W. Leonhardt et al., EFFECTS OF FLUVASTATIN THERAPY ON LIPIDS, ANTIOXIDANTS, OXIDATION OF LOW-DENSITY LIPOPROTEINS AND TRACE-METALS, European Journal of Clinical Pharmacology, 53(1), 1997, pp. 65-69
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.