Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials.

Academic Article


  • 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. METHODS AND 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

    Published In

  • Atherosclerosis  Journal
  • Keywords

  • Endothelial dysfunction, Endothelin-1, Lipophilicity, Statins, Therapy, Adult, Aged, Biomarkers, Chi-Square Distribution, Dyslipidemias, Endothelin-1, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Male, Middle Aged, Odds Ratio, Randomized Controlled Trials as Topic, Treatment Outcome
  • Digital Object Identifier (doi)

    Author List

  • Sahebkar A; Kotani K; Serban C; Ursoniu S; Mikhailidis DP; Jones SR; Ray KK; Blaha MJ; Rysz J; Toth PP
  • Start Page

  • 433
  • End Page

  • 442
  • Volume

  • 241
  • Issue

  • 2