on October 11, 2007
Published online before print October 11, 2007, doi: 10.1161/ATVBAHA.107.154831
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Submitted on June 27, 2007
Accepted on September 28, 2007
Serum Matrix Metalloproteinase-8 Concentrations Are Associated With Cardiovascular Outcome in Men
Anita M. Tuomainen *;
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., J.T.S.), University of Kuopio, Finland.
* To whom correspondence should be addressed. 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.
Key words: inflammation • atherosclerosis • cardiovascular diseases • myocardial infarction • metalloproteinases
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