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CLINICAL RESEARCH: CLINICAL TRIALS

Prognostic Value of B-Type Natriuretic Peptides in Patients With Stable Coronary Artery Disease

The PEACE Trial

Torbjørn Omland, MD, PhD, MPH^_*,,_*, Marc S. Sabatine, MD, MPH^,, Kathleen A. Jablonski, PhD^||, Madeline Murguia Rice, PhD^||, Judith Hsia, MD^||, Ragnhild Wergeland, MT^#, Sverre Landaas, MD, PhD^_**, Jean L. Rouleau, MD, FACC^,, Michael J. Domanski, MD, FACC, Christian Hall, MD, PhD^_*,, Marc A. Pfeffer, MD, PhD, FACC^,, Eugene Braunwald, MD, FACC^, for the PEACE Investigators

^_* Department of Medicine, Akershus University Hospital, Lorenskog, Norway
Faculty of Medicine, University of Oslo, Oslo, Norway
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts
Department of Medicine, Harvard Medical School, Boston, Massachusetts
^|| George Washington University, Rockville, Maryland, and Washington, DC
^# Department of Medical Biochemistry, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
^_** Department of Clinical Chemistry, Ullevaal University Hospital, Oslo, Norway
Montreal Heart Institute, Montreal, Quebec, Canada
Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada
National Heart, Lung, and Blood Institute, Bethesda, Maryland

Manuscript received December 6, 2006; revised manuscript received March 2, 2007, accepted March 6, 2007.

^_* Reprint requests and correspondence: Prof. Torbjørn Omland, Department of Medicine, Akershus University Hospital, NO-1478, Lørenskog, Norway. (Email: torbjorn.omland{at}medisin.uio.no).

Objectives: The purpose of this study was to assess the association between B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the incidence of specific cardiovascular events in low-risk patients with stable coronary disease, the incremental prognostic information obtained from these two biomarkers compared with traditional risk factors, and their ability to identify patients who may benefit from angiotensin-converting enzyme (ACE) inhibition.

Background: The prognostic value of BNPs in low-risk patients with stable coronary artery disease remains unclear.

Methods: Baseline plasma BNP and NT-proBNP concentrations were measured in 3,761 patients with stable coronary artery disease and preserved left ventricular function participating in the PEACE (Prevention of Events With Angiotensin-Converting Enzyme Inhibition) study, a placebo-controlled trial of trandolapril. Multivariable Cox regression was used to assess the association between natriuretic peptide concentrations and the incidence of cardiovascular mortality, fatal or nonfatal myocardial infarction, heart failure, and stroke.

Results: The BNP and NT-proBNP levels were strongly related to the incidence of cardiovascular mortality, heart failure, and stroke but not to myocardial infarction. In multivariable models, BNP remained associated with increased risk of heart failure, whereas NT-proBNP remained associated with increased risk of cardiovascular mortality, heart failure, and stroke. By C-statistic calculations, BNP and NT-proBNP significantly improved the predictive accuracy of the best available model for incident heart failure, and NT-proBNP also improved the model for cardiovascular death. The magnitude of effect of ACE inhibition on the likelihood of experiencing cardiovascular end points was similar, regardless of either BNP or NT-proBNP baseline concentrations.

Conclusions: In low-risk patients with stable coronary artery disease and preserved ventricular function, BNPs provide strong and incremental prognostic information to traditional risk factors.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   BNP = B-type natriuretic peptide   EDTA = ethylenediaminetetraacetic acid   NT-proBNP = N-terminal pro-B-type natriuretic peptide

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