Premium
Interaction between oxidative stress and high‐density lipoprotein cholesterol is associated with severity of coronary artery calcification in rheumatoid arthritis
Author(s) -
Rho Young Hee,
Chung Cecilia P.,
Oeser Annette,
Solus Joseph F.,
Gebretsadik Tebeb,
Shintani Ayumi,
Raggi Paolo,
Milne Ginger L.,
Stein C. Michael
Publication year - 2010
Publication title -
arthritis care and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.032
H-Index - 163
eISSN - 2151-4658
pISSN - 2151-464X
DOI - 10.1002/acr.20237
Subject(s) - medicine , rheumatoid arthritis , interquartile range , oxidative stress , endocrinology , creatinine , body mass index , cholesterol , isoprostane , excretion , coronary artery disease , gastroenterology , lipid peroxidation
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 F 2 ‐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 F 2 ‐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 F 2 ‐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, F 2 ‐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, F 2 ‐isoprostanes significantly modified the effect of HDL cholesterol on coronary calcification ( P = 0.02 for interaction) after adjustment for age, sex, and race. As F 2 ‐isoprostane levels increased, HDL lost its protective effect against coronary calcification. Conclusion Oxidative stress measured as F 2 ‐isoprostane excretion was higher in patients with RA than in control subjects. Among patients with RA, higher F 2 ‐isoprostane excretion and HDL cholesterol concentrations interacted significantly and were positively associated with the severity of coronary calcification.