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Circulation. 2002;105:1760-1763
Published online before print March 25, 2002, doi: 10.1161/01.CIR.0000015464.18023.0A
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(Circulation. 2002;105:1760.)
© 2002 American Heart Association, Inc.


Brief Rapid Communications

Multimarker Approach to Risk Stratification in Non-ST Elevation Acute Coronary Syndromes

Simultaneous Assessment of Troponin I, C-Reactive Protein, and B-Type Natriuretic Peptide

Marc S. Sabatine, MD; David A. Morrow, MD, MPH; James A. de Lemos, MD; C. Michael Gibson, MD, MS; Sabina A. Murphy, MPH; Nader Rifai, PhD; Carolyn McCabe, BS; Elliott M. Antman, MD; Christopher P. Cannon, MD; Eugene Braunwald, MD

From the TIMI Study Group (M.S.S., D.A.M., C.M., E.M.A., C.P.C., E.B.), Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass; UT-Southwestern Medical School (J.A.d.L.), Dallas, Tex; Harvard Clinical Research Institute (C.M.G., S.A.M.), Boston, Mass; and Children’s Hospital (N.R.), Boston, Mass.

Correspondence to Marc S. Sabatine, MD, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail msabatine{at}partners.org

Background In patients with acute coronary syndromes (ACS), troponin I (TnI), C-reactive protein (CRP), and B-type natriuretic peptide (BNP) each predict adverse cardiac events. Little is known, however, about the utility of these biomarkers in combination.

Methods and Results Baseline measurements of TnI, CRP, and BNP were performed in 450 patients in OPUS-TIMI 16. Elevations in TnI, CRP, and BNP each were independent predictors of the composite of death, myocardial infarction (MI), or congestive heart failure (CHF). When patients were categorized on the basis of the number of elevated biomarkers at presentation, there was a near doubling of the mortality risk for each additional biomarker that was elevated (P=0.01). Similar relationships existed for the endpoints of MI, CHF, and the composite, both at 30 days and through 10 months. In a validation cohort of 1635 patients in TACTICS-TIMI 18, the number of elevated biomarkers remained a significant predictor of the composite endpoint after adjustment for known clinical predictors: patients with one, two, and three elevated biomarkers had a 2.1- (P=0.006), 3.1- (P<0.001), and 3.7- (P=0.001) fold increase in the risk of death, MI, or CHF by 6 months.

Conclusions Troponin, CRP, and BNP each provide unique prognostic information in patients with ACS. A simple multimarker strategy that categorizes patients based on the number of elevated biomarkers at presentation allows risk stratification over a broad range of short- and long-term major cardiac events.


Key Words: coronary disease • prognosis • myocardial infarction • inflammation • natriuretic peptides




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R. Jarai, N. Iordanova, R. Jarai, A. Raffetseder, W. Woloszczuk, M. Gyongyosi, G. Geyer, J. Wojta, and K. Huber
Risk assessment in patients with unstable angina/non-ST-elevation myocardial infarction and normal N-terminal pro-brain natriuretic peptide levels by N-terminal pro-atrial natriuretic peptide
Eur. Heart J., February 1, 2005; 26(3): 250 - 256.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
R. Schnabel, H. J. Rupprecht, K. J. Lackner, E. Lubos, C. Bickel, J. Meyer, T. Munzel, F. Cambien, L. Tiret, S. Blankenberg, et al.
Analysis of N-terminal-pro-brain natriuretic peptide and C-reactive protein for risk stratification in stable and unstable coronary artery disease: results from the AtheroGene study
Eur. Heart J., February 1, 2005; 26(3): 241 - 249.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
R. Bassan, A. Potsch, A. Maisel, B. Tura, H. Villacorta, M. V. Nogueira, A. Campos, R. Gamarski, A. C. Masetto, and M. A. Moutinho
B-type natriuretic peptide: a novel early blood marker of acute myocardial infarction in patients with chest pain and no ST-segment elevation
Eur. Heart J., February 1, 2005; 26(3): 234 - 240.
[Abstract] [Full Text] [PDF]


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JAMAHome page
T. J. Gluckman, M. Sachdev, S. P. Schulman, and R. S. Blumenthal
A Simplified Approach to the Management of Non-ST-Segment Elevation Acute Coronary Syndromes
JAMA, January 19, 2005; 293(3): 349 - 357.
[Abstract] [Full Text] [PDF]


