European Heart Journal Advance Access originally published online on October 17, 2005
European Heart Journal 2006 27(2):150-156; doi:10.1093/eurheartj/ehi582
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Prognostic value of tissue inhibitor of metalloproteinase-1 for cardiovascular death among patients with cardiovascular disease: results from the AtheroGene study
1Department of Medicine II, Johannes Gutenberg-University, Langenbeckstraße 1, 55101 Mainz, Germany
2Innere Abteilung, Bundeswehrzentralkrankenhaus, Koblenz, Germany
3Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), Johannes Gutenberg-University, Mainz, Germany
4INSERM U525, Faculté de Médecine Pitié-Salpétrière, Paris, France
Received 29 March 2005; revised 9 September 2005; accepted 22 September 2005; online publish-ahead-of-print 17 October 2005.
* Corresponding author. Tel: +49 6131 176501; fax: +49 6131 175691. E-mail address: edithlubos{at}gmx.de
See page 121 for the editorial comment on this article (doi:10.1093/eurheartj/ehi639)
Aims Metalloproteinases are proteolytic enzymes, which decompose the extracellular matrix, influence cardiac remodelling, and are inhibited by tissue inhibitor of metalloproteinases (TIMPs). Little is known about the prognostic impact of the TIMP-1/matrix metalloproteinase complex in patients with future cardiovascular death.
Methods and results In 1979 patients with suspected coronary artery disease (CAD), TIMP-1 has been determined at baseline. Among 1945 (98.4%) patients with a mean follow-up period of 2.6±1.2 years, 75 patients died because of cardiovascular causes.
Mean concentrations of TIMP-1 were higher among patients who experienced a fatal cardiovascular event than among those who did not (820 vs. 692 ng/mL; P<0.001). Age and sex adjusted hazard ratio of future cardiovascular death associated with one standard deviation of TIMP-1 level, was 1.37 (95% CI: 1.17–1.61; P<0.001). The hazard ratio remained nearly identical after adjustment for clinical and therapeutic confounders. B-type natriuretic peptide (2.75, 95% CI: 1.94–3.89; P<0.001), C-reactive protein (1.79, 95% CI: 1.43–2.24; P<0.001), and TIMP-1 (1.30, 95% CI: 1.07–1.58; P=0.008) were independently associated with future cardiovascular death.
Conclusion In patients with CAD, TIMP-1 proves as an independent predictor for future cardiovascular death.
Key Words: Coronary artery disease • Tissue inhibitor of metalloproteinase-1 • Prognosis
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