title: Effects of atorvastatin on oxidized low-density lipoprotein, low-density lipoprotein subfraction distribution, and remnant lipoprotein in patients with mixed hyperlipoproteinemia.
abstract: Atorvastatin (10 to 20 mg/day) was administered for 3 months to 15 outpatients (average age 58 +/- 4 years) with hypercholesterolemia accompanied by hypertriglyceridemia without hypolipemic treatment. Changes in lipid profile, particularly oxidized low-density lipoprotein (LDL) (malondialdehyde LDL), subfractions of LDL, and remnant lipoprotein (RLP) cholesterol, were examined before and after administration. In addition, the influence of atorvastatin on lipoprotein(a) (known to be an independent risk factor for atherosclerosis), asymmetric dimethylarginine (known to be an endogenous inhibitor of nitric oxide synthase), and homocysteine (methionine metabolite) was also investigated. Administration of atorvastatin significantly decreased serum total cholesterol, LDL cholesterol, and triglycerides. Conversely, a significant increase in high-density lipoprotein cholesterol was shown. In LDL subfractions, large, buoyant LDL fractions were not influenced by treatment with atorvastatin (before administration, 99 +/- 14 mg/dl; after administration, 91 +/- 6 mg/dl, shown as a cholesterol content in each subfraction), but a marked decrease in small, dense LDL fractions (p <0.001) (before administration, 119 +/- 17 mg/dl; after administration, 43 +/- 10 mg/dl) was shown. Moreover, oxidized LDL was significantly decreased (p < 0.01) (before administration, 169 +/- 13 U/L; after administration, 119 +/- 10 U/L) and RLP cholesterol also was significantly decreased (p <0.01) (before administration, 11.9 +/- 2.0 mg/dl; after administration, 6.0 +/- 0.9 mg/dl) with atorvastatin treatment. No significant change was observed in fasting plasma glucose, hemoglobin A1c, lipoprotein(a), asymmetric dimethylarginine, homocysteine, and so on. These data suggest that administration of relatively low doses of atorvastatin to patients with hypercholesterolemia accompanied with hypertriglyceridemia results in a decrease not only in LDL cholesterol and triglycerides, but also in oxidized LDL and RLP cholesterol, with an increase in high-density lipoprotein cholesterol. Furthermore, small, dense LDL decreased with a shift in LDL subfractions to large, buoyant fractions, and these changes are considered to be involved in the inhibition of the onset and progression of atherosclerosis.
authors.affiliation: Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. sasaki@koto.kpu-m.ac.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Sasaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Kuwahara
authors.forename: Keiko
authors.initials: K
authors.lastname: Kunitomo
authors.forename: Sanae
authors.initials: S
authors.lastname: Harada
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Azuma
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takeda
authors.forename: Masao
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood*; D004591:Electrophoresis, Polyacrylamide Gel; D006538:Heptanoic Acids / Q000494:pharmacology*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood*; D017270:Lipoprotein(a) / Q000097:blood; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D017270:Lipoprotein(a); D011758:Pyrroles; D014280:Triglycerides; D006710:Homocysteine; D000069059:Atorvastatin