title: Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe.
abstract: BACKGROUND
  The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect.
  
  
  OBJECTIVE
  To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered.
  
  
  METHODS
  Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment.
  
  
  RESULTS
  The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function.
  
  
  CONCLUSIONS
  The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.
authors.affiliation: Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.
authors.forename: Maristela Magnavita Oliveira
authors.initials: MM
authors.lastname: Garcia
authors.affiliation: Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.
authors.forename: Carolina Garcez
authors.initials: CG
authors.lastname: Varela
authors.affiliation: Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.
authors.forename: Patricia Fontes
authors.initials: PF
authors.lastname: Silva
authors.affiliation: Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.
authors.forename: Paulo Roberto Passos
authors.initials: PR
authors.lastname: Lima
authors.affiliation: Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.
authors.forename: Paulo Meira
authors.initials: PM
authors.lastname: Góes
authors.affiliation: Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.
authors.forename: Marilia Galeffi
authors.initials: MG
authors.lastname: Rodrigues
authors.affiliation: Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.
authors.forename: Maria de Lourdes Lima Souza E
authors.initials: Mde L
authors.lastname: Silva
authors.affiliation: Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.
authors.forename: Ana Marice Teixeira
authors.initials: AM
authors.lastname: Ladeia
authors.affiliation: Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.
authors.forename: Armênio Costa
authors.initials: AC
authors.lastname: Guimarães
authors.affiliation: Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.
authors.forename: Luis Claudio Lemos
authors.initials: LC
authors.lastname: Correia
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D000069438:Ezetimibe / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D008875:Middle Aged; D015990:Placebo Effect; D012016:Reference Values; D019821:Simvastatin / Q000008:administration & dosage*; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000069438:Ezetimibe