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

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 oil 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. (C) 2008 American Association for Clinical Chemistry