Mediterranean diet, Metabolites, and cardiovascular Disease

地中海饮食、代谢物和心血管疾病

• 批准号: 8482202
• 负责人: Frank B Hu
• 金额: $ 64.6万
• 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8482202
• 关键词: Acute myocardial infarction; Address; American; Archives; Aromatic Amino Acids; Attention; Betaine; Biological; Biological Markers; Blood specimen; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cessation of life; Choline; Clinical; Control Groups; DASH diet; Data Set; Diagnosis; Diet; Dietary Intervention; Dietary Practices; Disease Outcome; Event; Fasting; Fat-Restricted Diet; Glutamine; Goals; Guidelines; Incidence; Institutes; Intervention; Intervention Trial; Life Style; Lipids; Measures; Mediating; Mediterranean Diet; Metabolic; Metabolic Pathway; Metabolic syndrome; Nature; Nuts; Olea; Olive oil preparation; Participant; Pathway interactions; Plasma; Primary Prevention; Public Health; Randomized; Randomized Controlled Trials; Recommendation; Risk; Sampling; Spain; Stroke; Technology; Time; Trees; acylcarnitine; arm; blood lipid; cardiovascular disorder prevention; cardiovascular disorder risk; cohort; cost effective; design; dietary supplements; fasting glucose; follow-up; good diet; innovation; lifestyle intervention; metabolomics; novel; public health relevance; randomized trial; urea cycle; Acute myocardial infarction; Address; American; Archives; Aromatic Amino Acids; Attention; Betaine; Biological; Biological Markers; Blood specimen; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cessation of life; Choline; Clinical; Control Groups; DASH diet; Data Set; Diagnosis; Diet; Dietary Intervention; Dietary Practices; Disease Outcome; Event; Fasting; Fat-Restricted Diet; Glutamine; Goals; Guidelines; Incidence; Institutes; Intervention; Intervention Trial; Life Style; Lipids; Measures; Mediating; Mediterranean Diet; Metabolic; Metabolic Pathway; Metabolic syndrome; Nature; Nuts; Olea; Olive oil preparation; Participant; Pathway interactions; Plasma; Primary Prevention; Public Health; Randomized; Randomized Controlled Trials; Recommendation; Risk; Sampling; Spain; Stroke; Technology; Time; Trees; acylcarnitine; arm; blood lipid; cardiovascular disorder prevention; cardiovascular disorder risk; cohort; cost effective; design; dietary supplements; fasting glucose; follow-up; good diet; innovation; lifestyle intervention; metabolomics; novel; public health relevance; randomized trial; urea cycle

DESCRIPTION (provided by applicant): In the U.S., one in every three deaths is attributable to cardiovascular disease (CVD). Healthy diet and lifestyle are crucial for CVD prevention. The traditional Mediterranean dietary pattern has received increasing attention because of its potential beneficial effects on CVD risk. Recently, the landmark PREDIMED randomized trial (n=7,447 participants free of diagnosed CVD at baseline) demonstrated that a Mediterranean dietary pattern, supplemented with either virgin olive oil or tree nuts, significantly reduced the risk of major clinical CVD events by ~30%, compared to a control diet, after a median follow-up of 4.8 years. The goal of this project is to examine the effects of the randomized PREDIMED dietary interventions on plasma levels of metabolites, and to determine whether these resulting metabolic profiles mediate the interventions' benefits on CVD risk. A nested case-cohort design will be used, incorporating all 288 incident cases of CVD and 745 (10%) randomly selected trial participants at baseline. Stored fasting blood specimens collected at baseline and at year 1 of the trial will be measured for a well-validated panel of ~300 metabolites, using the state-of-the-art LC-MS technology developed by the Broad Institute of MIT and Harvard. We will focus on classes of metabolites that have been implicated in cardio-metabolic risk. Our project includes three specific aims: 1) To examine the effects of the randomized dietary interventions on changes in plasma levels of metabolites from baseline to year 1 in 745 randomly selected trial participants; 2) To examine whether 1-year changes in plasma levels of metabolites mediate the effect of the randomized dietary interventions on subsequent clinical CVD outcomes from years 2 to 5, using the efficient case-cohort design; and 3) To examine whether baseline metabolite levels modify the effects of the randomized dietary interventions on CVD risk, using a case-cohort design. As a secondary aim, we will examine whether 1-year changes in metabolites mediate the benefits of dietary interventions on subsequent occurrence of the metabolic syndrome, among 745 randomly selected trial participants. The PREDIMED is the first randomized primary prevention trial to evaluate the effects of Mediterranean-style dietary interventions on hard CVD endpoints. The current proposal outlines an extremely efficient and innovative study that applies the state-of-the-art metabolomics technology to a rigorously conducted dietary intervention trial. This study provides an ideal opportunity to discover novel pathways through which diet influences CVD risk, with access to archived plasma samples at baseline and follow-up, well-documented CVD endpoints, and long-term, randomized interventions with excellent compliance. The 2010 Dietary Guidelines for Americans has recognized the Mediterranean dietary pattern, along with the Dietary Approaches to Stop Hypertension (DASH) diet, as a healthy diet for CVD prevention. Results from this study will provide further evidence to support public health recommendations for dietary prevention of CVD.

描述（由申请人提供）：在美国，每三分之一的死亡归因于心血管疾病（CVD）。健康的饮食和生活方式对于预防CVD至关重要。传统的地中海饮食模式因其对CVD风险的潜在有益影响而受到了越来越多的关注。最近，具有里程碑意义的预测随机试验（n = 7,447名参与者在基线时没有被诊断为CVD的参与者）表明，与对照饮食相比，与对照饮食相比，与对照饮食相比，接受了初生橄榄油或树坚果的补充，将主要临床CVD事件的风险大大降低了〜30％。该项目的目的是检查随机预测的饮食干预措施对代谢物血浆水平的影响，并确定这些产生的代谢概况是否介导了干预措施对CVD风险的好处。将使用嵌套的案例 - 霍特设计，并结合所有288例CVD事件和745例（10％）在基线时随机选择的试验参与者。使用MIT和哈佛大学广泛研究所开发的最先进的LC-MS技术，将对〜300代谢物的经过精心验证的面板进行测量，在基线时和试验的1年级收集的空腹血液标本。我们将重点关注与心脏代谢风险有关的代谢产物类别。我们的项目包括三个具体目标：1）研究随机饮食干预措施对从基线到745个随机选择的试验参与者的代谢物等血浆水平变化的影响； 2）使用有效的病例 - 果园设计，要检查代谢产物血浆水平的一年变化是否介导了随后的饮食干预措施对随后的临床CVD结局的影响； 3）检查基线代谢物水平是否使用案例 - 霍特设计是否改变了随机饮食干预措施对CVD风险的影响。作为次要目的，我们将研究代谢物的一年变化是否介导了745名随机选择的试验参与者中，饮食干预措施对随后发生代谢综合征的益处。 Predimed是第一个评估地中海式饮食干预措施对硬CVD终点的影响的首次随机预防试验。当前的提案概述了一项极其有效和创新的研究，该研究将最先进的代谢组学技术应用于严格进行的饮食干预试验。这项研究提供了一个理想的机会，可以发现饮食会影响CVD风险的新型途径，并在基线和随访，有据可查的CVD终点以及长期的随机干预措施中获取存档的等离子体样本，并具有出色的合规性。 2010年美国人的饮食指南已认识到地中海饮食模式，以及饮食中停止高血压（DASH）饮食的方法，是预防CVD的健康饮食。这项研究的结果将提供进一步的证据，以支持公共卫生预防CVD的建议。