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Published on: January 28, 2020
Serum matrix metalloproteinase-9 and coronary heart disease: a prospective study in middle-aged men
P Welsh1, P H Whincup, O Papacosta
1Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow.
Insights
Matrix metalloproteinase-9 (MMP-9) shows a slight link to coronary heart disease (CHD) risk. This association weakens with adjustments for smoking and inflammation markers, suggesting MMP-9 is not a standalone CHD biomarker.
Area of Science:
- Cardiovascular Disease Research
- Biomarker Discovery
- Inflammation and Hemostasis
Background:
- Matrix metalloproteinase-9 (MMP-9) is implicated in arterial plaque rupture.
- The precise relationship between MMP-9 and coronary heart disease (CHD) risk remains unclear.
Purpose of the Study:
- To investigate the prospective association between serum MMP-9 levels and CHD risk in a general male population.
- To determine if MMP-9 can serve as an independent predictor of incident CHD.
Main Methods:
- A case-control study nested within a prospective cohort of 5661 men followed for 16 years.
- Baseline serum MMP-9 levels were measured.
- Coronary heart disease events were recorded for 465 cases and 1076 controls.
Main Results:
- MMP-9 levels correlated with smoking and inflammatory/hemostatic markers.
- Men in the highest MMP-9 third had a higher age-adjusted odds ratio (OR) for CHD (1.37).
- This association became borderline significant (OR 1.28) after adjusting for smoking and further attenuated (OR 1.13) with inflammation markers (IL-6, CRP).
Conclusions:
- Serum MMP-9 has a modest association with incident CHD.
- This association is not independent of smoking and generalized inflammation markers.
- MMP-9 is unlikely to be a clinically useful biomarker for CHD risk prediction.
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.
Aim:
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).
Conclusion:
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.
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