OBJECTIVE: Citrullinated proteins have been found within atherosclerotic plaque. 
However, studies evaluating the association between anti-citrullinated protein 
antibodies (ACPAs) and imaging measures of atherosclerosis in patients with 
rheumatoid arthritis (RA) have been limited to seroreactive citrullinated 
fibrinogen or citrullinated vimentin and have rendered contradictory results. 
Therefore, our objective was to evaluate this association using an extended 
panel of ACPAs in a larger sample of RA patients without clinical cardiovascular 
disease (CVD).
METHODS: ACPAs were identified using a custom Bio-Plex bead assay in 270 
patients from 2 independent RA cohorts without clinical CVD, with the first one 
consisting of 195 patients and the other of 75 patients. Coronary artery calcium 
(CAC) was assessed by computed tomography as a measure of coronary artery 
disease.
RESULTS: High levels of anti-citrullinated histone H2B antibodies were strongly 
associated with higher CAC scores, compared with lower antibody levels 
(P = 0.001); this remained significant after adjustment for traditional CV and 
RA-specific risk factors (P = 0.03). No association between levels of ACPAs and 
CAC progression at 3 years was seen (P = 0.09); however, the number of 
progressors was small (n = 92).
CONCLUSION: Higher levels of ACPAs targeting Cit-histone H2B were associated 
with higher CAC scores when compared to lower antibody levels, suggesting a 
potential role for histone citrullination seroreactivity in atherosclerosis.