Serum matrix metalloproteinase-8 concentrations are associated with cardiovascular outcome in men.
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.


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.
Tuomainen
Anita M
AM
Institute of Dentistry, University of Helsinki, Haartmaninkatu 8, P.O.Box 63, FI-00014 Helsinki, Finland. anita.tuomainen@helsinki.fi
Nyyssönen
Kristiina
K
Laukkanen
Jari A
JA
Tervahartiala
Taina
T
Tuomainen
Tomi-Pekka
TP
Salonen
Jukka T
JT
Sorsa
Timo
T
Pussinen
Pirkko J
PJ
D050197:Atherosclerosis / Q000097:blood* / Q000150:complications / Q000401:mortality; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000401:mortality; D003327:Coronary Disease / Q000097:blood / Q000209:etiology; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D020784:Matrix Metalloproteinase 8