Beneficial effect of simvastatin treatment on LDL oxidation and antioxidant protection is more pronounced in combined hyperlipidemia than in hypercholesterolemia.

Aims: Beneficial effects of statin treatment on cardiovascular morbidity and mortality has been not entirely explained by the reduction in LDL-cholesterol level. We hypothesised that antioxidant activity of statins may contribute to their salutary cardiovascular effects. The aim of the present study was to examine effect of simvastatin treatment on some parameters of LDL oxidation and antioxidant protection in patients with hypercholesterolemia and combined hyperlipidemia. Furthermore, we were interested, whether the effect of treatment is related to the type of hyperlipidemia.

Patients And Methods: Fourty-two patients (12 males, 30 females, mean age 60+/-10 years) were included in the present study. Fourteen patients had hypercholesterolemia defined as total cholesterol>5.0 mmol/l. Twenty-eight patients had combined hyperlipidemia defined by total cholesterol>5.0 mmol/l and triglycerides>1.7 mmol/l. Simvastatin was administered to patients during 8-week period in a daily dose of 20mg. Oxidation of LDL was measured by assessment of circulating conjugated diene (CD) and malondialdehyde (MDA) level. Antioxidant properties of blood were assessed based on measurement of total antioxidant status (TAS) and glutathione peroxidase (GPx) activity.

Results: Besides expected significant decrease in total cholesterol, LDL-cholesterol, apolipoprotein B and triglyceride levels, simvastatin treatment also reduced significantly circulating CD by 41% (p<0.0001) and MDA level non-significantly by 6% (p=0.078). Simvastatin treatment resulted in an increase of GPx activity by 38% (p<0.0001), but did not have a significant effect on TAS. Patients with combined hyperlipidemia had significantly higher baseline CD (p<0.01) and consequently significantly greater absolute and relative decrease (46% versus 23%) in circulating CD (DeltaCD), when compared with patients with hypercholesterolemia. The increase in GPx activity was significant only in patients with combined hyperlipidemia (p<0.0001). In the multiple stepwise linear regression analysis, both baseline triglyceride (r(2)=0.32; p=0.004) and LDL cholesterol (r(2)=0.08; p=0.05) levels were significant independent predictors of DeltaCD after simvastatin treatment.

Conclusion: Simvastatin treatment significantly reduced circulating conjugated diene level and led to an increase in glutathione peroxidase activity. These effects were more pronounced in patients with combined hyperlipidemia than in hypercholesterolemia. The results suggest that simvastatin possesses certain antioxidant properties, which may contribute to its beneficial cardiovascular effect.