Effect of an Intensive Lifestyle Intervention on the Atrial Fibrillation Substrate

强化生活方式干预对心房颤动基质的影响

• 批准号: 10088010
• 负责人: Alvaro Alonso
• 金额: $ 14.23万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10088010
• 关键词: 3-nitrotyrosine; Adherence; Affect; Age; Ancillary Study; Anticoagulants; Arrhythmia; Atrial Fibrillation; Behavioral; Biological Markers; Blood; Body Weight; Body Weight decreased; Body mass index; Cardiac; Cardiac ablation; Cardiovascular Diseases; Cessation of life; Clinical; Cognitive; Data; Dementia; Development; Diet; Echocardiography; Etiology; Fat-Restricted Diet; Fibrosis; Functional disorder; Goals; Guidelines; Heart Atrium; Heart Diseases; Heart failure; Incidence; Individual; Inflammation; Intervention; Intervention Studies; Knowledge; Left; Left atrial structure; Life Style; Link; Maintenance; Measurement; Measures; Mediating; Mediation; Mediterranean Diet; Metabolic syndrome; Modification; Myocardial Infarction; Newly Diagnosed; Obesity; Observational Study; Olive oil preparation; Oral; Overweight; Oxidative Stress; Participant; Pathogenesis; Pathway interactions; Physical activity; Play; Predisposing Factor; Prevention; Primary Prevention; Process; Public Health; Public Policy; Randomized; Recommendation; Research Personnel; Risk; Risk Factors; Role; Spain; Stretching; Stroke; Structure; Time; Troponin; Weight Gain; Weight maintenance regimen; Woman; Work; adjudicate; base; cardiovascular disorder prevention; circulating biomarkers; coronary fibrosis; design; effective intervention; experimental study; follow-up; high risk; improved; insight; intervention effect; intervention program; lifestyle intervention; meetings; men; mortality; myocardial damage; myocardial injury; prevent; primary endpoint; pro-brain natriuretic peptide (1-76); procollagen type I carboxy terminal peptide; randomized trial; recruit; secondary endpoint; stroke risk

PROJECT SUMMARY / ABSTRACT Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke, heart failure, dementia, and mortality. Current treatments for AF, including antiarrhythmics, oral anticoagulants, and catheter ablation, have limited efficacy and carry significant risks, highlighting the need for prevention. Unfortunately, we currently lack effective interventions to prevent the onset of this common condition. Intervening on the cardiac substrate, characterized by atrial fibrosis and remodeling, to avert or reverse its development offers an attractive approach to AF prevention since this substrate is a key predisposing factor for AF onset. In our prior work in observational studies we have shown that increased body weight is a major risk factor for the development of AF. More recently, we also demonstrated in a randomized trial that individuals assigned to a Mediterranean diet enriched in extra-virgin olive oil had lower risk of AF than those assigned to a control diet. The pathophysiological mechanisms underlying the described associations are not completely understood, but changes in the atrial substrate are likely responsible. In this application, we propose to conduct an ancillary study to the recently-initiated PREDIMED-PLUS trial with the primary aim of assessing the effect of a weight-loss lifestyle intervention on the cardiac substrate of AF. The PREDIMED-PLUS study is a multi-center, randomized trial for the primary prevention of cardiovascular disease in 6,874 overweight and obese men and women with the metabolic syndrome in Spain. The trial will evaluate the effect of an intensive weight loss-focused lifestyle intervention program—including an energy-restricted Mediterranean diet, increased physical activity, and cognitive behavioral weight management—compared to a control intervention of low-intensity dietary advice on the Mediterranean diet. In the present application, we propose to conduct repeated assessments of the AF substrate performing repeated echocardiography and measurements of circulating biomarkers of pathways involved in the pathogenesis of the AF substrate (cardiac fibrosis, inflammation, oxidative stress, myocardial injury, atrial stretch) in 573 participants of the PREDIMED-PLUS trial with completed baseline echocardiographic exams. We will determine the effect of the intensive lifestyle intervention on cardiac structure and function, with a primary focus on the atria, and in biomarkers of AF-related pathways. Additionally, we will evaluate the association between the different components of the intervention (weight loss, compliance with the energy-restricted Mediterranean diet, increased physical activity) and changes in the atrial substrate. The proposed studies will determine the efficacy of an intensive lifestyle intervention on the pathophysiological substrate of AF and will inform the development of specific recommendations for the prevention of processes ending in the clinical onset of AF.

项目总结/摘要 心房颤动（AF）是一种常见的心律失常，与中风、心力衰竭、 痴呆和死亡率。目前的房颤治疗，包括抗纤溶酶原激活剂、口服抗凝剂和导管 消融术的疗效有限，并具有重大风险，突出了预防的必要性。不幸的是我们 目前缺乏有效的干预措施来预防这种常见疾病的发生。介入心脏 基质，其特征在于心房纤维化和重塑，以避免或逆转其发展， 这是一种有吸引力的AF预防方法，因为这种基质是AF发作的关键诱发因素。在我们之前的 在观察性研究中，我们已经表明，体重增加是一个主要的危险因素， 最近，我们还在一项随机试验中证明， 富含特级初榨橄榄油的地中海饮食与对照饮食相比，AF的风险较低。 所描述的相关性的病理生理机制尚未完全理解， 心房基质的变化可能是原因。 在本申请中，我们建议对最近启动的PREDIMED-PLUS试验进行辅助研究 主要目的是评估减肥生活方式干预对心脏基质的影响， AF. PREDIMED-PLUS研究是一项多中心、随机试验，用于以下疾病的一级预防： 西班牙6,874名超重和肥胖的代谢综合征患者的心血管疾病。 这项试验将评估一项以减肥为重点的生活方式干预计划的效果， 能量受限的地中海饮食，增加体力活动和认知行为体重 管理相比，控制干预的低强度饮食建议的地中海饮食。在 在本申请中，我们提出对AF基底进行重复评估， 超声心动图和参与发病机制的途径的循环生物标志物的测量 573例AF底物（心脏纤维化、炎症、氧化应激、心肌损伤、心房牵张） 完成基线超声心动图检查的PREDIMED-PLUS试验参与者。我们将 确定强化生活方式干预对心脏结构和功能的影响， 聚焦于心房和AF相关通路的生物标志物。此外，我们还将评估 干预的不同组成部分（体重减轻，遵守能量限制， 地中海饮食，增加体力活动）和心房基质的变化。拟议的研究将 确定强化生活方式干预对AF病理生理学基础的疗效，并将 通知制定具体建议，以防止临床结束的过程 AF发作。