HIGHER LEVELS OF NATURAL ANTI-PHOSPHORYLCHOLINE ANTIBODIES ARE ASSOCIATED WITH LOWER RISK OF INCIDENT CARDIOVASCULAR EVENTS IN YOUNGER PATIENTS WITH RHEUMATOID ARTHRITIS

• The increased cardiovascular (CV) risk in rheumatoid arthritis (RA), especially in seropositive RA, is not fully explained by traditional risk factors. Immuno-inflammatory mechanisms and autoantibodies could be involved in the pathogenesis of atherosclerotic disease. Recent studies have suggested that anti-phosporylcholine antibodies (anti-PC) of IgM subclass counteract the generation of senescent and IL-17+ T-cells, have atheroprotective effects and may play a role in formation and stabilization of atherosclerotic plaque.Objectives:To investigate the association between IgM anti-PC antibodies with cardiovascular (CV) morbidity in patients with RA in age and sex groups and by serostatus.Methods:The study population was derived from the BARFOT early RA cohort, recruited in 1994-1999. The outcome was CV events i.e. AMI, angina pectoris, coronary intervention, ischemic stroke and TIA tracked through the Swedish Hospital Discharge and the National Cause of Death Registries. The RA-disease measures and traditional risk factors were assessed according to the protocol. Sera collected at inclusion and the 2-year visit were analyzed with ELISA to determine levels of anti-PC IgM (Athera CVDefine kit, Athera Biotechnologies AB). The Kaplan-Meier estimates and Cox proportional-hazards regression models were applied. Analysis were stratified by median level of IgM anti-PC and performed within strata of age, sex and RA-autoantibodies.Results:In all, 654 patients with early RA, 68% women, mean (SD) age 55(14.7) years, DAS28 5.2(1.3), 60% RF-positive and 60% ACPA-positive without prevalent CVD were included in this analysis. The level of IgM anti-PC at baseline was median (IQR) of 60.9(36.4-94.9) and at 2 years 56.0(32.3-84.2) U/ml. During follow-up of > 10 years, 141 incident CV events (21.6%) were registered. The levels of anti-PC both at inclusion and after 2 years of observation were lower in participants who experienced CV event than in those who did not, p=0.020 and p=0.012.The CV event-free survival differed between patients with levels of anti-PC above median compared with those with levels below, p=0.003 by log-rank test. The risk for incident CV event showed a 0.6-fold hazard (95% CI, 0.4-0.8) among patients with higher anti-PC levels as compared with those with lower levels, p=0.003. In the age groups, the risk for incident CV event was lower in patients aged <55 years at inclusion than in those who were older, hazard ratio (HR) 0.40 (0.17-0.94), p=0.036. This result persisted when adjusted for sex and all traditional risk factors, HR 0.36 (0.14-0.92), p=0.032. Also, the risk for incident CV events was lower in patients with higher anti-PC levels in females, HR 0.61 (0-39-0.45), and double RF- and ACPA- negative patients, 0.44 (0.21-0.90), in crude analyses.The favourable effect of anti-PC at baseline and the CV outcome was not observed in ages >55 years, males, ACPA+ and RF+ patients. There were no significant association between anti-PC level at 2 years and outcome.Conclusion:These results suggest that higher levels of IgM anti-PC are associated with a lower risk of incident CV events over 10 years in younger patients. The favourable atheroprotective effect of IgM anti-PC may be a part of explanation of lower risk of atherosclerotic disease in younger persons, females and in those with seronegative RA.Acknowledgments :6th Framework Program of the European Union (grant LSHM-CT-2006-037227 CVDIMMUNE)Disclosure of Interests:Sofia Ajeganova: None declared, Maria Andersson: None declared, Johan Frostegård Grant/research support from: Unconditional competitive grant from Amgen, related only to PCSK9, not the topic of this abstract, Ingiäld Hafström: None declared

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