N-terminal pro-B-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes

Background - Elevated baseline levels of B-type natriuretic peptide (BNP) and the N-terminal fragments of its prohormone, N-terminal-pro-BNP (NT-proBNP), have been associated with adverse long-term outcome in patients with acute coronary syndromes, whereas the prognostic implications of serial NT-proBNP measurements have not been investigated to date. Methods and Results - NT-proBNP, troponin T, and C-reactive protein were measured at baseline and at 48 and 72 hours in 1791 patients with non-ST-elevation acute coronary syndromes. Death and myocardial infarction were recorded during 30 days of follow-up. After adjustment for independent predictors of cardiac risk, baseline NT-proBNP levels >250 ng/L were associated with higher event rates (adjusted OR, 3.7; 95% CI, 2.3 to 5.7; P < 0.001). In troponin T - negative patients, NT-proBNP identified a subgroup of high-risk patients (OR, 5.9; 95% CI, 2.6 to 13.3; P < 0.001). The risk in those patients (7.2%) did not significantly differ from that in troponin T - positive patients (9.8%; P = 0.25). Importantly, clinical stabilization without refractory ischemia was associated with a rapid (as soon as 48 hours after onset of symptoms) and significant (48 hours; -24%; 72 hours, -49%; both P < 0.001) decline in NT-proBNP levels. In patients with high NT-proBNP baseline levels, lack of a rapid decline in NT-proBNP levels (<= 250 ng/L) was linked to an adverse short-term prognosis (OR, 33.7; 95% CI, 8.2 to 138.8; P < 0.001). In patients with low NT-proBNP baseline levels, a rise in NT-proBNP levels over 72 hours to >250 ng/L was also linked to an adverse 30-day prognosis (OR, 24.0; 95% CI, 8.4 to 68.5; P < 0.001). Conclusions - Neurohumoral activation as evidenced by NT-proBNP appears as a unifying feature that is independent of other biochemical markers (myocardial necrosis, inflammation) and is a powerful and independent determinant of the short-term cardiac risk in patients with acute coronary syndromes. Whether serial measurements of NT-proBNP in patients with ACS may be used to more rapidly identify patients suitable for early discharge or more intensive therapy deserves future prospective studies.