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Relations of biomarkers of extracellular matrix remodeling to incident cardiovascular events and mortality
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.ORCID iD: 0000-0003-2247-8454
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2010 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 30, no 11, 2283-2288 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE-: To evaluate if biomarkers reflecting left ventricular/vascular extracellular matrix remodeling are associated with cardiovascular disease (CVD) and death in the community. METHODS AND RESULTS-: In 922 Framingham Study participants (mean age, 58 years; 56% women), we related circulating concentrations of matrix metalloproteinase-9 (binary variable: detectable versus undetectable), log of tissue inhibitor of matrix metalloproteinase-1, and log of procollagen type III aminoterminal peptide (PIIINP) to incident CVD and death. On follow-up (mean, 9.9 years), 51 deaths and 81 CVD events occurred. Each SD increment of log of tissue inhibitor of matrix metalloproteinase-1 and log-PIIINP was associated with multivariable-adjusted hazards ratios of 1.72 (95% CI, 1.30 to 2.27) and 1.47 (95% CI, 1.11 to 1.96), respectively, for mortality risk. Log-PIIINP concentrations were also associated with CVD risk (hazard ratio [95% CI] per SD, 1.35 [1.05 to 1.74]). Death and CVD incidence rates were 2-fold higher in participants with both biomarkers higher than the median (corresponding hazard ratio [95% CI], 2.78 [1.43 to 5.40] and 1.77 [1.04 to 3.03], respectively) compared with those with either or both less than the median. The inclusion of both biomarkers improved the C-statistic (for predicting mortality) from 0.78 to 0.82 (P=0.03). Matrix metalloproteinase-9 was unrelated to either outcome. CONCLUSION-: Higher circulating tissue inhibitor of matrix metalloproteinase-1 and PIIINP concentrations are associated with mortality, and higher PIIINP is associated with incident CVD, in the community.

Place, publisher, year, edition, pages
2010. Vol. 30, no 11, 2283-2288 p.
Keyword [en]
cardiovascular disease, extracellular matrix, left ventricle, matrix metalloproteinase-9, procollagen type III amino-terminal peptide, remodeling, tissue inhibitor of matrix metalloproteinase-1
National Category
Medical and Health Sciences
Research subject
Internal Medicine
URN: urn:nbn:se:uu:diva-139657DOI: 10.1161/ATVBAHA.110.208462ISI: 000283234800656PubMedID: 20798380OAI: oai:DiVA.org:uu-139657DiVA: diva2:381841
Available from: 2010-12-29 Created: 2010-12-29 Last updated: 2016-01-18Bibliographically approved

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Sundström, Johan
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Department of Medical SciencesUCR-Uppsala Clinical Research Center
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