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

基本信息

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
项目类别：
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

项目摘要

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）：相对于欧洲美国人（EAS），非裔美国人（AAS）具有更高的心肌梗塞率，可能反映出获得医疗保健的机会较差。相比之下，当提供平等的医疗保健机会时，AAS的心肌梗塞率比EAS低50％。一个相关的观察结果是，AA的亚临床心血管疾病（CVD）显着，测量为冠状动脉钙化斑块（CAC）。尽管AAS中存在更严重的常规CVD风险因素，但仍会发生这种情况。 CAC预测心肌梗塞的未来风险。基于我们早期的发现，AAS比EAS相比，AAS的生物学风险低于生物学风险。人口组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，以及与CVD相关的新型因素的存在，包括骨矿化和血清维生素D水平，两者都与CAC相关。该项目通过专注于CAC的发病机理亚临床CVD的种族差异，重点是骨骼健康，维生素D和CAC之间的研究研究。尽管维生素D含量较低，并且摄入饮食中的钙比EAS少了，但AAS也表现出较低的骨质疏松症。与维生素D相关的CAC和骨矿物质密度的变化并评估CVD风险高的AAS中这些因素的重要性仍然存在纵向数据跟踪CAC和骨矿物质密度的变化。此更新应用提出：（1）纵向测量CAC和骨矿物质密度，以及它们与新型CVD相关因素的相对关联，包括非裔美国人糖尿病心脏研究（AAA-DHS）参与者的血清维生素D和骨代谢，在最广泛的表现型AA COLORES中，有2型糖尿病的发展范围（2型糖尿病）〜2）（2型糖尿病型）〜2） CAC〜和（3）确定遗传变异，这导致AAS中CAC速率较低。在我们独特的AA-DHS队列中，糖尿病的存在可能导致其CAC得分更高。在良好的表型和基因分型AA-DHS队列中进行的后续考试将提供至关重要的数据，这将增加我们对AAS中CVD风险的理解。我们的糖尿病 - 持续性与Wake Forest糖尿病心脏研究中募集的1,200个EA的样本与全基因组关联数据相匹配，将允许在AAS中快速复制与CAC的遗传关联。维生素D和骨代谢在CAC发育和进展中的作用引起了人们的强烈关注，因为由于对冠状动脉和骨骼的潜在损伤，争议围绕着AAS补充维生素D的作用。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中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。