Dietary Biomarkers and Cardioprotective Mechanisms of the DASH-Sodium Diet.

项目概要/摘要 超过三分之一的美国成年人患有心血管疾病。近一半的原因是饮食因素 2012 年心脏代谢死亡人数。DASH-钠饮食是一种富含水果、蔬菜、 和低脂乳制品，钠、饱和脂肪和胆固醇含量低，可降低血压和 还被证明可以降低高血压、心血管疾病和死亡率的风险。美国人 心脏协会推荐 DASH-钠饮食模式来预防心血管疾病。 这一具有成本效益的建议最大限度地发挥了现有数据和标本的科学价值 通过开展高影响力和新颖的多中心、随机、对照 DASH-钠喂养研究 生物标志物研究。我们建议对矿物质进行非靶向代谢组学和靶向分析 代谢 [成纤维细胞生长因子-23 (FGF-23) 和磷] 和炎症 [C 反应蛋白 (CRP) 和可溶性尿激酶型纤溶酶原激活剂受体（suPAR）]使用在 低钠 DASH 饮食和高钠控制饮食干预阶段结束 (N=393)。这些 选择每种饮食模式中的钠相以最大化对比度并反映比较 心脏保护推荐饮食与典型美国饮食之间的比较。研究的具体目的 建议是： 1) 表征 DASH-钠饮食模式的血清代谢组指纹； 2）到 确定 DASH-钠饮食降压作用的血清代谢介质 图案； 3) 确定 DASH 钠饮食对心血管风险中间标志物的影响 （FGF-23、磷、CRP、suPAR 的血清水平）。 首席研究员 Casey M. Rebholz，博士、硕士、公共卫生硕士，是 K01 资助的早期研究员 拥有约翰·霍普金斯大学布隆伯格公共卫生学院助理教授的终身职位。 最初的 DASH 喂养研究的初步结果为当前的提议提供了令人信服的支持。 与相关研究领域（营养流行病学、生物标志物）的知名研究人员合作 研究、代谢组学和喂养研究）将促进拟议的研究。 NHBLI BioLINCC 拥有 批准了这项拟议研究的 DASH-钠数据和样本的请求。 拟议的研究将推进饮食评估方法，并为饮食提供新的见解 可改变的心血管疾病发病机制，旨在指导预防和治疗 通过饮食的方法，将由 Rebholz 博士在未来的拨款提案中进行测试。加强证据 通过拟议的研究进行的心脏保护饮食为改善心脏健康提供了机会 数百万美国人。

PROJECT SUMMARY / ABSTRACT More than 1 in 3 U.S. adults have cardiovascular disease. Dietary factors contributed to nearly half of all cardiometabolic deaths in 2012. The DASH-sodium diet is a dietary pattern that is high in fruits, vegetables, and low-fat dairy products and low in sodium, saturated fat, and cholesterol which lowers blood pressure and has also been shown to reduce the risk of hypertension, cardiovascular disease, and mortality. The American Heart Association recommends the DASH-sodium dietary pattern for the prevention of cardiovascular disease. This cost-effective proposal maximizes the scientific value of the existing data and specimens from the multi-center, randomized, controlled DASH-sodium feeding study by conducting high-impact and novel biomarker research. We propose to conduct untargeted metabolomics and targeted assays of mineral metabolism [fibroblast growth factor-23 (FGF-23) and phosphorus] and inflammation [C-reactive protein (CRP) and soluble urokinase-type plasminogen activator receptor (suPAR)] using serum specimens collected at the end of the intervention phase for the low-sodium DASH diet and the high-sodium control diet (N=393). These sodium phases within each dietary pattern were selected to maximize the contrast and to reflect a comparison between the recommended diet for cardioprotection vs. the typical U.S. diet. The specific aims of the research proposal are: 1) to characterize the serum metabolomic fingerprint of the DASH-sodium dietary pattern; 2) to identify serum metabolomic mediators of the blood pressure lowering effect of the DASH-sodium dietary pattern; and 3) to determine the effect of the DASH-sodium diet on intermediate markers of cardiovascular risk (serum levels of FGF-23, phosphorus, CRP, suPAR). The Principal Investigator, Casey M. Rebholz, PhD, MS, MPH, is a K01-funded early stage investigator with a tenure-track position as an Assistant Professor at Johns Hopkins Bloomberg School of Public Health. Preliminary findings in the original DASH feeding study provide compelling support for the current proposal. Collaboration with established investigators in relevant research areas (nutritional epidemiology, biomarkers research, metabolomics, and feeding studies) will catalyze the proposed research. The NHBLI BioLINCC has approved the request for DASH-sodium data and specimens for this proposed research. The proposed research will advance dietary assessment methodology and provide novel insights into diet- modifiable cardiovascular disease pathogenesis with the goal of guiding prevention and therapeutic approaches through diet, to be tested in future grant proposals by Dr. Rebholz. Strengthening the evidence for cardioprotective diets through the proposed research constitutes an opportunity to improve the heart health of millions of Americans.