Trajectories and cumulative burden of stressful life events in life-course with the risk of 14 incident chronic diseases: a prospective cohort study

The rising global burden of chronic disease highlights the need to understand life‑course determinants beyond conventional risk factors. This prospective study examined the associations of trajectories and cumulative burden of stressful life events with the risk of 14 incident chronic diseases. This analysis included 13,806 middle-aged and older adults from the China Health and Retirement Longitudinal Study (CHARLS). Participants were classified into four trajectories based on childhood and adulthood stressful life events: no exposure, childhood-only, adulthood-only, and persistent exposure. We used Cox proportional hazards models to estimate trajectory-specific hazard ratios (HRs) for 14 incident chronic diseases, with the no-exposure group as the reference. We then quantified dose-response associations between cumulative childhood and adulthood stressful life events and incident chronic diseases, and examined associations of specific stressful life events with chronic diseases. Compared with the no-exposure group, persistent exposure was associated with the broadest disease risk, including increased risks of diabetes (HR = 1.17, 95%CI: 1.01–1.39), chronic lung disease (HR = 1.45, 95%CI: 1.27–1.67), liver disease (HR = 1.39, 95%CI: 1.14–1.68), stroke (HR = 1.45, 95%CI: 1.22–1.74), kidney disease (HR = 1.53, 95%CI: 1.30–1.79), digestive disease (HR = 1.20, 95%CI: 1.05–1.36), psychiatric disease (HR = 1.41, 95%CI: 1.10–1.82), memory-related disease (HR = 1.31, 95%CI: 1.08–1.60), and arthritis or rheumatism (HR = 1.41, 95%CI: 1.25–1.58). Childhood-only and adulthood-only exposure were also associated with increased disease risk to varying degrees. In cumulative exposure analyses, each additional stressful event in childhood or adulthood was associated with increased risks of nine chronic diseases. Among middle-aged and older Chinese adults, different exposure trajectories and cumulative burden of stressful life events in childhood and adulthood were associated with increased risk of multiple diseases. These findings suggest that life-course stress exposure may be a relevant target for chronic disease prevention.