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: 8509675
• 负责人: BARRY Ira FREEDMAN
• 金额: $ 43.48万
• 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/8509675
• 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; genome wide association study; high risk; improved; interest; medical schools; member; mortality; non-diabetic; novel; population based; racial difference; 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(申请人提供)：与欧洲裔美国人(EA)相比，非裔美国人(AA)心肌梗死的发生率更高，这可能反映了他们更难获得医疗保健。相比之下，当提供平等的医疗保健机会时，AA的心肌梗死发生率比EA低50%。一个相关的观察是，以冠状动脉钙化斑块(CAC)衡量的亚临床心血管疾病(CVD)明显较少。尽管腹主动脉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预测未来心肌梗死的风险。一种范式的转变是基于我们早期的发现，即腹主动脉发生CAC(和相关的心肌梗死)的生物学风险比腹主动脉低。人群间频率不同的遗传多态可能导致CAC的种族差异，以及包括骨矿化和血清维生素D水平在内的新的心血管相关因素的存在， 两者都与CAC有关。这个项目的目标是CAC的发病机制，重点是 亚临床心血管疾病的种族差异，强调骨健康、维生素D和CAC之间的关系未被充分研究。AAS也表现出较低的骨质疏松发生率，尽管维生素D水平较低，饮食中钙的摄入量也低于EAS。仍然迫切需要收集跟踪CAC和骨密度与维生素D相关的变化的纵向数据，并评估这些因素在心血管疾病风险较高的AA中的重要性。这项新的应用建议：(1)纵向测量CAC和骨密度，以及它们与新的心血管相关因素的相关性，包括非裔美国人-糖尿病心脏研究(AA-DHS)参与者的血清维生素D和骨代谢，其中AA-DHS是2型糖尿病患者中表型最广泛的AA队列；(2)探索新的心血管危险因素在CAC发生和发展中的作用；(3)确定导致AAS中CAC发生率较低的基因变异。糖尿病在我们独特的AA-DHS队列中的存在可能是他们CAC得分较高的原因之一。在表型良好和基因分型良好的AA-DHS队列中的后续检查将提供至关重要的数据，这些数据将增加我们对AAS中心血管疾病风险的了解。我们在维克森林糖尿病心脏研究中招募的1,200名糖尿病持续时间匹配的样本以及全基因组关联数据将允许快速复制与AAS的CAC相关的遗传关联。维生素D和骨代谢在CAC的发生和发展中的作用引起了人们的极大兴趣，因为对冠状动脉和骨骼的潜在损伤，人们对补充维生素D在AAS中的应用存在争议。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AAS亚临床动脉粥样硬化的理解，并有助于开发新的治疗和预防策略。