This Article Figures Only Full Text Full Text (PDF) View Cardiosource Journal Scan Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Eggers, K. M. Articles by Lindahl, B. Search for Related Content PubMed PubMed Citation Articles by Eggers, K. M. Articles by Lindahl, B. Related Collections Related Articles

CLINICAL RESEARCH: BIOMARKERS

Prognostic Value of Biomarkers During and After Non–ST-Segment Elevation Acute Coronary Syndrome

Kai M. Eggers, MD, PhD^_*,_*, Bo Lagerqvist, MD, PhD^_*, Per Venge, MD, PhD, Lars Wallentin, MD, PhD^_* and Bertil Lindahl, MD, PhD^_*

^_* Department of Medical Sciences, Cardiology, Uppsala University Hospital and Uppsala Clinical Research Centre, Uppsala, Sweden
Department of Medical Sciences, Clinical Chemistry, Uppsala University Hospital, Uppsala, Sweden

Manuscript received October 20, 2008; revised manuscript received January 30, 2009, accepted March 10, 2009.

^_* Reprint requests and correspondence: Dr. Kai M. Eggers, Department of Medical Sciences, Cardiology, University Hospital Uppsala, S-751 85 Uppsala, Sweden (Email: kai.eggers{at}ucr.uu.se).

Objectives: The aim of this study was to assess risk prediction by different biomarkers in patients with an ongoing non–ST-segment elevation acute coronary syndrome (NSTE-ACS) and after clinical stabilization.

Background: Different biomarkers reflect different aspects of the pathobiology in NSTE-ACS. However, there is little information regarding their relative prognostic value during the time course of disease.

Methods: The N-terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), cardiac troponin I (cTnI), and the estimated glomerular filtration rate (eGFR) were measured at randomization and after 6 weeks and 6 months in 877 NSTE-ACS patients included in the FRISC (FRagmin and fast revascularization during InStability in Coronary artery disease) II trial. The biomarkers' prognostic value during 5-year follow-up was evaluated by Cox regression models, calculation of the c-statistics, and estimation of the net reclassification improvement (NRI).

Results: Among the biomarkers measured at randomization, NT-proBNP was the strongest predictor for mortality (adjusted hazard ratio [HR]: 1.7; 95% confidence interval [CI]: 1.3 to 2.1; p < 0.001). Even during follow-up, NT-proBNP demonstrated the strongest association to the composite end point of death/myocardial infarction (adjusted HR at 6 weeks: 1.5; 95% CI: 1.3 to 1.7; p < 0.001; adjusted HR at 6 months: 1.4; 95% CI: 1.2 to 1.7; p = 0.001). Even CRP was independently predictive at 6 months for the composite end point (adjusted HR: 1.3; 95% CI: 1.1 to 1.5; p = 0.003). Only 6-week results of NT-proBNP provided significant incremental prognostic value to established risk indicators regarding the composite end point (c-statistics 0.69 [p = 0.03]; NRI 0.11 [p = 0.03]).

Conclusions: The NT-proBNP is an independent risk predictor in patients with ongoing NSTE-ACS and after clinical stabilization. The CRP exhibits increasing predictive value at later measurements. However, only NT-proBNP provided incremental prognostic value and might therefore be considered as a complement for early follow-up controls after NSTE-ACS.

Key Words: acute coronary syndrome • biomarkers • risk assessment • stable coronary artery disease

Abbreviations and Acronyms   AMI = acute myocardial infarction   CRP = C-reactive protein   cTnI = cardiac troponin I   eGFR = estimated glomerular filtration rate   NRI = net reclassification improvement   NSTE-ACS = non–ST-segment elevation acute coronary syndrome   NT-proBNP = N-terminal pro-brain natriuretic peptide

Related Articles

Biomarkers for Prognostication After Acute Coronary Syndromes: New Times and Statistics

Christopher R. deFilippi and Stephen L. Seliger
J. Am. Coll. Cardiol. 2009 54: 365-367. [Full Text] [PDF]

This article has been cited by other articles:

