Mediating Effect of Depression on the Association Between Cardiovascular Disease and the Risk of All-cause Mortality: NHANES in 2005-2018

Background: Cardiovascular disease (CVD) patients are more likely to have depression than general populations, and meanwhile, depression increased all-cause mortality. However, the interaction effect of depression on CVD and all-cause mortality has not been reported yet.

Hypothesis: Herein, we speculate that depression may play an intermediate role in the association of CVD and all-cause mortality.

Methods: Demographic and clinical data of 33,156 adults (≥20 years old) were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2005-2018 in this retrospective cohort study. Weighted univariate and multivariate COX regression analyses were used to screen the covariates and to explore the relationship of CVD and depression. Distribution-of-product method was used to assess the mediating effect of depression on the association between CVD and all-cause mortality. The mediating effect of depression was also explored in age, gender, diabetes mellitus (DM), and dyslipidemia subgroups. The evaluation indexes were odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs).

Results: Among the participants, 11 514 had CVD, 5844 had depression, and 4759 were died. After adjusting for covariates, CVD was related to high odds of depression (OR = 1.94). Depression played an intermediate role in CVD and all-cause mortality (HR = 1.23) with a mediational percentage of 9.13%. Subgroup analyses also showed this mediating effect existed in adults of different age, gender, DM and dyslipidemia status (all p < .05).

Conclusion: The intermediate effect of depression may help clinicians to early identify high-risk populations and provide some reference for disease management and mortality reduction.