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

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. 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). 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. Our results reveal marked assay differences in analytical assay comparison, contrasting the overall comparable clinical performance in cardiovascular diagnostics or prognosis in the elderly.