Avaliação de risco cardiovascular em pacientes com artrite reumatoide: possível associação com atividade da doença, citocinas e a via NRF2/HO-1

Abstract

Cardiovascular risk assessment in patients with rheumatoid arthritis: possible association with disease activity, cytokines, and the NrF2/HO-1 pathway. Christiane Aguiar Nobre. Mirna Marques Bezerra. Doctoral thesis. Graduate Program in Translational Medicine. Center for Research and Development of Medicines, School of Medicine, UFC. Fortaleza, 2026. Introduction: Inflammation contributes to cardiovascular risk (CVR) in rheumatoid arthritis (RA), and oxidative stress mediated by erythroid factor 2 (Nrf2)/heme oxygenase 1 (HO-1) may also contribute to this process. Objective: To evaluate CVR, disease activity, serum cytokine levels, and Nrf2/HO-1 pathway expression in RA. Methods: Cross-sectional study with 120 participants, divided into RA and control groups. Clinical, laboratory, and ultrasound (US) data

were collected from the heart and carotid arteries; cytokines were measured by ELISA (TNF- α, IL-1β, IL-6, IL-4, IL-10) and gene expression (mRNA) of Nrf2 and HO-1 by qRT-PCR.

Disease activity was measured by DAS28, SDAI, and CDAI, while CVR was measured by serum pro-BNP, US, and clinical scores (Framingham and SCORE). Analyses were performed using SPSS v26.0 (p<0.05). Results: The sample was predominantly female (90%), with a mean age of 52 years. The control group had higher values for dyslipidemia (p=0.027), abdominal circumference (p=0.017), BMI (p=0.010), and blood glucose (p<0.001). In the RA group, the mean duration of the disease was 10.4 ± 7.5 years, with 63.3% positive for rheumatoid factor and/or anti-CCP. Regarding treatment, 91.7% used DMARDs, 21.7% used biologics, and 11.7% used target-specific agents. No differences were observed between the groups in clinical CVR scores and US findings. However, pro-BNP levels were higher in RA (p=0.009). We observed higher levels of IL-6 (p=0.002) and IL-10 (p=0.004), with a reduction in IL-1β (p=0.001). We found an increase in mRNA-Nrf2 (p<0.001) and a reduction in mRNA-HO-1 (p=0.030). Disease lasting more than 10 years was associated with hypertension (p=0.023), higher DAS28-ESR (p=0.017) and SDAI (p=0.025), as well as more frequent use of antihypertensive drugs (p<0.001), statins (p=0.011), hypoglycemic agents (p=0.038), and higher blood glucose levels (p=0.029). CDAI correlated with higher IL-6 levels (p=0.033) and DAS28-PCR with lower education (p=0.038), longer disease duration (p=0.012), ventricular dysfunction (p=0.044), and elevated triglycerides (p=0.030). Conclusion: Patients with RA presented with Nrf2/HO-1 pathway dysregulation and elevated pro-BNP. Higher disease activity and longer disease duration were associated with a higher prevalence of comorbidities and cardiovascular complications in RA.