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Clin. Chem.Home page
R. F. Salamonsen, H.-G. Schneider, M. Bailey, and A. J. Taylor
Cardiac Troponin I Concentrations, but Not Electrocardiographic Results, Predict an Extended Hospital Stay after Coronary Artery Bypass Graft Surgery
Clin. Chem., January 1, 2005; 51(1): 40 - 46.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
D. J. Campbell, M. Woodward, J. P. Chalmers, S. A. Colman, A. J. Jenkins, B. E. Kemp, B. C. Neal, A. Patel, and S. W. MacMahon
Prediction of Heart Failure by Amino Terminal-pro-B-Type Natriuretic Peptide and C-Reactive Protein in Subjects With Cerebrovascular Disease
Hypertension, January 1, 2005; 45(1): 69 - 74.
[Abstract] [Full Text] [PDF]


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CirculationHome page
L. M. Biasucci
CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Clinical Use of Inflammatory Markers in Patients With Cardiovascular Diseases: A Background Paper
Circulation, December 21, 2004; 110(25): e560 - e567.
[Abstract] [Full Text] [PDF]


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Clin. Chem.Home page
F. S. Apple, M. M. Murakami, L. A. Pearce, and C. A. Herzog
Multi-Biomarker Risk Stratification of N-Terminal Pro-B-Type Natriuretic Peptide, High-Sensitivity C-Reactive Protein, and Cardiac Troponin T and I in End-Stage Renal Disease for All-Cause Death
Clin. Chem., December 1, 2004; 50(12): 2279 - 2285.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
M. S. Sabatine, D. A. Morrow, J. A. de Lemos, T. Omland, M. Y. Desai, M. Tanasijevic, C. Hall, C. H. McCabe, and E. Braunwald
Acute changes in circulating natriuretic peptide levels in relation to myocardial ischemia
J. Am. Coll. Cardiol., November 16, 2004; 44(10): 1988 - 1995.
[Abstract] [Full Text] [PDF]


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CirculationHome page
C. Heeschen, C. W. Hamm, V. Mitrovic, N.-H. Lantelme, H. D. White, and for the Platelet Receptor Inhibition in Ischemic S
N-Terminal Pro-B-Type Natriuretic Peptide Levels for Dynamic Risk Stratification of Patients With Acute Coronary Syndromes
Circulation, November 16, 2004; 110(20): 3206 - 3212.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
C. M. Gibson, R. L. Dumaine, E. V. Gelfand, S. A. Murphy, D. A. Morrow, S. D. Wiviott, R. P. Giugliano, C. P. Cannon, E. M. Antman, E. Braunwald, et al.
Association of glomerular filtration rate on presentation with subsequent mortality in non-ST-segment elevation acute coronary syndrome; observations in 13307 patients in five TIMI trials
Eur. Heart J., November 2, 2004; 25(22): 1998 - 2005.
[Abstract] [Full Text] [PDF]


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CirculationHome page
R. Latini, A. P. Maggioni, G. Peri, L. Gonzini, D. Lucci, P. Mocarelli, L. Vago, F. Pasqualini, S. Signorini, D. Soldateschi, et al.
Prognostic Significance of the Long Pentraxin PTX3 in Acute Myocardial Infarction
Circulation, October 19, 2004; 110(16): 2349 - 2354.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J. Quilici, N. Banzet, P. Paule, J.-B. Meynard, M. Mutin, J.-L. Bonnet, P. Ambrosi, J. Sampol, and F. Dignat-George
Circulating Endothelial Cell Count as a Diagnostic Marker for Non-ST-Elevation Acute Coronary Syndromes
Circulation, September 21, 2004; 110(12): 1586 - 1591.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
S. D. Wiviott, D. A. Morrow, P. D. Frederick, R. P. Giugliano, C.M. Gibson, C. H. McCabe, C. P. Cannon, E. M. Antman, and E. Braunwald
Performance of the thrombolysis in myocardial infarction risk index in the National Registry of Myocardial Infarction-3 and -4: A simple index that predicts mortality in ST-segment elevation myocardial infarction
J. Am. Coll. Cardiol., August 18, 2004; 44(4): 783 - 789.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
A. I. Larsen and K. Dickstein
BNP in acute coronary syndromes: the heart expresses its suffering
Eur. Heart J., August 1, 2004; 25(15): 1284 - 1286.
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HeartHome page
R Bugiardini
Risk stratification in acute coronary syndrome: focus on unstable angina/non-ST segment elevation myocardial infarction
Heart, July 1, 2004; 90(7): 729 - 731.
[Abstract] [Full Text] [PDF]


