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European Heart Journal Advance Access published online on July 29, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn339
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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
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Growth-differentiation factor-15 for early risk stratification in patients with acute chest pain

Kai M. Eggers1,2,{dagger}, Tibor Kempf3,{dagger}, Tim Allhoff3, Bertil Lindahl1,2, Lars Wallentin1,2,* and Kai C. Wollert3,*

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

Received 26 November 2007; revised 20 June 2008; accepted 8 July 2008.

* Corresponding author. Tel: +46 18 6114953, Fax: +46 18 506638, Email: lars.wallentin{at}ucr.uu.se (L.W.) or Tel: +49 511 5324055, Fax: +49 511 5325412, Email: wollert.kai{at}mh-hannover.de (K.C.W.)

Aims: Growth-differentiation factor-15 (GDF-15) has emerged as a biomarker of increased mortality and recurrent myocardial infarction (MI) in patients diagnosed with non-ST-elevation acute coronary syndrome. We explored the usefulness of GDF-15 for early risk stratification in 479 unselected patients with acute chest pain.

Methods and results: Sixty-nine per cent of the patients presented with GDF-15 levels above the previously defined upper reference limit (1200 ng/L). The risks of the composite endpoint of death or (recurrent) MI after 6 months were 1.3, 5.1, and 12.6% in patients with normal (<1200 ng/L), moderately elevated (1200–1800 ng/L), or markedly elevated (>1800 ng/L) levels of GDF-15 on admission, respectively (P < 0.001). By multivariable analysis that included clinical characteristics, ECG findings, peak cardiac troponin I levels within 2 h (cTnI0–2 h), N-terminal pro-B-type natriuretic peptide, C-reactive protein, and cystatin C, GDF-15 remained an independent predictor of the composite endpoint. The ability of the ECG combined with peak cTnI0–2 h to predict the composite endpoint was markedly improved by addition of GDF-15 (c-statistic, 0.74 vs. 0.83; P < 0.001).

Conclusion: GDF-15 improves risk stratification in unselected patients with acute chest pain and provides prognostic information beyond clinical characteristics, the ECG, and cTnI.

Key Words: Growth-differentiation factor-15 • Acute chest pain • Risk stratification • Biomarker

{dagger} These authors contributed equally.


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