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European Heart Journal Advance Access published online on October 17, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi582
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European Heart Journal © The European Society of Cardiology 2005; all rights reserved
Received March 29, 2005
Revised September 9, 2005
Accepted September 22, 2005

Clinical research

Prognostic value of tissue inhibitor of metalloproteinase-1 for cardiovascular death among patients with cardiovascular disease: results from the AtheroGene study

Edith Lubos 1*, Renate Schnabel 1, Hans J. Rupprecht 1, Christoph Bickel 2, Claudia M. Messow 3, Susanne Prigge 2, François Cambien 4, Laurence Tiret 4, Thomas Münzel 1, and Stefan Blankenberg 1

1 Department of Medicine II, Johannes Gutenberg-University, Langenbeckstraße 1, 55101 Mainz, Germany
2 Innere Abteilung, Bundeswehrzentralkrankenhaus, Koblenz, Germany
3 Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), Johannes Gutenberg-University, Mainz, Germany
4 INSERM U525, Faculté de Médecine Pitié-Salpétrière, Paris, France

* To whom correspondence should be addressed.
Edith Lubos, E-mail: edithlubos{at}gmx.de


  Abstract

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

Keywords: Coronary artery disease; Tissue inhibitor of metalloproteinase-1; Prognosis.
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