Effect of an Intensive Lifestyle Intervention on the Atrial Fibrillation Substrate

项目摘要/摘要 房颤(AF)是一种常见的心律失常，与中风、心力衰竭、 痴呆症和死亡率。目前房颤的治疗方法包括抗心律失常药、口服抗凝剂和导管 消融，效果有限，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一常见情况的发生。心脏介入治疗 以心房纤维化和重构为特征的基质，为避免或逆转其发展提供了一种 预防房颤的方法很有吸引力，因为这种底物是房颤发生的关键易感因素。在我们之前的 我们在观察性研究中的工作表明，体重增加是导致 房颤的发展。最近，我们还在一项随机试验中证明，分配给 地中海饮食中富含特级初榨橄榄油的人比对照组的人患房颤的风险更低。 这些联系背后的病理生理学机制还不完全清楚，但是 心房基质的变化可能是原因之一。 在本申请中，我们建议对最近启动的PREDIMED-PLUS试验进行一项辅助研究 主要目的是评估减肥生活方式干预对心脏基质的影响 自动对焦。PREDIMED-PLUS研究是一项多中心、随机试验，用于初级预防 在西班牙，6874名患有代谢综合征的超重和肥胖男性和女性患有心血管疾病。 这项试验将评估集中减肥的生活方式干预计划的效果-包括 限制能量的地中海饮食、增加的体力活动和认知行为体重 管理--与地中海饮食低强度饮食建议的对照干预相比。在……里面 在本申请中，我们建议对重复执行的AF衬底进行重复评估 超声心动图和循环生物标记物的测定在高血压发病机制中的作用 573例房颤底物(心脏纤维化、炎症、氧化应激、心肌损伤、心房拉伸) PREDIMED+试验的参与者完成了基线超声心动图检查。我们会 确定强化生活方式干预对心脏结构和功能的影响，并进行初步的 重点放在心房和房颤相关通路的生物标记物上。此外，我们将对协会进行评估 在干预的不同组成部分之间(减肥、遵守能量限制 地中海饮食、增加体力活动)和心房底物的变化。拟议的研究将 确定强化生活方式干预对房颤和Will病理生理底物的疗效 告知制定具体的建议，以防止过程在临床上结束 房颤发作。

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.