Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Nov;30(11):2283-8.
doi: 10.1161/ATVBAHA.110.208462. Epub 2010 Aug 26.

Relations of biomarkers of extracellular matrix remodeling to incident cardiovascular events and mortality

Raghava S Velagaleti  1 , Philimon Gona, Johan Sundström, Martin G Larson, Deborah Siwik, Wilson S Colucci, Emelia J Benjamin, Ramachandran S Vasan
Affiliations

Relations of biomarkers of extracellular matrix remodeling to incident cardiovascular events and mortality

Raghava S Velagaleti et al. Arterioscler Thromb Vasc Biol. 2010 Nov.

Abstract

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.

Conclusions: 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.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interests: None to disclose

Figures

Figure 1
Figure 1
A: Cumulative incidence of all-cause mortality in participants with PIIINP above median and at or below median. B: Cumulative incidence of all-cause mortality in participants with TIMP-1 above median and at or below median.
Figure 1
Figure 1
A: Cumulative incidence of all-cause mortality in participants with PIIINP above median and at or below median. B: Cumulative incidence of all-cause mortality in participants with TIMP-1 above median and at or below median.
Figure 2
Figure 2
Cumulative incidence of all-cause mortality in participants with both TIMP-1 and PIIINP above median and either or both biomarkers at or below median.
See this image and copyright information in PMC

References

    1. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35:569–582. - PubMed
    1. Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med. 1994;330:1431–1438. - PubMed
    1. Sundstrom J, Vasan RS. Circulating biomarkers of extracellular matrix remodeling and risk of atherosclerotic events. Curr Opin Lipidol. 2006;17:45–53. - PubMed
    1. Quilliot D, Alla F, Bohme P, Bruntz JF, Hammadi M, Dousset B, Ziegler O, Zannad F. Myocardial collagen turnover in normotensive obese patients: relation to insulin resistance. Int J Obes (Lond) 2005;29:1321–1328. - PubMed
    1. Tayebjee MH, Nadar S, Blann AD, Gareth BD, MacFadyen RJ, Lip GY. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Am J Hypertens. 2004;17:764–769. - PubMed

Publication types