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). MATERIALS AND 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.