Aerobic Exercise Training, Biological Age, and Mortality in Chronic Heart Failure With Reduced Ejection Fraction

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.

The authors aimed to investigate the association between BA and mortality among individuals with HFrEF and assess whether AET modifies the association.

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.

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).

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.