title: 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.
abstract: 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.
authors.affiliation: Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. jacobg@post.tau.ac.il
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.forename: Shuki
authors.initials: S
authors.lastname: Patal
authors.forename: Dov
authors.initials: D
authors.lastname: Wexler
authors.forename: Arie
authors.initials: A
authors.lastname: Roth
authors.forename: David
authors.initials: D
authors.lastname: Sheps
authors.forename: Gad
authors.initials: G
authors.lastname: Keren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000097:blood*; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D010446:Peptide Fragments; D019715:Tissue Inhibitor of Metalloproteinase-1; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9