Association Between Anti–Citrullinated Fibrinogen Antibodies and Coronary Artery Disease in Rheumatoid Arthritis

Abstract

Objective: Antibodies against citrullinated fibrinogen (anti–Cit-fibrinogen) have been implicated in rheumatoid arthritis (RA) and associated with cardiovascular 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 containing information on CAD outcomes from medical record review. Using a published bead-based 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 additionally tested for association with CAD. Sensitivity analyses were also performed using a published International Classification of Disease, Ninth Revision code group for ischemic heart disease (IHD) as the outcome. Results: We studied 1,006 RA subjects (mean ± SD age 61.0 ± 13.0 years; 72.2% anti–cyclic citrullinated peptide positive). As a group, anti–Cit-fibrinogen was associated with CAD (P = 1.1 × 10−4). From the PCA analysis, we observed 3 main groups, of which only 1 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 = 2.9 × 10−4). 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.