Zhou Yaguan, Kivimäki Mika, Holt-Lunstad Julianne, Yan Lijing L, Zhang Yue, Wang Hui, Wang Sunyi, Xu Xiaolin
School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China.
EClinicalMedicine. 2025 May 2;83:103225. doi: 10.1016/j.eclinm.2025.103225. eCollection 2025 May.
Stressful life events, such as financial hardship, and death of own child, have been associated with various adverse health outcomes, but their impacts on complex multimorbidities remain unknown. This study examined the association between stressful life events in childhood and adulthood and later-life physical, psychological and cognitive multimorbidities.
We harmonised and pooled longitudinal data from three nationally representative cohort studies from the Program on Global Ageing, Health and Policy: the US Health and Retirement Study (HRS), the English Longitudinal Study on Ageing (ELSA), and the China Health and Retirement Longitudinal Study (CHARLS), encompassing the years 2011-2020. Participants were middle-aged and older adults free from physical, psychological and cognitive multimorbidities and with information on six stressful life events in childhood and six stressful life events in adulthood. Multimorbidities were measured according to the coexistence of physical, psychological and cognitive conditions. Three lifestyle factors, including physical inactivity, alcohol consumption, and smoking, were treated as potential mediators. We used Cox proportional hazards regression models and multi-state models to estimate the risk of developing or progressing multimorbidities at follow-up in the pooled population and in each study.
In the 24,955 participants (mean age 63.6 years, standard deviation 10.6), 4284 (17.2%) reported stressful life events in childhood, 6509 (26.1%) in adulthood, and 5364 (21.5%) in both. During a follow-up of 8-9 years, 10,913 (43.7%) participants developed physical, psychological and cognitive multimorbidities. After adjusting for age, sex, study, and education, individuals with both childhood and adulthood stressful life events experienced a 1.71 (vs. none, hazard ratio: 1.71, 95% confidence interval: 1.54-1.90), 1.26 (1.16-1.38), 1.58 (1.22-2.04), and 1.89 (1.69-2.11) times higher risk of physical-psychological multimorbidity, physical-cognitive multimorbidity, psychological-cognitive multimorbidity, and physical-psychological-cognitive multimorbidity respectively. The associations with multimorbidities that included a psychological condition as one component were stronger than those that included only physical or cognitive conditions. Childhood stressful life events were associated with transitions from baseline to physical-psychological and psychological-cognitive multimorbidities, while adulthood and life-course stressful events were associated with all transitions between baseline and multimorbidities (≥2 adulthood events vs. 0 and transition to physical, psychological and cognitive multimorbidity: 1.73, 1.43-2.09). Smoking status, physical inactivity, and alcohol consumption partially mediated the associations, and the strongest mediation effect was observed for alcohol consumption which accounted for 18.2% of the associations between childhood stressful life events and physical-cognitive multimorbidity.
From the studied cohorts middle-aged and older adults with a history of stressful life events in childhood or adulthood were seen to be at increased risk of developing multimorbidities involving psychological, physical and cognitive conditions. These findings emphasise the importance of preventive strategies targeting both social and lifestyle factors throughout the life course.
Natural Science Foundation of China, Hundred Talents Program Research Initiation Fund from Zhejiang University, Fundamental Research Funds for the Central Universities.
诸如经济困难和自己孩子死亡等生活应激事件已与各种不良健康结果相关联，但它们对复杂的多种慢性病的影响仍不明确。本研究考察了童年期和成年期的生活应激事件与晚年身体、心理和认知方面的多种慢性病之间的关联。
我们对来自全球老龄化、健康与政策项目的三项具有全国代表性的队列研究的纵向数据进行了整合和汇总：美国健康与退休研究（HRS）、英国老龄化纵向研究（ELSA）以及中国健康与退休纵向研究（CHARLS），涵盖2011年至2020年。参与者为中老年成年人，无身体、心理和认知方面的多种慢性病，且有关于童年期六个生活应激事件和成年期六个生活应激事件的信息。多种慢性病根据身体、心理和认知状况的共存情况进行衡量。包括缺乏身体活动、饮酒和吸烟在内的三种生活方式因素被视为潜在中介因素。我们使用Cox比例风险回归模型和多状态模型来估计汇总人群以及每项研究中随访时发生或进展为多种慢性病的风险。
在24955名参与者（平均年龄63.6岁，标准差10.6）中，4284人（17.2%）报告在童年期有生活应激事件，6509人（26.1%）在成年期有，5364人（21.5%）在童年期和成年期都有。在8至9年的随访期间，10913名（43.7%）参与者出现了身体及心理和认知方面的多种慢性病。在调整了年龄、性别、研究和教育因素后，童年期和成年期都有生活应激事件的个体发生身体 - 心理多种慢性病、身体 - 认知多种慢性病、心理 - 认知多种慢性病以及身体 - 心理 - 认知多种慢性病的风险分别高出1.71倍（与无此类事件者相比，风险比：1.71，95%置信区间：1.54 - 1.90）、1.26倍（1.16 - 1.38）、1.58倍（1.22 - 2.04）和1.89倍（1.69 - 2.11）。与包含心理状况作为一个组成部分的多种慢性病的关联比仅包含身体或认知状况的关联更强。童年期生活应激事件与从基线状态转变为身体 - 心理和心理 - 认知多种慢性病相关，而成年期和一生的生活应激事件与基线状态和多种慢性病之间所有的转变相关（≥2次成年期事件与0次事件相比，转变为身体、心理和认知多种慢性病：1.73，1.43 - 2.09）。吸烟状况、缺乏身体活动和饮酒部分介导了这些关联，其中饮酒的中介效应最强，占童年期生活应激事件与身体 - 认知多种慢性病之间关联的18.2%。
在所研究的队列中，童年期或成年期有生活应激事件史的中老年成年人发生涉及心理、身体和认知状况的多种慢性病的风险增加。这些发现强调了针对整个生命过程中的社会和生活方式因素的预防策略的重要性。
中国国家自然科学基金、浙江大学百人计划研究启动基金、中央高校基本科研业务费专项资金。
