Depressive symptoms, health-related quality of life, and cardiac event-free survival in patients with heart failure: A mediation analysis

Purpose: Health-related quality of life (HRQOL) and depressive symptoms both are associated with an adverse prognosis in heart failure (HF), although their associations with outcomes have been examined only in isolation. Therefore, it is unknown how HRQOL and depressive symptoms might interact in their associations with outcomes. The present study was conducted to determine whether the association between HRQOL and cardiac event-free survival is mediated by depressive symptoms in HF patients given that depressive symptoms are associated strongly with HRQOL. Methods: A total of 209 HF patients (61 ± 11 years, 24 % female, 49 % NYHA III/IV) participated. The Minnesota Living with HF Questionnaire and the Patient Health Questionnaire-9 were used to measure HRQOL and depressive symptoms, respectively. Patients were followed for a median of 357 days to determine cardiac event-free survival. Results: In Cox regression analysis, HRQOL [hazard ratio (HR) 1.013; 95 % confidence interval (CI) 1.001-1.026] and depressive symptoms (HR 1.075; 95 % CI 1.025-1.127) predicted cardiac event-free survival separately, controlling for demographic and clinical variables. HRQOL independently explained 38.7 % of the variance in depressive symptoms (p < 0.05; standardized β = 0.695) in a multiple regression. When HRQOL and depressive symptoms were entered in the model simultaneously, only depressive symptoms independently predicted cardiac event-free survival (HR 1.068; 95 % CI 1.001-1.139), demonstrating a mediation effect of depressive symptoms. Conclusions: Depressive symptoms mediated the relationship between HRQOL and cardiac event-free survival. Interventions targeting HRQOL to enhance patient outcomes must also address patient depressive symptoms to be fully efficacious.