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

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.

• Authors: S Frantz, S Störk, K Michels, M Eigenthaler, G Ertl, J Bauersachs, C E Angermann
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 10 Issue 4 Pg. 388-95 (Apr 2008) ISSN: 1388-9842 [Print] England
• PMID: 18343723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Tissue Inhibitor of Metalloproteinase-1
• Tumor Necrosis Factor-alpha
• Matrix Metalloproteinase 9

Topics

• Aged
• Biomarkers (blood)
• Cardiac Output, Low (blood, diagnosis, mortality)
• Cause of Death
• Echocardiography
• Female
• Heart Failure (blood, diagnosis, mortality)
• Humans
• Male
• Matrix Metalloproteinase 9 (blood)
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Proportional Hazards Models
• Prospective Studies
• Reference Values
• Tissue Inhibitor of Metalloproteinase-1 (blood)
• Tumor Necrosis Factor-alpha (blood)