Abstract P677: Association of Antibodies to Citrullinated Protein Antigens (ACPA) With Coronary Artery Calcium and Abdominal Aorta Calcium in a Multi-Ethnic Community-Dwelling Population
Authors: Hughes-Austin Jan M , Katz Ronit , Firestein Gary , Robinson William , Criqui Michael H , Ix Joachim H 
Published: March 2023

Background:
Patients with rheumatoid arthritis (RA) have double the risk of cardiovascular (CV) events and greater extent of coronary artery calcium (CAC) compared to the general population. Antibodies to citrullinated protein antigens (ACPA) have been linked to CAC in patients with RA; and RA-related autoimmunity has been associated with CAC in Black women without RA. ACPA are detectable years before RA onset and in some individuals who do not develop RA. Given the association between vascular calcification and CV events in the general population, we investigated associations between ACPA and coronary and abdominal aorta calcification (AAC).

Methods:
In a randomly selected subset of 1968 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), we measured ACPA using a multiplex array of 28 different ACPA. Each ACPA was defined as positive if >95
th
percentile cut-off in MESA. The number of (+) ACPA were summed for each participant (range 0-28). We measured AAC and CAC using computed tomography scans. We evaluated associations between number of ACPA, individual ACPA and AAC and CAC using multivariable linear regression, adjusting for covariates and testing for interactions with gender and race/ethnicity.

Results:
Among 1828 MESA participants with complete data, average age was 65(10); were 50% female, 40% White, 13% Chinese, 21% Black, 26% Hispanic/Latino and 27% positive (+) for at least one ACPA. Among ACPA(+) participants, median number of ACPA was 1 (1, 6) and ranged from 1-28 ACPA. Number of ACPA was neither significantly associated with CAC severity (p=0.06) nor AAC severity (p=0.48). These associations did not differ by gender or race. However, several individual ACPA were associated with CAC and AAC. In particular, for every SD higher citrullinated ApoA antibody concentration (anti-cit-ApoA), CAC severity was 0.15 (0.07)% higher (p=0.03); and AAC severity was 0.07 (0.04) % lower (p=0.08) in fully adjusted analysis. Associations between anti-cit-ApoA and AAC severity were modified by gender (p
interaction
=0.02), where in women for every SD higher anti-cit-ApoA, AAC severity was 0.15 (0.06)% lower (p=0.007); and in men, AAC severity was 0.03 (0.05)% higher, although this association was not statistically significant (p=0.55). For every SD higher citrullinated Fibrinogen antibody (anti-cit-Fibrinogen) concentration, CAC severity was 0.14 (0.07) % higher (p=0.05); and AAC severity was 0.10 (0.04) % lower (p=0.01) in fully adjusted analysis. There was no significant interaction between anti-cit-Fibrinogen and gender or race.

Conclusion:
In a community-dwelling population without RA, ACPA were associated with higher CAC severity and lower AAC severity, independent of traditional CV risk factors. Because we did not expect the inverse association between ACPA and AAC severity, continued research is needed to better understand mechanisms explaining this association.