title: Long-term serial kinetics of N-terminal pro B-type natriuretic peptide and carbohydrate antigen 125 for mortality risk prediction following acute heart failure.
abstract: OBJECTIVE
  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.
  
  
  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 71±11 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.
  
  
  CONCLUSIONS
  The combination of long-term longitudinal trajectories of CA125 and NT-proBNP improves risk stratification for all-cause mortality after a hospitalization for AHF.
authors.affiliation: 1 Servicio de Cardiología, Hospital Clínico Universitario, INCLIVA, Universitat de Valencia, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Núñez
authors.affiliation: 1 Servicio de Cardiología, Hospital Clínico Universitario, INCLIVA, Universitat de Valencia, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Núñez
authors.affiliation: 2 Servicio de Cardiología, Hospital Universitari Germas Trias i Pujol, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Bayés-Genís
authors.affiliation: 3 Division of Cardiology, UCLA, USA.
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: 1 Servicio de Cardiología, Hospital Clínico Universitario, INCLIVA, Universitat de Valencia, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Miñana
authors.affiliation: 1 Servicio de Cardiología, Hospital Clínico Universitario, INCLIVA, Universitat de Valencia, Spain.
authors.forename: Vicent
authors.initials: V
authors.lastname: Bodí
authors.affiliation: 4 Servicio de Cardiología, Universidad de Murcia, Spain.
authors.forename: Domingo
authors.initials: D
authors.lastname: Pascual-Figal
authors.affiliation: 1 Servicio de Cardiología, Hospital Clínico Universitario, INCLIVA, Universitat de Valencia, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Santas
authors.affiliation: 1 Servicio de Cardiología, Hospital Clínico Universitario, INCLIVA, Universitat de Valencia, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Garcia-Blas
authors.affiliation: 1 Servicio de Cardiología, Hospital Clínico Universitario, INCLIVA, Universitat de Valencia, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Chorro
authors.affiliation: 5 Department of Biostatistics, Erasmus University Medical Center, the Netherlands.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Rizopoulos
authors.affiliation: 1 Servicio de Cardiología, Hospital Clínico Universitario, INCLIVA, Universitat de Valencia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sanchis
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood*; D002423:Cause of Death / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000401:mortality; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
chemical_list: D015415:Biomarkers; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: B-type natriuretic peptide; Mortality; acute heart failure; carbohydrate antigen 125; longitudinal study