Adverse Life Events Across the Life Course and the Risk of New-Onset Cardiovascular-Kidney-Metabolic Multimorbidity...

Adverse life events (ALEs) across the life course have been linked to chronic diseases, but their impact on cardiovascular-kidney-metabolic (CKM) multimorbidity remains unclear. This study examined the associations between childhood and adulthood ALEs and the risk of new-onset CKM multimorbidity and explored the mediating role of mental health.

Data were obtained from 6258 participants aged ≥45 years without CKM multimorbidity at baseline in the CHARLS (China Health and Retirement Longitudinal Study, 2011-2018). CKM multimorbidity was defined as the coexistence of at least 2 among cardiovascular, kidney, and metabolic diseases. Childhood and adulthood ALEs (10 and 6 types, respectively) were retrospectively assessed. Multistate temporal models estimated transitions to partial and complete CKM multimorbidity, and mediation analyses evaluated the role of mental health.

Compared with participants without ALEs, the hazard ratios of CKM multimorbidity were 1.22 (95% CI, 1.06-1.40) for childhood-only, 1.18 (95% CI, 1.00-1.41) for adulthood-only, and 1.81 (95% CI, 1.52-2.15) for both-period ALEs. Each additional childhood and adulthood ALE increased the risk by 13% and 19%, respectively. ALEs mainly influenced transitions from baseline to partial CKM multimorbidity, whereas mental health partially mediated these associations.

Life course adversity, particularly experiences involving violence or deprivation, substantially increases the risk of CKM multimorbidity in later life. These findings emphasize the importance of integrated prevention addressing psychosocial and mental health factors. Key limitations include deviation from American Heart Association-recommended CKM definitions due to incomplete obesity data and self-reported chronic kidney disease, which may have led to misclassification.