title: Impact of epitope specificity and precursor maturation in pro-B-type natriuretic peptide measurement.
abstract: BACKGROUND
  Cardiac-derived natriuretic peptides are sensitive plasma markers of cardiac dysfunction. Recent reports have disclosed a more complex molecular heterogeneity of B-type natriuretic peptide precursor (proBNP)-derived peptides than previously suggested. In this study, we examined the impact of epitope specificity and precursor maturation on plasma measurement of proBNP-derived peptides.
  
  
  METHODS
  We compared 2 assays, N-terminal proBNP and proBNP 1-76, in a randomly collected set of human plasma specimens (n = 370). Additionally, we evaluated the clinical performance of 4 assays with different epitope specificities in a cohort of elderly patients presenting with symptoms associated with heart failure (n = 415).
  
  
  RESULTS
  Comparison of N-terminal proBNP with proBNP 1-76 measurement in plasma revealed a high correlation on regression analysis (r(2) = 0.91, P < 0.0001). Nevertheless, the proBNP 1-76 assay measured lower concentrations in the high range than the N-terminal proBNP assay. Correlations between assay measurements in a clinical setting were comparable for all the assays (r(2) approximately 0.57-0.83), and ROC analyses revealed area-under-the-curve values ranging between 0.77 and 0.81 for identifying reduced left ventricular ejection fraction. In parallel, all assays displayed comparable abilities in predicting long-term mortality.
  
  
  CONCLUSIONS
  Our results reveal marked assay differences in analytical assay comparison, contrasting the overall comparable clinical performance in cardiovascular diagnostics or prognosis in the elderly.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark. JPG@dadlnet.dk
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Goetze
authors.forename: Ulf
authors.initials: U
authors.lastname: Dahlström
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.forename: Urban
authors.initials: U
authors.lastname: Alehagen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D015331:Cohort Studies; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006333:Heart Failure / Q000097:blood; D006801:Humans; D007118:Immunoassay; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000032:analysis*; D011498:Protein Precursors / Q000032:analysis*; D015203:Reproducibility of Results
chemical_list: D000939:Epitopes; D011498:Protein Precursors; D020097:Natriuretic Peptide, Brain