Ratio of pro-B-type natriuretic peptide (BNP) to total BNP is decreased in mild, but not severe, acute decompensated heart failure patients: A novel compensatory mechanism for acute heart failure

Background: A recent study showed that both glycosylation of pro-B-type natriuretic peptide (BNP) and the proBNP/total BNP ratio are decreased in acute decompensated heart failure (ADHF). However, the following points regarding the proBNP/total BNP ratio have not been determined in patients with ADHF: 1) the relationship with the severity of ADHF, 2) the changes in the ratio during treatment, and 3) the relationship with cyclic guanosine monophosphate (cGMP)-generating activity. Methods: Plasma proBNP and total BNP (proBNP + mature BNP) were measured in patients with ADHF (n = 154). Measurement was performed on admission, 3 and 7 days after admission, and before discharge using recently developed sandwich chemiluminescence enzyme immunoassays. The percent proBNP was calculated as: (proBNP/total BNP) × 100. Results: On admission, %proBNP was higher in patients with severe ADHF than in patients with mild ADHF (median: 61.7% vs. 56.2%, respectively; p < 0.01), while the plasma cGMP/total BNP ratio, an index of the biological activity of BNP, was lower (p < 0.001). In patients with severe ADHF, the higher %proBNP and lower cGMP/total BNP ratio were unchanged during hospitalization, whereas %proBNP increased gradually in patients with mild ADHF and the cGMP/total BNP ratio also increased at 3 days after admission. Conclusion: These findings suggest that in patients with mild ADHF, compensation for heart failure occurs via increased proBNP processing, leading to increase of mature BNP and activation of the BNP/cGMP cascade. In contrast, this compensatory mechanism may be impaired in patients with severe ADHF and a vicious cycle can potentially occur.