title: Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction, and cause-specific mortality: cohort study.
abstract: OBJECTIVE
  Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective.
  
  
  METHODS
  The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991-1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163).
  
  
  RESULTS
  Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03-1.19; and 1.11, 1.02-1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09-1.37; and 1.18, 1.04-1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample.
  
  
  CONCLUSIONS
  In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hansson
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Johan
authors.initials: J
authors.lastname: Ärnlöv
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Karl
authors.initials: K
authors.lastname: Michaëlsson
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002423:Cause of Death; D015331:Cohort Studies; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009026:Mortality; D009203:Myocardial Infarction / Q000201:enzymology* / Q000209:etiology / Q000401:mortality; D011446:Prospective Studies; D012306:Risk; D020521:Stroke / Q000201:enzymology* / Q000209:etiology / Q000401:mortality; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9