Objective: Although the association between rheumatoid arthritis (RA) and cardiovascular disease (CVD) is established, the exact mechanism is unknown. We tested the hypothesis that RA-related autoantibodies are independent risk factors for subclinical atherosclerosis and subsequent clinical CVD events.
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) is a community-based cohort study prospectively collecting CVD outcome and risk factor data in middle-aged to elderly multiethnic participants since 2000. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP2) by enzyme-linked immunosorbent assay, and coronary artery calcium (CAC) by computed tomography, were measured at MESA baseline in 6,532 participants who were followed for 10.3 years for coronary heart disease (CHD) end points (myocardial infarction, cardiac arrest, CHD death) and CVD end points (included CHD end points, stroke, stroke death). Multivariable logistic regression and Cox regression assessed associations between RF/anti-CCP and CAC or CVD end points.
Results: IgM RF, IgA RF, anti-CCP, and either RF isotype predictors were positive in 15.8%, 8.7%, 2.0%, and 20.6%, respectively. A total of 12.2% had CAC ≥300, 7.1% had CHD end points, and 10.2% had CVD end points. IgA RF and anti-CCP were associated with CAC ≥300 in African American women (odds ratio [OR] 2.4 [95% confidence interval (95% CI) 1.2-5.1] and OR 4.1 [95% CI 1.3-12.7], respectively). RA-related autoantibodies were also associated with clinical CVD events in African American women (anti-CCP: OR 5.3 [95% CI 2.4-12.0]; either RF isotype: OR 2.4 [95% CI 1.4-4.0]). There was a trend for association between autoantibodies and CAC in white women. No associations were found in men.
Conclusion: RA-related autoantibodies are associated with subclinical and clinical atherosclerosis in African American women from a community-based non-RA cohort, indicating autoimmune factors may play a role in the pathogenesis of atherosclerosis.
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