Background: Antibodies to citrullinated proteins (ACPA) are elevated in patients with rheumatoid arthritis (RA) and have been linked to altered left ventricular (LV) structure and function in RA. ACPA are detectable years before RA onset and in some individuals who do not develop RA. Among individuals without RA and without heart failure in MESA, we investigated associations between ACPA, LV mass, and LV ejection fraction (LVEF).
Methods: In a cross-sectional subsample of 1232 MESA participants, we measured ACPA using a multiplex array of 38 different ACPA. Each ACPA was defined as positive (+) if > 95th percentile cut-off in MESA. Number of (+) ACPA were summed for each participant (range 0-38). We compared ACPA(-) to ACPA(+) participants, and examined the association of number of ACPA with both outcomes. LVmass (g) and LVEF (%) were measured on cardiac MRI. We analyzed associations using generalized linear regression and adjusted for covariates listed in the table.
Results: Mean age was 65 years. The sample was 50% women, 40% Caucasian; and 31% had ≥ 1 (+) ACPA. Among ACPA(+) participants, median number (+) was 2 (IQR 1-6). ACPA(+) participants were similar to ACPA(-) participants in age, gender, and race/ethnicity, but had higher IL-6 levels. Mean LVmass for ACPA(+) vs ACPA(-) participants was 147g(39) and 146g(39), respectively; mean LVEF was 69%(7) and 70%(8), respectively. In adjusted analysis, LVmass and LVEF did not differ significantly between ACPA(+) and ACPA(-) participants. However, for every higher number of (+) ACPA, LVEF was 0.07% lower (p=0.02). Among individual ACPA, antibodies to Filaggrin 48-65 arg2v1cyc (p=0.04), histone 2B (p=0.01), and histone 2Bcit (p=0.02) were significantly associated with lower LVEF. No individual ACPA was associated with LVmass.
Conclusion: In community-dwelling individuals without RA or heart failure, greater numbers of detectable ACPA were associated with lower LVEF, but not LVmass. Future studies are required to determine whether ACPA are associated with incident heart failure.