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Clinical Chemistry 54: 1780-1787, 2008. First published September 11, 2008; 10.1373/clinchem.2008.105635
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(Clinical Chemistry. 2008;54:1780-1787.)
© 2008 American Association for Clinical Chemistry, Inc.

Proteomics and Protein Markers

Impact of Epitope Specificity and Precursor Maturation in Pro-B–Type Natriuretic Peptide Measurement

Jens Peter Goetze1,a, Ulf Dahlström2, Jens F. Rehfeld1 and Urban Alehagen2

1 Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark; 2 Department of Cardiology, Linkoping University Hospital, Sweden.

aAddress correspondence to this author at: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. Fax: +45–3545-4640; e-mail JPG{at}dadlnet.dk.

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 (r2 = 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 (r2 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.






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Copyright © 2008 by the American Association for Clinical Chemistry.