EFFECTS OF FLUVASTATIN THERAPY ON LIPIDS, ANTIOXIDANTS, OXIDATION OF LOW-DENSITY LIPOPROTEINS AND TRACE-METALS

Objective: Oxidation of low density lipoproteins (LDL) is thought to b e an important step in the development of atherosclerosis. Trace metal s are involved in oxidative processes. It was of interest to determine whether lipid-lowering therapy with fluvastatin, a potent HMGCoA redu ctase inhibitor, affected LDL oxidation and trace metal levels. Method s: Twenty hypercholesterolemic patients were treated with fluvastatin (40 mg twice daily) or placebo for 8 weeks in a double-blind, randomiz ed study. LDL composition, antioxidants and oxidizability as well as p lasma zinc, copper, selenium and manganese concentrations were investi gated. Results: After fluvastatin treatment, total cholesterol was red uced by 24%, triglycerides fell by 26% and plasma Zn fell by 8%. Cu, S e and Mn changed insignificantly. LDL were separated by ultracentrifug ation. LDL were reduced by 18%, LDL-C by 29% and LDL-TG by 19%. The co ncentrations of alpha-tocopherol and retinol in LDL changed insignific antly. LDL preparations were incubated with copper ions (204 mu mol . l(-1) LDL-C/3.2 mu mol . l(-1) Cu) and formation of conjugated dienes was monitored at 234 nm for 5 h. Treatment with fluvastatin caused a r eduction of diene production by 16% and of diene production rate by 14 %, effects being significantly different from placebo (P=0.02). The ch ange of the lagtime did not reach significance; however, it was positi vely correlated with the change in LDL alpha-tocopherol. In the placeb o group, no significant effects were observed. Conclusion: Fluvastatin therapy had lipid-lowering and antioxidative effects.