Patients with rheumatoid arthritis (RA) and other inflammatory joint diseases (IJDs) have an increased risk of premature death compared with the general population, mainly because of the risk of ...cardiovascular disease, which is similar in patients with RA and in those with diabetes mellitus. Pathogenic mechanisms and clinical expression of cardiovascular comorbidities vary greatly between different rheumatic diseases, but atherosclerosis seems to be associated with all IJDs. Traditional risk factors such as age, gender, dyslipidaemia, hypertension, smoking, obesity and diabetes mellitus, together with inflammation, are the main contributors to the increased cardiovascular risk in patients with IJDs. Although cardiovascular risk assessment should be part of routine care in such patients, no disease-specific models are currently available for this purpose. The main pillars of cardiovascular risk reduction are pharmacological and nonpharmacological management of cardiovascular risk factors, as well as tight control of disease activity.
Immunologic research into pathogenic mechanisms operating in autoimmune-mediated atherosclerosis initially focused on adaptive immunity. Current interest is directed to more basic inflammatory ...mechanisms. Chronic inflammation (innate immunity-associated) may trigger initial events that can lead to atherosclerotic cardiovascular disease. This chronic inflammation may start early in life and be perpetuated by classic atherosclerosis risk factors. Lipid peroxidation of low-density lipoprotein seems to be a key event in the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein triggers inflammatory and immunogenic events that promote endothelial dysfunction and the synthesis and secretion of pro-inflammatory cytokines, leading to an autoimmune response capable of accelerating the intracellular accumulation of lipids within atherosclerotic plaques. Oxidized low-density lipoprotein binds β2-glycoprotein I to form circulating complexes found in both autoimmune and non-autoimmune atherosclerosis. It is likely that β2-glycoprotein I and/or these complexes contribute to early atherogenesis by stimulating pro-inflammatory innate immunity through endogenous sensors and inflammasome/interleukin-1 pathways. We discuss the chronic inflammatory (innate) and autoimmune (adaptive) responses operating in atherosclerosis to discern the role of autoimmunity in atherosclerotic cardiovascular disease.
To determine a concentration-effect curve of adalimumab in rheumatoid arthritis (RA) patients taking into account the effect of methotrexate (MTX) on concentration and effect and to identify a ...therapeutic range for adalimumab concentrations.
In a prospective observational cohort study, 221 consecutive patients with RA were treated with 40 mg adalimumab subcutaneously every other week. The relationship between adalimumab trough level and clinical efficacy after 28 weeks of follow-up was determined in a concentration-effect curve. A receiver-operator characteristics (ROC) curve established a therapeutic cut-off concentration. The effect of MTX on adalimumab trough levels was shown by dividing patients that are and are not concomitantly using MTX in the concentration-effect curve and a concentration table.
Clinical efficacy improved with increasing adalimumab concentration and reached a maximum (mean disease activity score in 28 joints improvement of 2) with levels between 5-8 μg/mL. Levels exceeding 8 μg/mL were illustrated to have no additional beneficial effect on disease activity. The ROC curve showed an area under the curve of 0.695 (95% CI 0.626 to 0.764) for European League Against Rheumatism response and adalimumab levels: good responders versus non-responders and moderate responders. A cut-off of 5 μg/mL had a sensitivity of 91% and a specificity of 43%. Adalimumab levels are influenced by concomitant MTX use: patients on adalimumab monotherapy had a median adalimumab level of 4.1 μg/mL (IQR 1.3-7.7), whereas patients concomitantly taking MTX had a median level of 7.4 μg/mL (IQR 5.3-10.6, p<0.001).
Adalimumab trough levels in a range of 5-8 μg/mL are sufficient to reach adequate clinical response. These levels are influenced substantially by concomitant MTX use.
To evaluate the risk of cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids.
Retrospective analysis of exposure to glucocorticoids in a prospective cohort of 353 ...patients with rheumatoid arthritis followed from June 2001 up to November 2011 for incident cardiovascular disease in a hospital-based outpatient cohort in the Netherlands. Hazard ratios with 95%-confidence intervals were calculated for the association between different types of exposure to glucocorticoids and incident cardiovascular disease. Associations were adjusted for demographics, cardiovascular risk factors and disease related parameters.
Recent and current exposure to glucocorticoids were associated with incident cardiovascular disease, as was a longer duration of exposure and cumulative exposure to glucocorticoids. Adjustment for disease activity and severity negated the association.
In observational studies the finding of incident cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids is strongly confounded by indication due to high disease activity. The adverse cardiovascular effects of glucocorticoids might be balanced by positive effects working through inflammation control.
Abstract The increased mortality in rheumatoid arthritis (RA) is mainly due to (atherosclerotic) cardiovascular disease. The cardiovascular morbidity is also increased in comparison with the general ...population. This increased cardiovascular burden could be caused by 1) an enhanced prevalence of cardiovascular risk factors 2) under treatment of cardiovascular risk factors or 3) RA itself, particularly due to its chronic inflammatory component. Cardiovascular risk factors only partially explain the increased cardiovascular risk and it is becoming increasingly acknowledged that the underlying inflammation in RA plays an essential role. This is probably related to the fact that atherosclerosis also has an inflammatory etiology that is accelerated by RA. Similarly, it can be expected that effective suppression of this inflammatory process by disease modifying antirheumatic drugs and/or biologicals lowers the cardiovascular risk. Altogether, there is accumulating evidence that the increased cardiovascular risk in RA is comparable to that of type 2 diabetes and actually RA should be seen as a new, independent, cardiovascular risk factor for which cardiovascular risk management is essential.
The risk for developing cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients is 1.5 times higher compared to the general population. This risk is partly due to the contribution of ...systemic inflammation in increased atherogenesis, while an increased prevalence of "traditional" cardiovascular risk factors, such as hypertension and dyslipidemia, is also attributed to nearly 50% of the total CVD risk. Most anti-rheumatic medication partly reduces this CVD risk, primarily by reducing inflammation. The increased risk is recognized by most guidelines, which advise consequent screening and multiplying calculated risk scores by 1.5. However, screening in daily clinical practice is poorly done, and RA patients often have undiagnosed and untreated risk factors. In conclusion, even nowadays, RA patients still have an increased risk of developing CVD. Advances in anti-inflammatory treatment partly mitigate this risk, but RA patients need mandatory screening for CV risk factors to turn their CVD risk towards that of the general population.
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