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Journal of Renin-Angiotensin-Aldosterone SystemHome page
A. Sharp and J. Mayet
Review: The utility of BNP in clinical practice
Journal of Renin-Angiotensin-Aldosterone System, June 1, 2004; 5(2): 53 - 58.
[Abstract] [PDF]


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Eur Heart JHome page
O. Bazzino, J. J Fuselli, F. Botto, D. Perez de Arenaza, C. Bahit, J. Dadone, and for the PACS group of investigators
Relative value of N-terminal probrain natriuretic peptide, TIMI risk score, ACC/AHA prognostic classification and other risk markers in patients with non-ST-elevation acute coronary syndromes
Eur. Heart J., May 2, 2004; 25(10): 859 - 866.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
J. P. Goetze, W. Yongzhong, J. F Rehfeld, E. Jorgensen, and J. Kastrup
Coronary angiography transiently increases plasma pro-B-type natriuretic peptide
Eur. Heart J., May 1, 2004; 25(9): 759 - 764.
[Abstract] [Full Text] [PDF]


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CirculationHome page
C. B. Granger, J. E. Van Eyk, S. C. Mockrin, N. L. Anderson, and on behalf of the Working Group Members
National Heart, Lung, and Blood Institute Clinical Proteomics Working Group Report
Circulation, April 13, 2004; 109(14): 1697 - 1703.
[Abstract] [Full Text] [PDF]


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HeartHome page
P L Sanchez, J L Morinigo, P Pabon, F Martin, I Piedra, I F Palacios, and C Martin-Luengo
Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome
Heart, March 1, 2004; 90(3): 264 - 269.
[Abstract] [Full Text] [PDF]


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CirculationHome page
A. Elsaesser and C. W. Hamm
Acute Coronary Syndrome: The Risk of Being Female
Circulation, February 10, 2004; 109(5): 565 - 567.
[Full Text] [PDF]


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CirculationHome page
S. D. Wiviott, C. P. Cannon, D. A. Morrow, S. A. Murphy, C. M. Gibson, C. H. McCabe, M. S. Sabatine, N. Rifai, R. P. Giugliano, P. M. DiBattiste, et al.
Differential Expression of Cardiac Biomarkers by Gender in Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18) Substudy
Circulation, February 10, 2004; 109(5): 580 - 586.
[Abstract] [Full Text] [PDF]


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ChestHome page
S. de Denus, C. Pharand, and D. R. Williamson
Brain Natriuretic Peptide in the Management of Heart Failure: The Versatile Neurohormone
Chest, February 1, 2004; 125(2): 652 - 668.
[Abstract] [Full Text] [PDF]


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JAMAHome page
C. Heeschen, S. Dimmeler, S. Fichtlscherer, C. W. Hamm, J. Berger, M. L. Simoons, and A. M. Zeiher
Prognostic Value of Placental Growth Factor in Patients With Acute Chest Pain
JAMA, January 28, 2004; 291(4): 435 - 441.
[Abstract] [Full Text] [PDF]


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Clin. Chem.Home page
A. Clerico and M. Emdin
Diagnostic Accuracy and Prognostic Relevance of the Measurement of Cardiac Natriuretic Peptides: A Review
Clin. Chem., January 1, 2004; 50(1): 33 - 50.
[Abstract] [Full Text] [PDF]


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CirculationHome page
K. Bibbins-Domingo, M. Ansari, N. B. Schiller, B. Massie, and M. A. Whooley
B-Type Natriuretic Peptide and Ischemia in Patients With Stable Coronary Disease: Data From the Heart and Soul Study
Circulation, December 16, 2003; 108(24): 2987 - 2992.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
T. Jernberg, B. Lindahl, A. Siegbahn, B. Andren, G. Frostfeldt, B. Lagerqvist, M. Stridsberg, P. Venge, and L. Wallentin
N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease
J. Am. Coll. Cardiol., December 3, 2003; 42(11): 1909 - 1916.
[Abstract] [Full Text] [PDF]