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CLINICAL RESEARCH

B-Type Natriuretic Peptide and the Risk of Cardiovascular Events and Death in Patients With Stable Angina

Results From the AtheroGene Study

Renate Schnabel, MD^_*,_*, Edith Lubos, MD^_*, Hans J. Rupprecht, MD^_*, Christine Espinola-Klein, MD^_*, Christoph Bickel, MD, Karl J. Lackner, MD, François Cambien, MD, Laurence Tiret, PhD, Thomas Münzel, MD, FAHA^_* and Stefan Blankenberg, MD^_*

^_* Department of Medicine II
Department of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg University, Mainz, Germany
INSERM U525, Faculté de Médecine Pitié-Salpétrière, Paris, France
Innere Abteilung, Bundeswehrzentralkrankenhaus, Koblenz, Germany

Manuscript received June 22, 2005; revised manuscript received September 13, 2005, accepted September 19, 2005.

^_* Reprint requests and correspondence: Dr. Renate Schnabel, Johannes Gutenberg-University, Cardiology, Langenbeckstrasse 1, Mainz, Rheinland-Pfalz 55131, Germany (Email: schnabelr{at}gmx.de).

OBJECTIVES: The aim of this study was to assess the predictive value of the cardiac hormone B-type natriuretic peptide (BNP) for long-term outcome in a large cohort of stable angina patients.

BACKGROUND: Recent data suggest a role of BNP in stable ischemic heart disease beyond its known value in heart failure and acute coronary syndromes.

METHODS: In 1,085 patients with coronary artery disease (CAD) baseline levels of BNP were prospectively associated with cardiovascular (CV) events during a mean follow-up of 2.5 years.

RESULTS: BNP concentrations were significantly elevated in patients with future CV events (median [25th/75th interquartile range] 119.2 [43.6/300.4] pg/ml vs. 36.2 [11.3/94.6] pg/ml; p < 0.001). Kaplan-Meier survival analysis showed a stepwise decrease in event-free survival across quartiles of BNP baseline concentration (p_{log rank} < 0.001). Patients in the highest quartile revealed a 6.1-fold increased risk (p = 0.001) compared to patients in the lowest quartile after adjustment for potential confounders. For a cut-off value of 100 pg/ml, an independently increased risk of adverse outcome (hazard ratio [HR] 4.4; p < 0.001) could be demonstrated. One standard deviation (SD) decrease in ejection fraction implied the most prominent increase in risk of future CV events (HR 1.69; p < 0.001) followed by one SD increase in BNP (HR 1.53; p < 0.001). The highest prognostic accuracy could be demonstrated for BNP (area under the curve 0.671).

CONCLUSIONS: The data of this large group of CAD patients provide independent evidence that BNP is a strong predictor of cardiovascular risk in patients with stable angina independent of left ventricular systolic performance and known risk factors.

Abbreviations and Acronyms   BNP = B-type natriuretic peptide   CAD = coronary artery disease   CRP = C-reactive protein   CV = cardiovascular   EF = left ventricular ejection fraction   HR = hazard ratio

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