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

Amirhossein Sahebkar, Kazuhiko Kotani, Corina Serban, Sorin Ursoniu, Dimitri P. Mikhailidis, Steven R. Jones, Kausik K. Ray, Michael J. Blaha, Jacek Rysz, Peter P. Toth, Paul Muntner, Gregory Y.H. Lip, Maciej Banach

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)433-442
Number of pages10
JournalAtherosclerosis
Volume241
Issue number2
DOIs
StatePublished - Aug 1 2015

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Keywords

  • Endothelial dysfunction
  • Endothelin-1
  • Lipophilicity
  • Statins
  • Therapy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Sahebkar, A., Kotani, K., Serban, C., Ursoniu, S., Mikhailidis, D. P., Jones, S. R., Ray, K. K., Blaha, M. J., Rysz, J., Toth, P. P., Muntner, P., Lip, G. Y. H., & Banach, M. (2015). Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials. Atherosclerosis, 241(2), 433-442. https://doi.org/10.1016/j.atherosclerosis.2015.05.022