title: The effects of low-dose simvastatin and ezetimibe compared to high-dose simvastatin alone on post-fat load endothelial function in patients with metabolic syndrome: a randomized double-blind crossover trial.
abstract: OBJECTIVE
  Insulin resistance is associated with postprandial hyperlipidemia and endothelial dysfunction. Patients with metabolic syndrome, characterized by insulin resistance, are at increased cardiovascular risk. The aim of the present study was to investigate whether a similar low-density lipoprotein cholesterol (LDL-c) reduction with combination therapy of low-dose simvastatin and ezetimibe or with high-dose simvastatin alone has similar effects on (post-fat load) endothelial function.
  
  
  METHODS
  Randomized, double blind, crossover trial in 19 male obese patients with metabolic syndrome with high-dose simvastatin 80 mg versus combination therapy of low-dose simvastatin 10 mg with ezetimibe 10 mg. Fasting and post-fat load lipids and endothelial function (brachial artery flow-mediated dilation) were determined.
  
  
  RESULTS
  Fasting LDL-c concentrations (2.1 +/- 0.5 mmol/L) and fasting endothelial function (6.9 +/- 0.8 vs. 7.6 +/- 1.2%) were the same after both treatments. Although post-fat load plasma triglycerides concentrations were higher (3.2 +/- 0.4 vs. 2.6 +/- 0.2 mmol x h/L) with combination therapy compared to monotherapy, ApoB particles were comparable (0.9 +/- 3.3 vs. -0.2 +/- 2.3 g x h/L). Combination therapy did not decrease post-fat load endothelial function (7.6 +/- 1.2 vs. 7.7 +/- 1.6%), contrary to high-dose simvastatin monotherapy (6.9 +/- 0.8 vs. 4.3 +/- 0.6%).
  
  
  CONCLUSIONS
  Combination therapy with low-dose simvastatin and ezetimibe preserved post-fat load endothelial function, contrary to treatment with high-dose simvastatin monotherapy in male metabolic syndrome patients. There were no differences in fasting lipid profiles and endothelial function.
authors.affiliation: Department of Vascular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Jobien K
authors.initials: JK
authors.lastname: Olijhoek
authors.forename: Gideon R
authors.initials: GR
authors.lastname: Hajer
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004041:Dietary Fats; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects; D000069438:Ezetimibe; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D019518:Postprandial Period; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D004041:Dietary Fats; D014280:Triglycerides; D019821:Simvastatin; D000069438:Ezetimibe