Abstract
BackgroundThe increased risk of cardiovascular events (CVE) in rheumatoid arthritis (RA) is not fully explained by traditional risk factors. Immuno-inflammatory mechanisms and autoantibodies could be involved in the pathogenesis of atherosclerotic disease. It has been suggested that anti-phosphorylcholine antibodies (anti-PC) of the IgM subclass may have atheroprotective effects. Here, we aimed to investigate the association between levels of IgM anti-PC antibodies with CVE in patients with early RA.MethodsThe study population was derived from the BARFOT early RA cohort, recruited in 1994–1999. The outcome of incident CVE (AMI, angina pectoris, coronary intervention, ischemic stroke, TIA) was tracked through the Swedish Hospital Discharge and the National Cause of Death Registries. Sera collected at inclusion and the 2-year visit were analyzed with ELISA to determine levels of anti-PC IgM. The Kaplan-Meier estimates and Cox proportional hazards regression models were used to compare CV outcome in the groups categorized by baseline median level of IgM anti-PC.ResultsIn all, 653 patients with early RA, 68% women, mean (SD) age 54.8 (14.7) years, DAS28 5.2 (1.3), 68% seropositive, and without prevalent CVD, were included. During the follow-up of mean 11.7 years, 141 incident CVE were recorded.Baseline IgM anti-PC above median was associated with a reduction in risk of incident CVE in patients aged below 55 years at inclusion, HR 0.360 (95% CI, 0.142–0.916); in males, HR 0.558 (0.325–0.958); in patients with BMI above 30 kg/m2, HR 0.235 (0.065–0.842); and in those who did not achieve DAS28 remission at 1 year, HR 0.592 (0.379–0.924). The pattern of associations was confirmed in the models with AUC IgM anti-PC over 2 years.ConclusionProtective effects of higher levels of innate IgM anti-PC autoantibodies on CVE were detected in younger patients with RA and those at high risk of CVE: males, presence of obesity, and non-remission at 1 year.
Highlights
The increased cardiovascular (CV) risk in rheumatoid arthritis (RA) is not fully explained by traditional risk factors and genetic markers [1, 2]
Patients and outcome assessment The study population was derived from the prospective observational BARFOT (Better Anti-Rheumatic PharmacO Therapy) cohort from secondary care in southern Sweden with newly diagnosed early RA according to the American College of Rheumatology (ACR) 1987 criteria [23]
Relative hazard ratios from Cox regression models were used to estimate the effect of IgM anti-PC on the outcome in total patient population and within the groups categorized by sex, ages, traditional risk factors, and disease characteristics with progressive adjustment if a p < 0.10: unadjusted, adjusted for age and sex, and further fully adjusted for traditional CV risk factors (BMI, smoking, hypertension, diabetes mellitus, hyperlipidemia)
Summary
The increased cardiovascular (CV) risk in rheumatoid arthritis (RA) is not fully explained by traditional risk factors and genetic markers [1, 2]. Anti-phosphorylcholine autoantibodies (anti-PC) have a role in maintaining the homeostasis of the immune system [8]. These autoantibodies serve “housekeeping” and could enhance clearance of damaged apoptotic cells, senescent IL-17+ T-cells, oxidized or otherwise modified lipoproteins, and induce intracellular blockade of inflammatory signaling cascades [7, 9]. The increased risk of cardiovascular events (CVE) in rheumatoid arthritis (RA) is not fully explained by traditional risk factors.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
