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


OBJECTIVE
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).


CONCLUSIONS
In stable CHF patients, TIMP-1 but not MMP-9 is of independent and incremental value regarding the prediction of all-cause death.
Frantz
S
S
Department of Internal Medicine I, Center of Cardiovascular Medicine, University of Würzburg, Würzburg, Germany.
Störk
S
S
Michels
K
K
Eigenthaler
M
M
Ertl
G
G
Bauersachs
J
J
Angermann
C E
CE
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002303:Cardiac Output, Low / Q000097:blood / Q000175:diagnosis / Q000401:mortality; D002423:Cause of Death; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012016:Reference Values; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9