Background/Purpose:
Citrullinated
proteins have been found in atherosclerotic plaques. However, contradictory results
currently exist regarding the association of anti-citrullinated peptide antibodies (ACPAs) with
coronary artery disease in RA patients.  Our objective was to test this
association in two different cohorts of RA patients without known
cardiovascular disease (CVD).

Methods:
One-hundred and
ninety-five patients underwent
cardiac multi-detector
row computed tomography for coronary artery calcium (CAC) measurement and concurrent serum testing of a
panel of 17 specific ACPAs using a custom Bio-Plex bead array. With a high ACPA
level defined as ≥ 75^th percentile, the association of each
ACPA and CAC was tested.  A second independent validation cohort of 75 RA
patients without CVD was investigated assessing the association of CAC with an
expanded panel of 30 ACPAs. CVD risk factors
and RA characteristics
were adjusted for.

Results: In cohort 1, the mean age was 59
±9, with 51% of the patients being females, 85% self-identified as white, 65%
were RF or anti-CCP positive, and had a median disease duration of 9years
(4-17). In cohort 2, the mean age was 54±13, predominantly females (85%), only 37%
were white, 79% were RF or anti-CCP positive, and had a median disease duration
of 7years (3-17). In both studies, the DAS28 CRP score was in the moderate
range, and about 40% were hypertensive. Cohort 2 study subjects were more
likely to have diabetes (13% vs. 7%), and fewer were smokers (7% vs. 12%). In cohort
1, no association between ACPA reactivity and CAC was found. In cohort 2, high
levels of ACPAs targeting citrullinated vimentin and the citrullinated
vimentin58-77 were associated with higher levels of CAC (p=0.05 and p=0.04,
respectively) in univariable linear regression models. However, when adjusted for
potential confounders, this association lost statistical significance (p=0.11
and p=0.12, respectively) (Figure 1). 

Conclusion: Higher levels of the ACPAs tested in
our panel were not significantly associated with CAC in two cohorts of RA
patients without known CVD. However, it is conceivable that other as yet
unidentified citrullinated vascular proteins could be targets for APCAs.

Figure
1. Association
of Anti-Citrullinated Vimentin with Coronary Artery Calcium Score.

Figure 1. Mean and 95% C.I. values of the log transformed coronary artery
calcium (CAC)+1* per category of ACPA reactivity against citrullinated
vimenin58-77 and citrullinated vimentin (dichotomized at the 75^th
percentile). **Adjusted analyses accounts for age, RA disease duration,
hypertension, diabetes and TNF-inhibitor use.