Life-course Stressful Life Events and Risk of Stroke in Middle-aged and Older Chinese Adults: Evidence from the China Health and Retirement Longitudinal Study

BACKGROUND: Stressful life events (SLEs) across the life course have been recognized as important psychosocial stressors that may adversely influence cardiometabolic and cerebrovascular health. However, the cumulative and stage-specific impact of SLEs on stroke risk, and the potential mediating role of intrinsic capacity, remain insufficiently understood in aging populations. METHODS: We analyzed data from 7,605 participants aged ≥45 years in the China Health and Retirement Longitudinal Study (CHARLS). Childhood and adulthood SLEs were retrospectively assessed using the 2011 baseline survey and 2014 Life History Survey, covering six domains in each life stage. Stroke was defined as self-reported physician diagnosis. Logistic regression models estimated the associations between SLEs and stroke, with sequential adjustment for demographic, lifestyle, clinical, and biochemical covariates, including heart disease and depressive symptoms as additional confounders. Subgroup and sensitivity analyses were performed across sex, residence, education, marital status, smoking, drinking, and geographic region. Causal mediation analysis further examined whether intrinsic capacity mediated the relationship between SLEs and stroke. RESULTS: Participants with stroke were older, more often male, and had higher prevalence of adulthood and cumulative SLEs, as well as higher rates of heart disease (36.1% vs. 17.6%) and depression (41.6% vs. 30.7%). Our findings demonstrate that adulthood and cumulative life-course SLEs are robustly associated with increased odds of stroke, while childhood SLEs alone show no independent association. Each one-unit increase in the cumulative SLEs score was associated with higher odds of stroke (fully adjusted OR=1.35, 95% CI: 1.12-1.64, p=0.002). Compared with no exposure, adulthood SLEs (OR=1.55, 95% CI: 1.06-2.26, p=0.023) and combined childhood and adulthood SLEs (OR=1.82, 95% CI: 1.22-2.70, p=0.003) were strongly associated with stroke, whereas childhood SLEs alone were not significant (OR=1.35, 95% CI: 0.94-1.92, p=0.102). These associations remained robust after additional adjustment for heart disease and depressive symptoms. Subgroup analyses indicated consistent associations across most strata, with stronger effects in urban residents, individuals with higher education, and drinkers. Notably, the association was stronger in females (OR=1.80, 95% CI: 1.32-2.46) than males. Mediation analyses reveal that intrinsic capacity partially mediates these relationships, accounting for approximately 4.6-17.3% of the total effect (proportion mediated declining from 17.3% in the unadjusted model to 4.6% after full adjustment), suggesting that maintaining functional reserve may partially mitigate the adverse cerebrovascular consequences of psychosocial stress. Sensitivity analyses excluding participants aged >80 years (OR=1.34, 95% CI: 1.10-1.63, p=0.003) and >85 years (OR=1.35, 95% CI: 1.11-1.64, p=0.002) confirmed the robustness of the findings. CONCLUSIONS: These results provide novel insights into the life-course mechanisms linking stress exposure to cerebrovascular health and highlight potential intervention targets for stroke prevention in aging populations. Life-course stressful life events, particularly those occurring in adulthood and cumulative across childhood and adulthood, are robustly associated with increased stroke risk in Chinese middle-aged and older adults. Intrinsic capacity partially mediates this relationship, suggesting that maintaining functional reserve may buffer the adverse effects of psychosocial stressors. These findings underscore the importance of life-course approaches to stroke prevention and highlight the need for integrated strategies targeting psychosocial stress and intrinsic capacity in aging populations.