title: Simvastatin improves flow-mediated dilation but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients.
abstract: 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.
authors.affiliation: Divison of Cardiology, Gil Medical Center, Gachon University, Incheon, Korea. kwangk@gilhospital.com
authors.forename: Kwang Kon
authors.initials: KK
authors.lastname: Koh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Quon
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Han
authors.forename: Yonghee
authors.initials: Y
authors.lastname: Lee
authors.forename: Jeong Yeal
authors.initials: JY
authors.lastname: Ahn
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yesl
authors.initials: Y
authors.lastname: Koh
authors.forename: Eak Kyun
authors.initials: EK
authors.lastname: Shin
mesh_terms: 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*
chemical_list: D052242:Adiponectin; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D002097:C-Reactive Protein; D019821:Simvastatin