Cytokines and multifocal atherosclerosis in rheumatoid arthritis

The aim – to investigate the relationship between cytokines (interleukin (IL) 6, tumor necrosis factor (TNF) α and IL-1 receptor antagonist (RA)) and multifocal atherosclerosis (MFA) in patients with rheumatoid arthritis (RA).

Materials and methods. The study included 71 patients with a confirmed diagnosis of RA, corresponding to the 2010 ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) classification criteria. Most of them (81.4%) were women, the average age was 47.0±10.9 years, the median duration of the disease was 120 [60.0; 204.0] months, 54 (76.1%) patients had advanced disease, and moderate to high disease activity according to the DAS28 (Disease Activity Score 28), SDAI (Simplified Disease Activity Index) and CDAI (Clinical Disease Activity Index) indices prior to the administration of genetically engineered biological drugs. All patients had their serum IL-6, TNF-α, and IL-1 RA levels determined by enzyme-linked immunosorbent assay (ELISA), and underwent ultrasound Doppler imaging (UDI) of the carotid (CA) and femoral (FA) arteries with assessment of intima-media thickness (IMT) and the presence of atherosclerotic plaque. The control group consisted of 30 healthy individuals matched for age and gender.

Results. Among the RA patients examined, atherosclerotic lesions of the CA were found in 22 (31%), FA in 20 (28.2%), including combined lesions of the CA and FA in 13 (18.3%) patients. In RA patients, CA and FA atherosclerosis was significantly more common than in the control group (p<0.05). In the group of RA patients, the levels of IL-6 and TNF-α cytokines were significantly higher than in the control group. The level of IL-1 RA did not differ significantly. The thickness of the CA IMT was higher with elevated TNF-α (0.65 vs. 0.56 mm; p<0.05), and the CA IMT was higher with elevated IL-1 RA (0.60 vs. 0.56 mm, p<0.05). No differences were found for IL-6. Cytokine levels (IL-6, TNF-α, IL-1 RA) did not differ between RA patients with MFA and those without (p>0.05). RA patients were analysed according to the combination of elevated cytokine levels. Three groups were identified: group 1 – with elevated levels of all three cytokines (CT) (n=14); group 2 – with elevated levels of 2 cytokines (n=36); group 3 – with elevated levels of 1 cytokine (n=19). It was found that the thickness of the FA IMT with an increase in 3 CT was 0.77 [0.62; 0.86] mm, with an increase in 2 CT it was 0.62 [0.49; 0.77] mm, and with an increase in 1 CT it was 0.62 [0.43; 0.63] mm (p<0.05). A statistically significant positive correlation was found between FA IMT and TNF-α concentration (r=0.4; p=0.003), CA IMT and IL-6 (r=0.2; p=0.05) and IL-1 RA (r=0.2; p=0.05).

Conclusion. MFA is frequently detected in patients with RA. Elevated levels of IL-1RA and IL-6 are more common in RA patients with MFA. The greatest thickness of the FA IMT was found with a simultaneous increase in IL-6, IL-1RA, and TNF-α levels. Patients with RA require UDI of the CA and FA to detect MFA and stratify the risk of cardiovascular events.

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