Interaction between Oxidative Stress and HDL Cholesterol Is Associated with Severity of Coronary Artery Calcification in Rheumatoid Arthritis

Objectives—We tested the hypothesis that oxidative stress is increased in patients with rheumatoid arthritis (RA) due to increased inflammation and contributes to the pathogenesis of atherosclerosis. Methods—The independent association between urinary F2-isoprostane excretion, a measure of oxidative stress, and RA was tested using multiple linear regression models in 169 patients with RA and 92 control subjects frequency-matched for age, race and sex. The relationship between F2-isoprostane excretion and coronary calcium, a marker of atherosclerosis, was examined in multivariable proportional odds logistic regression models that also assessed the interactions between oxidative stress and LDL and HDL cholesterol. Results—F2-isoprostane excretion (median [IQR]) was significantly higher in patients with RA (median 2.75 [interquartile range: 1.60-4.06] ng/mg creatinine (Cr)) than control subjects (1.86 [1.25-2.62] ng/mg Cr, adjusted p=0.006). In patients with RA, F2-isoprostanes were positively correlated with BMI (p<0.001) but not with disease activity or mediators of inflammation, such as DAS28 or serum TNF-α, IL-6 and CRP concentrations in adjusted multivariable models (al