title: Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C-reactive protein do not predict future allograft rejection in heart transplant recipients.
abstract: BACKGROUND
  Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR.
  
  
  METHODS
  From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 ± 4 (mean ± standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients.
  
  
  RESULTS
  The mean age of the patients at HTx was 49 ± 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ∼ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results.
  
  
  CONCLUSIONS
  The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.
authors.affiliation: 1 Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands. 2 Department of Biostatistics, Erasmus MC, Rotterdam, the Netherlands. 3 Department of Pathology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Battes
authors.forename: Kadir
authors.initials: K
authors.lastname: Caliskan
authors.forename: Dimitris
authors.initials: D
authors.lastname: Rizopoulos
authors.forename: Alina A
authors.initials: AA
authors.lastname: Constantinescu
authors.forename: Jan L
authors.initials: JL
authors.lastname: Robertus
authors.forename: Martijn
authors.initials: M
authors.lastname: Akkerhuis
authors.forename: Olivier C
authors.initials: OC
authors.lastname: Manintveld
authors.forename: Eric
authors.initials: E
authors.lastname: Boersma
authors.forename: Isabella
authors.initials: I
authors.lastname: Kardys
mesh_terms: D000328:Adult; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002097:C-Reactive Protein / Q000737:chemistry*; D018450:Disease Progression; D005260:Female; D006084:Graft Rejection; D006333:Heart Failure / Q000097:blood* / Q000601:surgery*; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D012189:Retrospective Studies; D013997:Time Factors; D066027:Transplant Recipients; D020107:Troponin T / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein