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(Circulation. 2004;110:3206-3212.)
© 2004 American Heart Association, Inc.

Coronary Heart Disease

N-Terminal Pro–B-Type Natriuretic Peptide Levels for Dynamic Risk Stratification of Patients With Acute Coronary Syndromes

Christopher Heeschen, MD; Christian W. Hamm, MD; Veselin Mitrovic, MD; Nicte-Ha Lantelme, MD; Harvey D. White, DSc, for the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Investigators

From J.W. Goethe University, Department of Cardiology, Frankfurt, Germany (C.H.); Kerckhoff Heart Center, Department of Cardiology, Bad Nauheim, Germany (C.W.H., V.M., N.-H.L.); and Green Lane Cadiovascular Research Unit, Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand (H.D.W.).

Correspondence to Dr Christopher Heeschen, J.W. Goethe University, Department of Cardiology, Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail c.heeschen{at}em.uni-frankfurt.de

Received June 22, 2004; revision received August 15, 2004; accepted August 25, 2004.

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.

Key Words: peptides • coronary disease • risk factors • ischemia • prognosis

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