Potential cardiovascular benefits of sustained improvement in depressive symptoms among middle-aged and older adults: a longitudinal hypothetical intervention study.

backgroundRandomized trials have not clearly characterized the long-term cardiovascular benefit and preventable disease burden that may correspond to sustained improvement in depressive symptoms in middle-aged and older adults. Under hypothetical intervention scenarios, we quantified the long-term cardiovascular risk differences relative to the natural course, aiming to reflect the potential benefit of non-specific strategies for sustained depressive symptom improvement.

methodsThis longitudinal hypothetical intervention study was conducted in two population-based ageing cohorts, the English Longitudinal Study of Ageing (ELSA) and the China Health and Retirement Longitudinal Study (CHARLS), including adults aged 50 years and older who were free of CVD at baseline. Depressive symptoms were modeled as binary depressive status or continuous CES-D score. Using the parametric g-formula, we estimated 9-10-year cumulative CVD risk under sustained depressive symptom-improvement scenarios versus the natural course, and quantified the absolute risk difference in CVD events and the number of potentially preventable events at the population level. Robustness was assessed through a series of sensitivity analyses, including alternative missing-data approaches, model specifications, CES-D cut-offs, within-wave time-ordering assumptions, lagged exposure definitions, exclusion of early CVD events, intervention probabilities, exclusion of potentially mediating behavioral covariates, inverse probability-of-censoring weighting treating death as a competing event, quantitative bias analyses for outcome and exposure misclassification, negative-control exposure analysis, and E-value analysis.

resultsAcross both cohorts, hypothetical sustained improvement in depressive symptoms was associated with lower cumulative CVD risk than the natural course. Under the intensive scenario, the 9-year risk difference (RD) in CHARLS was - 3.8% (95% CI, - 4.6% to - 2.9%), with a risk ratio (RR) of 0.85 (95% CI, 0.81 to 0.88) and a potential impact fraction (PIF) of 15.40%. In ELSA, the corresponding 10-year RD was - 1.7% (95% CI, - 2.2% to - 1.1%), with an RR of 0.91 (95% CI, 0.88 to 0.94) and a PIF of 8.89%. Feasible scenarios yielded smaller but directionally consistent reductions. Analyses using continuous CES-D score showed a graded pattern, with larger symptom reductions associated with progressively lower cumulative CVD risk. Findings were broadly consistent across sensitivity analyses.

conclusionsHypothetical sustained improvement in depressive symptoms was associated with lower cumulative CVD risk over 9-10 years in two population-based ageing cohorts. These findings provide quantitative reference estimates for the potential long-term cardiovascular benefit and preventable disease burden that may correspond to non-specific strategies for sustained depressive symptom improvement. Importantly, these estimates should be interpreted as modeled risk contrasts under hypothetical symptom-change scenarios, rather than as effect estimates for any specific pharmacological treatment, psychotherapy, social support, or other clinical or public health intervention.