title: Influence of glycosylation on diagnostic and prognostic accuracy of N-terminal pro-B-type natriuretic peptide in acute dyspnea: data from the Akershus Cardiac Examination 2 Study.
abstract: BACKGROUND
  The N-terminal part of pro-B-type natriuretic peptide (NT-proBNP) is glycosylated, but whether glycosylation influences the diagnostic and prognostic accuracy of NT-proBNP measurements is not known.
  
  
  METHODS
  We measured NT-proBNP concentrations of 309 patients with acute dyspnea by use of standard EDTA tubes and EDTA tubes pretreated with deglycosylation enzymes. The primary cause of dyspnea was classified as heart failure (HF) or non-HF, and the diagnosis was adjudicated by 2 independent physicians. We collected information on all-cause mortality during follow-up.
  
  
  RESULTS
  In all, 142 patients (46%) were diagnosed with HF. NT-proBNP concentrations in nondeglycosylated samples distinguished HF patients from patients with non-HF related dyspnea [median 3588 (quartiles 1-3 1578-8404) vs 360 (126-1139) ng/L, P < 0.001], but concentrations were markedly higher in samples pretreated with deglycosylation enzymes (total NT-proBNP) [7497 (3374-14 915) vs 798 (332-2296) ng/L, P < 0.001]. The AUC to separate HF patients from patients with non-HF related dyspnea was 0.871 (95% CI 0.829-0.907) for total NT-proBNP compared with 0.852 (0.807-0.890) for NT-proBNP measurements in standard EDTA plasma. During a median follow-up of 816 days, 112 patients (36%) died. Both NT-proBNP and total NT-proBNP concentrations were associated with mortality in separate multivariate models, but only total NT-proBNP concentrations provided added value to the basic risk model of our dataset as assessed by the net reclassification index: 0.24 (95% CI 0.003-0.384). There was a graded increase in risk across total NT-proBNP quartiles, in contrast with the results for NT-proBNP measurements.
  
  
  CONCLUSIONS
  NT-proBNP concentrations were higher, and diagnostic and prognostic accuracy was improved, by pretreating tubes with deglycosylation enzymes.
authors.affiliation: Division of Medicine, Akershus University Hospital, Lørenskog, Norway, and Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; helge.rosjo@medisin.uio.no.
authors.forename: Helge
authors.initials: H
authors.lastname: Røsjø
authors.affiliation: Department of Clinical Molecular Biology, Akershus University Hospital, Lørenskog, Norway, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Mai Britt
authors.initials: MB
authors.lastname: Dahl
authors.affiliation: Division of Medicine, Akershus University Hospital, Lørenskog, Norway, and Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Biology, Akershus University Hospital, Lørenskog, Norway, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Marit
authors.initials: M
authors.lastname: Jørgensen
authors.affiliation: Division of Medicine, Akershus University Hospital, Lørenskog, Norway, and Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Røysland
authors.affiliation: Division of Medicine, Akershus University Hospital, Lørenskog, Norway, and Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Jon
authors.initials: J
authors.lastname: Brynildsen
authors.affiliation: Institute for Experimental Medical Research, Oslo University Hospital, Ullevål, Oslo, Norway, and Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cataliotti
authors.affiliation: Institute for Experimental Medical Research, Oslo University Hospital, Ullevål, Oslo, Norway, and Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Geir
authors.initials: G
authors.lastname: Christensen
authors.affiliation: Division of Medicine, Akershus University Hospital, Lørenskog, Norway, and Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Arne Didrik
authors.initials: AD
authors.lastname: Høiseth
authors.affiliation: Section for Medical Biochemistry, Division for Diagnostics and Technology, Akershus University Hospital, Lørenskog, Norway, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Tor-Arne
authors.initials: TA
authors.lastname: Hagve
authors.affiliation: Division of Medicine, Akershus University Hospital, Lørenskog, Norway, and Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Omland
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001774:Blood Chemical Analysis / Q000295:instrumentation / Q000379:methods*; D004417:Dyspnea / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006031:Glycosylation; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood* / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain