Long-term serial kinetics of N-terminal pro B-type natriuretic peptide and carbohydrate antigen 125 for mortality risk prediction following acute heart failure

Aim: Baseline values of N-terminal pro B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) predict all-cause mortality in acute heart failure (AHF). However, there is limited information about the added prognostic benefit of using longitudinal values, and how this predictive ability is modified when modelling together. The aim of this study was to determine the mutually-adjusted association between the longitudinal trajectories of NT-proBNP and CA125 with all-cause mortality after an episode of AHF. Methods and results: We included 946 consecutive patients discharged for AHF. NT-proBNP and CA125 were measured at each physician-patient encounter (median (interquartile range (IQR)):3 (2-4)). The effect on mortality (time-dependent modelling) was assessed using joint modelling (JM) and multi-state Markov. The mean age was 7111 years and 51% exhibited left ventricular systolic dysfunction. At a median follow-up of 2.64 years (IQR=1.20-5.36), 498 patients died (52.6%). The observed trajectories of both biomarkers markedly differed over survival status, with sustained higher values in patients who died. After being adjusted by established risk factors and by each other, the baseline absolute change in CA125 and NT-proBNP were significantly associated to mortality (hazard ratio (HR)=1.05 (1.01-1.09); p=0.011 (area under the curve (AUC)=0.76) and HR=1.04 (1.02-1.06); p<0.001 (AUC=0.75), respectively). After merging the binary version of NT-proBNP (>= 1000 pg/ml) and CA125 (>35 U/ml) into a four-level variable, we found the highest risk when both were elevated, intermediate risk when either one was low, and lowest risk when both were low. Conclusion: The combination of long-term longitudinal trajectories of CA125 and NT-proBNP improves risk stratification for all-cause mortality after a hospitalization for AHF.