title: Vascular and metabolic effects of ezetimibe combined with simvastatin in patients with hypercholesterolemia.
abstract: BACKGROUND
  Ezetimibe demonstrates decreasing visceral fat and improving insulin sensitivity (IS) in animals and humans. We first reported that simvastatin dose-dependently worsens insulin sensitivity. Whether ezetimibe may compensate untoward effects of simvastatin, depending on dosages of simvastatin has not been investigated in patients with hypercholesterolemia, compared with simvastatin alone.
  
  
  METHODS
  This was a randomized, single-blind, placebo-controlled, parallel study. Fifty-one in each group were given placebo, ezetimibe 10mg combined with simvastatin 10mg (Vyto10), ezetimibe 10mg combined with simvastatin 20mg (Vyto20), or simvastatin 20mg alone (Simva20) daily for 2months.
  
  
  RESULTS
  Placebo, Vyto10, Vyto20, and Simva20 improved flow-mediated dilation relative to baseline measurements. Placebo therapy did not significantly change insulin and IS and adiponectin levels and visceral fat area (VFA) and VFA/subcutaneous fat area (SFA) relative to baseline measurements. Vyto10 therapy significantly decreased CRP and insulin levels and increased adiponectin levels and IS, and reduced VFA, VFA/SFA, and blood pressure. Vyto20 therapy did not significantly change insulin levels and IS and adiponectin levels but significantly reduced CRP levels and VFA, VFA/SFA, and blood pressure. Simva20 therapy significantly decreased adiponectin levels and IS but did not significantly change VFA, VFA/SFA, and blood pressure. Of note, these different effects of each therapy were significant by ANOVA.
  
  
  CONCLUSIONS
  Vyto10, Vyto20, and Simva20 showed significant reduction of LDL cholesterol levels and improvement of flow-mediated dilation in patients with hypercholesterolemia. However, Vyto10, Vyto20, and Simva20 showed significantly differential metabolic effects, depending on dosages of simvastatin.
authors.affiliation: Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea. Electronic address: kwangk@gilhospital.com.
authors.forename: Kwang Kon
authors.initials: KK
authors.lastname: Koh
authors.affiliation: Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea.
authors.forename: Pyung Chun
authors.initials: PC
authors.lastname: Oh
authors.affiliation: Cardiovascular Medicine, Hokko Memorial Clinic, Sapporo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.affiliation: Radiology, Gachon University Gil Medical Center, Incheon, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Department of Statistics, University of Seoul, Seoul, Republic of Korea.
authors.forename: Yonghee
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Geriatric Department, Nagoya University, Nagoya, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Han
authors.affiliation: Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea.
authors.forename: Yae Min
authors.initials: YM
authors.lastname: Park
authors.affiliation: Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Incheon, Republic of Korea.
authors.forename: Eak Kyun
authors.initials: EK
authors.lastname: Shin
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000368:Aged; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000187:drug effects; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000008:administration & dosage / Q000494:pharmacology*; D005216:Fat Body / Q000187:drug effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy; D006973:Hypertension / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D016037:Single-Blind Method
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007328:Insulin; D002097:C-Reactive Protein; D019821:Simvastatin; D000069438:Ezetimibe
keywords: Ezetimibe; Fat; Hypercholesterolemia hypertension; Insulin resistance; Statins