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Background Impaired macrovascular function is typically encountered in rheumatoid arthritis. Systemic inflammation and autoimmune-mediated atherosclerosis inherent in rheumatoid arthritis are considered to play a primary role in the development of macrovascular disease. On the contrary, the impact of rheological properties on macrovascular function in patients with rheumatoid arthritis remains substantially understudied. Objectives The aim of the present study was to investigate whether an association exists between macrovascular function and rheological parameters independent of inflammatory burden in a population of patients suffering from rheumatoid arthritis. Methods Consecutive patients with rheumatoid arthritis attending the Rheumatology Outpatient Clinic of our Department were included in the study. Blood sampling was performed for the measurement of biochemical and inflammatory markers. To evaluate macrovascular function, carotid ultrasound was used for the measurement of mean carotid intima-media thickness (cIMT). The non-invasive plethysmography technique of impedance cardiography was applied to all patients to detect the properties of the blood flow in the thorax and specifically measure hemodynamic parameters including stroke index (SI), cardiac index (CI), thoracic fluid content index (TFCI), and systemic vascular resistance index (SVRI). Results A total of 81 patients, 17 males and 64 females aged 61.8±12.2 years, with mean duration of 14.1±12.7 years of rheumatoid arthritis and a mean DAS28 score of 3.78±0.98 were included in the study. Mean body mass index (BMI) of the participants was 26.6±4.8 and mean systolic/diastolic blood pressure was 124.3±15.0/75.0±9.3 mmHg. Median erythrocyte sedimentation rate (ESR) was 16 (IQR: 10 – 29), median C-reactive protein (CRP) was 3.19 (IQR: 3.19 – 6.38) and total cholesterol levels were 205.0±34.4 mg/dl. Mean cIMT of the participants was 0.70±0.12 mm. Mean SI was 48.9±12.4 ml/m2, mean CI was 3.4±0.8 l/min/m2, mean TFCI was 18.2±3.5 l/kOhm/m2, and mean SVRI was 2063.5±669.3 dyn s cm-5m2. In the univariate analysis, only SVRI and CI among rheological parameters significantly correlated with cIMT (r=0.374, p=0.001 and r= -0.283, p=0.014, respectively). A significant association was observed between cIMT and ESR (r=0.304, p=0.024), but neither with DAS28 nor CRP. After adjustment for other parameters (age, sex, BMI, ESR, systolic blood pressure, cholesterol levels) in the multiple regression model, SVRI remained a significant independent predictor of cIMT (p=0.023). Conclusions Using non-invasive, easily applicable, low-cost technology, the present study demonstrates for the first time that impaired carotid vascular wall appears to be associated with hemodynamic parameters in rheumatoid arthritis patients, independent of inflammation and other factors potentially interfering. Whether appropriate pharmacological modification of hemodynamic parameters might result in an improvement of macrovascular function in patients with rheumatoid arthritis, and vice versa, warrants future studies. Disclosure of Interest None declared

Background Scleroderma is a disease hallmarked by microangiopathy; the extensive avascular areas developing in the course of the disease are clinically associated with severe tissue hypoxia and the formation of digital ulcers. Tissue oxygenation is further impaired through the development of tissue fibrosis. The proangiogenic factor VEGF is upregulated in all stages of the disease with little effect on efficient neovascularization. Surprisingly, no correlation between the expression of VEGF and HIF-1a could be documented in scleroderma skin biopsies in previous reports. Objectives The aim of this study was to investigate expression of HIF-1a and VEGF in naive scleroderma patients, and correlate histochemical findings with the capillaroscopic pattern and clinical manifestations. Methods Skin biopsies from 9 patients with scleroderma (diffuse/ limited) were analysed and compared to 10 normal skin biopsies. Patients were informed prior to the biopsy and gave their consent. Mean age of the patients was 52,22±14,37 yrs, and median duration of the symptoms 28 months [4-120]. Autoantibody profile, capillaroscopic pattern and clinical manifestations, e.g. digital ulcerations, was recorded. Paraffin sections of 3μm were stained with Abs against HIF-1a and VEGF according to standardized protocols. Results In the normal skin, there were rare immunoreactivecells for HIF-1a. In the dermis there was immunoreactivity of follicular keratinocytes of sweat and sebaceous glands and endothelial cells, in accordance with previously reported data. All skin biopsies from scleroderma patients were HIF-1a-positive. The staining was nuclear and it was observed throughout the keratinocytes of the epidermis. Nuclear expression of HIF-1a was also seen in sweat and sebaceous glands and in dermal inflammatory foci with distinct staining of endothelial cells and scattered staining of lymphocytes. In the normal skin, immunostaining for VEGF was mainly observed in suprabasal keratinocytes. In the dermis there was immunoreactivity of endothelial cells. In patients with scleroderma, immunostaining of epidermal keratinocytes was seen in all cases. The immunoreactivity was cytoplasmic. Immunostaining was also observed in endothelial cells of the dermis. No statistically significant differences in the expression of HIF-1a and VEGF, estimated semiquantitatively by immunohistochemistry, were recorded in patients at different stages at diagnosis according to capillaroscopic and clinical criteria. Conclusions To date, and despite low pO2 values measured in the skin of patients with systemic sclerosis, no pathophysiological connection could be proven between clinical hypoxia and increased levels of the oxygen-sensitive alpha-subunit of HIF-1. Our study is the first to show potent constitutive expression and accumulation of HIF-1a in the skin of scleroderma patients, even in early stages of the disease. The patients included in this study were treatment-naive, i.e. had not been previously exposed to any immuno- or vasomodulatory treatment. This observation contributes to the understanding of the pathophysiology of the disease. Further studies are needed in order to characterize downstream modulatory factors, which may interfere with efficient tissue neovascularization. Disclosure of Interest None Declared

We read with great interest the article by Genovese et al 1 on the effect of the B-cell activating factor (BAFF) antagonist tabalumab in rheumatoid arthritis patients with inadequate response to tumour necrosis factor (TNF)a blockade. The results of this study indicated a moderate effect of tabalumab early (week 6/week 9) after initiation of therapy, both in terms of clinical as well as laboratory markers of disease activity, which however was not significantly sustained later on in the course of treatment (week 16). In the previous decade, biological therapies that target the B cell have become established in the treatment of rheumatoid …