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European Heart Journal Advance Access originally published online on October 31, 2007
European Heart Journal 2007 28(23):2858-2865; doi:10.1093/eurheartj/ehm465
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org

Growth-differentiation factor-15 improves risk stratification in ST-segment elevation myocardial infarction

Tibor Kempf1,{dagger}, Erik Björklund2,{dagger}, Sylvia Olofsson2, Bertil Lindahl2, Tim Allhoff1, Timo Peter1, Jörn Tongers1, Kai C. Wollert1,* and Lars Wallentin2,*

1 Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany
2 Department of Cardiology and Uppsala Clinical Research Center, University of Uppsala, University Hospital, 75185 Uppsala, Sweden

Received 20 March 2007; revised 28 August 2007; accepted 24 September 2007; online publish-ahead-of-print 31 October 2007.

* Corresponding author. Tel: +46 18 6114953; fax: +46 18 506638. E-mail address: lars.wallentin{at}ucr.uu.se or Tel: +49 511 532 4055; fax: +49 511 532 5412. E-mail address: wollert.kai{at}mh-hannover.de

Aims: Growth-differentiation factor-15 (GDF-15) is a transforming growth factor-ß-related cytokine that is induced in the heart following ischaemia–reperfusion injury. We explored the prognostic utility of GDF-15 in patients with ST-segment elevation myocardial infarction (STEMI) receiving fibrinolytic therapy.

Methods and results: Circulating levels of GDF-15 were determined by an immunoradiometric assay in 741 STEMI patients who were included in the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 and ASSENT-plus trials. About 72.7% of the patients presented with GDF-15 levels ≥1200 ng/L, the upper limit of normal in apparently healthy elderly individuals. Increased levels of GDF-15 were associated with a higher risk of death during 1-year follow-up. Mortality rates at 1 year were 2.1, 5.0, and 14.0% in patients with GDF-15 levels <1200, 1200–1800, and >1800 ng/L, respectively (P < 0.001). GDF-15 remained an independent predictor of mortality after adjustment for clinical variables, troponin T, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). GDF-15 provided prognostic information in clinically relevant patient subgroups, defined according to age, gender, cardiovascular risk factors, haemodynamic status, and the TIMI risk score. Moreover, GDF-15 added prognostic information to the established biomarkers of adverse prognosis in STEMI, troponin T, and NT-proBNP.

Conclusion: GDF-15 is a new biomarker in STEMI that provides prognostic information beyond established clinical and biochemical markers.

Key Words: Biomarker • Growth-differentiation factor-15 • STEMI • Prognosis

{dagger} These authors have contributed equally.


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