title: Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials.
abstract: OBJECTIVE
  Raised plasma endothelin-1 (ET-1) levels may be a risk factor for vascular dysfunction and cardiovascular (CV) disease. This meta-analysis assessed the effect of statins on circulating ET-1 concentrations.
  
  
  RESULTS
  The search included PUBMED, Cochrane Library, Web of Science, Scopus, and EMBASE up to September 30, 2014 to identify randomized controlled trials (RCTs) with ET-1 measurement during statin therapy. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Data from 15 RCTs showed that statin therapy significantly reduces plasma ET-1 concentrations (WMD: -0.30 pg/mL, 95%CI: -0.47, -0.13; p < 0.01). This effect was robust in sensitivity analysis, and not largely affected by the duration of statin therapy (<12 weeks - WMD: -0.51 pg/mL, 95%CI: -0.89, -0.14, p < 0.01; >12 week -WMD: -0.19 pg/mL, 95%CI: -0.36, -0.02; p < 0.05) or by dose of statins (<40 mg/day - WMD: -0.27 pg/mL, 95%CI: -0.49, -0.05; p = 0.01; >40 mg/day - WMD: -0.38 pg/mL, 95%CI: -0.68, -0.08; p = 0.01). Lipophilic (atorvastatin, simvastatin, fluvastatin, and cerivastatin - WMD: -0.34 pg/mL, 95%CI: -0.55, -0.13; p < 0.01), but not a hydrophilic statin (pravastatin - WMD: -0.18 pg/mL, 95%CI: -0.44 -0.08; p > 0.05) had a significant effect in promoting ET-1 reduction.
  
  
  CONCLUSIONS
  Statin therapy significantly reduces circulating ET-1 concentrations, regardless of treatment duration or dose of statins. This effect of statins may be influenced by statin lipophilicity. There is a need to establish whether lowering ET-1 levels has a beneficial effect on CV events.
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.affiliation: Department of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kotani
authors.affiliation: Department of Functional Sciences, Discipline of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Corina
authors.initials: C
authors.lastname: Serban
authors.affiliation: Department of Functional Sciences, Discipline of Public Health, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Sorin
authors.initials: S
authors.lastname: Ursoniu
authors.affiliation: Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK.
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
authors.affiliation: The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Jones
authors.affiliation: Cardiovascular Sciences Research Centre, St George's University of London, Cranmer Terrace, London, UK; Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Poland.
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.affiliation: The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.affiliation: Cardiovascular Sciences Research Centre, St George's University of London, Cranmer Terrace, London, UK; Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Rysz
authors.affiliation: The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, IL, USA.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Toth
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Muntner
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland. Electronic address: maciejbanach@aol.co.uk.
authors.forename: Maciej
authors.initials: M
authors.lastname: Banach
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids
keywords: Endothelial dysfunction; Endothelin-1; Lipophilicity; Statins; Therapy