Simvastatin improves flow-mediated dilation but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients.
OBJECTIVE
We hypothesized that simvastatin may reduce adiponectin levels and insulin sensitivity in hypercholesterolemic patients.


METHODS
This was a randomized, double-blind, placebo-controlled, parallel study. Age, sex, and BMI were matched. Thirty-two patients were given placebo, and 30, 32, 31, and 31 patients were given daily 10, 20, 40, and 80 mg simvastatin, respectively, during a 2-month treatment period.


RESULTS
Simvastatin doses of 10, 20, 40, and 80 mg significantly reduced total cholesterol (mean changes 27, 25, 37, and 38%), LDL cholesterol (39, 38, 52, and 54%), and apolipoprotein B levels (24, 30, 36, and 42%) and improved flow-mediated dilation (FMD) (68, 40, 49, and 63%) after 2 months of therapy compared with baseline (P < 0.001 by paired t test) or compared with placebo (P < 0.001 by ANOVA). Simvastatin doses of 10, 20, 40, and 80 mg significantly decreased plasma adiponectin levels (4, 12, 5, and 10%) and insulin sensitivity (determined by the Quantitative Insulin-Sensitivity Check Index [QUICKI]) (5, 8, 6, and 6%) compared with baseline (P < 0.05 by paired t test) or compared with placebo (P = 0.011 for adiponectin and P = 0.034 for QUICKI by ANOVA). However, the magnitudes of these percent changes (FMD, adiponectin, and QUICKI) were not significantly different among four different doses of simvastatin despite dose-dependent changes in the reduction of apolipoprotein B levels.


CONCLUSIONS
Simvastatin significantly improved endothelium-dependent dilation, but reduced adiponectin levels and insulin sensitivity in hypercholesterolemic patients independent of dose and the extent of apolipoprotein B reduction.
Koh
Kwang Kon
KK
Divison of Cardiology, Gil Medical Center, Gachon University, Incheon, Korea. kwangk@gilhospital.com
Quon
Michael J
MJ
Han
Seung Hwan
SH
Lee
Yonghee
Y
Ahn
Jeong Yeal
JY
Kim
Soo Jin
SJ
Koh
Yesl
Y
Shin
Eak Kyun
EK
D052242:Adiponectin / Q000097:blood*; D001055:Apolipoproteins B / Q000097:blood / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007333:Insulin Resistance; D008297:Male; D010919:Placebos; D019821:Simvastatin / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects*
D052242:Adiponectin; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D002097:C-Reactive Protein; D019821:Simvastatin