European Heart Journal Advance Access originally published online on January 23, 2009
European Heart Journal 2009 30(9):1057-1065; doi:10.1093/eurheartj/ehn600
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Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction
Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK
Received 23 May 2008; revised 9 December 2008; accepted 22 December 2008; online publish-ahead-of-print 23 January 2009.
* Corresponding author. Tel:+44 1162523132, Fax: +44 1162523108, Email: sqk1{at}le.ac.uk
See page 1030 for the editorial comment on this article (doi:10.1093/eurheartj/ehp129)
Aims: Our aim was to assess the long-term prognostic value of growth differentiation factor-15 (GDF-15) in patients post-acute myocardial infarction (AMI). Growth differentiation factor-15 is a member of the transforming growth factor β family. Growth differentiation factor-15 is expressed in the myocardium and upregulated due to ‘stress’ and has been shown to have antiapoptotic actions. Its role in the cardiovascular system however is not well defined. We were interested to see if GDF-15 could provide long-term prognostic value in post-AMI patients. We compared GDF-15 with N-terminal pro-B-type natriuretic peptide (NT-proBNP).
Methods and results: We recruited 1142 consecutive post-AMI patients [820 men, median (range) age 67 (24–97) years] in a prospective study with a follow-up period of 505 (range 1–2837) days. Growth differentiation factor-15 levels increased with increasing Killip class (P < 0.001) and were correlated with NT-proBNP (r = 0.47, P < 0.001). Using a multivariable Cox proportional hazards model, log GDF-15 (HR 1.77), log NT-proBNP (HR 2.06), age (HR 1.03) Killip class above 1, (HR 1.62), use of beta-blockers (HR 0.54) and past history of MI (HR 1.44) were significant independent predictors of death or heart failure (HF). Predictors of death were log NT-proBNP, log GDF-15, age, eGFR, past history of MI, use of beta-blockers, and use of ACE inhibitors or angiotensin receptor blockers. The C-statistic for GDF-15 for predicting death or HF at 1 year was 0.73 (95% CI: 0.70–0.76, P < 0.001) and was 0.76 (95% CI: 0.70–0.80, P < 0.001) for NT-proBNP. Combining these markers yielded an AUC of 0.81 (95% CI: 0.77–0.85), which exceeded that of GDF-15 (P < 0.001) and NT-proBNP (P = 0.004) alone. The Kaplan–Meier analysis revealed that those patients with above median GDF-15 and NT-proBNP had the highest event rate for death and HF (log rank 50.22, P < 0.001).
Conclusion: Growth differentiation factor-15 is a new marker for predicting death and HF in post-AMI patients. GDF-15 provides prognostic information over and above clinical factors and the established biomarker NT-proBNP. Combined levels of GDF-15 with NT-proBNP can identify a high-risk group of patients.
Key Words: Myocardial infarction • Heart failure • Biomarkers • N-terminal B-type natriuretic peptide • Prognosis • Growth differentiation factor-15
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