Plasma matrix metalloproteinase-3 level is an independent prognostic factor in stable coronary artery disease.
BACKGROUND
Recent evidence suggests the important role of matrix metalloproteinases (MMPs) in the progression of atherosclerosis and development of clinical events. We assessed the prognostic value of different plasma MMPs in patients with stable coronary artery disease (CAD).


METHODS
A total of 165 consecutive nondiabetic patients with angiographically significant CAD (n = 150) or normal coronary angiograms despite exercise-induced myocardial ischemia (cardiac syndrome X, n = 15) and 17 normal subjects were evaluated. In each subject, plasma inflammatory markers including high sensitivity C-reactive protein (hsCRP) and MMP-2, 3 and 9 were measured. In CAD patients, major cardiovascular events including cardiac death, nonfatal myocardial infarction, unscheduled coronary revascularization and hospitalization as a result of unstable angina were prospectively followed up for more than 6 months.


RESULTS
Plasma levels of MMPs were significantly higher in CAD patients than in those with cardiac syndrome X and in normal subjects (MMP-2: 914.76 +/- 13.20 vs. 830.79 +/- 31.95 vs. 783.08 +/- 28.40 ng mL(-1), P = 0.002; MMP-3: 129.59 +/- 4.21 vs. 116.86 +/- 8.09 vs. 91.71 +/- 9.55 ng mL(-1), P = 0.011; MMP-9: 31.42 +/- 2.84 vs. 11.40 +/- 5.49 vs. 6.71 +/- 2.89 ng mL(-1), P = 0.006). In CAD patients, there were 48 major cardiovascular events during a mean follow-up period of 17.74 +/- 0.85 months. The numbers of diseased vessels (HR = 2.19, 95% CI 1.20-1.02, P = 0.011), plasma hsCRP (HR = 2.21, 95% CI 1.18-4.11, P = 0.013) and MMP-3 level (HR = 2.46, 95% CI = 1.15-5.28, P = 0.021) were associated with the development of cardiovascular events. However, only the plasma MMP-3 level was an independent predictor of the adverse events in CAD patients (HR = 2.47, 95% CI 1.10-5.54, P = 0.028).


CONCLUSIONS
Plasma MMP levels were increased in CAD patients. Plasma MMP-3 level, rather than hsCRP, was an independent prognostic marker for future cardiovascular events, suggesting its potential role in risk stratification and clinical management of stable CAD.
Wu
T C
TC
National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
Leu
H B
HB
Lin
W T
WT
Lin
C P
CP
Lin
S J
SJ
Chen
J W
JW
D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000201:enzymology; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D003324:Coronary Artery Disease / Q000097:blood* / Q000201:enzymology; D016757:Death, Sudden, Cardiac / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D017566:Microvascular Angina / Q000097:blood / Q000201:enzymology; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods
D015415:Biomarkers; D002097:C-Reactive Protein; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9