Amirhossein Sahebkar1, Kazuhiko Kotani2, Corina Serban3, Sorin Ursoniu4, Dimitri P Mikhailidis5, Steven R Jones6, Kausik K Ray7, Michael J Blaha6, Jacek Rysz7, Peter P Toth8, Paul Muntner9, Gregory Y H Lip10, Maciej Banach11. 1. 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. 2. Department of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Japan. 3. Department of Functional Sciences, Discipline of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. 4. Department of Functional Sciences, Discipline of Public Health, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. 5. Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK. 6. The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA. 7. 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. 8. The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, IL, USA. 9. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. 10. University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK. 11. Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland. Electronic address: maciejbanach@aol.co.uk.
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.
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: Camillo L C Junqueira; Maria Eliane C Magalhães; Andréa Araújo Brandão; Esmeralci Ferreira; Adriana S M Junqueira; José Firmino N Neto; Maria das Graças C Souza; Daniel Alexandre Bottino; Eliete Bouskela Journal: J Hum Hypertens Date: 2018-01-15 Impact factor: 3.012