Su Shu Yao, Wang Wan Yue, Yuan Chen Xi, Lin Zhen Nan, Lu Xiang Feng, Liu Fang Chao
Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China;Key Laboratory of Cardiovascular Epidemiology, Chinese Academy of Medical Sciences, Beijing 100037, China.
Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China;Key Laboratory of Cardiovascular Epidemiology, Chinese Academy of Medical Sciences, Beijing 100037, China;Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China.
Biomed Environ Sci. 2025 Mar 20;38(3):351-364. doi: 10.3967/bes2024.170.
Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators.
Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( = 487,647) and SI traits on IHD ( = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors.
Loneliness increased IHD risk ( = 2.129; 95% confidence interval [ ]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( = 1.815; 95% : 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found.
These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
观察性研究表明，孤独或社会隔离（SI）与缺血性心脏病（IHD）之间的关联并不一致，且中介因素不明。
利用主要为欧洲血统的全基因组关联研究数据，我们进行了一项双向双样本孟德尔随机化（MR）研究，以估计孤独（n = 487,647）和SI特征对IHD（n = 184,305）的因果效应。SI特征包括个体是否独居、参与各种社交活动的情况以及与朋友或家人的联系频率（n = 459,830至461,369）。进行了一项网络MR研究，以评估20种候选中介因素的中介作用，包括代谢、行为和心理因素。
孤独增加了IHD风险（比值比 = 2.129；95%置信区间[CI]：1.380至3.285），中介因素为体脂百分比、腰臀比、总胆固醇和低密度脂蛋白胆固醇。对于SI特征，只有社交活动较少会增加IHD风险（比值比 = 1.815；95%CI：1.189至2.772），中介因素为高血压、高密度脂蛋白胆固醇、甘油三酯、空腹胰岛素和戒烟。未发现IHD与孤独和SI之间存在反向因果关系。
这些发现表明，应更加关注感到孤独且社交活动较少的个体以预防IHD，将几种中介因素作为优先干预目标。
