Mediterranean diet, Metabolites, and cardiovascular Disease

心力衰竭(HF)、房颤(AF)和外周动脉疾病(PAD)已经出现 重要的心血管疾病(心血管疾病)导致慢性病和 美国和全球医疗保健成本不断攀升。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， 提供个人新陈代谢状态的全面情况，这可能是 饮食对疾病风险的影响。然而，很少有研究评估两者之间的联系 代谢物分布与心力衰竭、房颤和PAD的风险。在这个相互竞争的新应用程序中，我们建议 对事件进行靶向和非靶向代谢组学分析的嵌套式病例对照设计 心力衰竭(332例)、房颤(594例)和PAD(196例)病例和7,447名匹配的对照组 在2003年至2018年的积极干预和延长的随访期内的参与者 PREDIMED试验。我们的具体目标是：1)。来研究大约400人之间的联系 采用嵌套式病例对照设计，研究基线时已知的代谢物与心衰、房颤和PAD的风险。2)。 进行整合非靶向代谢物的途径分析和未知网络建模 用已知的代谢物来识别心力衰竭、房颤和PAD风险的新代谢学特征。3)。至 评估随机饮食干预是否改变了基线代谢物的影响 关于心衰、房颤和PAD风险的简介。此外，我们还将探索独特和常见的代谢物。 以及与入院时的HF、AF和PAD相关的代谢途径，并将复制新的 社区动脉粥样硬化风险(ARIC)前队列中确定的代谢物 学习，在美国一个独立的多种族队列。此竞争续订申请代表 将我们对地中海饮食和心血管疾病的长期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。这项研究具有重要的意义。 对于美国人来说，因为目前的美国人饮食指南建议 地中海饮食作为预防心血管疾病的健康饮食模式之一。当前的经济周期 格兰特效率很高，发表或提交了11篇论文，为新的 关于饮食和心血管疾病潜在机制的知识和新的统计分析方法 营养代谢组学数据。这一相互竞争的更新建立在 PREDIMED试验和一个多学科、有凝聚力的团队，有潜力推动我们的 了解心血管疾病的病理生理学，并产生可直接为特定患者提供信息的知识 预防整体心血管疾病及其亚型的饮食干预措施。

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.