Effects of simvastatin on serum paraoxonase activity

Background: High density lipoprotein (HDL)-associated paraoxonase activity may play an important role in the inhibition of low density lipoprotein (LDL) oxidation. Previous studies have demonstrated that serum paraoxonase activity is decreased in patients with hyperlipoproteinaemia and coronary heart disease, and a few investigators have suggested that the lipid-lowering statins may increase paraoxonase levels. Objective: To examine the effect of short-term treatment with simvastatin on lipids and paraoxonase activity in patients with hyperlipoproteinaemia. Design: Prospective nonblind single-group sequential study. Patients: 112 (52 male and 60 female) hyperlipoproteinaemic patients with Fredrickson type IIa and IIb hyperlipoproteinaemia (mean age 52.15 +/- 7.99 years, mean body mass index 27.53 +/- 4.30 kg/m(2)). Methods: Serum cholesterol, lipoproteins, triglycerides, apolipoproteins and liver function were measured, and serum paraoxonase activity was determined spectrophotometrically using paraoxon as substrate. Simvastatin 20 mg/day was administered for 1 month, and measurements were repeated. Results: Simvastatin significantly decreased serum cholesterol [from 10.25 +/- 2.73 (SD) to 8.85 +/- 2.02 mmol/L], triglyceride (from 3.95 +/- 2.51 to 3.15 +/- 1.47 mmol/L), LDL (from 6.36 +/- 1.70 to 4.94 +/- 1.48 mmol/L.) and apolipoprotein B 100 (from 1.93 +/- 0.41 to 1.56 +/- 0.35 g/L) levels, whereas HDL and apo A I levels did not change significantly (from 1.19 +/- 0.34 to 1.22 +/- 0.39 mmol/L, and from 1.56 +/- 1.99 to 1.64 +/- 0.24 g/L, respectively). HDL-associated paraoxonase activity did not change significantly (from 182.25 +/- 37.21 to 166.49 +/- 35.01 U/L) after simvastatin therapy. Conclusion: Short-term administration of simvastatin did not increase the activity of the HDL-associated antioxidant enzyme paraoxonase.