title: The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence.
abstract: BACKGROUND
  Matrix metalloproteinase-8 (MMP-8) is involved in the breakdown of the extracellular matrix increasing the vulnerability of atherosclerotic lesions. We analysed the diagnostic value of serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in acute coronary syndrome (ACS) and their prognostic value in ACS recurrence.
  
  
  METHODS
  The population comprised 343 patients with ACS [including 108 unstable angina pectoris and 235 acute myocardial infarctions (AMI)] and 326 healthy controls. Additionally, 157 (45.8%) patients were resampled during the recovery. The ACS patients were followed up for 6 years.
  
  
  RESULTS
  MMP-8, TIMP-1, and their molar ratio distinguished the cases from the controls; C-statistic of the multivariate model (95% CI, p-value) including the MMP-8/TIMP-1 ratio regarding its discriminating ability for AMI was 0.922 (0.893-0.950, p<0.001). After the acute phase of ACS, median MMP-8 and TIMP-1 concentrations decreased (p<0.001) by 34.5 and 28.7%, respectively, but ended up on a different level than those found in the controls. In the follow-up, acute phase and recovery period TIMP-1 concentrations associated with cardiovascular death with hazard ratios 4.31 (2.00-9.26, p<0.001) and 4.69 (1.10-20.01, p=0.037), respectively.
  
  
  CONCLUSIONS
  The increase of serum MMP-8 and TIMP-1 concentrations may reflect plaque instability and tissue damage. TIMP-1 concentrations are associated with poor outcome in patients with ACS. The findings may have practical implications in both diagnostics and therapeutics.
authors.affiliation: Institute of Dentistry, University of Helsinki, P.O. Box 63, FI-00014 Helsinki, Finland. pirkko.pussinen@helsinki.fi
authors.forename: Pirkko J
authors.initials: PJ
authors.lastname: Pussinen
authors.forename: Seppo
authors.initials: S
authors.lastname: Sarna
authors.forename: Mirja
authors.initials: M
authors.lastname: Puolakkainen
authors.forename: Hans
authors.initials: H
authors.lastname: Öhlin
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.forename: Erkki
authors.initials: E
authors.lastname: Pesonen
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood*; D008875:Middle Aged; D012008:Recurrence; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020784:Matrix Metalloproteinase 8