Lack of Association Between Asymmetric Dimethylarginine and in Vivo Microvascular and Macrovascular Endothelial Function in Patients with Rheumatoid Arthritis

Objectives: The aim of the present study was to investigate if assymetric dimethylarginine (ADMA) is increased in patients with rheumatoid arthritis (RA) compared to healthy controls and to examine associations between ADMA, RA disease activity and in vivo assessments of microvascular and macrovascular endothelial function.

Methods: Sixty-seven RA patients (age [mean ± standard deviation]: 56 ± 12 years, disease duration median [25th-75th percentile]: 8 [3-15] years, 48 women) and 29 healthy controls (age [mean ± standard deviation]: 42 ± 12, 21 women) underwent assessments of microvascular endothelial function (Laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside), and macrovascular endothelial function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation) as well as arterial stiffness. ADMA levels were measured in contemporary specimens using an immunoassay ELISA kit.

Results: ADMA levels were significantly higher (p=0.004) in RA patients compared with healthy controls after adjustment for age (difference=0.088, 95% confidence interval 0.029-0.147). ADMA levels did not correlate with demographic or disease characteristics. No correlation was found between ADMA and microvascular and macrovascular endothelial function or with arterial stiffness.

Conclusions: ADMA levels are increased in patients with RA but there was no significant correlation with in vivo assessments of endothelial function. Further studies are needed to unfold the pathophysiological role of nitric oxide/ADMA pathway derangement in endothelial dysfunction and cardiovascular risk in RA.