title: Novel association between plasma matrix metalloproteinase-9 and risk of incident atrial fibrillation in a case-cohort study: the Atherosclerosis Risk in Communities study.
abstract: BACKGROUND
  Previous cross-sectional studies have suggested that biomarkers of extracellular matrix remodelling are associated with atrial fibrillation (AF), but no prospective data have yet been published. Hence, we examine whether plasma matrix metalloproteinases (MMP) and their inhibitors are related to increased risk of incident AF.
  
  
  METHODS
  We used a case-cohort design in the context of the prospective Atherosclerosis Risk in Communities (ARIC) study. From 13718 eligible men and women free from AF in 1990-92, we selected a stratified random sample of 500 individuals without and 580 with incident AF over a mean follow-up of 11.8 years. Using a weighted proportional hazards regression model, the relationships between MMP-1, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2 and C-terminal propeptide of collagen type-I with incident AF were examined after adjusting for confounders.
  
  
  RESULTS
  In models adjusted for age, sex and race, all biomarkers were associated with AF, but only the relationship between plasma MMP-9 remained significant in the fully-adjusted model: each one standard deviation increase in MMP-9 was associated with 27% (95% Confidence Interval: 7% to 50%) increase in risk of AF with no evidence of an interaction with race or sex. Individuals with above mean levels of MMP-9 were more likely to be male, white and current smokers.
  
  
  CONCLUSIONS
  The findings suggest that elevated levels of MMP-9 are independently associated with increased risk of AF. However, given the lack of specificity of MMP-9 to atrial tissue, it remains to be determined whether the observed relationship reflects the impact of atrial fibrosis or more generalized fibrosis on risk of incident AF.
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA. rhuxley@umn.edu
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Huxley
authors.forename: Faye L
authors.initials: FL
authors.lastname: Lopez
authors.forename: Richard F
authors.initials: RF
authors.lastname: MacLehose
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
authors.forename: David
authors.initials: D
authors.lastname: Couper
authors.forename: Catherine
authors.initials: C
authors.lastname: Leiendecker-Foster
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.forename: Lin Yee
authors.initials: LY
authors.lastname: Chen
authors.forename: Elsayed Z
authors.initials: EZ
authors.lastname: Soliman
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000453:epidemiology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk
chemical_list: D015415:Biomarkers; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
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