Prospective study of matrix metalloproteinase-9 and risk of myocardial infarction and stroke in older men and women.
OBJECTIVE
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.
Jefferis
Barbara J
BJ
Department of Primary Care & Population Health, UCL Medical School, London, United Kingdom. b.jefferis@pcps.ucl.ac.uk
Whincup
Peter
P
Welsh
Paul
P
Wannamethee
Goya
G
Rumley
Ann
A
Lennon
Lucy
L
Thomson
Andy
A
Lawlor
Debbie
D
Carson
Claire
C
Ebrahim
Shah
S
Lowe
Gordon
G
D000368:Aged; D050197:Atherosclerosis / Q000378:metabolism; D015331:Cohort Studies; D005194:Family Practice; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism* / Q000401:mortality; D011446:Prospective Studies; D012016:Reference Values; D012306:Risk; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology* / Q000453:epidemiology*
D020780:Matrix Metalloproteinase 9