Independent association of matrix metalloproteinase-10, cardiovascular risk factors and subclinical atherosclerosis

OBJECTIVES: Circulating levels of matrix metalloproteinase (MMP)-10 are related to inflammation in asymptomatic subjects with cardiovascular risk factors. Whether MMP-10 is associated with the severity of atherosclerosis remains to be determined. This study examines the relationship of systemic MMP-10 levels with atherosclerotic risk factors and subclinical atherosclerosis. METHODS AND RESULTS: Circulating levels of MMP-1, -9 and -10, and markers of inflammation [fibrinogen, interleukin-6, von Willebrand factor, and high-sensitivity C-reactive protein (hs-CRP)] were measured in 400 subjects (mean age 54.3 years, 77.7% men) with cardiovascular risk factors but free from clinical cardiovascular disease. Subclinical atherosclerosis was evaluated by both the mean carotid intima-media thickness (IMT) and the presence of atherosclerotic plaques with the use of B-mode ultrasound in all subjects. MMP-10 levels were positively correlated with fibrinogen (r = 0.24, P < 0.001), hs-CRP (r = 0.14, P < 0.01) and carotid IMT (r = 0.17, P < 0.01). The association between MMP-10 and IMT remained significant in multiple regression analysis (P < 0.02) when controlling for traditional atherosclerotic risk factors and inflammatory markers. Such an association was not observed for MMP-1 and -9. Subjects in the highest MMP-10 tertile had significantly higher carotid IMT (adjusted odds ratio 6.3, 95% confidence interval 1.3-31.4, P = 0.024). In addition, MMP-10 levels were significantly higher in patients with carotid plaques (n = 78) than in those with no plaques after adjusting for age and sex (P < 0.01). CONCLUSION: Higher serum MMP-10 levels were associated with inflammatory markers, increased carotid IMT and atherosclerotic plaques in asymptomatic subjects. Circulating MMP-10 may be useful to identify subclinical atherosclerosis in subjects free from cardiovascular disease.