Vitamin D Intervention and Atherosclerosis Progression in African American Women

描述（由申请人提供）：心血管疾病（CVD）仍然是美国（US）女性的头号杀手。重要的是，非洲裔美国妇女的心血管疾病死亡率超过了白色妇女，尽管男女的心血管疾病死亡率总体上都在下降，但非洲裔美国妇女的下降速度最慢。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更大问题。CVD风险的种族差异的解释是多因素和复杂的，维生素D不足提供了一个挑衅性和可检验的假设，作为CVD风险因素（特别是非洲裔美国人的高血压）和非洲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缺乏症和心血管疾病之间存在因果关系的可能性得到了许多研究以及强大的生物相容性的支持。鉴于人口老龄化和肥胖症发病率迅速增加，维生素D不足正成为一个日益重要的公共卫生问题，可能导致CVD。这可能与非洲裔美国妇女特别相关，她们特别容易患心血管疾病，因为皮肤色素沉着增加会降低皮肤合成维生素D的能力，并且由于肥胖症中维生素D的生物利用度降低，这不成比例地影响非洲裔美国妇女。尽管数据表明维生素D补充剂在减少CVD方面可能具有有益作用，但来自随机对照试验的直接抗动脉粥样硬化作用有限。这项提案的目的是将动脉粥样硬化成像的辅助研究整合到母试验“维生素D和老年非裔美国人骨质疏松症预防”中，这是一项为期4年的随机、双盲、安慰剂对照研究，旨在调查维生素D状态对老年非裔美国妇女的影响。将250名血清25-羟基维生素D（25（OH）D）水平大于20 nmol/L但小于65 nmol/L的>65岁的非裔美国妇女随机分配至每日一次充足的维生素D3补充剂，以将血清25（OH）D水平提高至75 nmol/L至172 nmol/L，与安慰剂相比。将确定维生素D3补充对亚临床颈动脉粥样硬化进展的影响，所述亚临床颈动脉粥样硬化进展测量为计算机图像处理的B型超声图中的颈总动脉（CCA）内膜-中层厚度（IMT）的变化率和CCA刚度（扩张性、弹性和顺应性）的变化。这项辅助研究提供了一个具有成本效益的机会，以解决维生素D补充剂是否能减少动脉粥样硬化的进展，特别是在一个未充分研究的独特的老年非裔美国妇女队列中。

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.