Background/Purpose: The main cause of death in rheumatoid arthritis patients are cardiovascular events which cannot be entirely explained by traditional risk factors, suggesting, that systemic inflammation may accelerate them.Anti-cyclic citrullinated peptides (Anti-CCP) antibodies are well known as predictors and markers of clinical activity in RA. Cytokines play an important role in RA. It has been shown that carotid intima media thickness (IMT) values are higher in patients positive for anti-CCP positive.

The aim of this work is to evaluate the relationship of interleukin-6 (IL-6), Tumor Necrosis Factor α (TNF-α), anti-CCP titers and carotid IMT in patients with RA evaluated by bilateral carotid ultrasound.

Methods: Cross-sectional study. The study population was recruited from 2010 to 2012 and included patients with RA of 18 years or older who met the ACR criteria (1987). For the controls we included blood donators matched by gender and by age range. The exclusion criteria for both groups were history of ischemic cardiovascular disease (CVD), hypertension, diabetes mellitus type II, thyroid disease, liver disease, renal impairment, malignancy, dyslipidemia and premature menopause. We also excluded patients treated with high doses of steroids (>10 mg/day).  RA disease activity was measured by the Disease Activity Score 28 (DAS28). Carotid IMT was measured using a high-resolution B-mode ultrasound with a 12-MHz transducer.  Both left and right carotid arteries were examined. All measurements were performed by a single operator. Anti-CCP and other laboratory measurements: ESR, mm/h was measured using the Winthrobe method; hs-CRP levels were calculated by the nephelometric method and expressed as milligrams per liter. Triglycerides, HDL-cholesterol and LDL-cholesterol were measured and expressed as milligrams per deciliter.  Serum was obtained and stored at -70°C for determination of anti-CCP antibodies, IL-6 and TNFα by ELISA. Statistical analysis. Variables were tested for normality using the Kolmogorov-Smirnov test. Student’s t-test or Mann–Whitney U-test was applied for comparison between continuous variables, as well as chi-square or Fisher’s exact test for categorical variables. Multiple regression analysis was performed to assess independent associations between carotid IMT and various clinical and laboratory factors that had p<0.2. All data were analyzed using SPSS 8.0 software, considering a two-tailed level of p<0.05 statistically significant for univariate and multivariate analysis.

Results: Correlation coefficients between carotid IMT and characteristics of the evaluated groups showed a r and p values of 0.319 and 0.02 for age, TNF-α  0.791 and <0.001, IL-6 0.794 and <0.001, anti-CCP 0.539 and <0.001. It was also found an increased carotid IMT between blood donors and RA patients of 61.3 vs 90% (<0.001). The patients were classified as negative or positive for anti-CCP antibodies and we found an association of increased carotid IMT with higher anti-CCP titers (p<0.001).

Conclusion: Pro-inflammatory cytokines are highly correlated with the presence of anti-CCP antibodies and carotid IMT in RA patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/correlation-of-carotid-intima-media-thickness-with-interleukin-6-tumor-necrosis-factor-%ce%b1-and-anti-cyclic-citrullinated-peptides-in-rheumatoid-arthritis/