Objectives Reverse cholesterol transport (RCT) is a major antiatherogenic function of high density lipoprotein (HDL). In the current work, the authors evaluated whether the RCT capacity of HDL from rheumatoid arthritis (RA) patients is impaired when compared to healthy controls. Methods HDL was isolated from 40 patients with RA and 40 age and sex matched healthy controls. Assays of cholesterol efflux, HDL’s antioxidant function and paraoxanase-1 (PON-1) activity were performed as described previously. Plasma myeloperoxidase (MPO) activity was assessed by a commercially available assay. Results Mean cholesterol efflux capacity of HDL was not significantly different between RA patients (40.2%±11.1%) and controls (39.5%±8.9%); p=0.75. However, HDL from RA patients with high disease activity measured by a disease activity score using 28 joint count (DAS28>5.1), had significantly decreased ability to promote cholesterol efflux compared to HDL from patients with very low disease activity/clinical remission (DAS28<2.6). Significant correlations were noted between cholesterol efflux and the DAS28 (r=−0.39, p=0.01) and erythrocyte sedimentation rate, (r=−0.41, p=0.0009). Higher plasma MPO activity was associated with worse HDL function (r=0.41/p=0.009 (antioxidant capacity); r=0.35, p=0.03 (efflux)). HDL’s ability to promote cholesterol efflux was modestly but significantly correlated with its antioxidant function (r=−0.34, p=0.03). Conclusions The cholesterol efflux capacity of HDL is impaired in RA patients with high disease activity and is correlated with systemic inflammation and HDL’s antioxidant capacity. Attenuation of HDL function, independent of HDL cholesterol levels, may suggest a mechanism by which active RA contributes to increased cardiovascular (CV) risk.

Objective. To characterize the antiinflammatory function of high-density lipoprotein (HDL) in patients with rheumatoid arthritis (RA) and to identify specific differences in HDL-associated proteins and enzymes that distinguish proinflammatory HDL from normal, antiinflammatory HDL.Methods. We studied 132 RA patients. The antiinflammatory function of HDL was assessed by a cellfree assay, and proinflammatory HDL was defined by an HDL inflammatory index >1. Plasma and HDLassociated protein levels of apolipoprotein A-I (Apo A-I), haptoglobin, hemopexin, hemoglobin, and myeloperoxidase (MPO) were measured by direct and sandwich enzyme-linked immunosorbent assays, respectively. Lecithin:cholesterol acyltransferase (LCAT) activity was measured by a commercially available assay.Results. Age, disease activity, the presence of erosive disease, non-Caucasian race, and smoking were significantly associated with proinflammatory HDL on multivariate analysis. Patients with proinflammatory HDL had higher measures of systemic inflammation, and a significant correlation was observed between RA disease activity (using the Disease Activity Score in 28 joints) and the HDL inflammatory index (r ‫؍‬ 0.54, P < 0.0001). Compared with patients with antiinflammatory HDL, patients with proinflammatory HDL had significantly higher levels of haptoglobin, hemoglobin, Apo A-I, and MPO associated with HDL (P < 0.05 for all comparisons except MPO, which was P ‫؍‬ 0.05). LCAT activity was lowest in patients with proinflammatory HDL, but was also significantly reduced in RA patients with antiinflammatory HDL as compared with healthy controls (P ‫؍‬ 0.001).Conclusion. Proinflammatory HDL in this RA patient cohort was associated with active disease and an altered protein cargo as compared with antiinflammatory HDL in RA patients and in healthy controls. The antiinflammatory function of HDL was inversely correlated with systemic inflammation in RA patients and may warrant further investigation as a mechanism by which active RA increases cardiovascular morbidity and mortality.Premature cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with

Objective. To assess the course of the modified Rodnan skin thickness score (MRSS) in 3 large, multicenter, double-blind, randomized controlled trials (RCTs) of patients with diffuse cutaneous systemic sclerosis (dcSSc) with different baseline disease durations, as defined from the date of onset of the first dcSSc symptom (excluding Raynaud's phenomenon) or from the date of onset of the first dcSSc-related symptom (including Raynaud's phenomenon). Conclusion. Our study confirms recent findings that in patients entered into these 3 RCTs, skin thick- Methods. Data from 3 RCTs examining high-dose versus low-dose D-penicillamine (D-Pen

Objective-To assess gender differences in disease characteristics and treatment responses over time in a DMARD-naïve seropositive early rheumatoid arthritis (RA) cohort.Methods-DMARD-naïve, seropositive early RA (<14 months) patients with polyarticular disease were recruited by the Western Consortium of Practicing Rheumatologists. Each patient was examined at study entry, after 6 and 12 months, and yearly thereafter. Clinical and demographic data were collected. We investigated gender differences in baseline disease characteristics and treatment using Chi-square, Mann-Whitney and t tests. We used generalized estimating equations (GEE) models for repeated measures to examine whether the rate of change of specific disease outcomes during the first 2 years after DMARD initiation were significantly influenced by gender.Results-At baseline, men (n=67) and women (n=225) had similar disease activity and radiographic damage; men, however, had significantly worse erosion, while women had worse joint space narrowing. Despite similar treatment, women had worse disease progression over the 2-year follow up, as assessed by trends in DAS28ESR4, physician global scores and tender joint counts. In the GEE model, gender was significantly associated with the rate of change of DAS28ESR4 scores (p=0.009), though not being independently associated with disease activity. Self-reported measures (HAQ-DI, patient global scores, fatigue, pain) were worse among women at baseline and throughout the study period. Men were more likely to achieve remission. Conclusion-At baseline, men and women had similar disease activity and joint damage. Responses to treatment over time were, however, better among men in this pre-biologic era; women had worse progression despite similar treatment.

Objective To evaluate the effect of sustained ACR/EULAR Boolean remission on residual joint inflammation assessed by magnetic resonance imaging (MRI) and to secondarily evaluate other clinical definitions of remission, within an early seropositive rheumatoid arthritis (RA) cohort. Methods A subcohort of 118 RA patients were enrolled from patients who completed the two-year double-blind randomized Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Patients received a single contrast enhanced 1.5 Tesla MRI of their most involved wrist. Two readers scored MRI for synovitis, osteitis, tenosynovitis, and erosions. Clinical assessments were performed every three months during the trial and at time of MRI. Results The subcohort was 92% seropositive with mean age 51 years, duration 4.1 months, and DAS28-ESR 5.8 at TEAR entry. Total MRI Inflammatory Scores (tenosynovitis+synovitis+osteitis) were lower among patients in clinical remission. Lower MRI scores were correlated with longer duration of CDAI remission (rho=0.22, p=0.03). At the time of MRI, 89 patients had no wrist pain/tenderness/swelling; however, all 118 patients had MRI evidence of residual joint inflammation after two years. No statistically significant differences in damage or MRI inflammatory scores were observed across treatment groups. Conclusion This is the first detailed appraisal describing the relationship between clinical remission cut-points and MRI inflammatory scores within a RA RCT. The most stringent remission criteria (2011 ACR/EULAR and CDAI) best differentiate the total MRI inflammatory scores. These results document that 2-years of triple therapy or TNF+methotrexate treatment in early RA does not eliminate MRI evidence of joint inflammation.