Association between anti-citrullinated fibrinogen antibodies and coronary artery disease in rheumatoid arthritis


Objective: Antibodies against citrullinated fibrinogen (anti‐cit‐fibrinogen) have been implicated in both rheumatoid arthritis (RA) and cardiovascular (CV) risk in RA. The objective of this study was to examine the association between anti‐cit‐fibrinogens and coronary artery disease (CAD) outcomes. Methods: We performed the study in an RA cohort based in a large academic institution linked with electronic medical record data (EMR) containing data on CAD outcomes from medical record review. Using a published bead assay method, we measured 10 types of anti‐cit‐fibrinogens. We applied a score test to determine the association between the anti‐cit‐fibrinogens as a group with CAD outcomes. Principal components analysis (PCA) was performed to assess whether the anti‐cit‐fibrinogens clustered into groups. Each group was then also tested for association with CAD. Sensitivity analyses were also performed using a published ICD9 code group for ischemic heart disease (IHD) as the outcome. Results: We studied 1,006 RA subjects with mean age 61.0 (SD 13.0) years and 72.2% anti‐CCP positive. As a group, anti‐cit‐fibrinogen was associated with CAD (p=1.1e‐4). From the PCA analysis, we observed 3 main groups, of which only one group, containing 7 of the 10 anti‐cit‐fibrinogens, was significantly associated with CAD outcomes (p=0.015). In the sensitivity analysis, all anti‐cit‐fibrinogens as a group remained significantly associated with IHD (p=2.9e‐4) Conclusion: Anti‐cit‐fibrinogen antibodies as a group were associated with CAD outcomes in our RA cohort, with the strongest signal for association arising from a subset of the autoantibodies.

Arthritis Care & Research, in press