Objective: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and a well-established biomarker of endothelial dysfunction and cardiovascular risk. Patients with rheumatoid arthritis (RA) exhibit increased cardiovascular morbidity, partially attributable to inflammation-mediated endothelial injury. The impact of modern biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) on ADMA levels remains incompletely understood. To evaluate serum ADMA levels in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors (TNFi) or the Janus kinase inhibitor upadacitinib, and to identify clinical and lifestyle factors associated with ADMA concentration Design and method: In a cross-sectional observational study, serum ADMA levels were measured using a validated competitive ELISA in 79 patients with RA (41 treated with TNFi and 38 treated with upadacitinib) and 30 healthy controls. Associations between ADMA and treatment type, disease activity indices (Disease Activity Score-28 for Rheumatoid Arthritis with Erythrocyte Sedimentation Rate - DAS28-ESR, DAS28-C-reactive protein, Clinical Disease Activity Index -CDAI), disease duration, cardiovascular risk (Framingham Risk Score), and smoking status were evaluated using correlation and multivariable regression analyses. Results: No statistically significant differences in ADMA levels were observed between RA patients and healthy controls (Mean 0.770 vs 0.772; Mean diff 0.00181; p = 0.974), nor between TNFi- and upadacitinib-treated patients (Mean 0.795 vs 0.744; Mean diff. = 0.0510 p = 0.624). ADMA concentrations were not associated with disease activity, disease duration, arterial stiffness parameters, or cardiovascular risk scores. In contrast, current smoking was consistently and independently associated with higher ADMA levels across treatment groups (beta coefficient = 0.197, p < 0.001; beta coefficient = 0.177, p = 0.001). Conclusions: In patients with rheumatoid arthritis receiving biologic or targeted synthetic therapy, serum ADMA levels are not influenced by treatment modality or disease activity but are strongly determined by smoking status. These findings highlight smoking as a major modifiable driver of endothelial dysfunction in RA, independent of immunomodulation therapy, and underscore the importance of smoking cessation in cardiovascular risk management in this population.
Dimova et al. (Fri,) studied this question.
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