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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

    237617_237617.pdf (315.6Kb)
    Access Status
    Open access
    Authors
    Huxley, Rachel
    Lopez, F.
    MacLehose, R.
    Eckfeldt, J.
    Couper, D.
    Leiendecker-Foster, C.
    Hoogeveen, R.
    Chen, L.
    Soliman, E.
    Agarwal, S.
    Alonso, A.
    Date
    2013
    Type
    Journal Article
    
    Metadata
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    Citation
    Huxley, R. and Lopez, F. and MacLehose, R. and Eckfeldt, J. and Couper, D. and Leiendecker-Foster, C. and Hoogeveen, R. et al. 2013. Novel Association between Plasma Matrix Metalloproteinase-9 and Risk of Incident Atrial Fibrillation in a Case-Cohort Study: The Atherosclerosis Risk in Communities Study. PLoS ONE. 8 (3): pp. e59052.
    Source Title
    PLoS ONE
    DOI
    10.1371/journal.pone.0059052
    School
    School of Public Health
    Remarks

    This open access article is distributed under the Creative Commons license http://creativecommons.org/licenses/by/4.0/

    URI
    http://hdl.handle.net/20.500.11937/35490
    Collection
    • Curtin Research Publications
    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. © 2013 Huxley et al.

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