Mediterranean diet, Metabolites, and cardiovascular Disease

地中海饮食、代谢物和心血管疾病

• 批准号: 9388404
• 负责人: Frank B Hu
• 金额: $ 59.24万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9388404
• 关键词: Adverse effects; American; Arteries; Atherosclerosis Risk in Communities; Atrial Fibrillation; Attenuated; Biological Assay; Blood Volume; Branched-Chain Amino Acids; Cardiovascular Diseases; Carnitine; Ceramides; Cessation of life; Chronic Disease; Clinical; Data; Diet; Dietary Intervention; Dietary Practices; Disease; Functional disorder; Glutamates; Goals; Grant; Guidelines; Health Care Costs; Heart failure; Incidence; Individual; Intervention; Knowledge; Link; Measures; Mediterranean Diet; Metabolic; Metabolic Pathway; Myocardial Infarction; Nutritional; Nuts; Olive oil preparation; Paper; Participant; Pathway Analysis; Pathway interactions; Peripheral arterial disease; Plasma; Population; Prevention; Prevention trial; Primary Prevention; Public Health; Publishing; Randomized; Recommendation; Research; Research Personnel; Risk; Risk Factors; Statistical Methods; Stroke; Techniques; Tryptophan; United States; burden of illness; cardiovascular disorder prevention; cardiovascular disorder risk; case control; cohesion; cohort; design; disorder risk; disorder subtype; follow-up; good diet; metabolic profile; metabolomics; multidisciplinary; network models; novel; prevent; small molecule

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.

心力衰竭（HF）、心房颤动（AF）和外周动脉疾病（PAD）已成为 重要的心血管疾病（CVD）导致慢性疾病和疾病负担的增加 美国和全球的医疗保健费用不断上升。代谢组学的最新进展 允许研究人员从少量血液中检测数百种代谢物， 提供个人代谢状况的全面了解，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关联 代谢特征以及 HF、AF 和 PAD 的风险。在这个竞争性的 rewewal 申请中，我们建议 嵌套病例对照设计，对事件进行有针对性和无针对性的代谢组学分析 心力衰竭 (n=332)、房颤 (n=594) 和 PAD (n=196) 病例以及 7,447 例队列中的匹配对照 积极干预和延长随访期间（2003-2018）的参与者 PREDIMED 试验。我们的具体目标是：1）。检查大约 400 个之间的关联 使用嵌套病例对照设计，了解基线代谢物以及 HF、AF 和 PAD 的风险。 2）。 进行整合非目标代谢物的通路分析和不可知网络建模 与已知的代谢物一起识别 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物的影响 HF、AF 和 PAD 风险概况。 此外，我们将探索独特和常见的代谢物 以及与 HF、AF 和 PAD 事件相关的代谢途径，并将复制新的 在社区动脉粥样硬化风险 (ARIC) 的 PREDIMED 队列中发现的代谢物 研究是美国的一个独立的多种族队列。这个竞争性续订申请代表 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 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 对于美国人来说，因为现行的美国人膳食指南推荐 地中海饮食作为预防心血管疾病的健康饮食模式之一。当前周期 资助成果丰硕，已发表或提交了 11 篇论文，为新的研究做出了贡献 有关饮食和心血管疾病潜在机制的知识以及用于分析的新统计方法 营养代谢组学数据。这种竞争性的更新建立在众多优势的基础上 PREDIMED 试验和多学科、有凝聚力的团队有潜力推进我们的研究 了解 CVD 病理生理学并产生可直接告知特定疾病的知识 预防整体心血管疾病及其亚型的饮食干预措施。