A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations

被引:161
作者
Serban, Corina [1 ]
Sahebkar, Amirhossein [2 ,3 ]
Ursoniu, Sorin [4 ]
Mikhailidis, Dimitri P. [5 ]
Rizzo, Manfredi [6 ]
Lip, Gregory Y. H. [7 ]
Hovingh, G. Kees [8 ]
Kastelein, John J. P. [8 ]
Kalinowski, Leszek [9 ]
Rysz, Jacek [10 ]
Banach, Maciej [11 ]
机构
[1] Victor Babes Univ Med & Pharm, Dept Funct Sci, Discipline Pathophysiol, Timisoara, Romania
[2] Mashhad Univ Med Sci, Biotechnol Res Ctr, Mashhad, Iran
[3] Univ Western Australia, Royal Perth Hosp, Sch Med & Pharmacol, Metabol Res Ctr, Perth, WA 6009, Australia
[4] Victor Babes Univ Med & Pharm, Dept Funct Sci, Chair Publ Hlth, Timisoara, Romania
[5] UCL, Sch Med, Dept Clin Biochem, London W1N 8AA, England
[6] Univ Palermo, Biomed Dept Internal Med & Med Specialties, I-90133 Palermo, Italy
[7] Univ Birmingham, City Hosp, Ctr Cardiovasc Sci, Birmingham, W Midlands, England
[8] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands
[9] Med Univ Gdansk, Dept Med Lab Diagnost, Gdansk, Poland
[10] Med Univ Lodz, Dept Nephrol Hypertens & Family Med, Chair Nephrol & Hypertens, Lodz, Poland
[11] Med Univ Lodz, Dept Hypertens, Chair Chair Nephrol & Hypertens, Lodz, Poland
关键词
ACUTE CORONARY EVENTS; ENDOTHELIAL DYSFUNCTION; SYMMETRIC DIMETHYLARGININE; ATHEROSCLEROTIC DISEASE; CARDIOVASCULAR-DISEASE; CLINICAL-TRIALS; DDAH ACTIVITY; ADMA; RISK; SIMVASTATIN;
D O I
10.1038/srep09902
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 mu M, 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 mu M, 95%CI: -0.427 to + 0.013, Z = -7.250, p < .0001) and a non-significant effect of hydrophobic statins (WMD: -0.101 mu M, 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.
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页数:8
相关论文
共 49 条
[1]   Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus [J].
Anderssohn, Maike ;
Schwedhelm, Edzard ;
Lueneburg, Nicole ;
Vasan, Ramachandran S. ;
Boeger, Rainer H. .
DIABETES & VASCULAR DISEASE RESEARCH, 2010, 7 (02) :105-118
[2]   Role of Asymmetrical Dimethylarginine in Inflammation-Induced Endothelial Dysfunction in Human Atherosclerosis [J].
Antoniades, Charalambos ;
Demosthenous, Michael ;
Tousoulis, Dimitris ;
Antonopoulos, Alexios S. ;
Vlachopoulos, Charalambos ;
Toutouza, Marina ;
Marinou, Kyriakoula ;
Bakogiannis, Constantinos ;
Mavragani, Kleio ;
Lazaros, George ;
Koumallos, Nikolaos ;
Triantafyllou, Costas ;
Lymperiadis, Dimitris ;
Koutsilieris, Michael ;
Stefanadis, Christodoulos .
HYPERTENSION, 2011, 58 (01) :93-U167
[3]   Association of plasma asymmetrical dimethylarginine (ADMA) with elevated vascular superoxide production and endothelial nitric oxide synthase uncoupling: implications for endothelial function in human atherosclerosis [J].
Antoniades, Charalambos ;
Shirodaria, Cheerag ;
Leeson, Paul ;
Antonopoulos, Alexios ;
Warrick, Nicholas ;
Van-Assche, Tim ;
Cunnington, Colin ;
Tousoulis, Dimitris ;
Pillai, Ravi ;
Ratnatunga, Chandi ;
Stefanadis, Christodoulos ;
Channon, Keith M. .
EUROPEAN HEART JOURNAL, 2009, 30 (09) :1142-1150
[4]   Effects of Atorvastatin on Vascular Intimal Hyperplasia: An Experimental Rodent Model [J].
Aydin, Unal ;
Ugurlucan, Murat ;
Gungor, Funda ;
Ziyade, Sedat ;
Inan, Bekir ;
Banach, Maciej ;
Kalko, Yusuf ;
Yasar, Tahsin .
ANGIOLOGY, 2009, 60 (03) :370-377
[5]   The L-arginine paradox:: Importance of the L-arginine/asymmetrical dimethylarginine ratio [J].
Bode-Boeger, Stefanie M. ;
Scalera, Fortunato ;
Ignarro, Louis J. .
PHARMACOLOGY & THERAPEUTICS, 2007, 114 (03) :295-306
[6]  
Böger RH, 2005, ALTERN MED REV, V10, P14
[7]   Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality-An update on patient populations with a wide range of cardiovascular risk [J].
Boeger, Rainer H. ;
Maas, Renke ;
Schulze, Friedrich ;
Schwedhelm, Edzard .
PHARMACOLOGICAL RESEARCH, 2009, 60 (06) :481-487
[8]   Plasma asymmetric dimethylarginine predicts restenosis after coronary angioplasty [J].
Derkacz, Arkadiusz ;
Protasiewicz, Marcin ;
Poreba, Rafal ;
Doroszko, Adrian ;
Poreba, Malgorzata ;
Antonowicz-Juchniewicz, Jolanta ;
Andrzejak, Ryszard ;
Szuba, Andrzej .
ARCHIVES OF MEDICAL SCIENCE, 2011, 7 (03) :444-448
[9]   Proprotein Convertase Subtilisin/Kexin 9 Inhibitors: An Emerging Lipid-Lowering Therapy? [J].
Dragan, Simona ;
Serban, Maria-Corina ;
Banach, Maciej .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS, 2015, 20 (02) :157-168
[10]   Increased levels of asymmetric dimethylarginine in populations at risk for atherosclerotic disease. Effects of pravastatin [J].
Eid, HM ;
Eritsland, J ;
Larsen, J ;
Arnesen, H ;
Seljeflot, I .
ATHEROSCLEROSIS, 2003, 166 (02) :279-284