Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

Objectives: To develop evidence-based EULAR

Risk of cardiovascular (CV) disease is increased among RA patients. High inflammatory burden associated with RA appears to be a key driver of the increased cardiovascular risk. Inflammation is linked with accelerated atherosclerosis and associated with a paradoxical inversion of the relationship between CV risk and lipid levels in patients with untreated RA, recently coined the lipid paradox. Furthermore, the inflammatory burden is also associated with qualitative as well as quantitative changes in lipoproteins, with the anti-inflammatory and atheroprotective roles associated with high-density lipoprotein cholesterol significantly altered. RA therapies can increase lipid levels, which may reflect the normalization of lipids due to their inflammatory-dampening effects. However, these confounding influences of inflammation and RA therapies on lipid profiles pose challenges for assessing CV risk in RA patients and interpretation of traditional CV risk scores. In this review we examine the relationship between the increased inflammatory burden in RA and CV risk, exploring how inflammation influences lipid profiles, the impact of RA therapies and strategies for identifying and monitoring CV risk in RA patients aimed at improving CV outcomes.

Established risk models generally underestimate (Systematic Coronary Risk Evaluation score, Framingham Risk Score, Reynolds risk score) or overestimate (QRisk II) CV risk in patients with RA.

In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.

Objective-Based on its role in inflammation and matrix degradation, we hypothesized a role for osteoprotegerin (OPG), RANK, and RANK ligand (RANKL) in coronary artery disease. Methods and Results-We examined the expression of various members of the OPG/RANKL/RANK axis in patients with stable and unstable angina and in the atherosclerotic lesions of apolipoprotein E-deficient (apoE Ϫ/Ϫ ) mice. Our findings were: (1) Serum levels of OPG were raised in patients with unstable angina (nϭ40), but not in those with stable angina (nϭ40), comparing controls (nϭ20); (2) mRNA levels of RANKL were increased in T-cells in unstable angina patients accompanied by increased expression of RANK in monocytes; (3) strong immunostaining of OPG/RANKL/RANK was seen within thrombus material obtained at the site of plaque rupture during acute myocardial infarction; (4) OPG/RANKL/RANK was expressed in the atherosclerotic plaques of apoE Ϫ/Ϫ mice, with RANKL located specifically to the plaques; and (5) Key Words: arteriosclerosis Ⅲ inflammation Ⅲ plaque stability N umerous inflammatory mediators seem to play a pathogenic role in coronary artery disease (CAD), promoting atherogenesis and plaque destabilization, leading to thrombus formation with development of acute coronary syndromes. 1,2 However, although the participation of inflammatory mediators in the atherosclerotic process has become widely recognized, the identification and characterization of the different actors are not fulfilled.Receptor activator of nuclear factor-kB ligand (RANKL), its membrane-bound receptor RANK and its soluble decoy receptor osteoprotegerin (OPG) are members of the tumor necrosis factor (TNF) receptor superfamily. These factors have been identified as candidate mediators for paracrine signaling in bone metabolism but are also involved in modulation of the immune response through interaction with dendritic cells, T-cell activation, and B-cell maturation. 3,4 The pleiotropic effects of the OPG/RANKL/RANK system, such as modulation of cell survival, mineralization and inflammation, make it an interesting candidate mediator in the progression and destabilization of atherosclerotic lesions. mRNA and protein expression of OPG and RANKL have been detected in atherosclerotic plaques in humans. 5,6 Moreover, raised serum levels of OPG are reported in CAD patients and have also been shown to predict cardiovascular mortality in elderly women. 7-9 Although these findings may suggest the involvement of the OPG/RANKL/RANK system in atherogenesis, our knowledge of the role of this system in human CAD, and particularly in acute coronary syndromes, is still limited.Based on its involvement in inflammation and matrix degradation, we in the present study attempted to further clarify the potential role of the OPG/RANKL/RANK system in atherogenesis and acute coronary syndromes by different approaches including clinical studies in patients with sta-

BackgroundExercise is considered important in the management of patients with rheumatic diseases, but the effect of high intensity exercises on disease activity is unknown.ObjectiveTo investigate the effectiveness of high intensity exercises on disease activity in patients with axial spondyloarthritis (axSpA).MethodAssessor blinded multicentre randomised controlled trial. 100 patients (aged from their 20s to their 60s) with axSpA were randomly assigned to an exercise group or to a no-intervention control group. The exercise group performed cardiorespiratory and muscular strength exercises at high intensity over 3 months. The control group received standard care and was instructed to maintain their usual physical activity level. Primary outcome was disease activity measured with the Ankylosing Spondylitis (AS) Disease Activity Scale (ASDAS, higher score=worst) and the Bath AS Disease Activity Index (BASDAI, 0–10, 10=worst). Secondary outcomes were inflammatory markers, physical function and cardiovascular (CV)-health. There was patient involvement in the design and reporting of this study.Results97 of the 100 (97%) randomised patients completed the measurements after the intervention. There was a significant treatment effect of the intervention on the primary outcome (ASDAS: −0.6 [–0.8 to –0.3], p<0.001 and BASDAI: −1.2 [–1.8 to –0.7], p<0.001). Significant treatment effects were also seen for inflammation, physical function and CV-health.ConclusionHigh intensity exercises reduced disease symptoms (pain, fatigue, stiffness) and also inflammation in patients with axSpA. It improves patients’ function and CV health. This debunks concerns that high intensity exercise might exacerbate disease activity in patients with axSpA.Trial registration numberNCT02356874.

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