Meta-Analysis of Asymmetric Dimethylarginine Concentrations in Rheumatic Diseases

Gian Luca Erre, Arduino Aleksander Mangoni, Floriana Castagna, Panagiotis Paliogiannis, Ciriaco Carru, Giuseppe Passiu, Angelo Zinellu

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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.

Original languageEnglish
Article number5426
Number of pages11
JournalScientific Reports
Volume9
DOIs
Publication statusPublished - 1 Apr 2019

Bibliographical note

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Keywords

  • rheumatic diseases
  • rheumatology

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    Erre, G. L., Mangoni, A. A., Castagna, F., Paliogiannis, P., Carru, C., Passiu, G., & Zinellu, A. (2019). Meta-Analysis of Asymmetric Dimethylarginine Concentrations in Rheumatic Diseases. Scientific Reports, 9, [5426]. https://doi.org/10.1038/s41598-019-41994-5