Calcification of coronary arteries in early rheumatoid arthritis prior to anti-rheumatic therapy.

Accelerated coronary atherosclerosis is common in patients with rheumatoid arthritis (RA). To examine coronary artery calcification (CAC) frequency and severity, its correlation with traditional risk factors (TRF) of cardiovascular diseases (CVD) and inflammatory markers in patients with early RA prior to anti-rheumatic therapy. RA adult patients (ACR/EULAR criteria, 2010, duration ≤ 12 months, without prior administration of disease-modifying anti-rheumatic drugs, glucocorticoids) underwent 32-row scanning for CAC scoring. Agatston, volume and mass calcium scores were calculated. Additionally, we used calculators on the website of the Multi-Ethnic Study of Atherosclerosis. 74 RA patients (women n = 54 (73%), median age 56 years, median RA duration 6 months) with moderate/high RA activity (median DAS28 [ESR] 5.4) were enrolled within the framework of the observational study. Most of the patients had multiple TRFs of CVD and subclinical organ damage. CAC has been detected in 34 (46%) early RA patients. Calcification severity was significantly higher in men and in patients with ischemic heart disease (IHD). In patients younger than 45 years (n = 16) CAC was not detected. Among patients older than 45 years (n = 58), the frequency of CAC was 59%: asymptomatic patients-n = 46 (48%), IHD patients-n = 12 (100%). Among asymptomatic patients the presence of CAC associated with a significantly higher frequency of arterial hypertension (1.6 fold) compared with cases without CAC. Coronary age in asymptomatic patients with CAC and IHD patients was significantly greater than their actual age. More than half of early RA patients older 45 years had CAC. The presence and severity of CAC correlated positively with TRFs, but not with lipid levels and RA activity.

The Effects of Rituximab on Lipids, Arterial Stiffness and Carotid Intima-Media Thickness in Rheumatoid Arthritis.

The aim of the study was to examine lipid profiles, arterial stiffness (AS), carotid intima-media thickness (cIMT), in 55 women with RA without overt cardiovascular disease (СVD) treated with rituximab (RTX).The following parameters were recorded before and 24 weeks after RTX therapy (2 infusions of 500 or 1,000 mg RTX intravenously, fortnightly): plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, DAS 28-ESR, serum C-reactive protein (CRP), RF IgM, AS (SI - stiffness index, RI - reflection index) by digital volume pulse contour analysis (Micro Medical, UK), and common cIMT by high-resolution B-mode carotid ultrasound. Based on the European League Against Rheumatism (EULAR) criteria, patients were divided into two groups: 1) moderate/good response to RTX therapy after 24 weeks (41 patients, 75%), 2) no response to RTX therapy (14 patients, 25%). Effective RTX therapy resulted in 9% increase in TC, 23% increase in HDL-C and 14% decrease in atherogenic index, 57% decrease in SI and 24% decrease in RI. We observed a 9% decrease of cIMTmax at 24 weeks. The improvement of cardiovascular parameters was accompanied by statistically significant decreases of CRP, ESR, RF IgM and DAS 28 in group 1 (P < 0.05). There were not significant changes in lipid profile, AS parameters, and cIMT in group 2. Two infusions of RTX in case of moderate/good EULAR effect of therapy exerted favorable effects on lipid profile, AS and cIMT in women with RA without overt CVD.

Rituximab Downregulates Gene Expression Associated with Cell Proliferation, Survival, and Proteolysis in the Peripheral Blood from Rheumatoid Arthritis Patients: A Link between High Baseline Autophagy-Related ULK1 Expression and Improved Pain Control.

Objective. To clarify molecular mechanisms for the response to rituximab in a longitudinal study. Methods. Peripheral blood from 16 RA patients treated with rituximab for a single treatment course and 26 healthy controls, blood and knee articular cartilages from 18 patients with long-standing RA, and cartilages from 14 healthy subjects were examined. Clinical response was assessed using ESR, ACPA, CRP, RF, DAS28 levels, CD19+ B-cell counts, bone erosion, and joint space narrowing scores. Protein expression in PBMCs was quantified using ELISA. Gene expression was performed with quantitative real-time PCR. Results. A decrease (p < 0.05) in DAS28, ESR, and CRP values after rituximab treatment was associated with the downregulation of MTOR, p21, caspase 3, ULK1, TNFα, IL-1ß, and cathepsin K gene expression in the peripheral blood to levels found in healthy subjects. MMP-9 expression remained significantly higher compared to controls although decreased (p < 0.05) versus baseline. A negative correlation between baseline ULK1 gene expression and the number of tender joints at the end of follow-up was observed. Conclusions. The response to rituximab was associated with decreased MTOR, p21, caspase 3, ULK1, TNFα, IL-1ß, and cathepsin K gene expression compared to healthy subjects. Residual increased expression in MMP-9, IFNα, and COX2 might account for remaining inflammation and pain. High baseline ULK1 gene expression indicates a good response in respect to pain.