title: A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations.
abstract: The impact of statin therapy on plasma asymmetric dimethylarginine (ADMA) levels has not been conclusively studied. Therefore the aim of the meta-analysis was to assess the effect of statins on circulating ADMA levels. We searched selected databases (up to August 2014) to identify randomized controlled trials (RCTs) that investigate the effect of statins on plasma ADMA concentrations. A weighted meta-regression (WMD) using unrestricted maximum likelihood model was performed to assess the impact of statin dose, duration of statin therapy and baseline ADMA concentrations as potential variables on the WMD between statin and placebo group. In total, 1134 participants in 9 selected RCTs were randomized; 568 were allocated to statin treatment and 566 were controls. There was a significant reduction in plasma ADMA concentrations following statin therapy compared with placebo (WMD: -0.104 μM, 95% confidence interval: -0.131 to -0.077, Z = -7.577, p < 0.0001). Subgroups analysis has shown a significant impact of hydrophilic statins (WMD: -0.207 μM, 95%CI: -0.427 to +0.013, Z = -7.250, p < .0001) and a non-significant effect of hydrophobic statins (WMD: -0.101 μM, 95%CI: -0.128 to -0.074, Z = -1.845, p = 0.065). In conclusion, this meta-analysis of available RCTs showed a significant reduction in plasma ADMA concentrations following therapy with hydrophilic statins.
authors.affiliation: Department of Functional Sciences, Discipline of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Corina
authors.identifier: 0000000333520398
authors.initials: C
authors.lastname: Serban
authors.affiliation: 1] Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran [2] 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 Functional Sciences, Chair 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: Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Italy.
authors.forename: Manfredi
authors.initials: M
authors.lastname: Rizzo
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 Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Kees Hovingh
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: Department of Medical Laboratory Diagnostics, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kalinowski
authors.affiliation: Department of Nephrology, Hypertension and Family Medicine, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Rysz
authors.affiliation: Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Banach
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine