

• 批准号: 8690833
• 负责人: BARRY Ira FREEDMAN
• 金额: $ 38.16万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8690833
• 关键词: Adipose tissue; Admixture; African American; Albuminuria; American; Architecture; Arterial Fatty Streak; Atherosclerosis; Benefits and Risks; Biochemical Genetics; Biological Markers; Blood Vessels; Bone Density; Calcified; Calcium; Cardiovascular Diseases; Cells; Clinical; Clinical Chemistry; Clinical Research; Cohort Studies; Communities; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Development; Diabetes Mellitus; Dietary Calcium; Disease susceptibility; Enrollment; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; European; Event; Exhibits; Family; Frequencies; Future; Genetic; Genetic Polymorphism; Genetic Risk; Genetic Variation; Genotype; Health Services Accessibility; Health Status; Healthcare; Heart; Homeostasis; Hormones; Ingestion; Inherited; Injury; Letters; Link; Linkage Disequilibrium; Literature; Maps; Measures; Metabolic; Morbidity - disease rate; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Osteoporosis; Outcome; Parathyroid gland; Participant; Pathogenesis; Pathway interactions; Patients; Phenotype; Phosphorus; Physiologic calcification; Population; Population Group; Predisposition; Prevention strategy; Process; Public Health; Race; Recruitment Activity; Relative (related person); Renal function; Reporting; Risk; Risk Factors; Role; Sampling; Serum; Single Nucleotide Polymorphism Map; Supplementation; United States Department of Veterans Affairs; Variant; Vitamin D; Work; X-Ray Computed Tomography; base; bone; bone health; bone metabolism; cardiovascular disorder risk; cohort; diabetic; disorder risk; exome; follow-up; forest; genetic analysis; genetic association; genetic risk factor; genetic variant; genome wide association study; high risk; improved; interest; medical schools; member; mortality; non-diabetic; novel; population based; racial difference; rare variant; risk variant; skeletal; treatment strategy

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.

描述（由申请人提供）：相对于欧洲裔美国人 (EA)，非洲裔美国人 (AA) 的心肌梗塞发病率更高，这可能反映出他们获得医疗保健的机会较差。相比之下，如果提供平等的医疗保健机会，AA 的心肌梗死率比 EA 低 50%。一项相关的观察结果是，以冠状动脉钙化斑块 (CAC) 衡量的 AA 亚临床心血管疾病 (CVD) 明显较少。尽管 AA 中存在更严重的传统 CVD 危险因素，但这种情况还是发生了。 CAC 预测未来心肌梗塞的风险。基于我们之前的发现，AA 发生 CAC（及相关心肌梗死）的生物学风险低于 EA，这一范式转变得以发展。人群之间表现出不同频率的遗传多态性可能导致 CAC 的种族差异，以及新的 CVD 相关因素的存在，包括骨矿化和血清维生素 D 水平， 两者都与 CAC 相关。 该项目针对 CAC 的发病机制，重点关注 亚临床 CVD 的种族差异，重点是骨骼健康、维生素 D 和 CAC 之间的关系。 尽管维生素 D 水平较低且膳食钙摄入量低于 EA，但 AA 的骨质疏松症发病率也较低。仍然迫切需要收集追踪 CAC 和骨矿物质密度与维生素 D 相关变化的纵向数据，并评估这些因素对 CVD 高风险 AA 的重要性。该更新申请旨在：(1) 纵向测量非裔美国人糖尿病心脏研究 (AA-DHS) 参与者的 CAC 和骨矿物质密度，以及它们与新的 CVD 相关因素（包括血清维生素 D 和骨代谢）的相关性，这是表型最广泛的 AA 2 型糖尿病队列 ~ (2) 探索新的 CVD 危险因素对发生和进展的作用 (3) 确定导致 AA 中 CAC 发生率较低的遗传变异。我们独特的 AA-DHS 队列中糖尿病的存在可能导致他们的 CAC 分数较高。表型和基因型良好的 AA-DHS 队列的后续检查将提供至关重要的数据，这将增加我们对 AA CVD 风险的了解。我们将维克森林糖尿病心脏研究中招募的 1,200 个 EA 的糖尿病持续时间样本与全基因组关联数据进行匹配，将允许在 AA 中快速复制与 CAC 的遗传关联。维生素 D 和骨代谢在 CAC 发生和进展中的作用引起了人们的强烈兴趣，因为由于对冠状动脉和骨骼的潜在损伤，围绕 AA 中补充维生素 D 存在争议。探索遗传风险、骨骼健康和维生素 D 之间的联系将提高我们对 AA 亚临床动脉粥样硬化的理解，并有助于制定新的治疗和预防策略。