Paraoxonase-1 activity and pleiotropic properties of simvastatin in obese and non-obese patients with stable coronary artery disease (CAD).

OBJECTIVES The study was aimed to assess paraoxonase-1 (PON1) activity, pleiotropic effects of simvastatin, and its relationship to Q192R and M55L polymorphisms in obese and non-obese subjects with stable coronary artery disease (CAD). PATIENTS AND METHODS The study included 53 subjects (22 obese) aged from 35 to 65 years with CAD. The control group consisted of 53 (18 obese) police officers without CAD. Patients with CAD were treated with simvastatin 40 mg/day for 12 months. The lipid profile, flow mediated dilation (FMD), intima media-thickness (IMT), fibrinogen, hs-CRP, TNF-α, urine 8-iso-PGF2α, and PON1 activity were evaluated in definite time points. PON1 polymorphisms were assessed at baseline in all observed individuals. RESULTS The patients with CAD and obesity presented at baseline significantly increased hs-CRP level, insignificantly decreased FMD and lower PON1 activity compared to non-obese individuals. There was no association of obesity with 8-iso-PGF2α in the CAD and control group. The PON1 activity was significantly higher in 192R carriers in patients and controls, irrespective of obesity. Obesity was not associated with the effects of simvastatin on PON1 activity, urine 8-iso-PGF2α, and TNF-α, whereas it blunted its effect on the FMD improvement. The Q192R polymorphism was associated with simvastatin effectiveness on hs-CRP and FMD. CONCLUSION Obesity and Q192R PON1 polymorphism are significantly associated with pleiotropic effects of simvastatin therapy in patients with stable CAD.