Prospective study of matrix metalloproteinase-9 and risk of myocardial infarction and stroke in older men and women.
Jefferis BJ., Whincup P., Welsh P., Wannamethee G., Rumley A., Lennon L., Thomson A., Lawlor D., Carson C., Ebrahim S., Lowe G.
OBJECTIVES: The endopeptidase matrix metalloproteinase-9 (MMP-9) is implicated in atherosclerotic plaque rupture. We investigate prospective associations between MMP-9 and MI or stroke in an older general population cohort, accounting for established and novel cardiovascular risk factors. METHODS: Baseline serum MMP-9 was measured in incident MI (n=368) and stroke (n=299) cases and two controls per case, 'nested' in prospective studies of 4252 men and 4286 women aged 60-79 years, sampled from General Practices in Britain in 1998-2000, with 7-year follow-up for fatal and non-fatal MI and stroke. RESULTS: Geometric mean MMP-9 was 528 ng/mL (IQR 397, 743) in MI cases compared to 501 ng/mL (IQR 370, 743) in controls, p=0.10. Participants in the top compared to bottom third of MMP-9 levels had an age-adjusted odds ratio for MI of 1.53 (95% CI 1.09, 2.13), which attenuated to 1.18 (95% CI 0.81, 1.70) after adjustment for established and novel cardiovascular risk factors. There was weak evidence that OR differed according to pre-existing CVD; the OR for MI in 187 participants with pre-existing CVD was 2.20 (1.04, 4.64) and 1.24 (0.84, 1.82) in 715 participants without (LR test for interaction p=0.06). Geometric mean MMP-9 levels were higher in stroke cases than controls; 522ng/mL (IQR 363, 673) vs 487 (IQR 393, 704), p=0.045; however adjustments similarly attenuated the associations. CONCLUSIONS: While serum MMP-9 is univariately associated with risk of MI and stroke, it is not a strong independent risk marker for either.