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)危险因素引起了关注。然而，关于维生素D与特定的心血管疾病事件的关系，以及低水平的维生素D对非裔美国人的影响，仍有许多未知之处。非裔美国人特别容易患维生素D缺乏症，这是因为皮肤黑色素含量增加导致25(OH)D合成减少。鉴于大约40%-60%的普通人群的维生素D水平低于最佳水平，可以通过增加阳光暴露和/或饮食补充来纠正，阐明维生素D在心血管疾病风险中的作用具有至关重要的公共卫生意义。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(FGF23)的水平是否也影响CVD风险，这些生物标志物与25(OH)D密切相关。为了解决关于25(OH)D、PTH和FGF23与特定心血管疾病预后的关系的关键研究问题，我们建议从基于人群的社区动脉粥样硬化风险(ARIC)队列的访问2(1990-1992)中测量存储的血清中的这些生物标记物，该队列跟踪了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水平是否与发生冠心病、中风、房颤、充血性心力衰竭和外周动脉疾病的风险有关。我们还将评估这些生物标志物是否与心血管疾病风险因素有关，包括糖尿病和高血压。此外，我们将报告种族分层的关联，并探索在这些生物标记物与心血管疾病危险因素和事件的关系中是否存在种族交互作用。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，以及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)。这项研究将在两个民族的人群中，提供一些关于25(OH)D、PTH和FGF23与多种心血管疾病表型发生率之间关系的初步信息，允许探索这些生物标志物对心血管疾病风险的相对贡献，并加强对维生素D遗传影响的理解。鉴于维生素D缺乏的普遍性，以及通过增加阳光暴露和/或饮食补充来进行经济有效的纠正的可能性，这项研究的发现可能对心血管疾病的预防具有重大意义。

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.