Racial/Ethnic Differences in 25(OH)D and PTH Levels and CVD among Women

描述(由申请人提供)：医学研究所(IOM)最近关于维生素D的报告强调了进一步研究的必要性，以澄清维生素D的最佳水平 非骨骼结局，包括心血管疾病(CVD)，并评估这些关系是否因种族/民族而异。观察性研究表明，低25-羟基维生素D[25(OH)D]、高甲状旁腺激素(PTH)水平与心血管疾病风险增加之间存在相互关系。维生素D结合蛋白(VDBP)是维生素D的主要载体蛋白，在调节维生素D的生物利用度方面起着关键作用，可能是心血管事件的预测因子或25(OH)D和/或甲状旁腺素与心血管疾病关系的效应调节剂。维生素D代谢物主要与VDBP和白蛋白结合，维生素D代谢物中游离的非结合部分可能是最具生物学活性的，因此与心血管疾病风险预测最相关。然而，还没有研究专门评估游离或生物可利用的25(OH)D水平与心血管疾病之间的联系。关于25(OH)D总水平和心血管健康的现有证据也仍然不一致和不确定，而且很少有研究有足够的规模和种族/民族多样性来检查大范围循环的25(OH)D水平的这些关系。显然，临床和公共卫生需要确定维生素D生物标志物和心血管疾病之间的关系是否因种族/民族而异，以及这种差异是否有助于解释心血管疾病风险的种族/民族差异。妇女健康倡议观察性研究(WHI-OS)是绝经后妇女群体中规模最大、种族/民族最多样化的研究之一，提供了关于心血管疾病风险因素、中间表型和结果的全面信息，提供了一个独特且具有成本效益的机会，可以及时回答有关维生素D生物标记物在心血管疾病风险方面的种族/民族差异的重要问题。我们建议在WHI-OS中进行一项前瞻性病例队列研究，以评估种族/种族差异，评估总的和游离的25(OH)D、VDBP和PTH水平与主要心血管事件(非致命性心肌梗死[MI]、非致命性中风和CVD死亡率的组合)的相关性。我们将包括所有发生在非裔美国人(黑人)妇女中的心血管疾病病例(N=650)和随机抽样的白人妇女发生的心血管疾病病例(N=1500)。非病例将从WHI-OS中的黑人(N=1,300)和白人妇女(N=1,500)中随机抽取。此外，我们将检查总的和游离的25(OH)D、VDBP和PTH水平是否与各种中间的心血管疾病表型相关，包括直接测量的人体测量指数、血压、血脂和全身炎症、血糖状态、胰岛素抵抗、胰岛素分泌和肾功能的生物标记物。总之，WHI-OS提供了一个难得的机会，可以对总的和游离的25(OH)D、VDBP和PTH水平的变化进行全面的评估，并检查它们对绝经后妇女心血管疾病风险的种族/民族差异的潜在独立和联合贡献。

DESCRIPTION (provided by applicant): The recent report on vitamin D from the Institute of Medicine (IOM) highlighted the need for further research to clarify the optimal levels of vitamin D for nonskeletal outcomes, including cardiovascular disease (CVD), and to assess whether the relationships vary by race/ethnicity. Observational studies have suggested interrelationships between low 25-hydroxy vitamin D [25(OH) D], high parathyroid hormone (PTH) levels, and increased risk of CVD. Vitamin D binding protein (VDBP), the major vitamin D carrier protein, plays a key role in regulating vitamin D bioavailability and could potentially be a predictor of CVD events or an effect modifier of the relation between 25(OH) D and/or PTH and CVD. Vitamin D metabolites are mostly bound to VDBP and albumin, and it is possible that the free, unbound portions of vitamin D metabolites are the most biologically active and therefore most relevant for CVD risk prediction. However, no studies have specifically assessed the association between free or bioavailable 25(OH) D levels and CVD. Available evidence on total 25(OH)D levels and cardiovascular health also remains inconsistent and inconclusive, and few studies have had sufficient size and racial/ethnic diversity to examine these relationships across a broad range of circulating 25(OH)D levels. Clearly, there is a clinical and public health need to determine whether the relationships between vitamin D biomarkers and CVD vary by race/ethnicity and whether such differences can help to explain racial/ethnic disparities in CVD risk. The Women's Health Initiative Observational Study (WHI-OS), one of the largest and most racially/ethnically diverse cohorts of postmenopausal women with comprehensive information on CVD risk factors, intermediate phenotypes, and outcomes, offers a unique and cost-effective opportunity to answer important and timely questions about racial/ethnic differences in vitamin D biomarkers with regard to CVD risk. We propose to conduct a prospective case-cohort study in the WHI-OS to assess racial/ethnic differences in the associations of total and free 25(OH)D, VDBP, and PTH levels with major cardiovascular events (a composite of nonfatal myocardial infarction [MI], nonfatal stroke, and CVD mortality). We will include all incident CVD cases in African-American (black) women (N=650) and a random sample of incident CVD cases in white women (N=1,500). Noncases will be drawn from a random subcohort of black (N=1,300) and white women (N=1,500) in the WHI-OS. In addition, we will examine whether total and free 25(OH)D, VDBP, and PTH levels correlate with a variety of intermediate CVD phenotypes, including directly measured anthropometric indices, blood pressure, lipids, and biomarkers of systemic inflammation, glycemic status, insulin resistance, insulin secretion, and renal function. In summary, the WHI-OS provides an exceptional opportunity to conduct a comprehensive evaluation of the full spectrum of variation in levels of total and free 25(OH) D, VDBP, and PTH and to examine their potential independent and joint contributions to racial/ethnic disparities in CVD risk among postmenopausal women.