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Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by excess morbidity and mortality from cardiovascular disease. In addition, metabolic alterations have been observed in these patients, which significantly contributes to the cardiovascular risk burden. Thus, the identification of therapies able to mitigate the cardiometabolic alterations in RA is essential. In addition, numerous studies suggest that cardiometabolic risks are mediated through adipocytokines. However, this relationship is not completely defined in RA. Objectives: 1) To evaluate the relationship among cardiometabolic risk factors and the levels of adipocytokines and autoantibodies in RA patients. 2) To analyze the effects anti-TNFα and anti-IL6 therapies on the cardiometabolic alterations. Methods: 1.- A cross-sectional study including 100 RA patients and 50 age-matched healthy donors was carried out. Different parameters related to the cardiometabolic risk were analyzed, including: lipid profile, atherogenic index, ratio ApoB/ApoA, insulin resistance (IR), obesity, hypertension, and the SCORE. Levels of adipocytokines (TNFα, IL6, IL1β, visfatin, adiponectin, leptin and resistin) were evaluated in serum. Carotid intima media thickness (CIMT) was evaluated as atherosclerosis marker. 2.-A prospective study in 15 RA patients before and after 3 months of anti-TNFα therapy and 15 RA patients before and after 3 months of treatment with tocilizumab (TCZ) was performed. All the parameters evaluated in the cross-sectional cohort were tested in this prospective study. Results: RA patients had elevated levels of leptin/adiponectin ratio, visfatin, resistin and inflammatory markers in serum. Our cohort of RA patients displayed increased rates of cardiometabolic risk factors, such as insulin resistance, hypertension, SCORE, pathologic CIMT, atherogenic index and ratio apoB/apoA. The alteration in the levels of adipocytokines were closely related to the autoimmunity, disease activity and clinical inflammatory markers. Of note, visfatin and C3 complement levels were determinant for IR, high levels of SCORE, increased parameters of CVD risk defined by apoB/apoA ratio and pathologic CIMT. Both biological therapies reduced clinical inflammatory markers and disease activity after 3 months of treatment. Anti-TNFα therapy modulated the cytoadipokine profile, reducing serum levels of IL-6, IL-1β, resistin and visfatin, decreasing IR. After treatment with tocilizumab, serum levels of C3 complement, IL-1β and resistin were reduced. Conclusion: 1) Altered adipocytokine profile is closely related to the increased cardiometabolic risk factors associated with RA, where autoimmunity and systemic inflammation play a key role. 2) Anti-TNFα and anti-IL6R therapies, administered for 3 months, could have beneficial effects in the reduction of cardiometabolic risk factors in RA. Acknowledgement: Funded by ISCIII (PI18/00837, CP15/00158, PI17/01316 and RIER RD16/0012/0015) co-funded with FEDER Disclosure of Interests: None declared |
