title: Probrain natriuretic peptide and C-reactive protein as markers of acute rejection, allograft vasculopathy, and mortality in heart transplantation.
abstract: BACKGROUND
  N-terminal probrain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) are useful in risk stratification of patients with congestive heart failure. They could also be markers of distinctly altered hormonal and immunological milieus, but the combined prognostic value of these biomarkers in heart transplant (HTx) recipients has not been assessed previously.
  
  
  METHODS
  We sought to assess the individual and combined value of NT-proBNP and CRP as markers of acute rejection, cardiac allograft vasculopathy (CAV) and all-cause mortality in HTx recipients. We evaluated 101 patients for acute rejection and 210 patients for CAV and all-cause mortality. Patients evaluated for rejection had serial endomyocardial biopsies and plasma sampling performed during the first year postHTx. All other patients had plasma samples taken upon inclusion at an annual visit. Median follow-up for CAV and all-cause mortality was 2.2 years and 5.4 years, respectively.
  
  
  RESULTS
  Altogether, 1131 biopsy procedures were performed, and increased NT-proBNP and CRP levels were not useful markers of acute cellular rejection. In total, 78 (37%) patients developed CAV, and 39 (19%) patients died. Neither biomarker was a predictor of CAV, but both were independent predictors of mortality. When combining both biomarkers, elevated levels of both NT-proBNP and CRP identified patients at highest risk for CAV (HR 2.10, P=0.01) and all-cause mortality (HR 3.14, P=0.01).
  
  
  CONCLUSIONS
  In HTx recipients, NT-proBNP and CRP are not useful as markers of acute cellular rejection during the first year postHTx, but combined analysis adds significantly to their predictive value for development of CAV and all-cause mortality.
authors.affiliation: Department of Cardiology, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. satish.arora@medisin.uio.no
authors.forename: Satish
authors.initials: S
authors.lastname: Arora
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Wergeland
authors.forename: Svein
authors.initials: S
authors.lastname: Simonsen
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Holm
authors.forename: Aina
authors.initials: A
authors.lastname: Hognestad
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Odd
authors.initials: O
authors.lastname: Geiran
authors.forename: Arne
authors.initials: A
authors.lastname: Andreassen
mesh_terms: D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood*; D016027:Heart Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D016019:Survival Analysis; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein