The effects of lipid-lowering therapy on paraoxonase activities and their relationship with the oxidant-antioxidant system in patients with dyslipidemia

Background: Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is used for lipid-lowering therapy, is an effective statin modulating process involved in atherosclerosis. Paraoxonase (PON) associated with high-density lipoprotein (HDL) has been postulated to have a role in protecting low-density lipoprotein (LDL) against oxidative modification. Oxidation of serum LDL is an important early step in the development of atherosclerosis and auto-antibodies against oxidized LDL (AuAb-oxLDL) reflect in-vivo LDL oxidation. Design and methods: To examine the effect of atorvastatin (10 mg/day) therapy on PON activity in serum and HDL, the study group included 40 patients with dyslipidemia (19 women and 21 men), 25 of whom had hypercholesterolemia and of 15 of whom had mixed-type hyperlipidemia. By taking blood samples from the patients, levels of serum lipids, lipid peroxidation product as malondialdehyde (MDA), total antioxidant status (TAS) and AuAb-oxLDL and the activities of PON in serum and isolated HDL were determined. Results: The mean levels of total cholesterol, triglyceride, LDL-cholesterol, MDA and AuAb-oxLDL were decreased while HDL-cholesterol and TAS were increased significantly after lipid-lowering therapy in patients with dyslipidemia. On the other hand, PON activities in serum and HDL were increased significantly. The percentage increase in serum PON activity was associated significantly with the percentage decrease in serum AuAb-oxLDL (r = -0.32, P = 0.047) and that of HDL PON activity was associated with the percentage increase in HDL-cholesterol level after atorvastatin therapy (r = 0.52, P = 0.001). The therapy was more effective in increasing PON activity in patients with HDL levels above 35 mg/dl. Conclusion: It was concluded that atorvastatin therapy in dyslipidemic patients decreases the level of oxidative stress and increases PON activity, especially in patients with HDL levels above 35 mg/dl. © 2004 Lippincott Williams & Wilkins.