Introduction: Tobacco smoking is the leading atherosclerosis risk factor and substantially influences its pathophysiology.
Objectives: The aim of this study was to assess the impact of tobacco smoking on paraoxonase-1 (PON1) activity and the relationship with pleiotropic effects of simvastatin therapy and PON1 gene polymorphisms.
Patients and methods: 53 patients with stable coronary artery disease (CAD) and hypercholesterolemia were enrolled in the patients group (35 smokers) and 53 healthy controls (27 smokers). Individuals in the patients group were treated with simvastatin (40 mg) for 12 months. Markers of oxidative stress, inflammation, endothelial function and PON1 activity at baseline, after 6 and 12 months were evaluated in the patients group.
Results: The baseline mean levels of serum high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNFα), plasma fibrinogen, urine 8-iso-prostaglandin F₂α (8-iso- PGF₂α), PON1 activity, flow-mediated dilation (FMD) and intima-media thickness (IMT) value did not significantly correlated with smoking habit in the patients and controls group. The significant decrease of hs-CRP (p = 0.017) and TNFα (p = 0.003) concentration after simvastatin was found in smokers, and 8-iso-PGF₂α in smokers and 192QQ allele carriers (p = 0.038). Whereas the FMD significantly improved only in the subgroup of non-smokers (p = 0.019) and 192QQ allele carriers (p = 0.049).
Conclusions: Smoking significantly modified pleiotropic effects of simvastatin on proinflammatory markers and endothelial function. No effect of simvastatin therapy and no correlation of smoking habit with PON1 activity could be affected by the distribution of PON1 polymorphism, concomitant diseases and their treatment, as well as relatively stable level of oxidative stress markers during the observational period.