The purpose of the study was to determine the contribution of RANKL/OPG transmembrane molecule system into the development of pathological arterial stiffness in rheumatoid arthritis (RA). RA patients (n=181) were randomized into 4 groups based on RF/ACCP (rheumatoid factor/antibodies to cyclic citrullinated peptide) positivity and disease duration (less than or more than 2 years). Serum osteoprotegerin (OPG) and soluble receptor activator of NF-kB ligand (sRANKL) concentrations, as well as pulse wave contour analysis were evaluated in all patients. The largest OPG level was detected in Group 1 patients; sRANKL concentration with maximal RANKL/OPG ratio was predominant in Group 4 patients. Prolonged course of RF/ACCP-seropositive RA was characterized by more significant arterial rigidity shifts (increases in augmentation (AIp), stiffness (SI), reflection (RI) indices). Correlation analysis revealed the presence of significant relations between the RANKL/OPG transmembrane molecule system and arterial rigidity parameters in RA.

The study objective is to evaluate Tofacitinibum (TOFA) impact on the vasomotor endothelial function and arterial stiffness in patients with rheumatoid arthritis (RA). 26 patients were examined; they had active RA and either inefficient prior methotrexate therapy or contraindications to its administration. Initially and after 6 months of TOFA (10 mg/day) treatment, the pulse wave contour analysis and reactive hyperemia test were performed. It was revealed that TOFA had a vasoprotective impact on large elastic vessels (4-fold (p=0.001) and 1.3-fold (p<0.01) decrease of augmentation and stiffness indices, respectively), large vessels (1.8-fold increase in inter-channel phase shift value (p=0.008)) and small muscular arteries (normalization of amplitude occlusion parameters and reflection index which reached the control group values).

The article presents the results of evaluation of leflunomide impact on endothelial function and vascular stiffness parameters in patients with rheumatoid arthritis (RA), but without cardiovascular diseases. 46 patients with RA satisfying ACR (1987) or ACR/EULAR (2010) classification criteria were examined. Investigations of endothelial function and arterial stiffness, based on the pulse wave contour analysis and the reactive hyperemia test (“AngioScan-01” device used), were conducted before the treatment and 12 months thereafter. It was determined that patients with RA suffered from subclinical damage of large arteries, characterized by endothelial dysfunction at micro- and macrocirculatory levels, and the increase in augmentation (AIp), stiffness (SI), and reflection (RI) indices, whose value correlated with RA duration, DAS28 activity index, RF level, and ACCP concentration. Leflunomide use in patients with RA was accompanied by statistically significant decrease in DAS28 index. It was shown that along with high anti-inflammatory activity leflunomide is also able of decreasing the signs of subclinical arterial damage, which is confirmed by the restoration of the endothelial function both in the system of small resistant vessels (increase in amplitude occlusion index) and large muscular arteries (increase in the value of phase shift between channels), and the decrease in stiffness of large arteries.

There were analyzed 86 minutes of duplex scanning of the common carotid arteries and pulse wave contour analysis performed in patients with rheumatoid arthritis (RA) not accompanied with cardiovascular disease at the age of 18 to 50 years, with case history of less than two years. There were found the signs of remodeling of the common carotid arteries (increased intima-media thickness and в stiffness index) and increase of regional stiffness of vascular wall (increased augmentation index (AIp75), stiffness (SI) and reflection (RI)) already at the early stages of the disease, more expressed in the RF / anti-CCP-positive RA variant. Correlation analysis confirmed the contribution of the disease-related factors (activity of chronic immunological process seropositivity for IgM RF and anti-CCP) to change of the architectonics of the vascular wall, progression of arterial stiffness, both at the local and regional levels.

The study of the relationship of proinflammatory mediators (hs-CRP, TNF-α, IL-6 and IL-1β) with indicators of endothelial function at the micro level and makrotsirkulyatornom vascular bed in RA patients without concomitant cardiovascular disease. Take into account the clinical and immunological variant and disease duration. The results suggest that overproduction of TNF-α and IL-1β in the early stages of RA induces endothelial dysfunction mainly on the microcirculatory level, while the excessive synthesis of IL-6 and hs-CRP as the disease progresses potentiates the development of macrovascular endothelial dysfunction, more degree at RF / CCPA-seropositive subtype.

FIELD: medicine. SUBSTANCE: leflunomide in a dose of 100 mg a day for the first 3 days, 20 mg once a day continuously is prescribed orally as a standard baseline anti-inflammatory therapy in a patient with the active clinical course of the disease if the previous therapy with methotrexate appeared ineffective or the patient shows counter-indications for the use thereof. EFFECT: method provides the effective correction of the structural-functional arterial bed disorders in the patients of the above category by the fact that leflunomide combined the immunomodulatory and anti-inflammatory effects and vasoprotective action on the walls of greater vessels of elastic type and small arteries of muscular type. 1 ex, 1 tbl

