Serum Vitamin D and Cardiovascular Disease Risk in the Biethnic ARIC Cohort

描述（由申请人提供）：维生素D不足，由低循环25-羟基维生素D [25(OH)D]评估，最近作为潜在的心血管疾病（CVD）危险因素引起了人们的关注。然而，关于维生素D与特定心血管疾病事件的关系，以及维生素D水平低对非洲裔美国人的影响，仍有很多未知之处。非裔美国人尤其容易患维生素D缺乏症，这是由于皮肤黑色素含量增加导致25(OH)D合成减少所致。鉴于大约40%-60%的普通人群维生素D水平不理想，这可以通过增加阳光照射和/或膳食补充来纠正，阐明维生素D在心血管疾病风险中的作用对公共卫生至关重要。此外，尚不清楚与25(OH)D密切相关的生物标志物甲状旁腺激素（PTH）或成纤维细胞生长因子-23 （FGF23）的水平是否也会影响心血管疾病的风险。为了解决关于25(OH)D、PTH和FGF23与特定CVD结局的关系的关键研究问题，我们建议在前瞻性、基于人群的社区动脉粥样硬化风险（ARIC）队列的第2次访问（1990-1992）中测量储存血清中的这些生物标志物，该队列随访了15,792名非裔美国人（27%）和白人（73%）参与者20年。然后我们将评估25(OH)D、PTH和FGF23水平是否与冠心病、中风、心房颤动、充血性心力衰竭和外周动脉疾病的发生风险相关。我们还将评估这些生物标志物是否与CVD危险因素相关，包括糖尿病和高血压。此外，我们将报告种族分层的关联，并探讨这些生物标志物与心血管疾病危险因素和事件的关系中是否存在种族相互作用。在探索性分析中，我们还将评估维生素D受体（VDR）基因多态性与CVD风险的关系，并评估25(OH)D与CVD的关系是否受到VDR基因多态性的修饰。最后，为了确定25(OH)D水平的遗传决定因素，我们建议在ARIC白种人和非裔美国人中进行25(OH)D全基因组关联研究（GWASs）。本研究将在双种族人群中提供有关25(OH)D、PTH和FGF23与多种CVD表型发病率关系的一些第一手信息，允许探索这些生物标志物对CVD风险的相对贡献，并增强对维生素D遗传影响的理解。鉴于维生素D不足的普遍存在，以及通过增加阳光照射和/或膳食补充来经济有效地纠正维生素D不足的潜力，这项研究的发现可能对心血管疾病的预防有重要意义。

DESCRIPTION (provided by applicant): Insufficient vitamin D, as assessed by low circulating 25-hydroxyvitamin D [25(OH)D], has recently drawn attention as a potential cardiovascular disease (CVD) risk factor. However, much remains unknown about the relation of vitamin D to specific CVD events, and the impact of low vitamin D levels in the African-American population. African-Americans are particularly prone to hypovitaminosis-D due to reduced 25(OH)D synthesis as a consequence of greater cutaneous melanin content. Given that approximately 40%-60% of the general population has suboptimal vitamin D levels, which are amenable to correction through increased sunlight exposure and/or dietary supplementation, elucidating the role of vitamin D in CVD risk is of vital public health importance. Further, it is unclear whether levels of parathyroid hormone (PTH) or fibroblast growth factor-23 (FGF23), biomarkers closely linked to 25(OH)D, also influence CVD risk. In order to address key research questions about the relation of 25(OH)D, PTH, and FGF23 to specific CVD outcomes, we propose to measure these biomarkers in stored serum from visit 2 (1990-1992) of the prospective, population-based Atherosclerosis Risk in Communities (ARIC) cohort, which has followed 15,792 African-American (27%) and white (73%) participants for 20 years. We will then evaluate whether levels of 25(OH)D, PTH, and FGF23 are related to risk of incident coronary heart disease, stroke, atrial fibrillation, congestive heart failure, and peripheral artery disease. We will also evaluate whether these biomarkers are related to CVD risk factors, including diabetes and hypertension. Further, we will report race-stratified associations, and explore whether there are race-interactions present in the relation of these biomarkers to CVD risk factors and events. In exploratory analyses, we will also assess the relation of vitamin D receptor (VDR) gene polymorphisms to CVD risk, and evaluate whether relations of 25(OH)D to CVD are modified by VDR gene polymorphisms. Lastly, in order to identify genetic determinants of 25(OH)D levels, we propose to conduct genome wide association studies (GWASs) of 25(OH)D among ARIC Caucasians and African-Americans. This study will, in a biethnic population, provide some of the first information on the relation of 25(OH)D, PTH, and FGF23 to incidence of numerous CVD phenotypes, allow for exploration of the relative contributions of these biomarkers to CVD risk, and enhance understanding of the genetic influences on vitamin D. Given the pervasiveness of vitamin D insufficiency, and its potential for cost-effective correction through increased sunlight exposure and/or dietary supplementation, the findings of this study may have major implications for cardiovascular disease prevention.