Background Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease. The incidence of cardiovascular (CV) disease is increased in patients with RA, compared with the general population, which is related to the fact that atherosclerosis has an inflammatory etiology. Several studies revealed that RA is associated with systemic bone loss, and long-term glucocorticoid therapy is also known to affect CV events as well as bone health such as osteoporosis. Especially in postmenopausal women, the prevalence of osteoporosis and its complications are important medical issues. Objectives In the present study, we investigated the bone mineral density (BMD) for the carotid plaque formation in RA patients in the Kyungpook National University Hospital Atherosclerosis Risk in Rheumatoid Arthritis (KARRA) cohort study. Methods After a baseline evaluation for KARRA enrollment, RA patients were prospectively followed up for 5 years or until deaths. We analysed the demographic findings, conventional CV risk factors and RA disease activity. Carotid ultrasound at baseline and year 5 was performed to evaluation of the intima-medial thickness (IMT) and presence and progression of carotid plaque. A total 323 patients (272 female) with RA, who performed dual-photon x-ray absorptiometry and carotid ultrasound, were included. We assessed disease activity of RA, risk factors for atherosclerosis including hypertension, diabetes mellitus and dyslipidemia, presence of carotid plaque, BMD and cumulative glucocorticoid doses. Results A total of 417 RA patients were included in the baseline KARRA cohort, and 327 patients with RA were followed for the 5 year period. Of the 417 baseline RA patients, 212 patients had no carotid plaque. At year 5, new carotid plaque formation was found in 91 of 214 patients who underwent BMD examination. The BMD in the l-spine, femur, and radius was significantly lower in patients with carotid plaques (n=154), compared to patients without plaques (n=172) (1.016 g/cm2±0.22 vs. 1.066±0.18, p=0.013 for l-spine; 0.817±0.15 vs. 0.865±0.14, p<0.001 for femur; 0.542±0.14 vs. 0.605±0.13, p<0.001 for radius. In postmenopausal patients, the BMD was significantly lower in carotid plaque group (n=93) than non-plaque group (n=109) (0.962±0.171 vs. 1.056±0.174, p<0.001 for L spine; 0.780±0.14 vs. 0.857±0.12, p<0.001 for femur; 0.502±0.110 vs. 0.593±0.112, p<0.001 for radius). The cumulative steroid dose was confirmed in postmenopausal female patients, and the glucocorticoid dose was correlated with new carotid plaque formation. (r=0.334, p=0.04). Multivariate logistic regression analysis revealed that but radius BMD (p=0.04) was independent risk factors for new carotid plaque formation during the 5 year followed period after correlation with cumulative glucocorticoid dose, but l-spine (p=0.06) and femur BMD (p=0.07) were not statistically significant. Conclusions This study shows formation of new plaques after long-term follow-up depends on the juxta-articular bone health in postmenopausal RA patients. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA), which is an autoimmune chronic arthritis, leads to elevated rates of disability and mortality. The main causes of mortality identified among RA patients are increased incidences of cardiovascular (CV) disease, which accounts for one-third to one-half of the premature deaths, infection and cancer. In our previous study, we identified that cumulative inflammatory burden contributes to the development of carotid atherosclerosis through a synergistic interaction with conventional CV risk factors in patients with RA. During the 2 years follow-up period, the mortality rate was 2.4% (10/412), and the main causes of death were infection (4/10) and CV disease (3/10). Objectives To investigate the incidences of mortality and CV disease in patients with RA in the 5 year Kyungpook National University Hospital Atherosclerosis Risk in Rheumatoid Arthritis (KARRA) prospective study. Methods A total of 372 patients with RA and 162 healthy controls were followed up for 5 years or until deaths in a prospective KARRA cohort study (412 patients and 221 controls at baseline). To detect the presence and progression of carotid atherosclerosis, we performed carotid ultrasound at baseline and 5 year. We analysed the incidence of CVD, conventional CV risk factors, RA disease activity and severity markers, medication histories, mortality rate, and causes of death. Results During 5 year follow-up period, the