Circulating matrix metalloproteinase-2 but not matrix metalloproteinase-3, matrix metalloproteinase-9, or tissue inhibitor of metalloproteinase-1 predicts outcome in patients with congestive heart failure

Background Extracellular matrix remodeling is thought to play an important role in the progression of heart failure (HF). Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are matrix-degrading enzymes that have been demonstrated to influence left ventricular properties and serve as targets of potential anti-remodeling agents. Herein we evaluated the potential significance of circulating MMP and TIMP levels in patients with congestive HF (CHF) speculating it may assume prognostic value. Methods Serum samples were obtained from 88 consecutive patients attending the outpatient HF clinic and analyzed for MMP-2, -3, -9, and TIMP-1 as well as N-terminal probrain natriuretic peptide (NT-ProBNP). Patients were followed up for the occurrence of either mortality or hospitalizations due to CHF or either of each. Results Circulating levels of MMP-2, -9, and TIMP-1 but not of MMP-3 were increased in patients with CHF as compared with age-matched controls. Only MMP-2 and NT-ProBNP levels correlated significantly with New York Heart Association class. Matrix metalloproteinase-2 and NT-ProBNP levels did not correlate. Patients with circulating MMP-2 above 352 ng/mL were 4.2 times more likely to die, 2.2 times more likely to be hospitalized because of CHF, and 2.3 times more likely to experience either of the 2 end points as compared with patients with MMP-2 concentrations below this threshold. Both MMP-2 and NT-ProBNP were found to be independent predictors of mortality over a 24-month follow-up period. Conclusions Matrix metalloproteinase-2 but not MMP-3, -9, or TIMP-1 serum levels is an independent predictor of mortality in patients with CHF.