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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease associated with a high index of morbidity and mortality from cardiovascular diseases. We used 1H NMR to characterize the plasma glycoprotein and lipoprotein profiles of a cohort of patients with RA (n = 210) versus healthy individuals (n = 203) to associate them with the RA disease and its severity. Using 1H NMR, we developed a line-shape method to characterize the two peaks associated with glycoproteins (GlycA and GlycB) and its derived variables: areas of GlycB (Area GlycB) and GlycA (Area GlycA), shape factors of these two peaks (H/W = height/width), and the distance between them (Distance GlycB–GlycA). We also used the advanced lipoprotein test Liposcale (CE) to characterize the lipoprotein subclasses. The standard lipid panel and traditional inflammatory markers such as C-reactive protein, the erythrocyte sedimentation rate, fibrinogen, the rheumatoid factor, anticitrullinated peptide antibodies, and the DAS28 index have also been determined. RA patients presented a significant 10.65% increase in the GlycA associated area compared with the control group (p = 2.21 × 10–10). They also presented significantly higher H/W GlycA and GlycB ratios than the control population (H/W GlycB p = 7.88 × 10–8; H/W GlycA p = 5.61 × 10–8). The prediction model that uses the traditional inflammatory variables and the 1H NMR-derived parameters presented an AUC that was almost 10% higher than the model that only uses the traditional inflammatory variables (from 0.7 to 0.79 AUC). We have demonstrated that GlycA and GlycB variables derived from 1H NMR, along with classic inflammatory parameters, help to improve the classification of individuals with high RA disease activity.

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We aimed to study arterial stiffness variables in patients with rheumatoid arthritis (RA), specifically considering their associations with path model mediation analysis. We examined arterial stiffness expressed by the pulse wave velocity (PVW), augmentation index (AIx), distensibility, and clinical and biochemical characteristics in a cohort of 214 RA patients. Variable associations were analysed using multivariate linear regression analysis. We also used path model mediation analysis for PWV variable. Our results indicate that age, systolic blood pressure (SBP), and body mass index (BMI) were significantly associated with PWV, and collectively accounted for 32% of PWV variability. The parallel mediation analysis showed that SBP and BMI accounted for 21% and 7% (a total of 28%) of the total effect of age on PWV, respectively, indicating a partial mediation effect. The associated variables with AIx were age and tender joint count, while those with distensibility were BMI and sex, overall accounting for 16.5% and 4.7% of the variation in AIx and distensibility, respectively. We observed no associations of arterial stiffness with inflammatory variables, disease activity and duration, or cholesterol levels. In conclusion, in our population of RA patients, age is the most important variable that determines the increase in PWV. We have also shown that a significant proportion of the negative effects of age on PWV occurs through increases in SBP and BMI. In our study, lipid and inflammation variables were not associated with an increase in arterial stiffness.

ObjectiveTo advance the study of variables associated with subclinical atherosclerosis in rheumatoid arthritis (RA) with special consideration for the degree of disease activity, age and gender.MethodsThe carotid intima-media thickness (cIMT) and the presence of carotid atherosclerotic plaques along with clinical and biochemical characteristics were determined in 214 RA patients.ResultsAdjusted analysis reveals that men had a 0.059 mm significantly increased cIMT compared with women (p = 0.001; R2 = 3.8%) and that age was associated with cIMT (β = 0.0048 mm; p = 0.0001; R2 = 16%). Interestingly, we observed a significant interaction between gender and age. Thus, the effect of age on cIMT was significantly increased (12%) in men compared with women (p-value for interaction term = 0.041). Moreover, adjusted multivariable linear regression analysis revealed that disease activity score (DAS28) was significantly associated with cIMT in women (β = 0.021; p = 0.018: R2 = 0.03) but not men. In particular, women with high disease activity had a 0.079 mm increased cIMT compared with women in remission (p = 0.026). In addition, men in remission had a 0.134 mm increased cIMT compared with women in remission (p = 0.003; R2 = 8.7%). Active patients did not exhibit differences in cIMT values. Furthermore, 43% of patients presented carotid plaques. The variables independently associated with carotid plaques were age, smoking, health assessment questionnaire, erythrocyte sedimentation rate and rheumatoid factor (p<0.0001; R2 = 46%).ConclusionIn our cohort of patients with RA, DAS28 and age are differentially associated with cIMT in men and women. Our findings could explain the contradictory results that have previously been published in the literature.

Type 2 diabetes mellitus (T2DM), cardiovascular disease (CvD) and the cardiovascular effect of antidiabetic drugs are today critical medical issues, with the prevalence of T2DM in particular showing a steep increase worldwide, mainly due to unhealthy lifestyle habits. T2DM in association with obesity and other cardiovascular risk factors, results in the development of CvD, the leading cause of morbidity and mortality in patients with T2DM. Thus, treatment of T2DM is an individualized and complex challenge in which targeting cardiovascular risk factors is an important component in the decision making. given the cardiovascular adverse events associated with rosiglitazone, both the food and Drug Administration and the european Medicines Agency currently require the demonstration of cardiovascular safety of new antidiabetic drugs. Consequently, clinical trials to guarantee their cardiovascular safety are now obligatory. This review aims to summarize the available evidence on the cardiovascular effects and safety of the major drugs used in T2DM treatment and also to provide an overview of upcoming and ongoing clinical trials in this field. Our belief is that this review will be of substantial assistance to all medical doctors who are treating diabetic patients, namely primary care physicians, internal medicine doctors, endocrinologists, diabetologists and less well experienced personnel such as young doctors in training.

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Objectives We sought to determine if the status (primed/activated) of NADPH oxidase of articular PMN was correlated with rheumatic disease activity and TNF, IL-8 and GM-CSF synovial concentrations. Methods Knee joint fluid aspiration was performed in 17 patients, 11 with RA and 6 with spondyloarthropathy (SpA). Usual clinical and biological data were recorded for each patient, allowing a DAS28 scoring. NADPH oxidase activity was analysed with cytochrome c reduction technique. Phosphorylation of p47phox was evaluated with isoelectrofocusing and immunoblotting using a specific antibody. Cytokines concentrations were measured with ELISA kits. Results NADPH oxidase activity was increased in the majority of RA knee joints, and to a lesser extent in the SpA group. In the RA group, the NADPH oxidase activity was correlated positively with DAS28, with the PMN count in the synovial fluid, with the degree of p47phox phosphorylation, and with the synovial concentrations of TNF and IL-8. Concentrations of GM-CSF remained very low or undetectable in all patients. In the RA group only, the DAS28, the PMN count and the phosphorylation of p47phox were correlated with synovial concentrations of TNF and IL-8. Conclusion NADPH oxidase activation, through an increased phosphorylation of p47phox, seems to be implicated in joint inflammation during RA. This phenomenon could be related to high level of TNF and IL-8.