Effects of low-dose simvastatin on the distribution of plasma cholesterol and oxidized low-density lipoprotein in three ultra-centrifugally separated low-density lipoprotein subfractions: 12- month, open-label trial.
OBJECTIVE
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
Simvastatin 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 high-density 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.


CONCLUSIONS
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.
Homma
Yasuhiko
Y
Health Evaluation and Promotion Center, Tokai University Hospital, 143 Shimokasuya, Isehara, Japan. homma@is.icc.u-tokai.ac.jp
Michishita
Ichiro
I
Hayashi
Hiroshi
H
Shigematsu
Hiroshi
H
D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D008077:Lipoproteins, LDL / Q000097:blood*; D019821:Simvastatin / Q000008:administration & dosage*; D013997:Time Factors; D014461:Ultracentrifugation
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D019821:Simvastatin