Xiang Hao, Gan Xiaoqin, Zhang Yanjun, Zhang Yuanyuan, Ye Ziliang, Yang Sisi, Huang Yu, Wu Yiting, Zhang Yiwei, Qin Xianhui
State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Arterioscler Thromb Vasc Biol. 2025 Feb;45(2):332-340. doi: 10.1161/ATVBAHA.124.322112. Epub 2024 Dec 26.
To explore the association of social isolation with venous thromboembolism (VTE) risk and the mediating role of metabolomics on this association.
Overall, 236 026 participants free of VTE and with complete metabolomics data at baseline from the UK Biobank were included. Social isolation was constructed based on the frequency of friend/family visits, weekly group activities, and living alone. The study outcome was incident VTE, including deep vein thrombosis or pulmonary embolism. Least absolute shrinkage and selection operator regression was applied to create a social isolation-associated metabolic signature. We estimated hazard ratios of study outcomes in relation to social isolation/metabolic signature and calculated the proportion of social isolation-VTE association mediated by the metabolic signature.
During a median follow-up of 12.5 years, 6681 VTE cases were recorded. Social isolation was positively associated with VTE risk (versus without social isolation; hazard ratio, 1.17 [95% CI, 1.09-1.27]). A metabolic signature for social isolation was constructed using 28 metabolites. This metabolic signature showed significant association with VTE risk (per SD increment; hazard ratio, 1.16 [95% CI, 1.13-1.19]) and mediated 11.0% (95% CI, 7.0-19.8) of the increased VTE risk associated with social isolation. 11 metabolites in the metabolic signature also significantly mediated the association between social isolation and VTE risk, with mediation proportions ranging from 0.5% to 2.6%. Similar results were found for incident deep vein thrombosis and pulmonary embolism, respectively.
Social isolation was positively associated with VTE risk. The metabolic signature for social isolation, especially the 11 major metabolites included, significantly mediated the association between social isolation and VTE risk.
探讨社会隔离与静脉血栓栓塞症（VTE）风险之间的关联以及代谢组学在此关联中的中介作用。
总共纳入了英国生物银行中236026名无VTE且基线时有完整代谢组学数据的参与者。基于朋友/家人探访频率、每周集体活动情况以及独居情况构建社会隔离指标。研究结局为VTE事件，包括深静脉血栓形成或肺栓塞。应用最小绝对收缩和选择算子回归创建与社会隔离相关的代谢特征。我们估计了研究结局与社会隔离/代谢特征相关的风险比，并计算了代谢特征介导的社会隔离与VTE关联的比例。
在中位随访12.5年期间，记录到6681例VTE病例。社会隔离与VTE风险呈正相关（与无社会隔离相比；风险比为1.17[95%CI，1.09 - 1.27]）。使用28种代谢物构建了社会隔离的代谢特征。该代谢特征与VTE风险显著相关（每标准差增加；风险比为1.16[95%CI，1.13 - 1.19]），并介导了与社会隔离相关的VTE风险增加的11.0%（95%CI，7.0 - 19.8）。代谢特征中的11种代谢物也显著介导了社会隔离与VTE风险之间的关联，中介比例范围为0.5%至2.6%。分别在深静脉血栓形成和肺栓塞事件中发现了类似结果。
社会隔离与VTE风险呈正相关。社会隔离的代谢特征，尤其是其中包含的11种主要代谢物，显著介导了社会隔离与VTE风险之间的关联。
