Association of Anti-Citrullinated Peptide Antibodies With Coronary Artery Calcification in Rheumatoid Arthritis

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).

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.

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).

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.