title: Association between serum levels of pro-metalloproteinase 1, tissue inhibitor of metalloproteinases 1 and 2 and prevalent cardiovascular disease in a population-based study.
abstract: OBJECTIVE
  The aim of the study was to test the association between circulating levels of matrix prometalloproteinase1 (pro-MMP1) and its tissue inhibitors TIMP1 and TIMP2 with prevalent cardiovascular events.
  
  
  METHODS
  Prevalent cardiovascular events were documented in 500 participants of the Cyprus study (46% men) over the age of 40. Serum levels of pro-MMP1, TIMP1 and TIMP2 were measured with ELISA and the association between quartiles of serum levels and presence of cardiovascular disease (CVD) was tested using multivariable binary regression models.
  
  
  RESULTS
  Lower serum levels of pro-MMP1 and TIMP1 were strongly associated with presence of CVD at baseline even after adjustment for conventional risk factors (P(for trend)=0.006 and P=0.001, respectively) and inflammatory factors (P(for trend)=0.005 and P=0.002, respectively) with people in the highest quartile of pro-MMP1 having a reduced odds for cardiovascular disease by about 70% compared to the lowest quartile (OR(adjusted)=0.26; 95% CI=0.19 to 0.75; P=0.01), whereas people with TIMP1 levels >1000 ng/mL had a 75% reduced odds for CVD compared to the rest (OR(adjusted)=0.25; 95% CI=0.11 to 0.60; P(for trend)=0.002). TIMP2 levels were not associated with prevalent cardiovascular disease.
  
  
  CONCLUSIONS
  A strong association between lower levels of circulating pro-MMP1 and TIMP1 and risk of prevalent cardiovascular disease in a general population cohort over 40 years is evident, independent from common cardiovascular and inflammatory risk factors. The role of MMP1 and its tissue inhibitors, should be tested further in prospective studies of cardiovascular disease.
authors.affiliation: Cyprus International Institute for Environmental and Public Health in association with the Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus - andrie.panayiotou@cut.ac.cy.
authors.forename: A G
authors.initials: AG
authors.lastname: Panayiotou
authors.forename: E
authors.initials: E
authors.lastname: Kamilari
authors.forename: M
authors.initials: M
authors.lastname: Griffin
authors.forename: T
authors.initials: T
authors.lastname: Tyllis
authors.forename: N
authors.initials: N
authors.lastname: Georgiou
authors.forename: D
authors.initials: D
authors.lastname: Bond
authors.forename: D
authors.initials: D
authors.lastname: Hoppensteadt
authors.forename: J
authors.initials: J
authors.lastname: Fareed
authors.forename: A
authors.initials: A
authors.lastname: Nicolaides
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology; D003535:Cyprus / Q000453:epidemiology; D004792:Enzyme Precursors / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D015999:Multivariate Analysis; D016017:Odds Ratio; D015995:Prevalence; D012307:Risk Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
chemical_list: D015415:Biomarkers; D004792:Enzyme Precursors; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1