Background/Purpose: Although the association between rheumatoid arthritis (RA) and cardiovascular disease (CVD) is established, the exact mechanism is not known. Subjects who later develop RA were shown to have increased risk of myocardial infarction (MI) in the preclinical period prior to RA symptoms indicating that autoimmunity might be a risk factor for CVD. Therefore, we tested the hypothesis that RA-related autoantibodies are independent risk factors for subclinical atherosclerosis and subsequent clinical CVD events.

Methods: MESA is a multicenter population based study cohort prospectively collecting CVD outcome and risk factor data in 6814 middle-aged to elderly multi-ethnic participants since 2000. At MESA baseline, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP-2) by ELISA and coronary artery calcium (CAC) by CT were measured in 6557 AA, Caucasian, Hispanic and Chinese participants who were then followed for 7.1 years for coronary heart disease (CHD) Hard endpoints (MI, resuscitated cardiac arrest, CHD death) and CVD Hard endpoints (MI, cardiac arrest, CHD death, stroke, stroke death). We assessed the associations between baseline RF/anti-CCP and CAC stratified by race/gender using logistic regression adjusting for traditional CVD risk factors. We used Cox regression to determine race/gender-specific associations between RF/anti-CCP and clinical CVD endpoints.

Results: 12.2% had CAC >=300; After 7.1 years, 3.0% had Hard CHD endpoints; 4.8% had Hard CVD endpoints. RF IgM, RF IgA and anti-CCP were positive in 15.9%, 8.7%, and 2.0%, respectively. 4.0% were positive for both and 20.6% were positive for either RF isotype. RA-related autoantibody positivity varied with race and was highest in AA’s (RF: p<0.001, anti-CCP: p<0.003). RF and anti-CCP were associated with CAC in Caucasian and AA women after adjustment for traditional risk factors (Table 1). Table 2 demonstrates strong associations between RA-related autoantibodies and clinical CVD events in AA women. There were no clear associations in Hispanic and Chinese participants.

Table 1.  Adjusted* Odds Ratios (95% CI) of Having Degrees of CAC by Autoantibody Positivity in Caucasian Women and AA Women

RA-related Autoantibodies CAC Levels 0 99 CAC>300 vs. CAC=0 Caucasian Women (N=1,323) RF IgM 2.2 (1.5 – 3.3) 1.4 (0.8 – 2.7) 1.5 (0.8 – 2.8) RF IgA 1.7 (0.9 – 3.1) 0.9 (0.3 – 2.5) 2.3 (1.0 – 5.5) Either RF isotypes 2.0 (1.4 – 3.0) 1.2 (0.7 – 2.2) 1.7 (1.0 – 3.1) Both RF isotypes 2.2 (0.9 – 5.0) 1.5 (0.5 – 4.9) 2.1 (0.7 – 6.7) CCP 0.9 (0.3 – 2.7) 1.5 (0.5 – 5.3) 0.9 (0.2 – 4.4) AA Women (N=1000) RF IgM 1.2 (0.8 – 1.8) 1.4 (0.8 – 2.5) 1.5 (0.8 – 2.8) RF IgA 1.0 (0.6 – 1.8)         2.2 (1.1 – 4.2) 2.4 (1.2 – 5.0) Either RF isotypes 1.2 (0.8 – 1.7) 1.6 (0.9 – 2.7) 1.4 (0.8 – 2.6) Both RF isotypes 1.1 (0.5 – 2.3) 2.7 (1.1 – 6.3) 4.0 (1.6 – 9.6) CCP 2.0 (0.9 – 4.8) 1.1 (0.2 – 5.1) 4.0 (1.3 – 12.5) *Adjusted for age, smoking status, BP, BMI, HDL-c, LDL-c, DM, aspirin use, and cholesterol and BP medication use

Table 2. Adjusted* Hazard Ratios (95% CI) for the Incidence of Clinical Cardiovascular Events over 7.1 Years Follow Up by Autoantibody Positivity  Caucasian Women RA-related Autoantibodies CHD Hard Endpoints (N=31) CVD Hard Endpoints (N=56) RF IgM 1.2 (0.4 – 3.0) 1.8 (0.9 – 3.4) RF IgA 1.1 (0.3 – 4.5) 0.5 (0.1 – 2.2) Either RF isotypes 1.2 (0.5 – 3.0) 1.6 (0.8 – 3.0) Both RF isotypes 0.8 (0.1 – 6.1) 0.4 (0.1 – 3.1) CCP NA NA AA Women CHD Hard Endpoints (N=19) CVD Hard Endpoints (N=37) RF IgM 1.7 (0.7 – 4.5) 2.1 (1.1 – 4.0) RF IgA 5.0 (1.9 – 12.7) 3.4 (1.7 – 6.9) Either RF isotypes 2.5 (1.0 – 6.4) 2.7 (1.4 – 5.1) Both RF isotypes 4.5 (1.6 – 13.0) 3.3 (1.5 – 7.3) CCP 1.1 (0.1 – 8.3) 2.3 (0.7 – 7.7) *Adjusted for age, smoking status, BP, BMI, HDL-c, LDL-c, DM, aspirin use, and cholesterol and BP medication use. CHD Hard event outcomes include MI, resuscitated cardiac arrest, and CHD death.  CVD Hard events include MI, cardiac arrest, CHD death, stroke, and stroke death.

Conclusion: This study demonstrates that RA-related autoantibodies are associated with subclinical and clinical atherosclerosis in a population based cohort. These findings indicate autoimmune factors may play a role in the pathogenesis of atherosclerosis, even in individuals without RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibodies-are-associated-with-subclinical-atherosclerosis-and-cardiovascular-endpoints-in-caucasian-and-african-american-women-in-a-prospective-study-the-multi-ethnic-study-of-atherosclero/