Background: Anti-Tumor Necrosis Factor (TNF)-α therapy seems to improve cardiovascular risk in patients with inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). ADMA competes with L-arginine as a substrate for NOS, and the L-arginine/ADMA ratio is suggested to be important for modulation of NOS activity. Objective: To examine the effect of anti-TNF-α therapy on ADMA and L-arginine/ADMA, and the associations between ADMA, L-arginine/ADMA and aortic stiffness in patients with inflammatory arthropathies.

Methods: Fifty-five patients with RA, AS or PsA and a clinical indication for anti-TNF-α therapy were included. 36 patients started with a TNF-α antagonist and were compared with a non-treated group of 19 patients. Plasma ADMA, L-arginine and aortic stiffness (aortic pulse wave velocity, aPWV) were assessed at baseline and after 3 and 12 months.

Results: Baseline aPWV was associated with ADMA (P=0.02) and L-arginine/ADMA (P=0.02) in multiple linear regression analyses. One-year anti-TNF-α therapy improved the L-arginine/ADMA ratio (median [interquartile range]) in the treatment group compared to the control group (5 [−4, 16] vs. −10 [−20, 2], respectively; P=0.04), but did not affect ADMA (0.01 [−0.03, 0.04] μmol/L vs. 0.00 [−0.05, 0.06] μmol/L, respectively; P=0.78). The L-arginine/ADMA ratio was longitudinally associated with aPWV in a multivariable mixed analysis (P=0.03).

Conclusion: Plasma ADMA levels were associated with aortic stiffness in patients with inflammatory arthropathies. Anti-TNF-α therapy improved the L-arginine/ADMA ratio. The L-arginine/ADMA ratio was associated with aortic stiffness over time.