Abstract

Background:The causes of accelerated atherosclerosis in rheumatoid arthritis (RA) are not completely understood [1]. Therefore, there is a need to identify new biomarkers of increased cardiovascular risk in RA.Objectives:To establish the relationship of adipocytokines (adiponectin and leptin) with metabolic and inflammatory markers of subclinical atherosclerosis in RA patients.Methods:The study included 88 women with RA according to the ACR (American College of Rheumatology)/EULAR (European League Against Rheumatism) criteria, 2010 [2] who visited the adaptation therapy clinic of Orenburg State Medical University. The mean±SD age was 46.43±8.5 years and the mean±SD disease duration was 8.21±5.56 years.We evaluated the following laboratory parameters in all patients: erythrocyte sedimentation rate (ESR), total cholesterol, triglycerides (TAG), high-density lipoproteins (HDL), low-density lipoproteins (LDL) and C-reactive protein (CRP). Serum concentrations of adiponectin, leptin, rheumatoid factor (RF), tumor necrosis factor-α (TNF-α), and interleukin-17 (IL-17) were determined by enzyme-linked immunosorbent assay (ELISA).We carried out ultrasound (US) duplex scanning of the carotid arteries by the device “Philips Epiq 7” with linear transducer with frequency of 4-18 MHz with the division into 2 groups of patients: group I consisted of 44 women with US signs of subclinical atherosclerosis, group II – 44 women without these signs. The control group included 30 women without inflammatory joint diseases and US signs of subclinical atherosclerosis and similar in gender, age and body mass index (BMI) to RA patients.The program STATISTICA, 12.0 was used for statistical analysis.Results:The serum adiponectin level was significantly higher in RA patients compared to the control group (p<0.0001): 40.88±13.60 ng/ml versus 22.75±11.27 ng/ml. The level of leptin in the blood serum of women with RA and healthy individuals was approximately the same and amounted to 18.07±14.02 ng/ml and 16.60±11.45 ng/ml respectively. When comparing the levels of adipocytokines in RA patients, the predominance of concentrations of both adipokines in patients with paraclinical atherosclerosis were noted. The adiponectin concentration was 46.08±14.44 ng/ml versus 35.70±10.51 ng/ml (p<0.001). The leptin level was 26.40±20.06 ng/ml versus 14.96±16.62 ng/ml (p<0.01).Correlation analysis showed an negative relationship between adiponectin levels and metabolic markers of atherosclerosis: BMI (r=-0.52; p<0.05), neck circumference (NC) (r=-0.50; p<0.05), levels of LDL (r=-0.77; p<0.001) and TAG (r=-0.59; p<0.05) as well as proinflammatory cytokines: TNF-α (r=-0,48; p<0.05), IL-17 (r= -0.60; p<0.01) in patients of both groups. The increase in adiponectin concentration in group II patients was associated with the duration of administration of methotrexate (r=0.49; p<0.05) and glucocorticosteroids (r=0.71; p<0.001). Direct correlations were found between the level of leptin and BMI (r=0.48; p<0.05), NC (r=0.48; p<0.05), LDL (r=0.54; p<0.05) and TAG (r=0.45; p<0.05), CRP (r=0.49; p<0.05) and IL-17 (r= 0.52; p<0.05) in group I patients.Conclusion:There is a significant increase in the production of adipocytokines in RA with subclinical atherosclerosis. Correlations of levels of adipokines with metabolic and inflammatory markers of atherosclerosis, on the one hand, indicate the influence of adipose tissue on systemic inflammation and, on the other hand, confirm the involvement of proinflammatory cytokines in the development of atherosclerotic vascular damage in patients with RA.

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