Mediterranean diet, Metabolites, and cardiovascular Disease

心力衰竭（HF）、心房颤动（AF）和外周动脉疾病（PAD）已经出现， 导致慢性疾病负担增加的重要心血管疾病（CVD）， 美国和全球医疗保健成本不断上升。代谢组学研究进展 使研究人员能够从少量血液中分析数百种代谢物， 提供了一个人的代谢状态的全面图片，可能是基础， 饮食对疾病风险的影响。然而，很少有研究评估了 代谢产物谱和HF、AF和PAD的风险。在这个竞争性的rewewal应用程序中，我们建议 一种巢式病例对照设计，用于对事件进行靶向和非靶向代谢组学分析， 7，447例队列中的HF（n=332）、AF（n=594）和PAD（n=196）病例和匹配对照 在积极干预和延长的后续行动期间（2003-2018年）， PREDIMED试验。我们的具体目标是：1）。为了研究大约400个 使用巢式病例对照设计，研究基线时已知代谢产物与HF、AF和PAD风险之间的关系。2）。 进行整合非靶向代谢物的途径分析和不可知网络建模 与已知的代谢物，以确定HF，AF和PAD风险的新代谢组学特征。3）。到 评估随机饮食干预是否改变基线代谢产物的影响 HF、AF和PAD风险的特征。 此外，我们还将探索独特和常见的代谢产物 以及与HF、AF和PAD事件相关的代谢途径， 在社区动脉粥样硬化风险（ARIC）的PREDIMED队列中确定的代谢物 一项独立的多种族队列研究。这种竞争性的续期申请代表了 我们长期以来对地中海饮食和心血管疾病的研究扩展到新的临床 在具有里程碑意义的PREDIMED试验背景下的终点。这项研究具有重要意义 因为目前的美国人膳食指南建议 地中海饮食是预防CVD的健康饮食模式之一。本周期 格兰特一直非常富有成效，发表或提交了11篇论文，为新的 了解饮食和心血管疾病的潜在机制，以及分析心血管疾病的新统计方法 营养代谢组学数据。这种竞争性的更新，建立在众多的优势， PREDIMED试验和一个多学科和有凝聚力的团队，有可能推进我们的研究。 了解心血管疾病的病理生理学和产生的知识，可以直接告知具体的 饮食干预，以预防总体CVD及其亚型。

Heart failure (HF), atrial fibrillation (AF), and peripheral artery disease (PAD) have emerged as important cardiovascular diseases (CVDs) contributing to the increasing burden of chronic diseases and escalating health care costs in the United States and globally. Recent advances in metabolomics have allowed investigators to assay hundreds of metabolites from a small volume of blood, providing a comprehensive picture of an individual’s metabolic status that may underlie the effects of diet on disease risk. However, few studies have assessed the association between metabolite profiles and risk of HF, AF, and PAD. In this competing rewewal application, we propose a nested case-control design to conduct targeted and untargeted metabolomics analyses of incident cases of HF (n=332), AF (n=594), and PAD (n=196) and matched controls in a cohort of 7,447 participants during the active intervention and extended follow-up periods (2003-2018) in the PREDIMED trial. Our specific aims are: 1). To examine the associations between approximately 400 known metabolites at baseline and risk of HF, AF, and PAD, using a nested case-control design. 2). To conduct pathway analysis and agnostic network modeling that integrate non-targeted metabolites with known metabolites to identify novel metabolomic signatures of risk of HF, AF, and PAD. 3). To assess whether the randomized dietary interventions modify the effect of baseline metabolite profiles on HF, AF, and PAD risk. In addition, we will explore both unique and common metabolites and metabolic pathways associated with incident HF, AF, and PAD and will replicate novel metabolites identified in the PREDIMED cohort in the Atherosclerosis Risk in Communities (ARIC) study, an independent multi-ethnic cohort in the US. This competing renewal application represents an extension of our long-standing research on the Mediterranean diet and CVD to new clinical endpoints in the context of the landmark PREDIMED trial. This research has important implications for the US population because the current Dietary Guidelines for Americans recommend the Mediterranean diet as one of healthy dietary patterns for CVD prevention. The current cycle of the grant has been highly productive with 11 papers published or submitted, contributing to new knowledge about mechanisms underlying diet and CVD and new statistical methods for analyzing nutritional metabolomics data. This competing renewal, built on the numerous strengths of the PREDIMED trial and a multi-disciplinary and cohesive team, has the potential to advance our understanding of CVD pathophysiology and produce knowledge that can directly inform specific dietary interventions to prevent overall CVD and its subtypes.