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Biomarkers of Extracellular Matrix Metabolism (MMP-9 and TIMP-1) and Risk of Stroke, Myocardial Infarction, and Cause-Specific Mortality: Cohort Study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
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2011 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 6, no 1, e16185- p.Article in journal (Refereed) Published
Abstract [en]

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.

Design: 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.

Conclusion: 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.

Place, publisher, year, edition, pages
2011. Vol. 6, no 1, e16185- p.
National Category
Medical and Health Sciences Surgery
Research subject
Orthopaedics
Identifiers
URN: urn:nbn:se:uu:diva-146287DOI: 10.1371/journal.pone.0016185ISI: 000286520600027PubMedID: 21283828OAI: oai:DiVA.org:uu-146287DiVA: diva2:397931
Available from: 2011-02-16 Created: 2011-02-16 Last updated: 2011-06-15Bibliographically approved

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Larsson, AndersMichaëlsson, Karl

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Internal MedicineGeriatricsDepartment of Medical SciencesClinical ChemistryOrthopaedicsUCR-Uppsala Clinical Research Center
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