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Published Online
on July 7, 2003

Circulation. 2003
Published online before print July 7, 2003, doi: 10.1161/01.CIR.0000079170.10579.DC
A more recent version of this article appeared on July 22, 2003
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Submitted on February 18, 2003
Revised on April 22, 2003
Accepted on April 25, 2003

N-Terminal Pro-Brain Natriuretic Peptide and Other Risk Markers for the Separate Prediction of Mortality and Subsequent Myocardial Infarction in Patients With Unstable Coronary Artery Disease. A Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV Substudy

Stefan K. James MD, PhD*, Bertil Lindahl MD, PhD, Agneta Siegbahn MD, PhD, Mats Stridsberg MD, PhD, Per Venge MD, PhD, Paul Armstrong MD, Elliot S. Barnathan MD, Robert Califf MD, Eric J. Topol MD, Maarten L. Simoons MD, PhD, and Lars Wallentin MD, PhD

From the Department of Medical Sciences, Cardiology (S.K.J., B.L., L.W.) and Clinical Chemistry (A.S., M.S., P.V.), University of Uppsala, Uppsala, Sweden; the Department of Medicine (P.A.), University of Alberta, Edmonton, Canada; Centocor (E.S.B.), Malvern, Pa; Duke University Clinical Research Institute (R.C.), Durham, NC; Cleveland Clinic of Medicine, Case Western Reserve University (E.J.T.), Cleveland, Ohio; and the Thoraxcenter (M.L.S.), Erasmus Medical Center Rotterdam, the Netherlands.

* To whom correspondence should be addressed. E-mail: stefan.james{at}thorax.uas.lul.se.

Background--Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients.

Methods and Results--NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.5 hours from symptom onset in 6809 of 7800 ACS patients in the Global Utilization of Strategies To Open occluded arteries-IV (GUSTO-IV) trial. Levels of NT-proBNP were correlated independently with age, female gender, low body weight, diabetes, renal dysfunction, history of MI, heart failure, heart rate, ongoing myocardial damage, and time since onset of ischemia. Increasing quartiles of NT-proBNP were related to short- and long-term mortality that reached 1.8%, 3.9%, 7.7%, and 19.2%, (P<0.001), respectively, at 1 year. Levels of troponin T, CRP, heart rate, and creatinine clearance, in addition to ST-segment depression, were also correlated independently with 1-year mortality, but NT-proBNP was the marker with the strongest relation. In contrast, only troponin T, creatinine clearance, and ST-segment depression were independently related to future MI. The combination of NT-proBNP and creatinine clearance provided the best prediction, with a 1-year mortality of 25.7% with both markers in the top quartile vs 0.3% with both markers in the bottom quartile.

Conclusions--The use of NT-proBNP appears to add critical prognostic insight to the assessment of patients with ACS.


Key words: angina • myocardial infarction • coronary disease • natriuretic peptides • mortality


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Future of Biomarkers in Acute Coronary Syndromes: Moving Toward a Multimarker Strategy
David A. Morrow and Eugene Braunwald
Circulation 2003 108: 250-252. [Extract] [Full Text]