Folic Acid, B-Vitamins and AMD: Blood and Diet-based Studies

描述(由申请人提供)：这项申请建议进行几项及时和成本效益高的血液和饮食研究，以扩大最近在女性抗氧化剂叶酸心血管研究(WAFACS)中关于年龄相关性黄斑变性(AMD)的随机试验结果。WAFACS是一项随机、双盲、安慰剂对照试验，在40岁或40岁以上的心血管事件高危女性健康专业人员中进行。WAFACS对服用叶酸的5205名妇女进行了平均7.3年的治疗和随访，结果表明，每天服用叶酸(2.5毫克)、维生素B6(50毫克)和维生素B12(每天1毫克)积极治疗的患者确诊为老年性黄斑变性的风险降低了34%(55例比82例)，这在统计学上具有显著意义。众所周知，补充叶酸和维生素B可以降低血浆同型半胱氨酸水平。因此，这项建议的一个主要目的是通过利用WAFACS、妇女健康研究和医生健康研究II的现有数据对女性和男性的血浆同型半胱氨酸和AMD进行第一次前瞻性研究，以解决同型半胱氨酸与AMD的因果关系。在这些队列中，有基线血液样本的参与者中总共记录了829例确诊的AMD病例，并可用于分析。我们还将利用WAFACS中300名参与者在基线和随访时收集的存档血液样本，检查补充叶酸/B6/B12对在观察性研究中被发现与AMD风险相关的四个炎症和内皮功能障碍生物标志物的影响。最后，我们将利用基线收集的存档血液样本，对比基线同型半胱氨酸水平高于中位数与低于中位数的女性的风险降低幅度，以探索在WAFACS中观察到的AMD风险降低是否反映了叶酸和维生素B的同型半胱氨酸降低效果。我们还将探讨血浆叶酸、维生素B6和维生素B12的基线水平对叶酸/B6/B12补充效果的调节作用。这项建议代表了一个极具成本效益的机会，可以将WAFACS中关于AMD的有希望的总体发现扩展到重要的基于血液和饮食的亚群。来自这些研究的信息将解决关于同型半胱氨酸-AMD假说的重要知识空白，并将有助于在其他人群中有效地设计未来试验，以关键地评估补充叶酸和维生素B对AMD可能的有益影响。

DESCRIPTION (provided by applicant): This application proposes to conduct several timely and cost-efficient blood-based and diet-based studies to expand upon recent randomized trial findings for age-related macular degeneration (AMD) in the Women's Antioxidant Folic Acid Cardiovascular Study (WAFACS). WAFACS was a randomized, double-blind, placebo-controlled trial conducted among female health professionals aged 40 years or older who were at high risk of cardiovascular events. The findings for AMD in WAFACS, based on an average of 7.3 years of treatment and follow-up of 5,205 women in the folic acid arm, indicate a statistically-significant 34% reduced risk of confirmed AMD (55 cases vs. 82 cases) for those assigned to active treatment with folic acid (2.5 mg/d), vitamin B6 (50 mg/d), and vitamin B12 (1 mg/d). Supplementation with folic acid and B vitamins is known to reduce plasma levels of homocysteine. Therefore, a primary aim of this proposal is to address the causal relevance of homocysteine to AMD by conducting the first prospective studies of plasma homocysteine and AMD in women and men utilizing available data from WAFACS, the Women's Health Study, and Physicians' Health Study II. A total of 829 cases of confirmed AMD have been documented among participants with baseline blood specimens in these cohorts and are available for analysis. We will also utilize archived blood specimens collected at baseline and at follow-up for 300 participants in WAFACS to examine the effect of folic acid/B6/B12 supplementation on four biomarkers of inflammation and endothelial dysfunction found to be associated with risks of AMD in observational studies. Finally, we will explore whether the reduced risk of AMD observed in WAFACS reflects the homocysteine-lowering effect of folic acid and B vitamins by utilizing archived blood specimens collected at baseline to contrast the magnitude of risk reduction in women with baseline homocysteine level above, as compared to below, the median value. We will also explore the modifying effect of baseline levels of plasma folate, vitamin B6, and vitamin B12 on the effectiveness of folic acid/B6/B12 supplementation. This proposal represents an extraordinarily cost-efficient opportunity to extend the promising overall findings for AMD in WAFACS to important blood-based and diet-based subgroups. The information derived from these studies will address important gaps in knowledge regarding the homocysteine-AMD hypothesis, and should contribute to the efficient design of future trials in other populations to critically evaluate the possible beneficial effect of folic acid and B vitamin supplementation in AMD.