TY - JOUR
T1 - An updated systematic review and meta-analysis of the effect of statins on asymmetric dimethylarginine
AU - Zinellu, Angelo
AU - Mangoni, Arduino A.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Objectives: We conducted an updated systematic review and meta-analysis of the effect of statins on serum or plasma concentrations of the endogenous inhibitor of endothelial nitric oxide synthase, asymmetric NG,NG-dimethyl-L-arginine (ADMA). Methods: A systematic literature search was conducted in the electronic databases PubMed, Web of Science, and Scopus, from inception to July 2021. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for analytical studies and GRADE, respectively. Results: In 23 studies, reporting 25 treatment arms in 845 participants (mean age 53 years, 57% males, treatment duration 4–48 weeks), statins significantly reduced ADMA concentrations (SMD = -0.39, 95% CI -0.62 to -0.16, p = 0.001; moderate certainty of evidence). The extreme heterogeneity observed was substantially reduced in study subgroups of specific class and individual statins, regional areas, and analytical methods for ADMA concentrations. There was no publication bias. In sensitivity analysis, the corresponding SMD values were not substantially modified when individual studies were sequentially removed. Significant associations were observed, in meta-regression, between the SMD and publication year (t = -3.25, p = 0.003), but not baseline cholesterol concentrations. Conclusion: Statin treatment significantly lowers ADMA concentrations. This effect is independent of baseline cholesterol. Prospective studies are required to determine whether ADMA-lowering mediates, at least partly, the protective effects of statins against atherosclerotic cardiovascular disease. (PROSPERO registration number: CRD42021275123)
AB - Objectives: We conducted an updated systematic review and meta-analysis of the effect of statins on serum or plasma concentrations of the endogenous inhibitor of endothelial nitric oxide synthase, asymmetric NG,NG-dimethyl-L-arginine (ADMA). Methods: A systematic literature search was conducted in the electronic databases PubMed, Web of Science, and Scopus, from inception to July 2021. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for analytical studies and GRADE, respectively. Results: In 23 studies, reporting 25 treatment arms in 845 participants (mean age 53 years, 57% males, treatment duration 4–48 weeks), statins significantly reduced ADMA concentrations (SMD = -0.39, 95% CI -0.62 to -0.16, p = 0.001; moderate certainty of evidence). The extreme heterogeneity observed was substantially reduced in study subgroups of specific class and individual statins, regional areas, and analytical methods for ADMA concentrations. There was no publication bias. In sensitivity analysis, the corresponding SMD values were not substantially modified when individual studies were sequentially removed. Significant associations were observed, in meta-regression, between the SMD and publication year (t = -3.25, p = 0.003), but not baseline cholesterol concentrations. Conclusion: Statin treatment significantly lowers ADMA concentrations. This effect is independent of baseline cholesterol. Prospective studies are required to determine whether ADMA-lowering mediates, at least partly, the protective effects of statins against atherosclerotic cardiovascular disease. (PROSPERO registration number: CRD42021275123)
KW - Asymmetric dimethylarginine
KW - Atherosclerosis
KW - Statins
UR - http://www.scopus.com/inward/record.url?scp=85123004569&partnerID=8YFLogxK
U2 - 10.1016/j.niox.2022.01.001
DO - 10.1016/j.niox.2022.01.001
M3 - Review article
AN - SCOPUS:85123004569
SN - 1089-8603
VL - 120
SP - 26
EP - 37
JO - Nitric Oxide - Biology and Chemistry
JF - Nitric Oxide - Biology and Chemistry
ER -