title: Lipid-lowering therapy with fluvastatin inhibits oxidative modification of low density lipoprotein and improves vascular endothelial function in hypercholesterolemic patients.
abstract: This prospective randomized trial was designed to elucidate clinically the effect of fluvastatin on inhibiting oxidation of the low density lipoprotein (LDL) and improving the vascular endothelial function as well as its lipid-lowering effects, in comparison with pravastatin. Of 64 consecutive dyslipidemic patients, 40 patients, whose level of total cholesterol or LDL-cholesterol maintained the criteria of the hypercholesterolemia in spite of 12-week dietary therapy, were randomly assigned to receive either fluvastatin (n=20) or pravastatin (n=20). We assessed the titer of antibody against oxidized LDL (anti-Ox-LDL) as a biomarker for LDL-oxidation, and the forearm blood flow response during reactive hyperemia by venous occlusion plethysmography, which indicates the endothelium-dependent vasodilator capacity. After the 16-week lipid-lowering therapy, the anti-Ox-LDL titer significantly decreased in the fluvastatin group (P<0.01) but did not change in the pravastatin group. The percent increase in the forearm blood flow at the peak reactive hyperemia from the baseline value (%RH) significantly increased in the fluvastatin group (P<0.001) but did not change in the pravastatin group. The ratio of the %RH after the therapy over the baseline value negatively correlated with that of the anti-Ox-LDL titer (R=0.73, P<0.001) in all patients. Fluvastatin may serve as an ideal drug for reducing the risk of atherosclerosis, not only by its cholesterol-lowering effect but also by its unique effects of inhibiting LDL oxidation and improving the vascular endothelial function.
authors.affiliation: Department of Cardiology, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50 Minamikoshigaya, Koshigaya City, Saitama 343-8555, Japan. inouet@dokkyomed.ac.jp
authors.forename: Teruo
authors.initials: T
authors.lastname: Inoue
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hayashi
authors.forename: Kan
authors.initials: K
authors.lastname: Takayanagi
authors.forename: Shigenori
authors.initials: S
authors.lastname: Morooka
mesh_terms: D004730:Endothelium, Vascular / Q000503:physiopathology*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D005542:Forearm / Q000098:blood supply; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007211:Indoles / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D017035:Pravastatin / Q000494:pharmacology; D011446:Prospective Studies; D014664:Vasodilation / Q000502:physiology*
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D000077340:Fluvastatin; D017035:Pravastatin