Cross-national associations between adulthood stressful life events and incident heart disease: a multicohort harmonized analysis

Background: Whether links between adulthood stressful life events (SLEs) and heart disease are comparable across countries-and whether they follow a dose-response pattern-remains uncertain. Methods: We harmonized exposure, outcome, covariates, and model specifications across three nationally representative aging cohorts in China (CHARLS), the United States (HRS), and the United Kingdom (ELSA). Cox models using attained age as the time scale estimated the association between adulthood SLEs (any vs. none) and incident heart disease; we also assessed dose-response (0, 1, 2, ≥3 events). Robustness was evaluated using alternative exposure definitions, an alternative event-date specification, multiple imputation, Fine-Gray competing-risk models (where mortality was available), alternative handling of physical activity, exclusion of events occurring within the first 1 or 2 years of follow-up, and an alternative time scale. Exploratory subgroup analyses with multiplicative interaction terms probed potential effect modification. Results: The analysis included 11,240 (CHARLS), 13,099 (HRS), and 3,390 (ELSA) participants and documented 2,074, 2,124, and 678 incident events over 84.2, 95.3, and 26.7 thousand person-years, respectively. Compared with no SLEs, reporting at least one SLE was associated with a higher risk of incident heart disease: adjusted HR 1.20 (95% CI 1.09-1.31) in CHARLS, 1.23 (1.11-1.36) in HRS, and 1.53 (1.27-1.85) in ELSA. Under the original six-item definition, risk increased across SLE-count categories in HRS and ELSA, whereas in CHARLS, risk was elevated in the 1- and 2-event categories but did not show a clear further increase in the ≥3 category. Most sensitivity analyses yielded similar estimates; however, associations were attenuated under alternative exposure definitions excluding health- and injury-related items, particularly in HRS and ELSA. Effect modification was limited to HRS, where associations were stronger in women and in participants without hypertension or diabetes. Conclusion: Across three national cohorts, adulthood SLEs were associated with a small-to-moderate increase in incident heart disease, although the graded association varied across cohorts. The present study adds cross-nationally comparable evidence on adulthood adversity and heart disease risk under a harmonized analytic framework.