Rheumatic diseases (RD), such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, vasculitis, gout are associated with increase in cardiovascular morbidity and mortality. The main causes of increased cardiovascular risk are inflammatory heart and vascular lesions, accelerated progression of atherosclerosis and side effects of drug therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in clinical practice and are on the list of the most prescribed medications. It is known that NSAIDs have a negative effect on the cardiovascular system (CVS). However NSAIDs may decrease the intensity of inflammation, which is an independent risk risk factor for CVS pathology. Therefore in patients with RD it is theoretically possible to reduce the severity of cardiovascular side effects when using NSAIDs. The article discusses the issues of NSAID’s cardiovascular safety, the molecular mechanisms underlying the negative effect of them on CVS, critically evaluated the results of main studies concerning the cardiovascular safety of NSAIDs in chronic inflammatory diseases.

The purpose of this study was to determine the level of nesfatin-1 (NF-1) in the blood serum of healthy volunteers and patients with rheumatoid arthritis (RA) to establish the threshold for normal values of this parameter and to reveal the relationship between the level of NF-1 and clinical manifestations of RA. We examined 170 people, of which 110 patients with RA and 60 donors who made up the comparison group. The mean level of serum nesfatin-1 in healthy subjects was 31.61 ± 3.17 ng/ml (M ± σ). The level of normal values of nesfatin-1 in healthy individuals, defined as M ± 2σ, was from 25.27 to 37.95 ng/ml. These studies showed the relationship between the concentration of NF-1 and the severity of clinical manifestations of RA. We found that a higher serum level of NF-1 was characteristic of patients with a more severe clinical course of the disease. The data obtained indicate that high level of NF-1 positively correlates with higher concentrations of C-reactive protein and ESR. This data indirectly proves the pro-inflammatory effect of NF-1 and confirms the hypothesis about the primary role of systemic inflammation in the pathogenesis of RA.

BackgroundRecent studies have been suggested that adipokines and myokines may be implicated in bone metabolism and pathogenesis of osteoporosis (OP).1 Previous studies have revealed inverse correlation between irisin levels and vertebral fragility fractures, but no significant correlation was found between irisin and bone mineral density (BMD) as well as with lean weight. There is no previously published data about irisin levels in rheumatoid arthritis (RA) patients.2–4 ObjectivesTo investigate serum irisin levels in patients with RA.MethodsWe studied 170 people: 110 RA patients (mean age 53.58±12.32; hereinafter M±SD) and 60 healthy controls. All patients with RA were examined using dual-energy X-ray absorptiometry using LUNAR DPX-Pro densitometer. Osteoporotic fractures were confirmed by X-ray examination and/or by anamnesis data. All patients were passed through extensive clinical and laboratory examination, including N-terminal propeptide of procollagen type I, C-telopeptide of type I collagen, 25(OH)-vitamin D concentration. Serum irisin levels were measured by ELISA (BioVender test system, Cat №RAG018R).ResultsThe mean concentration of irisin in RA group was 14.48±7.07 mg/ml, which was significantly lower than of healthy donors – 20.49±4.82 mg/ml (p<0,001). We subsequently divided all of RA patients into two groups: the first one (n=44) included patients with reduced serum irisin levels (below 10.85 mg/mL), and the second one (n=66) with normal irisin levels (above 10.85 mg/ml). The first group had significantly higher activity (DAS28), increased frequency of extra-articular manifestations, disease duration more than 5 years, class III of functional joints disability and lower levels of 25(OH)-vitamin D. We also observed higher incidence of pathological bone fractures in this group (p=0,047). There wasn’t any significant correlation between serum irisin level and BMD at any localization, lean, or fat weight. We did not reveal any difference of bone turnover markers (serum C-terminal telopeptide of type I collagen, serum N-terminal propeptide of type I procollagen (P1NP)) between these groups.ConclusionsWe have therefore revealed relationships between decreased serum irisin levels, 25(OH)-vitamin D concentration and higher incidence of pathological bone fractures in RA patients. We found no connexion between serum irisin levels and BMD at any site and body composition. We could consequently suppose, that irisin levels may reflect bone quality or increased fall risk.References[1] Palermo A, Strollo R, Maddaloni E, et al. Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity. Clin Endocrinol (Oxf)2015;82(4):615–9.[2] Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature2012;481(7382):463–8.[3] Colaianni G, Cuscito C, Mongelli T, et al. Irisin enhances osteoblast differentiation in vitro. Int J Endocrinol2014;2014:902186.[4] Sivordova LE, Zavodo...

Objective: Analysis and generalization of data related to visfatin involvement in the pathogenesis of inflammation at various stages of rheumatoid arthritis. Data Synthesis: Visfatin is an adipocytokine which has also been identified in non-adipose tissues. It influences directly on the maturation of B cells, which are involved in autoantibody production and T cell activation. Visfatin can promote inflammation via regulation of pro-inflammatory cytokines including TNF, IL-1β and IL-6. The concentration of circulating visfatin in rheumatoid arthritis patients is higher compared to healthy individuals. Several studies suggest that visfatin level is associated with rheumatoid arthritis activity, and its elevation may precede clinical signs of the relapse. In murine collagen-induced arthritis, visfatin levels were also found to be elevated both in inflamed synovial cells and in joint vasculature. Visfatin blockers have been shown to confer fast and long-term attenuation of pathological processes; however, most of their effects are transient. Other factors responsible for hyperactivation of the immune system can participate in this process at a later stage. Treatment of rheumatoid arthritis with a combination of these blockers and inhibitors of other mediators of inflammation can potentially improve treatment outcomes compared to current therapeutic strategies. Recent advances in the treatment of experimental arthritis in mice as well as the application of emerging treatment strategies obtained from oncology for rheumatoid arthritis management could be a source of novel adipokine-mediated anti-rheumatic drugs. Conclusion: The ongoing surge of interest in anticytokine therapy makes further study of visfatin highly relevant as it may serve as a base for innovational RA treatment.

Both drugs demonstrated a good tolerability and a low incidence of side effects. The efficacy of etoricoxib was significantly higher than that of meloxicam.