CA125 outperforms NT-proBNP in the prediction of maximum aerobic capacity in heart failure with preserved ejection fraction and kidney dysfunction

Abstract

Background Heart failure with preserved ejection fraction (HFpEF) often coexists with chronic kidney disease (CKD). Exercise intolerance is a major determinant of quality of life and morbidity in both scenarios. We aimed to evaluate the associations between NT-proBNP and CA125 with maximal aerobic capacity (peakVO2) in ambulatory HFpEF and whether these associations were influenced by kidney function. Methods This single-center study prospectively enrolled 133 patients with HFpEF who performed maximal cardiopulmonary exercise testing (CPET). Patients were stratified across glomerular filtration rate (eGFR) categories (<60 mL/min/1.73m2 vs. ≥60 mL/min/1.73m2). Results The mean age of the sample was 73.2 ± 10.5 years, and 56.4% were female. The median [p25-p75] of peakVO2 was 11.0 mL/Kg/min [9.0–13.0]. 67 (50.4%) patients displayed eGFR<60 ml/min/1.73m2. Those patients had higher levels of NT-proBNP and lower peakVO2, without differences in CA125. In the whole sample, NT-proBNP and CA125 were inversely correlated with peakVO2 (r=−0.43, P < 0.001 and r=−0.22, P = 0.010, respectively). After multivariate analysis, we found a differential association between NT-proBNP and peakVO2 across eGFR strata (p-value for interaction = 0.045). In patients with eGFR≥60 mL/min/1.73m2, higher NT-proBNP identified patients with poorer maximal functional capacity. In individuals with eGFR<60 mL/min/1.73m2, NT-proBNP was not significantly associated with peakVO2 (β-coefficient = 0.02, CI 95%:−0.19 to 0.23, P = 0.834). Higher CA125 was linear and significantly associated with worse functional capacity without evidence of heterogeneity across eGFR strata (p-value for interaction = 0.620). Conclusions In patients with stable HFpEF, NT-proBNP was not associated with maximal functional capacity when CKD was present. CA125 emerged as a useful biomarker for estimating effort intolerance in HFpEF irrespective of the presence of CKD.