Interaction between oxidative stress and high-density lipoprotein cholesterol is associated with severity of coronary artery calcification in rheumatoid arthritis.
OBJECTIVE
To test 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 low-density lipoprotein and high-density lipoprotein (HDL) cholesterol.


RESULTS
F₂-isoprostane excretion was significantly higher in patients with RA (median 2.75 [interquartile range (IQR) 1.60-4.06] ng/mg creatinine) than in control subjects (median 1.86 [IQR 1.25-2.62] ng/mg creatinine; adjusted P = 0.006). In patients with RA, F₂-isoprostanes were positively correlated with body mass index (P < 0.001), but not with disease activity or mediators of inflammation such as the Disease Activity Score in 28 joints or serum tumor necrosis factor α, interleukin-6, and C-reactive protein concentrations in adjusted multivariable models (P > 0.05 for all). In patients with RA, F₂-isoprostanes significantly modified the effect of HDL cholesterol on coronary calcification (P = 0.02 for interaction) after adjustment for age, sex, and race. As F₂-isoprostane levels increased, HDL lost its protective effect against coronary calcification.


CONCLUSIONS
Oxidative stress measured as F₂-isoprostane excretion was higher in patients with RA than in control subjects. Among patients with RA, higher F₂-isoprostane excretion and HDL cholesterol concentrations interacted significantly and were positively associated with the severity of coronary calcification.
Rho
Young Hee
YH
Vanderbilt University, Nashville, Tennessee 37232-6602, USA.
Chung
Cecilia P
CP
Oeser
Annette
A
Solus
Joseph F
JF
Gebretsadik
Tebeb
T
Shintani
Ayumi
A
Raggi
Paolo
P
Milne
Ginger L
GL
Stein
C Michael
CM
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000473:pathology / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002114:Calcinosis / Q000097:blood* / Q000473:pathology / Q000652:urine; D008076:Cholesterol, HDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood* / Q000473:pathology / Q000652:urine; D003430:Cross-Sectional Studies; D028441:F2-Isoprostanes / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers; D008076:Cholesterol, HDL; D028441:F2-Isoprostanes