More than three fourths of patients with heart failure (HF) are 65 years and older, and older age is associated with worse symptoms and prognoses than is younger age. Reduced exercise capacity is a chief HF complaint and indicates poorer prognosis, especially among elderly persons, but the mechanisms underlying functional decline in older patients with HF are largely unknown.

Baseline cardiopulmonary exercise testing data from the HF-ACTION trial were assessed to clarify age effects on peak oxygen consumption (VO₂) and ventilation–carbon dioxide production (VE/VCO₂) slope.

Among 2,331 New York Heart Association class II-IV patients with HF, increased age corresponded to decreased peak VO₂ (−0.14 mL kg⁻¹ min⁻¹ per year >40 years; P < .0001) and increased VE/VCO₂ slope (0.30 U/y >70 years; P < .0001). In a multivariable model with 34 other potential determinants, age was the strongest independent predictor of peak VO₂ (partial R² 0.130, total R² 0.392; P < .001) and a significant but relatively weaker predictor of VE/VCO₂ slope (partial R² 0.037, total R² 0.199; P < .001). Blunted peak heart rate was also a strong predictor of peak VO₂. Although peak heart rate and age were strongly correlated, both were significant independent predictors of peak VO₂ when analyzed simultaneously in a model. Aggregate comorbidity increased significantly with age but did not account for age effects on peak VO₂.

Age is the strongest predictor of peak VO₂ and a significant predictor of VE/VCO₂ slope in the HF-ACTION population. Age-dependent comorbidities do not explain changes in peak VO₂. Age-related changes in cardiovascular physiology, potentially magnified by the HF disease state, should be considered a contributor to the pathophysiology and a target for more effective therapy in older patients with HF.