title: N-terminal pro-atrial natriuretic peptide measurement in plasma suggests covalent modification.
abstract: BACKGROUND
  The N-terminal fragment of cardiac-derived pro-B-type natriuretic peptide is a glycosylated polypeptide. It is unknown whether N-terminal pro-atrial natriuretic peptide (proANP) fragments are also covalently modified. We therefore evaluated the clinical performance of 2 distinctly different proANP assays on clinical outcome.
  
  
  METHODS
  We examined 474 elderly patients with symptoms of heart failure presenting in a primary healthcare setting. Samples were analyzed with an automated immunoluminometric midregion proANP (MR-proANP) assay and a new processing-independent assay (PIA) developed in our laboratory. The results were compared with Bland-Altman plots, and clinical performance was assessed by generating ROC curves for different clinical outcomes.
  
  
  RESULTS
  Despite linear regression results indicating a good correlation (r = 0.85; P < 0.0001), the PIA measured considerably more proANP than the MR-proANP assay (mean difference, 663 pmol/L; SD, 478 pmol/L). In contrast, the clinical performances of the 2 assays [as assessed by the area under the ROC curve (AUC)] in detecting left ventricular dysfunction were similar [proANP PIA, 0.71 (95% CI, 0.63-0.79); MR-proANP assay, 0.74 (95% CI, 0.66-0.81); P = 0.32]. The prognostic ability to report cardiovascular mortality during a 10-year follow-up revealed AUC values of 0.66 (95% CI, 0.60-0.71) for the proANP PIA and 0.69 (95% CI, 0.63-0.74) for the MR-proANP assay (P = 0.08, for comparing the 2 assays).
  
  
  CONCLUSIONS
  Our data suggest that N-terminal proANP fragments in patient plasma differ from the calibrator peptides used but that the difference does not affect ROC curves in an elderly cohort of patients with mild to moderate heart failure. We suggest that human N-terminal proANP fragments can be covalently modified.
authors.affiliation: Department of Small Animal Clinical Sciences, KU-LIFE, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hunter
authors.forename: Urban
authors.initials: U
authors.lastname: Alehagen
authors.forename: Ulf
authors.initials: U
authors.lastname: Dahlström
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.forename: Dan L
authors.initials: DL
authors.lastname: Crimmins
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
mesh_terms: D009320:Atrial Natriuretic Factor / Q000097:blood*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000401:mortality; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000401:mortality; D006801:Humans; D007118:Immunoassay; D016014:Linear Models; D011237:Predictive Value of Tests; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood*; D012372:ROC Curve
chemical_list: D011498:Protein Precursors; D009320:Atrial Natriuretic Factor