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

Background-Paraoxonase is an HDL-associated enzyme that protects lipoprotei ns from oxidative modifications. Smoking is a major cardiovascular risk fac tor that promotes lipid peroxidation. Cigarette smoke has been shown in vit ro to inhibit paraoxonase. The present study examined the hypothesis that s moking is associated with modulated serum activities and concentrations of paraoxonase. Methods and Results-Coronary artery disease was assessed with the use of co ronary arteriography in participants recruited from a hospital cardiology d ivision. Medical and lifestyle data were obtained, and a fasting blood samp le was provided. Three smoking categories were established (never, ex-smoke rs, and current smokers), and serum paraoxonase variables were compared amo ng them. The activities and concentrations of paraoxonase were significantl y 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; v alues returned to the levels of never smokers within 2 years of cessation o f smoking. Smoking status was an independent determinant of paraoxonase act ivity and concentration in multivariate analysis. Finally, lower paraoxonas e was associated with more severe coronary disease and a reduced capacity t o 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 d ata are consistent with the hypothesis that smoking modifies serum paraoxon ase such that there is an increased risk of coronary artery disease due to a diminished capacity to protect lipoproteins from oxidative stress.