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Novel association between plasma matrix metalloproteinase-9 and risk of incident atrial fibrillation in a case-cohort study: the Atherosclerosis Risk in Communities study.

TitleNovel association between plasma matrix metalloproteinase-9 and risk of incident atrial fibrillation in a case-cohort study: the Atherosclerosis Risk in Communities study.
Publication TypeJournal Article
Year of Publication2013
AuthorsHuxley RR, Norby FL, Maclehose RF, Eckfeldt JH, Couper DJ, Leiendecker-Foster C, Hoogeveen RC, Chen LYee, Soliman EZ, Agarwal SK
Secondary AuthorsAlonso A
JournalPLoS One
Volume8
Issue3
Paginatione59052
Date Published2013
ISSN1932-6203
KeywordsAged, Atrial Fibrillation, Biomarkers, Case-Control Studies, Extracellular Matrix, Female, Humans, Male, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Middle Aged, Proportional Hazards Models, Risk
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.

DOI10.1371/journal.pone.0059052
Alternate JournalPLoS One
PubMed ID23554968
PubMed Central IDPMC3598956
Grant ListRC1HL099452 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States