Antibodies to Citrullinated Protein Antigens are Associated with Risk of Cardiovascular Disease in Community Dwelling Women: The Multi-Ethnic Study of Atherosclerosis

Background/Purpose:

Risk for cardiovascular (CV) events in patients with RA is double what it is for the general population. Antibodies to citrullinated proteins (ACPA) are detectable years before RA onset and in some individuals who do not develop RA. It is not known whether ACPA, in the absence of clinical RA , is associated with CV events. Among men and women without RA in a multi-ethnic community dwelling population, we investigated associations between ACPA and incident CV events.

Methods:

Among a randomly selected subset of 1617 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study designed to determine risk factors and progression of subclinical and clinical cardiovascular disease, we measured ACPA using a multiplex array of 38 different individual 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 0-38). We examined the association of the number of ACPA with all-cause mortality, incident heart failure, angina, MI, and a composite of all CV events using Cox proportional hazards models and adjusting for covariates and tested for interaction by sex.

Results:

Mean age was 65 years. The sample was 50% women, 40% Caucasian; and 31% had ≥ 1 (+) ACPA. Among ACPA(+) participants, the median number (+) was 2 (IQR 1-6). ACPA(+) and ACPA(-) participants were similar in age, gender, and race/ethnicity, but ACPA(+) participants had higher IL-6 concentrations. Associations between number of ACPA and incident CV events differed significantly by sex (p_interaction < 0.05 ). In women, but not men, higher number of (+) ACPA was significantly associated with risk of angina, MI, and CV events. No associations were observed among men.

Conclusion:

In a community-living population without RA, higher number of ACPA was associated with incident angina, MI, and CV events in women, but not men. To better understand mechanisms, future studies are needed to determine whether ACPA are associated with subclinical CVD markers in people without RA, but with RA-related autoimmunity, and whether these associations differ by sex.