Oxidative Stress Biomarkers and Peripheral Endothelial Dysfunction in Rheumatoid Arthritis: A Monocentric Cross-Sectional Case-Control Study

Previous studies have suggested that oxidative stress may heighten atherosclerotic burden in rheumatoid arthritis (RA), but direct evidence is lacking. To evaluate the relationship between established plasma oxidative stress biomarkers and peripheral endothelial dysfunction (ED), a marker of early atherosclerosis, in RA. Paroxonase-1 (PON-1), protein-SH (PSH), and malondialdehyde (MDA) were measured in 164 RA patient s and 100 age- and sex-matched healthy controls without previous cardiovascular events. Peripheral ED, evaluated by flow-mediated pulse amplitude tonometry, was defined by log-transformed reactive hyperemia index (Ln-RHI) values < 0.51. PON-1 activity and PSH concentrations were significantly reduced in RA patients compared to controls. In regression analysis, increased plasma MDA levels were significantly associated with reduced Ln-RHI [B coefficient (95% CI) = -0.003 (-0.005 to -0.0008), = 0.008] and the presence of peripheral ED (OR (95% CI) = 1.75 (1.06-2.88), = 0.028). Contrary to our expectations, increased PON-1 activity was significantly associated, albeit weakly, with the presence of ED (OR (95% CI) = 1.00 (1.00-1.01), = 0.017). In this first evidence of a link between oxidative stress and markers of atherosclerosis, MDA and PON-1 showed opposite associations with peripheral vasodilatory capacity and the presence of ED in RA. Further studies are needed to determine whether this association predicts atherosclerotic events in the RA population.