title: Response to statin therapy in obstructive sleep apnea syndrome: a multicenter randomized controlled trial.
abstract: BACKGROUND
  Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA). Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA.
  
  
  METHODS
  This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint) measured by peripheral arterial tone (PAT). Secondary endpoints included office blood pressure (BP), early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV), and metabolic parameters.
  
  
  RESULTS
  51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m(2). In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (-0.29; 0.28), P = 0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: -6.34 mmHg (-12.68; -0.01), P = 0.050) whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group.
  
  
  CONCLUSIONS
  In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695.
authors.affiliation: University Grenoble Alpes, HP2, Inserm U1042, Grenoble, France ; CHU de Grenoble, Laboratoire EFCR, Clinique Universitaire de Physiologie, Grenoble, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Joyeux-Faure
authors.affiliation: University Grenoble Alpes, HP2, Inserm U1042, Grenoble, France ; CHU de Grenoble, Laboratoire EFCR, Clinique Universitaire de Physiologie, Grenoble, France ; Laboratoire EFCR, Pôle Thorax et Vaisseaux, CHU de GRENOBLE CS 10217, 38043 Grenoble, France.
authors.forename: Renaud
authors.identifier: 0000-0003-1128-6529
authors.initials: R
authors.lastname: Tamisier
authors.affiliation: CHU de Grenoble, Clinique de Cardiologie, Grenoble, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Baguet
authors.affiliation: University Grenoble Alpes, HP2, Inserm U1042, Grenoble, France ; CHU de Grenoble, Laboratoire EFCR, Clinique Universitaire de Physiologie, Grenoble, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Dias-Domingos
authors.affiliation: Laboratoire du Sommeil, Service de Neuropsychiatrie, Hôpital Belle Idée, Genève, Switzerland.
authors.forename: Stephen
authors.identifier: 0000-0002-1891-3911
authors.initials: S
authors.lastname: Perrig
authors.affiliation: Laboratoire d'explorations Fonctionnelles Vasculaires, CHU d'Angers, Angers, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Leftheriotis
authors.affiliation: Service de Pneumologie, Hôpital Universitaire de Genève, Genève, Switzerland.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Janssens
authors.affiliation: CHU d'Angers, Département de Pneumologie, Angers, France ; Université d'Angers, Inserm 1063 "SOPAM", Angers, France.
authors.forename: Wojciech
authors.identifier: 0000-0003-0426-3273
authors.initials: W
authors.lastname: Trzepizur
authors.affiliation: University Grenoble Alpes, HP2, Inserm U1042, Grenoble, France ; CHU de Grenoble, Laboratoire EFCR, Clinique Universitaire de Physiologie, Grenoble, France.
authors.forename: Sandrine H
authors.initials: SH
authors.lastname: Launois
authors.affiliation: University Grenoble Alpes, HP2, Inserm U1042, Grenoble, France ; CHU de Grenoble, Département de Biochimie, Toxicologie et Pharmacologie, Grenoble, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Stanke-Labesque
authors.affiliation: University Grenoble Alpes, HP2, Inserm U1042, Grenoble, France ; CHU de Grenoble, Laboratoire EFCR, Clinique Universitaire de Physiologie, Grenoble, France.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Lévy
authors.affiliation: CHU d'Angers, Département de Pneumologie, Angers, France ; Université d'Angers, Inserm 1063 "SOPAM", Angers, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gagnadoux
authors.affiliation: University Grenoble Alpes, HP2, Inserm U1042, Grenoble, France ; CHU de Grenoble, Laboratoire EFCR, Clinique Universitaire de Physiologie, Grenoble, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pepin
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000188:drug therapy; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D008078:Cholesterol, LDL / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin