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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2722.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Serum Matrix Metalloproteinase-8 Concentrations Are Associated With Cardiovascular Outcome in Men

Anita M. Tuomainen; Kristiina Nyyssönen; Jari A. Laukkanen; Taina Tervahartiala; Tomi-Pekka Tuomainen; Jukka T. Salonen; Timo Sorsa; Pirkko J. Pussinen

From the Institute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital (A.M.T., T.T., T.S., P.J.P.), and the Research Institute of Public Health (K.N., J.A.L., T.-P.T.), University of Kuopio, Finland, Oy Jurilab Ltd. (J.T.S.).

Correspondence to Anita Tuomainen, Institute of Dentistry, University of Helsinki, Haartmaninkatu 8, P.O.Box 63, FI-00014 Helsinki, Finland. E-mail anita.tuomainen{at}helsinki.fi

Objective— In culture studies matrix metalloproteinase (MMP)-8 thins the protecting fibrous cap of the atherosclerotic plaque thereby increasing its vulnerability. Results on the association of serum MMP-8 concentrations and cardiovascular diseases (CVD) are, however, scarce and contradictory.

Methods and Results— We analyzed the association between CVD or subclinical atherosclerosis and serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations of 1018 men with the follow-up time of 10 years. MMP-8 concentrations or MMP-8/TIMP-1 ratios were higher in men with prevalent CVD or subclinical atherosclerosis at baseline than those without. In men free of CVD at baseline, MMP-8 concentrations associated with acute myocardial infarction, death from coronary heart disease (CHD), CVD, or from any cause with relative risks (RR) (95% CI) of 1.138 (1.009 to 1.284), 1.188 (1.034 to 1.365), 1.171 (1.026 to 1.338), and 1.136 (1.018 to 1.269), respectively, and MMP-8/TIMP-1 ratio with CHD death with an RR of 1.206 (1.028 to 1.414) per standard deviation (SD) increase. In men with no prevalent CVD but with subclinical atherosclerosis at baseline, elevated serum MMP-8 concentration predicted CVD death with an RR of 3.03 (1.09 to 8.44). TIMP-1 concentrations alone had no predictive value.

Conclusions— The results indicate that serum MMP-8 concentrations are elevated in prevalent or subclinical atherosclerosis and associate with the worst cardiovascular outcome.

We evaluated the predictive value of serum MMP-8 (MMP-8) concentration for cardiovascular disease (CVD) events in a prospective sample of men without cardiovascular events. The results show a 3.0-fold increase in risk for CVD death in men with both elevated MMP-8 level and subclinical atherosclerosis.

Key Words: inflammation • atherosclerosis • cardiovascular diseases • myocardial infarction • metalloproteinases

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