mortality rate was 10.7% (44/412) in RA patients and 1.4% (3/221) in healthy controls (p<0.001), while the incidence of CVD were 11.4% (47/412) in RA patients and 0.9% (2/221) in healthy controls (p<0.001). Among CVD in RA patients, cerebrovascular accident (CVA) and cardiovascular event (CVE) were 17 (36.2%) and 30 (63.8%) events, respectively. Major causes of death included infection (21/44, 47.7%), CVD (12/44, 27.3%), and others (11/44, 25%). The mean age, presence and number of carotid plaques, functional class, modified Korean version of the HAQ (mKHAQ), tender joint count (TJC), swollen joint count (SJC), ESR and CRP, and conventional CV risk factors at baseline and cumulative ESR (ESR area under the curve), DAS28-ESR and DAS28-CRP at year 5 were significantly associated with mortality in RA patients. Multivariate logistic regression analysis showed that the presence of carotid plaque (OR 6.22 [95% CI 1.08–24.99; p=0.031]), mKHAQ (OR 1.04 [95% CI 1.01–1.12; p=0.014]), and ESR (OR 1.09 [95% CI 1.03–1.16; p<0.001]) at baseline and cumulative ESR (ESR area under the curve) (OR 1.047 [95% CI 1.01–1.13; p=0.048]) and DAS28-ESR (OR 1.55 [95% CI 1.08–2.21; p=0.016]) at year 5 were independent risk factors for mortality of RA patients. Conclusions During the follow-up period of 5 years, the mortality rate and prevalence of CV disease were significantly increased in RA patients, compared to the controls. Furthermore, main causes of death were infectious disease and CV disease. Furthermore the risk factor for CVD and mortality is carotid plaque which is determined by disease activity and CV risk factors. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease which causes juxta-articular and generalized bone loss. Several studies revealed that bone mineral density (BMD) is associated with atherosclerosis. Objectives In the present study, we investigated the association between BMD and RA disease activity and the carotid atherosclerosis in RA patients based Kyungpook National University Hospital Atherosclerosis Risk in Rheumatoid Arthritis (KARRA) cohort study. Methods A total of 323 patients with RA, who performed dual-photon x-ray absorptiometry and carotid ultrasound, were included. We assessed RA disease activity, risk factors for atherosclerosis including hypertension, diabetes mellitus and dyslipidemia, presence of carotid plaque, carotid intima-media thickness (IMT), and BMD. BMD was measured at the lumbar spine (L-spine, L1-L4), femur neck (total femur neck) and distal forearm (total radius), and low BMD was defined as a T score of -1.0 or less. Results The BMD in the L-spine, femur, and radius was significantly lower in patients with carotid plaques (n=152), compared to patients without plaques (n=171) (1.014 g/cm2 ± 0.21 vs. 1.066 g/cm2 ± 0.18, p=0.016 for L-spine; 0.816 g/cm2 ± 0.16 vs. 0.863 g/cm2 ± 0.13, p<0.001 for femur; 0.542 g/cm2 ± 0.13 vs. 0.603 g/cm2 ± 0.12, p<0.001 for radius). The frequency of low BMD in these areas was also higher in patients with carotid plaques, compared to patients without plaques (52.7% vs. 47.5%, p=0.045 for L-spine; 56.0% vs. 44.0%, p=0.001 for femur; 60.6% vs. 39.4%, p<0.001 for radius). Carotid IMT showed a significant difference between patients with low BMD and those with normal BMD (0.84 mm ± 0.14 vs. 0.80 mm ± 0.19, p=0.025 for L-spine; 0.83 mm ± 0.15 vs. 0.80 mm ± 0.18, p=0.045 for femur; 0.85 mm ± 0.15 vs. 0.77 mm ± 0.18, p <0.001 for radius). In subgroup analysis, patients with the highest IMT quartile had a significantly lower BMD in all the regions than those with the lowest IMT quartile (61.2% vs. 37.7%, p=0.004 for L-spine; 59.5% vs. 35.1%, p=0.003 for femur; and 71.4% vs. 28.6%, p<0.001 for radius). Multivariate logistic regression analysis demonstrated that BMD at radius (OR 4.995, 95% CI [1.067–10.276], p<0.001), DAS28-ESR (OR 1.906, 95% CI [1.042–3.046], p=0.036), and dyslipidemia (OR 2.334, 95% CI [1.164–3.156], p=0.02) were risk factors for presence of carotid plaques. Conclusions The present study showed that carotid atherosclerosis was influenced by both disease activity and impaired bone health. References Im CH et al. Inflammatory burden interacts with conventional cardiovascular risk factors for carotid plaque formation in rheumatoid arthritis. Rheumatology (Oxford). 2015 May;54(5):808–15. Disclosure of Interest None declared

