Meta-Analysis of Asymmetric Dimethylarginine Concentrations in Rheumatic Diseases

Abstract

Raised circulating concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), have been reported in several rheumatic diseases (RDs). However, the strength of this relationship is unclear. Therefore, the aim of this systematic review and meta-analysis was to evaluate the magnitude and the robustness of the association between ADMA concentrations and RDs. We calculated standardized mean differences (SMD, with 95% confidence intervals, CI). Study heterogeneity was evaluated by meta-regressions and sensitivity analyses according to type of RDs, conventional cardiovascular risk factors, inflammatory markers, and type of ADMA assessment methodology. Thirty-seven studies with a total of 2,982 subjects (1,860 RDs patients and 1,122 healthy controls) were included in our meta-analysis. Pooled results showed that ADMA concentrations were significantly higher in patients with RDs than in healthy controls (SMD = 1.27 µmol/L, 95% CI 0.94–1.60 µmol/L; p < 0.001). However, the between-studies heterogeneity was high. Differences in ADMA concentrations between controls and RDs patients were not significantly associated with inflammatory markers, increasing age, lipid concentrations, body mass index, blood pressure, or methodology used to assess ADMA. Furthermore, subgroup analysis showed no difference across RDs. This meta-analysis showed that, in the context of significant between-study heterogeneity, circulating concentrations of ADMA are positively related to RDs.

Comprehensive arginine metabolomics and peripheral vasodilatory capacity in rheumatoid arthritis: A monocentric cross-sectional study

“…Consistent with previous reports 14,15 , RA patients had higher plasma ADMA concentrations than controls. Different mechanisms have been reported to explain the increase of plasma ADMA concentrations in RA 21 , including an inhibitor effect of inflammatory cytokines on ADMA catabolism by dimethylarginine dimethylaminohydrolase 22 .…”

“…J o u r n a l P r e -p r o o f predictor of cardiovascular and all-cause mortality 13 . Increased ADMA concentrations have been demonstrated in RA 14 , and have been linked to ED and impaired endothelial repair 15 . However, little is known about the relationship between methylarginines, and other arginine metabolites potentially influencing vascular homeostasis such as arginine, L-homoarginine (hArg), and Lcitrulline (Cit), and peripheral vasodilatory capacity in RA.…”

Endothelial dysfunction and increased carotid intima–media thickness in patients with spondyloarthritis without traditional cardiovascular risk factors

“… 28 Asymmetric dimethylarginine, an endogenous NO inhibitor and marker of endothelial function, was significantly increased in the serum of patients with SpA. 29 30 Wang and Wang demonstrated that serum vaspin levels were significantly decreased and strongly associated with impaired endothelial function, measured by FMD in patients with SpA. 31 In a large series of patients (n=510 patients), vaspin was found to be associated with CV risk factors that may influence the atherosclerotic process in SpA.…”

A Pilot Study: Hypertension, Endothelial Dysfunction and Retinal Microvasculature in Rheumatic Autoimmune Diseases

“…Erre and his colleagues. carried out a meta-analysis and concluded that there is an elevated level of ADMA in autoimmune diseases [ 77 ].…”