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

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，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心血管疾病风险的潜在有益影响而受到越来越多的关注。最近，具有里程碑意义的 PREDIMED 随机试验（n = 7,447 名基线时未诊断出 CVD 的参与者）表明，在中位随访 4.8 年之后，补充初榨橄榄油或木本坚果的地中海饮食模式与对照饮食相比，可显着降低约 30% 的主要临床 CVD 事件风险。该项目的目标是检查随机 PREDIMED 饮食干预措施对血浆代谢物水平的影响，并确定这些产生的代谢特征是否介导了干预措施对 CVD 风险的益处。将使用嵌套病例队列设计，纳入所有 288 例 CVD 事件病例和 745 名 (10%) 随机选择的基线试验参与者。将使用麻省理工学院和哈佛大学布罗德研究所开发的最先进的 LC-MS 技术，对基线和试验第一年收集的储存的空腹血液样本进行约 300 种代谢物的经过充分验证的检测。我们将重点关注与心脏代谢风险有关的代谢物类别。我们的项目包括三个具体目标：1）研究随机饮食干预对 745 名随机选择的试验参与者从基线到第一年血浆代谢物水平变化的影响； 2) 使用有效的病例队列设计，检查血浆代谢物水平的 1 年变化是否介导随机饮食干预对随后 2 至 5 年临床 CVD 结果的影响； 3) 使用病例队列设计来检查基线代谢水平是否会改变随机饮食干预措施对 CVD 风险的影响。作为次要目标，我们将在 745 名随机选择的试验参与者中检查代谢物的 1 年变化是否介导饮食干预对随后发生代谢综合征的益处。 PREDIMED 是第一个随机一级预防试验，旨在评估地中海式饮食干预措施对硬性 CVD 终点的影响。目前的提案概述了一项极其高效和创新的研究，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，可以发现饮食影响 CVD 风险的新途径，可以获取基线和随访时存档的血浆样本、有据可查的 CVD 终点，以及具有良好依从性的长期随机干预措施。 2010 年美国人膳食指南承认地中海饮食模式以及预防高血压的饮食方法 (DASH) 饮食是预防 CVD 的健康饮食。这项研究的结果将为支持通过饮食预防心血管疾病的公共卫生建议提供进一步的证据。