Kaisaier Wulamiding, Ye Min, Wu Zexuan, Liu Chen, He Jiangui, Lip Gregory Y H, Chen Yili, Zhu Wengen
Department of Cardiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; The National Health Commission Key Laboratory of Assisted Circulation and Vascular Diseases Key Laboratory of Assisted Circulation and Vascular Diseases, Sun Yat-sen University, Guangzhou, China.
Department of Cardiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; The National Health Commission Key Laboratory of Assisted Circulation and Vascular Diseases Key Laboratory of Assisted Circulation and Vascular Diseases, Sun Yat-sen University, Guangzhou, China; Department of Medical Ultrasonics, Institute for Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
JACC Asia. 2025 Aug;5(8):983-996. doi: 10.1016/j.jacasi.2025.04.008. Epub 2025 Jun 24.
Lower socioeconomic status, intelligence, and cognition are linked to a higher likelihood of atrial fibrillation (AF). However, whether these factors directly cause AF or whether others mediate this relationship is unclear.
Our study aimed to determine the causal link between lower socioeconomic status, intelligence, cognition, and AF, and identify mediators.
We conducted a 2-sample Mendelian randomization analysis with data from European ancestry genome-wide association studies. Genetic instruments for education, intelligence, cognition, income, and occupation (n = 248,847-1,131,881) evaluated their relationship with AF (FinnGen study: 50,743 cases and 210,652 control subjects; 6 European studies: 60,620 and 970,216).
The pooled results from meta-analysis combining data from 2 studies indicated that education, intelligence, and cognition were causally associated with AF (P < 0.05). Genetically predicted, each 1-SD increase in educational attainment was associated with a 19% decreased risk of AF (OR: 0.81; 95% CI: 0.71-0.92), independent of intelligence and cognition. Among 44 candidate mediators, 8 factors were identified to mediate the education-AF association, including heart failure (mediation proportion: 95.35%), body fat mass (44.05%), waist circumference (42.93%), coronary heart disease (30.1%), body mass index (29.0%), myocardial infarction (28.8%), diastolic blood pressure (21.7%), and waist-to-hip ratio (14.3%).
Our study suggests that education exerts a causal and protective effect against AF, independent of intelligence and cognition. Heart failure, obesity, and ischemic heart disease serve as mediating factors in the pathway from education to AF, underscoring the importance of considering these conditions in preventing AF associated with education inequality.
较低的社会经济地位、智力和认知与心房颤动（AF）的较高可能性相关。然而，这些因素是直接导致房颤，还是其他因素介导了这种关系尚不清楚。
我们的研究旨在确定较低的社会经济地位、智力、认知与房颤之间的因果关系，并确定中介因素。
我们利用欧洲血统全基因组关联研究的数据进行了两样本孟德尔随机化分析。教育、智力、认知、收入和职业的遗传工具（n = 248,847 - 1,131,881）评估了它们与房颤的关系（芬兰基因组研究：50,743例病例和210,652名对照受试者；6项欧洲研究：60,620例病例和970,216名对照受试者）。
两项研究数据合并的荟萃分析结果表明，教育、智力和认知与房颤存在因果关系（P < 0.05）。基因预测显示，教育程度每增加1个标准差，房颤风险独立于智力和认知降低19%（OR：0.81；95% CI：0.71 - 0.92）。在44个候选中介因素中，有8个因素被确定为介导教育与房颤关联的因素，包括心力衰竭（中介比例：95.35%）、体脂量（44.05%）、腰围（42.93%）、冠心病（30.1%）、体重指数（29.0%）、心肌梗死（28.8%）、舒张压（21.7%）和腰臀比（14.3%）。
我们的研究表明，教育对房颤具有因果性保护作用，独立于智力和认知。心力衰竭、肥胖和缺血性心脏病是从教育到房颤途径中的中介因素，强调了在预防与教育不平等相关的房颤时考虑这些情况的重要性。
