Abstract

BACKGROUND: Among individuals with chronic heart failure with reduced ejection fraction (HFrEF), the predictive value for mortality by biomarker-based biological age (BA) and whether aerobic exercise training (AET) modifies the association are understudied. OBJECTIVES: The authors aimed to investigate the association between BA and mortality among individuals with HFrEF and assess whether AET modifies the association. METHODS: Including participants in HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), BA acceleration was constructed by the Klemera-Doubal method, using the residual of a linear model of BA and chronological age. The associations between BA and all-cause mortality, cardiovascular death, and all-cause hospitalization were investigated by treating BA acceleration into continuous and quintiles in the overall cohort. RESULTS: Among the 1,732 individuals, during a median of 31.5 (IQR: 20.7-43.1) months of follow-up, 301 deaths were observed. A 1-SD increase in BA acceleration was associated with a 31% higher risk of all-cause mortality (HR: 1.31; 95% CI: 1.13-1.51), a 31% higher risk of cardiovascular mortality (HR: 1.31; 95% CI: 1.12-1.54), and a 9% higher risk of all-cause hospitalization (HR: 1.09; 95% CI: 1.01-1.17). The association of all-cause mortality was significantly different between treatment arms (P interaction = 0.024). BA acceleration was associated with a 53% higher risk of all-cause mortality in usual care (HR: 1.53; 95% CI: 1.25-1.89), but the association was not significant in AET (HR: 1.10; 95% CI: 0.89-1.36). CONCLUSIONS: Among individuals with HFrEF, BA has a good prediction value in HFrEF endpoints. AET may be associated with a reduction in all-cause mortality driven by aging.