Effects of low-dose simvastatin on the distribution of plasma cholesterol and oxidized low-density lipoprotein in three ultracentrifugally separated low-density lipoprotein subfractions: 12-month,open-label trial

Aim: the effects of statins on the distribution of oxidized ldl in plasma ldl subfractions have not been well defined. effects of 12-month treatment with low-dose simvastatin on the distribution of cholesterol and oxidized ldl in 3 ultracentrifugally separated plasma ldl subfractions were compared in patients with hypercholesterolemia. methods: simvastain was administered to 30 hypercholesterolemic subjects for 12 months at an initial dose of 5 mg/day,which was increased to 20 mg/day via 10mg/day to decrease plasma ldl- cholesterol (c) lower than 130 mg/dl. simvastatin dose was fixed after 3 months of treatment. the amounts of cholesterol and oxidized ldl in 3 ultracentrifugally separated plasma ldl subfractions were compared between 0 and 12 months of treatment. results: the distribution of ox-ldl skewed to denser ldl fractions,compared with cholesterol in plasma ldl subfractions. plasma cholesterol in low-density ldl,medium-density ldl and highdensity ldl decreased significantly by 31%,30%,and 25%,respectively (p<0.0001) after 12 months of simvastatin treatment. plasma oxidized ldl was decreased from 70 u/l to 56 u/l in medium-density ldl (p = 0.042). oxidized ldl in low-density ldl and high-density ldl did not change significantly after 12 months of treatment. conclusion: treatment with low-dose simvastatin decreased plasma cholesterol in 3 ldl subfractions and oxidized ldl in medium-density ldl. the decrease of oxidized ldl seemed to be not due to the decrease of cholesterol in plasma ldl subfractions because the decreasing patterns of cholesterol and ox-ldl were different in 3 ldl subfractions.