Serum matrix metalloproteinase-9 and coronary heart disease: a prospective study in middle-aged men.
BACKGROUND
Matrix metalloproteinase-9 (MMP-9) has a potential role in arterial plaque rupture, but its relation to risk of coronary heart disease (CHD) is uncertain.


OBJECTIVE
To determine whether circulating levels of serum MMP-9 are prospectively related to the risk of CHD in the general population.


METHODS
We measured baseline MMP-9 levels in stored serum samples of subjects in a case-control study nested within a prospective study of 5661 men followed up for 16 years for CHD events (465 cases, 1076 controls).


RESULTS
MMP-9 values were associated with cigarette smoking, and with several inflammatory and haemostatic markers, but not with age, body mass index, blood pressure or lipid measurements. Men in the top third of baseline MMP-9 levels had an age-adjusted odds ratio (OR) for CHD of 1.37 (95% CI 1.04-1.82) compared with those in the bottom third. Adjustment for conventional risk factors (smoking in particular) reduced the odds ratio to borderline significance: OR 1.28 (95% CI 0.95-1.74), while additional adjustment for two markers of generalized inflammation, interleukin-6 and C-reactive protein, further attenuated the association: OR 1.13 (0.82-1.56).


CONCLUSIONS
Serum MMP-9 has a modest association with incident CHD in the general population, which is not independent of cigarette smoking exposure and circulating markers of generalized inflammation. MMP-9 is unlikely to be a clinically useful biomarker of CHD risk, but may still play a role in the pathogenesis of CHD.
Welsh
P
P
Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow.
Whincup
P H
PH
Papacosta
O
O
Wannamethee
S G
SG
Lennon
L
L
Thomson
A
A
Rumley
A
A
Lowe
G D O
GD
D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000201:enzymology / Q000209:etiology*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies
D015415:Biomarkers; D020780:Matrix Metalloproteinase 9