FRI0078 SERUM IRISIN LEVEL IN RHEUMATOID ARTHRITIS PATIENTS: ITS RELATIONSHIP TO DISEASE ACTIVITY AND CARDIOVASCULAR MANIFESTATIONS

Abstract

Background:Active Rheumatoid Arthritis (RA) is associated with considerable changes in body composition, lipids, adipokines and insulin sensitivity. RA is an independent risk factor for CVD. The mechanisms leading to synovial inflammation are similar to those found in unstable atherosclerotic plaque. Irisin is a metabolic hormone and a novel adipomyokine related to insulin resistance and endothelial functions (1).Objectives:To investigate the relationship between serum irisin levels, disease activity and cardiovascular risk in RA patients, and to test its performance in predicting subclinical atherosclerosis in RA patients.Methods:60 RA patients fulfilling the 2010 ACR/EULAR RA Classification Criteria and 30 healthy controls were recruited for serological testing of irisin levels. BMI was calculated. Waist/hip ratio was measured. RA disease activity was assessed by DAS28-ESR. Disability was assessed by HAQ-DI in its Arabic version. Serum ESR, CRP, glycated hemoglobin (HbA1c), lipid profile (serum level of cholesterol, triglyceride, HDL, LDL and cholesterol/ LDL ratio), insulin levels were measured in all patients and controls. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used to calculate insulin resistance. Carotid intimal medial thickness (C-IMT), an indicator of atherosclerosis, was measured by carotid doppler ultrasonography. Echocardiography was performed to assess cardiac abnormalities. Our RA patients were classified twice; first, according to cardiovascular abnormalities and second, according to cut-off values of DAS28.Results:Serum irisin levels were significantly lower in RA patients (9.84 ± 10.56)ng/ml compared to controls (20.48±13.82)ng/ml (p<0.001). BMI values were significantly higher in all patients than controls (P= 0.035), while waist/hip ratio in female patients only were significantly higher (P= 0.007).We found a negative correlation between serum irisin and DAS28-ESR (r = -0.455, P-value 0.005)& HAQ-DI (r = -0.309, P-value 0.016). There was a negative correlation between serum irisin level and parameters of cardiovascular risk including anthropometric measurements (BMI and waist/hip ratio), HOMA-IR (r=−0.371, p=0.009) and C-IMT (r=−0.511, p<0.001). No correlation could be detected between irisin and lipid profile. The frequency of cardiovascular (CV) involvement in RA patients was 45% (27 patients) (11.6 % with echocardiographic abnormalities and 40% having increased C-IMT). Patients with CV involvement showed lower serum irisin level, increased disease activity assessed by DAS28 and increased disease disability assessed by HAQ-DI with statistically significant difference (P < 0.001, P < 0.05 and P < 0.001 respectively). Classifying the patients based on cut-off values of DAS28 into 3 groups (low disease activity, moderate and high disease activity), we found a statistically significant difference between the irisin levels of the 3 groups, being lowest among highly active patients (P= 0.014). c-IMT values were significantly higher in highly active patients (P= 0.04). Assessing the biomarker’s performance as an independent indicator of subclinical atherosclerosis in RA patients using ROC curve, it showed an excellent ability (AUC 0.8, P <0.001). As regarding its ability to differentiate patients with high disease activity, it showed a very good performance (AUC 0.73, P <0.001).Conclusion:In RA patients, serum irisin level was significantly lower and perform better than traditional yardsticks in identifying disease activity. It may act as an independent indicator of subclinical atherosclerosis in RA patients. Serum irisin level may be responsible for increased cardiovascular risk in those patients.