Background In our previous study, we identified that cumulative inflammatory burdern contributes to the development of carotid atherosclerosis through a synergistic interaction with conventional cardiovascular (CV) risk factors in patients with rheumatoid arthritis (RA). However, it is controversial whether the presence of joint destruction which result from inflammatory burden may be a risk factor for carotid atherosclerosis. Objectives To investigate whether intima-media thickness (IMT) and plaques of carotid artery are influenced by radiographic joint destruction in patients with RA. Methods A total of 186 patients with RA were included in the present study. Plain X-ray of joints were used to assess the severity of joint destruction. We developed a new radiographic scoring system, named Rheumatoid Arthritis-Radiographic Severity Score (RA-RSS), which scores 21 joint groups with the modified Steinbrocker method. The following joint groups were included: 2 proximal interphalangeal (PIP) joint group, 2 metacarpophalangeal (MCP) joint group, 2 wrist joint group, 2 elbow joint group, 2 shoulder joint group, 1 atlantoaxial joint group, 2 hip joint group, 2 knee joint group, 2 ankle joint group, 2 tarsometatarsal (TMT) joint group, and 2 metatarsophalangeal (MTP) joint group. The grade was determined by the worst changes in each joint group of PIP, MCP, TMT, and MTP joints. RA-RSS grades are assigned as follows: 0 = No radiographic changes; 1 = mild destruction of bone and cartilage; 2 = moderate destruction of bone and cartilage or joint deformities; 3 = Severe destruction of bone and cartilage or bony ankylosis (Score ranges from 0–63). We performed carotid ultrasound to detect the presence of carotid atherosclerosis. Results Among 186 patients who were graded using RA-RSS, 110 patients had carotid plaques (59.1%). RA-RSS was significantly higher in patients with plaques compared to patients without plaques (11.2±8.79 vs. 7.6±7.72, p=0.004). Patients were divided into two groups by the cut-off value of plaque development as determined using receiver operating characteristic (ROC) curves: 115 (61.8%) patients with RA-RSS <10 and 71 (38.2%) with RA-RSS ≥10. There was a significant difference between the groups with respect to the presence of plaques (48.7% vs. 76.1%, p<0.001), while there was no difference in mean carotid IMT (0.87±0.19 vs. 0.88±0.14, p=0.684). The mean age, the presence of conventional CV risk factors, Korean version of the modified HAQ (mKHAQ), DAS28-ESR, and RA-RSS ≥10 were significantly associated with plaque development. Multivariate logistic regression analysis showed that RA-RSS ≥10 (OR 2.94 [95% CI 1.48–5.84]) and the presence of conventional CV risk factors (OR 2.30 [95% CI 1.21–4.35]) were independent risk factors for plaque development. Conclusions The present study shows that radiographic destruction over peripheral joints, which directly reflects cumulative inflammatory burden, is a strong independent risk factor for plaque development that is associated with CV events and mortality. References Churl Hyun Im, et al. Inflammatory burden interacts with conventional cardiovascular risk factors for carotid plaque formation in rheumatoid arthritis. Rheumatology (Oxford). 2015 May;54(5):808–15. Disclosure of Interest None declared

AimTo investigate the effects of LY2405319, an analogue of fibroblast growth factor 21 (FGF21), on glucose homeostasis in streptozotocin (STZ)‐induced insulin‐deficient mice (STZ mice).MethodsNine‐week‐old male C57BL/6J mice were administered a single intraperitoneal injection of STZ (150 mg/kg). One week later, after confirmation of hyperglycaemia, saline or LY2405319 (5 mg/kg) was injected subcutaneously daily for 4 weeks. Changes in glucose homeostasis, energy metabolism and brown adipose tissue (BAT) function were assessed.ResultsThe STZ mice had elevated blood glucose and reduced plasma FGF21 levels, impaired glucose uptake in the BAT, and BAT mitochondria with absent or swollen cristae and fewer lipid vacuoles. LY2405319 significantly reduced blood glucose levels and this was associated with increased BAT glucose uptake and changes in gene expression and morphology, indicating improved mitochondrial lipid metabolism in the BAT. Importantly, the ability of LY2405319 to lower blood glucose in STZ mice was compromised after removing interscapular BAT.ConclusionsOur results show that LY2405319 reduces blood glucose levels in insulin‐deficient diabetes by improving BAT metabolism. Additional studies investigating the therapeutic potential of FGF21 for the treatment of type 1 diabetes are warranted.