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Abstract
Background Angiotensin II (AnII) is not only involved in the pathogenesis of endothelial dysfunction (ED) due vasoconstrictor effect, but also has a powerful pro-inflammatory and remodeling properties, stimulating the production of proinflammatory cytokines (TNFα, IL-1, IL-6 et al.), adhesion molecules (ICAM-1), and growth factors (vascular endothelial growth factor - VEGF), which play an important role in the pathogenesis of rheumatoid arthritis (RA). The use of ACE inhibitors in vivo and in vitro on cell cultures demonstrated anti-cytokine and anti-inflammatory effect.
Objectives to study the effectiveness of combined therapy of RA with ramipril use
Methods The study included 84 patients with RA. Mean age was 40.12 ± 10.2 years. Mean RA disease duration was 4.22 ± 3.43 years. The concentration of ICAM-1, VEGF and TNFα in blood was determined by enzyme immunoassay. Endothelial regulation of vascular tone was studied in all the patients (by Celermayer-Sorensen method, 1992), which revealed the presence of ED in examined patients: reduction of endothelium-dependent vasodilation (EDVD) till less than 10%, endothelium-independent vasodilation (EIVD) – till less than 15%, the coefficient of the sensitivity of the endothelium to the (transverse strain) shere stress (K) <0.59. The average value of the examined EDVD RA patients was 9.2 ± 2.3%, ENVD – 13.9 ± 2.9%, K – 0.37 ± 0.21.
All the patients studied were randomly divided into two groups: I - 43 patients received standard RA therapy according to protocols of rheumatic diseases treatment, II - 41 patients received 12 months complex treatment, which included standard therapy with an ACE inhibitor addition - ramipril 2.5 -5 mg per day. The initial dose was 2.5 mg/day for a week, then the dose was increased to 5 mg/day under the blood pressure control. Patients of the I and II groups were not statistically different in all investigated indices prior to treatment.
Results The dynamics of indicators of ED in the groups (Table. 1) revealed that all parameters in the both groups significantly improved (p<0.001) after treatment, but the increase was significantly more in group II (p<0.05). The positive dynamics of immune inflammation RA activity markers (CRP, TNFα, DAS28) after the treatment was in both groups, but the gain power was statistically more significant in group II (p<0.05). It should be noted, that DAS28 in group II decreases by more than 1.2 (according to the EULAR criteria for the RA treatment effectiveness), while in group I - only by 0.65.
Thus, inclusion of ramipril in the complex therapy of RA led to an improvement in endothelial regulation of vascular tone, helped to reduce blood levels of ICAM-1 by 16%, VEGF by 36%, CRP by 13%, TNFα by 12% as opposed to standard therapy.
Conclusions The use of ramipril in the treatment of RA for one year contributed to the effective reduction of markers of autoimmune inflammation, improved endothelial dysfunction, and significantly reduced the activity index of the disease compared with standard therapy.
Disclosure of Interest None declared