Vitamin D Intervention and Atherosclerosis Progression in African American Women

描述(申请人提供)：心血管疾病(CVD)仍然是美国女性的头号杀手。重要的是，非裔美国女性的心血管疾病死亡率超过白人女性，尽管男性和女性的心血管疾病死亡率总体上都在下降，但非洲裔美国女性的下降速度最慢。随着美国人口老龄化和寿命延长，心血管疾病的发病率将成为非裔美国女性面临的一个不成比例的更大问题。对心血管疾病风险的种族差异的解释是多因素和复杂的，维生素D不足提供了一个具有挑衅性和可验证性的假说，作为心血管疾病危险因素(特别是非裔美国人的高血压)和非裔美国人动脉粥样硬化风险增加之间的可能联系。维生素D缺乏和心血管疾病之间存在因果联系的可能性得到了许多研究的支持，也有很强的生物学合理性。随着人口老龄化和肥胖率的迅速上升，维生素D缺乏正成为一个越来越重要的公共卫生问题，可能会导致心血管疾病。这可能与非裔美国女性特别相关，她们患心血管疾病的风险特别大，因为皮肤色素沉着增加降低了皮肤合成维生素D的能力，而且肥胖患者维生素D的生物利用度降低，这对非裔美国女性的影响不成比例。尽管数据显示补充维生素D可能有益于减少心血管疾病，但随机对照试验的直接抗动脉粥样硬化作用是有限的。这项建议的目标是将动脉粥样硬化成像的辅助研究整合到父试验“老年非裔美国人中维生素D和骨质疏松症的预防”中，这是一项为期4年的随机、双盲、安慰剂对照研究，旨在调查老年非裔美国妇女维生素D状况的影响。将250名65岁的非裔美国妇女随机分为两组，每天补充一次充足的维生素D3，以将血清25(OH)D水平提高到75nmol/L和172nmol/L之间，与安慰剂组比较。观察补充维生素D3对亚临床型颈动脉粥样硬化进展的影响，通过计算机图像处理的B超图像测量颈总动脉(CCA)内膜-中层厚度(IMT)的变化率和颈总动脉硬度(扩张性、弹性和顺应性)的变化。这项辅助研究提供了一个机会，可以经济有效地解决补充维生素D是否会减少动脉粥样硬化的进展，特别是在一个研究不足的独特的老年非裔美国女性队列中。

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) remains the number 1 killer of women in the United States (US). Importantly, CVD mortality of African American women exceeds that of white women and although the rates of CVD mortality are declining overall in men and women, they are declining most slowly in African American women. As the US population ages and lives longer the incidence of CVD will become a disproportionately greater problem for African American women. The explanation for ethnic differences in CVD risk is multifactorial and complex with insufficiency of vitamin D providing a provocative and testable hypothesis as a possible link between CVD risk factors (particularly hypertension in African Americans) and increased risk of atherosclerosis in African Americans. The possibility of a causal link between vitamin D deficiency and CVD is supported by many studies as well as strong biological plausibility. Given the aging population and rapidly increasing incidence of obesity, vitamin D insufficiency is becoming an increasingly important public health issue that may contribute to CVD. This may be particularly relevant for African American women, who are at particular risk for CVD since increased skin pigmentation reduces the capacity of skin to synthesize vitamin D and due to decreased bioavailability of vitamin D in obesity, which disproportionately affects African American women. Although data suggest a possible beneficial effect of vitamin D supplementation in reducing CVD, a direct anti- atherogenic effect from randomized controlled trials is limited. The goal of this proposal is to integrate an ancillary stuy of atherosclerosis imaging into the parent trial, "Vitamin D and Osteoporosis Prevention in Elderly African Americans," a 4-year, randomized, double-blind, placebo-controlled study designed to investigate the effect of vitamin D status in elderly African American women. 250 African American women >65 years old with serum 25-hydroxyvitamin D (25(OH)D) levels greater than 20 nmol/L but less than 65 nmol/L will be randomized to sufficient vitamin D3 supplementation once daily to raise serum 25(OH)D levels to between 75 nmol/L and 172 nmol/L versus placebo. The effect of vitamin D3 supplementation on the progression of subclinical carotid artery atherosclerosis measured as the rate of change of common carotid artery (CCA) intima-media thickness (IMT) and change of CCA stiffness (distensibility, elasticity and compliance) in computer image processed B-mode ultrasonograms will be determined. This ancillary study provides the opportunity to cost-effectively address whether vitamin D supplementation reduces the progression of atherosclerosis, specifically in an understudied unique cohort of elderly African American women.