Fuwai Hospital, National Center for Cardiovascular Diseases, National Key Laboratory, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Eur J Clin Invest. 2024 Jun;54(6):e14194. doi: 10.1111/eci.14194. Epub 2024 Mar 4.
Substantial focus has been placed on atrial fibrillation (AF) treatment and associated stroke prevention rather than preventing AF itself. We employed Mendelian randomization (MR) approach to examine the causal relationships between 50 modifiable risk factors (RFs) and AF.
Instrumental variables for genetically predicted exposures were derived from corresponding genome-wide association studies (GWASs). Summary-level statistical data for AF were obtained from a GWAS meta-analysis (discovery dataset, N = 1,030,836) and FinnGen (validation dataset, N = 208,594). Univariable and multivariable MR analyses were performed, primarily using inverse variance weighted method with a series of robust sensitivity analyses.
Genetic predisposition to insomnia, daytime naps, apnea, smoking initiation, moderate to vigorous physical activity and obesity traits, including body mass index, waist-hip ratio, central and peripheral fat/fat-free mass, exhibited significant associations with an increased risk of AF. Coffee consumption and ApoB had suggestive increased risks. Hypertension (odds ratio (OR) 95% confidence interval (CI): 5.26 (4.42, 6.24)), heart failure (HF) (OR 95% CI, 4.77 (2.43, 9.37)) and coronary artery disease (CAD) (OR 95% CI: 1.20 (1.16, 1.24)) were strongly associated with AF, while college degree, higher education attachment and HDL levels were associated with a decreased AF risk. Reverse MR found a bidirectional relationship between genetically predicted AF and CAD, HF and ischemic stroke. Multivariable analysis further indicated that obesity-related traits, systolic blood pressure and lower HDL levels independently contributed to the development of AF.
This study identified several lifestyles and cardiometabolic factors that might be causally related to AF, underscoring the importance of a holistic approach to AF management and prevention.
人们对房颤（AF）的治疗和相关的卒中预防给予了大量关注，而不是预防 AF 本身。我们采用孟德尔随机化（MR）方法来研究 50 种可改变的风险因素（RFs）与 AF 之间的因果关系。
通过相应的全基因组关联研究（GWASs）得出遗传预测暴露的工具变量。通过 GWAS 荟萃分析（发现数据集，N=1,030,836）和 FinnGen（验证数据集，N=208,594）获得 AF 的汇总统计数据。主要使用逆方差加权法进行单变量和多变量 MR 分析，并进行了一系列稳健敏感性分析。
失眠、白天小睡、呼吸暂停、吸烟起始、中等到剧烈的身体活动和肥胖特征（包括体重指数、腰臀比、中心和外周脂肪/无脂肪质量）的遗传易感性与 AF 风险增加显著相关。咖啡消费和 ApoB 具有提示性的风险增加。高血压（比值比（OR）95%置信区间（CI）：5.26（4.42, 6.24））、心力衰竭（HF）（OR 95% CI，4.77（2.43, 9.37））和冠状动脉疾病（CAD）（OR 95% CI：1.20（1.16, 1.24））与 AF 强烈相关，而大学学位、高等教育附属和 HDL 水平与 AF 风险降低相关。反向 MR 发现遗传预测 AF 与 CAD、HF 和缺血性卒中之间存在双向关系。多变量分析进一步表明，肥胖相关特征、收缩压和较低的 HDL 水平独立促成 AF 的发生。
本研究确定了几种与生活方式和心脏代谢相关的因素可能与 AF 有因果关系，这强调了采用整体方法来管理和预防 AF 的重要性。
