Received on February 21, 2008
Accepted on August 12, 2008

Proteomics and Protein Markers

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

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

^* To whom correspondence should be addressed. 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.