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European Heart Journal Advance Access originally published online on March 12, 2008
European Heart Journal 2008 29(9):1096-1102; doi:10.1093/eurheartj/ehn071
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Concurrent evaluation of novel cardiac biomarkers in acute coronary syndrome: myeloperoxidase and soluble CD40 ligand and the risk of recurrent ischaemic events in TACTICS-TIMI 18

David A. Morrow1,*, Marc S. Sabatine1, Marie-Luise Brennan2, James A. de Lemos3, Sabina A. Murphy4, Christian T. Ruff5, Nader Rifai6, Christopher P. Cannon1 and Stanley L. Hazen2,7,8

1 TIMI Study Group/Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA
2 Department of Cell Biology, Cleveland Clinic, Cleveland, OH, USA
3 Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
4 TIMI Study Group, Boston, MA, USA
5 Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA
6 Children’s Hospital Medical Center, Boston, MA, USA
7 Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic Foundation, Cleveland, OH, USA
8 Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA

Received 7 May 2007; revised 4 January 2008; accepted 28 January 2008; online publish-ahead-of-print 12 March 2008.

* Corresponding author. Tel: +1 617 278-0145, Fax: +1 617 734 7329, Email: dmorrow{at}partners.org

See page 1079 for the editorial comment on this article (doi:10.1093/eurheartj/ehn143)

Aims: We investigated the prognostic performance of myeloperoxidase (MPO), and soluble CD40 ligand (sCD40L) along with B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), and cardiac troponin I (cTnI) for non-fatal recurrent ischaemic events in non-ST elevation acute coronary syndrome (ACS).

Methods and results: We measured plasma MPO and sCD40L in 1524 patients with ACS treated with tirofiban and randomized to early invasive vs. conservative management in the TACTICS-TIMI 18 trial who survived to 180 days. Patients with elevated baseline MPO (>884 pM) were at higher risk of non-fatal myocardial infarction or rehospitalization for ACS at 30 days (9.3 vs. 4.6%, P < 0.001). In contrast, no difference was observed with higher sCD40L (>989 pg/mL, 7.6 vs. 6.3%, P = 0.31). MPO remained associated with recurrent ischaemic events after adjustment for age, ST-deviation, diabetes, prior coronary artery disease, heart failure, cTnI, hsCRP, and sCD40L (OR 2.10; 95% CI 1.36–3.23, P = 0.001). This association was attenuated by 180 days (OR 1.26; 0.95–1.68). Stratification using baseline MPO, BNP, and cTnI identified a >3-fold gradient of risk.

Conclusion: MPO adds to BNP and cTnI for short-term risk assessment for recurrent ischaemic events in non-ST elevation ACS. sCD40L was not associated with risk in this population treated with a platelet GPIIb/IIIa receptor antagonist.

Key Words: Unstable angina • Myocardial infarction • Biomarkers • Prognosis


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