Smoking is associated with reduced serum paraoxonase activity and concentration in patients with coronary artery disease

Abstract

Background - Paraoxonase is an HDL-associated enzyme that protects lipoproteins from oxidative modifications. Smoking is a major cardiovascular risk factor that promotes lipid peroxidation. Cigarette smoke has been shown in vitro to inhibit paraoxonase. The present study examined the hypothesis that smoking is associated with modulated serum activities and concentrations of paraoxonase. Methods and Results - Coronary artery disease was assessed with the use of coronary arteriography in participants recruited from a hospital cardiology division. Medical and lifestyle data were obtained, and a fasting blood sample was provided. Three smoking categories were established (never, ex-smokers, and current smokers), and serum paraoxonase variables were compared among them. The activities and concentrations of paraoxonase were significantly lower in current than in never smokers. Ex-smokers had values comparable to those of never smokers. Ex-smokers who had recently stopped (<3 months) had activities and concentrations comparable to those of current smokers; values returned to the levels of never smokers within 2 years of cessation of smoking. Smoking status was an independent determinant of paraoxonase activity and concentration in multivariate analysis. Finally, lower paraoxonase was associated with more severe coronary disease and a reduced capacity to protect LDL from oxidation. Conclusions - Smoking is independently associated with significant decreases in serum paraoxonase activities and concentrations, which normalize within a relatively short time of cessation. Lower serum paraoxonase is linked to more severe coronary artery disease and a lower antioxidant capacity. The data are consistent with the hypothesis that smoking modifies serum paraoxonase such that there is an increased risk of coronary artery disease due to a diminished capacity to protect lipoproteins from oxidative stress.