Mediterranean diet, Metabolites, and Cardiovascular Disease

摘要 代谢组学技术有望更好地了解饮食在心血管疾病(CVD)中的作用 流行病学和预防。具体地说，一种多液多代谢相结合的方法，尿液和 血浆代谢组学可能会提高营养生物标志物的准确性和精密度，具有很强的 在精确营养研究中开发新的膳食评估工具的潜力。这种相互竞争的更新 旨在检查随机地中海饮食(MedDiet)干预对尿液的影响 代谢产物水平和评估饮食生物标记物对未来心血管疾病风险的预测能力 PREDIMED试验。我们将通过病例队列设计评估尿液代谢组学与心血管疾病的关系， 包括从所有预治疗参与者(10%，n=779)中随机抽样的有代表性的子队列，以及 心血管事件(包括心肌梗死、中风、心力衰竭和心血管死亡) 至2017年12月(n=529)。拟议的具体目标是：(1)识别特定的尿代谢物 和多代谢物特征的MedDiet模式及其主要食物成分；(2)检查 随机膳食干预对高血压病患者尿多代谢产物特征变化的影响 从基线到第一年的医学饮食模式及其主要食物成分(干预后)；(3)调查 MedDiet模式的尿多代谢物特征的基线和1年变化 个别食物与随后的心血管疾病风险有关；以及(4)发展为多液体(尿液和 血浆)多种代谢物特征，有力地预测心血管疾病的风险，并评估1年内 信号调节了饮食干预对综合心血管疾病结局的影响。作为一个子目标，我们 将比较MedDiet模式的血浆和尿代谢物对心血管疾病风险的预测作用。这 正在进行的赠款始于2013年，并于2017年续签。到目前为止，已发表或 提交的论文(包括当前赠款周期中的20篇论文)。Preedimed代谢组学数据已经 用作复制几个美国队列中心血管疾病结果的代谢组学分析的资源。这 竞争性的续订申请将把我们对MedDiet和CVD的长期研究扩展到多液体多... 一项大型随机干预试验中的代谢物分析。该项目充分利用了 PREDIMED Trial，一个多学科和高生产率的团队，尖端代谢组学技术，以及 高维数据分析。已确定的饮食生物标志物将提高质量和严格性 营养研究和加强制定膳食建议和营养的证据基础 政策。拟议的工作将促进2020-2030年期间概述的精确营养研究议程 美国国立卫生研究院营养研究战略计划。

ABSTRACT Metabolomics technique holds promise for better understanding the role of diet in cardiovascular disease (CVD) epidemiology and prevention. In particular, a multi-fluid multi-metabolite approach combining urinary and plasma metabolomics will likely enhance the accuracy and precision of nutritional biomarkers, with strong potential to develop novel tools for dietary assessment in precision nutrition research. This competing renewal is aimed to examine the effects of the randomized Mediterranean diet (MedDiet) interventions on urinary metabolite levels and to assess dietary biomarkers' predictive ability for future CVD risk in the landmark PREDIMED trial. We will assess urinary metabolomics in relation to CVD through a case-cohort design, including a representative subcohort randomly sampled from all PREDIMED participants (10%, n=779), and incident CVD cases (including myocardial infarction (MI), stroke, heart failure, and cardiovascular deaths) through December 2017 (n=529). The proposed Specific Aims are: (1) To identify specific urinary metabolites and multi-metabolite signatures of the MedDiet pattern and its main food components; (2) To examine the effects of the randomized dietary interventions on changes in the urinary multi-metabolite signatures of the MedDiet pattern and its major food components from baseline to year 1 (post intervention); (3) To investigate whether baseline and 1-year changes in urinary multi-metabolite signatures of the MedDiet pattern and of individual foods are associated with subsequent risk of CVD; and (4) To develop a multi-fluid (urine and plasma) multi-metabolite signature that robustly predicts risk of CVD and assess whether 1-year changes in the signature mediate the effects of the dietary interventions on the composite CVD outcome. As a sub-aim, we will compare the predictive roles of plasma and urinary metabolites of the MedDiet pattern on CVD risk. This ongoing grant started in 2013 and was renewed in 2017. To date, 36 papers have been published or submitted (including 20 papers in the current grant cycle). The PREDIMED metabolomics data have been used as a resource for replicating metabolomics analyses of CVD outcomes in several US cohorts. This competing renewal application will extend our long-standing research on MedDiet and CVD to multi-fluid multi- metabolite profiling in a large randomized intervention trial. This project leverages numerous strengths of the PREDIMED trial, a multi-disciplinary and highly productive team, cutting-edge metabolomics technologies, and high-dimensional data analytics. The identified dietary biomarkers will enhance the quality and rigor of nutrition research and strengthen the evidence base for developing dietary recommendations and nutrition policies. The proposed work will facilitate the precision nutrition research agenda outlined in the 2020-2030 Strategic Plan for NIH Nutrition Research.