Abstract

Osteopontin (OPN) mRNA was shown to be highly expressed in atherosclerotic plaques. We reported plasma OPN levels to be high in patients (pts) with coronary artery disease. Moreover, OPN levels were recently shown to be high in acute coronary syndrome. Increased OPN mRNA expression was also shown in rat arteries after balloon injury. OPN transgenic mice showed markedly increased neointimal formation after arterial injury. OPN may play a role in the development of restenosis after percutaneous coronary intervention (PCI). Methods: We investigated the prognostic value of pre-procedural plasma OPN levels by ELISA on restenosis and clinical outcome in 130 pts undergoing PCI, of whom 89 (68%) had bare metal stent. Pts with AMI were excluded. Restenosis was defined as >50% diameter stenosis at follow-up angiography. Pts were followed up for 3 years for major adverse cardiovascular events (MACE) (death, MI, unstable angina, stroke). Results: At 7±3 months after PCI, re-angiography was performed in 91 (70%) pts, of whom 40 had restenosis. Between 40 pts with restenosis and 51 without it, plasma OPN (492±200 vs 482±224 ng/ml) and C-reactive protein (CRP) (median 0.78 vs 0.70 mg/l) levels did not differ. In multivariate analysis, reference diameter and smoking were independent predictors for angiographic restenosis, but OPN or CRP levels were not. During the 3-year follow-up, MACE occurred in 21 pts. Compared with 109 pts without MACE, 21 with it had higher OPN (586±230 vs 438±195 ng/ml, P<0.005) and CRP (1.30 vs 0.70 mg/l, P<0.002) levels. Pts with MACE more often had OPN level >500 ng/ml (62% vs 35%) and CRP >3.0 mg/l (33% vs 12%) than without it (P<0.05). OPN did not correlate with CRP levels. To clarify the association between MACE and OPN, pts were divided into 2 groups by OPN levels. Kaplan Meier analysis showed a lower event-free survival rate in pts with OPN level >500 ng/ml than those without it (P<0.05). In multivariate analysis, both OPN and CRP levels were independent predictors for MACE. Hazard ratios for MACE were 2.9 (95%CI=1.3–5.5) for OPN >500 ng/ml and 4.3 (1.3–14.0) for CRP >3.0 mg/l. Conclusion: Plasma levels of OPN as well as CRP were found to be independent predictors for cardiovascular events in pts undergoing PCI, but they were not predictors for restenosis.

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