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

描述（由申请方提供）：通过低循环25-羟基维生素D [25（OH）D]评估，维生素D不足最近作为潜在的心血管疾病（CVD）风险因素引起了关注。然而，关于维生素D与特定CVD事件的关系，以及低维生素D水平对非洲裔美国人的影响，还有很多未知之处。非洲裔美国人特别容易患维生素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。鉴于大约40%-60%的普通人群具有次优的维生素D水平，这可以通过增加阳光照射和/或膳食补充剂来纠正，阐明维生素D在CVD风险中的作用具有至关重要的公共卫生重要性。此外，目前还不清楚甲状旁腺激素（PTH）或成纤维细胞生长因子-23（FGF 23）（与25（OH）D密切相关的生物标志物）的水平是否也会影响CVD风险。 为了解决25（OH）D、PTH和FGF 23与特定CVD结局关系的关键研究问题，我们建议从访视2开始测量储存血清中的这些生物标志物（1990-1992年）的前瞻性，基于人群的动脉粥样硬化风险社区（ARIC）队列，该队列随访了15，792名非洲裔美国人（27%）和白色（73%）参与者20年。 然后我们将评估25（OH）D、PTH和FGF 23水平是否与冠心病、中风、房颤、充血性心力衰竭和外周动脉疾病的风险相关。我们还将评估这些生物标志物是否与CVD风险因素相关，包括糖尿病和高血压。此外，我们将报告种族分层的相关性，并探讨这些生物标志物与CVD风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VDR基因多态性是否改变了25（OH）D与CVD的关系。最后，为了确定25（OH）D水平的遗传决定因素，我们建议在ARIC高加索人和非洲裔美国人中进行25（OH）D的全基因组关联研究（GWAS）。 这项研究将在一个双种族人群中提供25（OH）D，PTH和FGF 23与许多CVD表型发生率关系的一些初步信息，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不足的普遍性，以及通过增加阳光照射和/或膳食补充剂进行成本效益校正的潜力，这项研究的结果可能对心血管疾病的预防产生重大影响。

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.