Abstract
Background Oxidative stress along with chronic inflammation and hyperuricemia links gout to arteriosclerotic vascular changes. Studies examining the connection between the level of oxidative stress and arteriosclerotic carotid arteries changes in gout patients (pts) are not enough. Objectives To establish the association between the serum levels of reactive oxygen species (ROS) products, nitric oxide (NO) radicals and ascorbate radicals with intima-media thickness (IMT) and common carotid artery resistive index (CCARI) in gout pts, and to find out whether the connection is more pronounced when tophi are present. Methods This was a cross-sectional study including 71 gout pts in a mean age 56.86±11.95 years, 61 males and 10 females (45 without tophi pts and 26 gouty tophi pts). Serum levels of ROS products, NO radicals and ascorbate radicals were determined by ex vivo electron paramagnetic resonance (EPR) study. All EPR measurements were performed on an X-band EMXmicro, spectrometer Bruker, Germany, equipped with Standard Resonator. Spectral processing was done by using Bruker WIN-EPR and Sinfonia software. By applying ultrasound of the common carotid arteries, conducted with 10 MHz linear transducer working with pulse Doppler frequency of 5 MHz, were measured IMT and CCARI. Statistical analyses were done by One-Sample Kolmogorov-Smirnov, Chi-Square, Fisher’s exact test, Mann-Whitney, t-test and Pearson correlation. Results Gouty arthritis without tophi and gouty tophi pts were age-matched, (p=0.309). The mean values of serum uric acid (p=0.569) and distribution of the subjects with gout attack (p=0.173), smoking (p=0.828), arterial hypertension (p=0.735), dyslipidemia (p=0.646), chronic renal failure (p=0.233) and obesity (p=0.623) was equal in the groups. In the tophi group CRP and the number of pts who had suffered a cardiovascular event were higher (p=0.048; p=0.031). Serum levels of ROS products, NO radicals and ascorbate radicals were comparable in gouty arthritis without tophi and in gouty tophi pts (p=0.783; p=0.521; p=0.651). In the groups no difference was registered in CCARI (p=0.273) but intima-media was thicker in the presence of tophi, (p=0.027). No correlation existed between ROS products, NO radicals and ascorbate radicals with IMT (r= -0.100, p=0.405; r= -0.186, p=0.121; r=0.154, p=0.201). ROS products, NO radicals and ascorbate radicals did not correlate with CCARI (r= -0.110, p=0.359; r= -0.066, p=0.587; r=0.094, p=0.436). Among treated and untreated with Allopurinol pts no difference was found in the mean values of ROS products (p=0.169), NO radicals (p=0.167), ascorbate radicals (p=0.460), IMT (p=0.873) and CCARI (p=0.930). Among treated and untreated with Febuxostat pts the mean values of ROS products (p=0.546), ascorbate radicals (p=0.309), IMT (p=0.842) and CCARI (p=0.100) were similar. A tendency of higher serum NO radicals was established in pts taking Febuxostat in comparison to those not treated with it (p=0.076). Conclusion Although between the earlier and the later stage of the disease there was no difference in the level of oxidative stress, the level of chronic inflammation was higher in gouty tophi pts. No connection was found between serum ROS products, NO radicals and ascorbate radicals with arteriosclerotic changes of the carotid arteries and use of xanthine oxidase inhibitors. We suggest that in gout pts chronic inflammation has an important role in the process of atherogenesis. Disclosure of Interests Rada Gancheva: None declared, Atanas Koundurdjiev: None declared, Galina Nikolova: None declared, Mariana Ivanova Goycheva Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Todor Kundurzhiev: None declared, Zlatimir Kolarov: None declared, Veselina Gadjeva: None declared
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