Abstract 12245: Serum High-Density Lipoprotein-Associated Paraoxonase-1 Levels Predict Recurrent Cardiovascular Events After Stent Implantation in Patients With Stable Angina Pectoris
Background: High-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease. Its antioxidant properties are attributed mainly to the HDL-bound enzyme, paraoxonase-1 (PON-1). Recently, myeloperoxidase (MPO) has been shown to attenuate the atheroprotective function of HDL. This study investigated the relationship between plasma MPO and serum PON-1 levels in patients with stable angina pectoris (SAP), and whether PON-1 levels predict cardiovascular events in SAP patients after stent implantation.
Methods: Plasma MPO levels and serum PON-1 concentration and activity were measured in patients with SAP (n=226) and in control subjects (n=96). In addition, we assessed the prognostic significance of serum PON-1 concentrations on admission after stent implantation in 263 SAP patients. Cardiac events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction and other non-fatal events including unstable angina pectoris or coronary revascularization.
Results: Plasma MPO levels in SAP patients were significantly higher than those in control subjects (P≤0.0001). Serum PON-1 concentrations and PON-arylesterase activity in SAP patients were significantly lower than those in control subjects (PON-1 concentrations, P≤0.0001; PON-arylesterase activity, P≤0.05). Plasma MPO levels showed a weak inverse correlation with serum PON-1 concentrations (r = - 0.216, P≤0.0001) and PON-arylesterase activity (r = - 0.147, P=0.0084) in all subjects. During a mean follow-up period of 24±16 months, 117 patients (44%) had cardiac events. Kaplan-Meier survival analysis showed that the low-PON-1 group (≤56.5μg/ml, median) had a significantly worse outcome than the high-PON-1 group (P=0.017). Multivariate analysis found that a low serum PON-1 concentration was the only independent predictor of cardiovascular events (odds ratio, 1.56; 95% confidence interval, 1.02 to 2.38, P=0.039).
Conclusions: These findings suggest that low serum PON-1 levels predict recurrent cardiovascular events in SAP patients, and an imbalance between MPO as a pro-oxidant and PON-1 as an antioxidant may contribute to the progression and destabilization of human coronary atherosclerotic lesions.
- © 2013 by American Heart Association, Inc.