Objective. To study the effect of infliximab (INF) on serum levels of RANKL and osteoprotegerin (OPG), as well as on structural and functional properties of the vascular wall in patients with rheumatoid arthritis (RA). Material and Methods. A total of 79 RA patients who corresponded to the classification criteria ACR (1987) or ACR/EULAR (2010) and were seronegative for IgM rheumatoid factor (RF) were examined. The mean age of patients was 43.6±8.5 years. The serum levels of OPG and RANKL were determined by ELISA (Biomedica, Austria); the common carotid arteries (CCAs) were visualized using an Acuson X/10 ultrasonic complex equipped with a 7 MHz linear sensor in the β-mode prior to therapy and after 12-month therapy with INF. Results and Discussion. An increased OPG level was observed mostly in patients with RA duration up to 1 year; an increase in RANKL level was pronounced stronger in patients with PA duration over 2 years. The disturbance of structural and functional properties of the arterial bloodstream was revealed, manifesting itself as an increase in the intimamedia complex thickness, diameter and rigidity index of CCA that were stronger pronounced in patients with late onset RA. A correlation analysis showed the presence of reliable relationship between the RANKL and OPG levels and CCA remodeling parameters. INF therapy showed high clinical effectiveness and correction effect on the RANKL/OPG system. In addition, it was accompanied by a reduction of signs of CCA remodeling, which was stronger pronounced in patients with early RA. Conclusion. The results prove the reasonability of using INF at early stages of RA in order to optimize the therapy and achieve more efficient control of cardiovascular complications.

The article presents the results of researching the arterial wall endothelial function and stiffness parameters in 44 patients with various duration of IgM RF-seropositive rheumatoid arthritis (RA). The research of the endothelial function and arterial stiffness included the pulse wave contour analysis and reactive hyperemia test carried out with the use of “Angioscan-01” device (“Angioscan-Electronics” LLC, Russia). The pulse wave contour analysis in patients with RA determined the presence of “A”and “B”-type curves; augmentation (Alp), reflection (RI) and stiffness (SI) indices were significantly higher in patients with RA compared to the controls, more prominent changes of the researched parameters were determined in patients with the disease duration exceeding 2 years. When analyzing the parameters of reactive hyperemia test in patients with RA, a significant decrease in the occlusion index and the value of phase shift between channels was determined; such changes advanced along with the increase in the disease duration. Direct correlation relationships were determined between Аpl and SI indices and RA duration; inverse correlation relationships were determined between the occlusion index by amplitude and Apl, SI, RI indices in patients with the RA duration exceeding 2 years.

This article presents the results of research of serum levels of growth factors (VEGF-A, TGF-β1, FGF) and vasculature rigidity parameters in 54 patients with the Jg M-RF-seronegative variant of rheumatoid arthritis against the background of treatment with infliximab. Increase of serum levels of VEGF-A, TGF-β1, FGF was determined in examined patients compared to the control group. Disturbances of arterial vasculature structural-functional properties were also found out – all examined patients with RA had a significant decrease of pulse wave transmission time (РТТ), increase of rigidity and augmentation indices, as well as of pulse wave transmission velocity. It was determined that arterial vasculature rigidity correlated with serum levels of growth factors in the blood serum of examined patients with RA. Treatment with infliximab is accompanied by significant decrease of serum levels of VEGF-A, TGF-β1, FGF and decrease of vasculature rigidity in patients with RA.

В данной статье представлены результаты исследования сывороточного содержания ФНО-α, ИЛ-6, вч-СРБ, лептина и структурно-функциональных свойств сосудистого русла у 54 больных серонегативным по JgM РФ ревматоидным артритом (РА). Установлено повышение концентрации ФНО-α, ИЛ-6, вч-СРБ, лептина в сыворотке крови у обследованных больных в сравнении с контролем. Выявлены нарушения структурно-функциональных свойств артериального русла, характеризующиеся достоверным снижением у всех обследованных больных РА времени распространения пульсовой волны (РТТ), увеличением индексов ригидности, аугментации и скорости распространения пульсовой волны (СРПВ). Определены достоверные корреляционные связи между показателями активности иммунного воспаления, уровнем лептина и параметрами ремоделирования сосудистого русла у больных РА. Терапия инфликсимабом наряду с противовоспалительной эффективностью (снижение сывороточной концентрации вч-СРБ, ФНО-α, ИЛ-6) уменьшает гиперлептинемию, что сопровождается достоверным улучшением структурно-функциональных свойств сосудистого русла (снижением скорости пульсовой волны, индексов аугментации и ригидности, КИМ и диаметра ОСА).

The article introduces the investigation results of the proinflammatory cytokine concentration (Il-1β, Il-6, TNF-α), TNF-R1 in the blood of 54 patients with rheumatoid arthritis. The research has revealed the differences between the levels of the analyzed cytokines in the patients with different duration of rheumatoid arthritis (RA) that has shown the considerable increase in the concentration of TNFα, TNF-R1, IL-1β, at the extensive stage of the disease. The patients with the tardy RA revealed the highest possible concentration of IL-6 in the blood serum. Rituximab therapy was associated with the corrective influence on the cytokine status in the blood serum in the patients with the extensive stage of RA.

This article contains the results of research of serum levels of IL-6, sIL-6r, highly sensitive C-reactive protein (hsCRP), transforming growth factor-1 (TGF-1), leptin, as well as vasculature rigidity parameters in 118 patients with arterial hypertension (AH) and metabolic syndrome (MS). It was found out that the combination of AH and MS is accompanied by the higher activity of subclinical inflammation, hyperleptinemia and more prominent vasculature rigidity when compared to patients with AH. Significant correlation relationships were determined between immune status parameters, leptin level and vasculature remodeling parameters in patients with AH and MS. It was determined that telmisartan, apart from its antihypertensive activity, has a corrective impact on immune status parameters and pathological vasculature rigidity in patients with AH and MS.