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European Journal of Heart Failure 2008 10(4):388-395; doi:10.1016/j.ejheart.2008.02.015
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© 2008 European Society of Cardiology

Tissue inhibitor of metalloproteinases levels in patients with chronic heart failure: An independent predictor of mortality

S. Frantz1, S. Störk1,*, K. Michels, M. Eigenthaler, G. Ertl, J. Bauersachs and C.E. Angermann

Department of Internal Medicine I / Center of Cardiovascular Medicine, University of Würzburg Germany

* Corresponding author. Department of Internal Medicine I / Center of Cardiovascular Medicine, Klinikstraβe 6–8, University of Würzburg, 97070 Würzburg, Germany. Tel.: +49 931 201 36147; fax: +49 931 201 70380. E-mail address: stoerk_s{at}klinik.uni-wuerzburg.de (S. Störk).


  Abstract

Background: Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved in cardiac remodelling. The prognostic utility of TIMP is unknown in chronic heart failure (CHF).

Aims: We investigated the association of plasma levels of soluble MMP-9 and TIMP-1 with clinical, laboratory and echocardiographic parameters and estimated their prognostic value in the prediction of all-cause death.

Methods: MMP-9, TIMP-1, tumour necrosis factor-{alpha}, and amino-terminal pro-brain natriuretic peptide were measured in 249 consecutively enrolled CHF patients and 74 healthy individuals.

Results: After adjustment for age, sex and creatinine, levels of TIMP-1 (1640 vs. 735 ng/ml, P < 0.001) but not MMP-9 were elevated in CHF patients compared to controls. During a median follow-up period of 2.5 years, 66 patients (27%) died. In multivariable Cox regression models TIMP-1 but not MMP-9 emerged as an independent predictor of all-cause death (hazard ratio per tertile, 3.5; 95% confidence interval [CI], 2.2–5.1). In addition to the full set of univariately predictive clinical and serological markers, information on TIMP-1 significantly increased the area under the receiver operating characteristic curve from 0.77 (95% CI, 0.71–0.84) to 0.87 (95% CI, 0.82–0.92).

Conclusion: In stable CHF patients, TIMP-1 but not MMP-9 is of independent and incremental value regarding the prediction of all-cause death.

Key Words: Heart failure • Matrix metalloproteinase • Tissue inhibitor of metalloproteinases • Prognosis

Received January 15, 2007; Revised December 13, 2007; Accepted February 21, 2008

1 Both authors contributed equally to the work.


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