				C. J. Knight and A. D. Timmis Almanac 2011: acute coronary syndromes. The national society journals present selected research that has driven recent advances in clinical cardiology Heart, November 15, 2011; 97(22): 1820 - 1827. [Full Text] [PDF]

				I. Tzoulaki, G. Liberopoulos, and J. P. A. Ioannidis Use of reclassification for assessment of improved prediction: an empirical evaluation Int. J. Epidemiol., August 1, 2011; 40(4): 1094 - 1105. [Abstract] [Full Text] [PDF]

				B. M. Scirica, M. S. Sabatine, P. Jarolim, S. A. Murphy, J. L. de Lemos, E. Braunwald, and D. A. Morrow Assessment of multiple cardiac biomarkers in non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 Trial Eur. Heart J., March 2, 2011; 32(6): 697 - 705. [Abstract] [Full Text] [PDF]

				R. P. Giugliano and E. Braunwald The Year in Non-ST-Segment Elevation Acute Coronary Syndrome J. Am. Coll. Cardiol., December 14, 2010; 56(25): 2126 - 2138. [Full Text] [PDF]

				P. Panduranga, A. A. Riyami, K. J. Sulaiman, and M. Mukhaini C-reactive protein in unstable angina: clinical and angiographic correlation Heart Asia, December 3, 2010; 2(1): 140 - 144. [Abstract] [Full Text] [PDF]

				A. S. Jaffe Chapter 33 The use of biomarkers for acute cardiovascular disease The ESC Textbook of Acute and Intensive Cardiac Care, December 1, 2010; 1(1): med-9780199584314-chapter - med-9780199584314-chapter. [Abstract] [Full Text] [PDF]

				B. M. Scirica, D. A. Morrow, C. Bode, W. Ruzyllo, M. Ruda, A. J. M. Oude Ophuis, J. Lopez-Sendon, K. Swedberg, M. Ogorek, N. Rifai, et al. Patients with acute coronary syndromes and elevated levels of natriuretic peptides: the results of the AVANT GARDE-TIMI 43 Trial Eur. Heart J., August 2, 2010; 31(16): 1993 - 2005. [Abstract] [Full Text] [PDF]

				H. C. Kim, P. Greenland, J. E. Rossouw, J. E. Manson, B. B. Cochrane, N. L. Lasser, M. C. Limacher, D. M. Lloyd-Jones, K. L. Margolis, and J. G. Robinson Multimarker Prediction of Coronary Heart Disease Risk: The Women's Health Initiative J. Am. Coll. Cardiol., May 11, 2010; 55(19): 2080 - 2091. [Abstract] [Full Text] [PDF]

				Q. A. Truong, E. Siegel, M. Karakas, J. L. Januzzi Jr., F. Bamberg, A. A. Mahabadi, S. Dasdemir, T. J. Brady, A. Bergmann, J. Kunde, et al. Relation of Natriuretic Peptides and Midregional Proadrenomedullin to Cardiac Chamber Volumes by Computed Tomography in Patients without Heart Failure: From the ROMICAT Trial Clin. Chem., April 1, 2010; 56(4): 651 - 660. [Abstract] [Full Text] [PDF]

				K. M. Eggers, T. Kempf, B. Lagerqvist, B. Lindahl, S. Olofsson, F. Jantzen, T. Peter, T. Allhoff, A. Siegbahn, P. Venge, et al. Growth-Differentiation Factor-15 for Long-Term Risk Prediction in Patients Stabilized After an Episode of Non-ST-Segment-Elevation Acute Coronary Syndrome Circ Cardiovasc Genet, February 1, 2010; 3(1): 88 - 96. [Abstract] [Full Text] [PDF]

				A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, G. K. Feld, B. H. Greenberg, J. Hall, M. Hlatky, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, et al. Highlights of the Year in JACC 2009 J. Am. Coll. Cardiol., January 26, 2010; 55(4): 380 - 407. [Full Text] [PDF]

				C. R. deFilippi and S. L. Seliger Biomarkers for Prognostication After Acute Coronary Syndromes: New Times and Statistics J. Am. Coll. Cardiol., July 21, 2009; 54(4): 365 - 367. [Full Text] [PDF]