Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Anti-b2-Glycoprotein-1 (b2GP1) IgA Ab Are Highly Prevalent and Predict Vulnerable Coronary Plaque in Asymptomatic Patients with Rheumatoid Arthritis (RA).

Karpouzas1,  George A., Ahmadi2,  Naser, Choi2,  Tae-Young, Hajsadeghi2,  Fereshteh, Munoz2,  Silvia, Budoff2,  Mathew

Harbor-UCLA, Long Beach, CA
Harbor-UCLA

Background:

B2GP1 is present in atherosclerotic plaque and b2GP1 IgA Ab have been associated with documented atherosclerosis, including myocardial infarction (MI). RA pts have higher risk of MI; however, the prevalence of b2GP1 IgA Ab in RA and their relevance to plaque characteristics are unknown. We evaluated prospectively the presence of b2GP1 IgA and its associations with coronary plaque prevalence, burden and consistency in asymptomatic pts with RA.

Methods:

We report on the first 74 of 150 recruited pts from a single center (table 1). Lupus Anticoagulant (LA), Anticardiolipin (ACL), and b2GP1 IgG, IgM and IgA were assessed by standard methods (DRVVT, Varelisa, and Bindazyme Elisa respectively). Positive (+) tests were confirmed 3 months later. Pts underwent coronary plaque evaluation with 64+ slice cardiac Computed Tomography Angiography (CTA); this non-invasive modality includes an initial non-contrast phase assessing coronary calcium, followed by a contrast scan that detects plaque with equal accuracy to conventional angiography, and is superior in the assessment of non-calcified, lipid-rich, non-obstructive or "vulnerable" plaque. Coronary trees were graded in a standard fashion according to AHA. Non-parametric tests were used for data analysis; linear regressions between disease parameters and plaque, as well as relative risk regression models for plaque burden and consistency were constructed after adjustments for age, sex, classic coronary risk (CRF), RA duration and severity.

Results:

B2GP1 IgA was highly prevalent in asymptomatic RA pts, by contrast to all other Ab classes and isotypes (p<0.0001). No differences in age, disease duration, or laboratory parameters were seen in (+) vs. negative (-) pts.The number of diseased arterial segments was not different in (+) vs. (-) pts; however, the total plaque burden, and more importantly the NC/mixed plaque was significantly higher in the affected arteries of the b2GP1 IgA (+) ones (p=0.0001). In fact, b2GP1 IgA had the strongest correlation with NC/ mixed plaque burden than any other factors tested (p=0.003). After adjustments for all CRF, RA duration and severity (DAS28-3v), b2GP1 IgA (+) pts had a 47% higher plaque burden risk for total and 52% higher risk for "vulnerable" plaque (p=0.01 and 0.004 respectively).

Conclusions:

B2GP1 IgA Ab previously reported in symptomatic pts with documented atherosclerosis, are highly prevalent in asymptomatic RA pts. They independently predict higher total, but more importantly higher vulnerable, NC plaque burden more robustly than the composite of classic CRF. As such, they may represent a useful screening test for "high-risk" plaque in asymptomatic pts with RA.

Table 1. Patient Characteristics

Positive testX1X2(>=3 months later)
Any ACL (%)1.60
LA (%)7.74.6
Any a-b2GP1 (%)39***29***
a-b2GP1-IgA (%)39†29†
a-b2GP1-IgM (%)1.41.4
a-b2GP1-IgG (%)1.40
*** p < 0.0001 for b2GP1 vs. any ACL & LA.† p<0.0001 for b2GP1-IgA vs. IgM & IgG.
Variableb2GP1-IgA (-): 41b2GP1-IgA (+): 33p
DAS28-3v-ESR3.1 ± 13.2 ± 0.90.5
TNFi-treated (%)59.674.10.3
n (%) with plaque26 (63.3)20 (60.6)0.7
n (%) assessed segments164 (100)132 (100)
n (%) diseased segments38 (22)29 (22)0.9
  Non-calcified/mixed25 (15.2)23 (17.4)0.5
  Calcified13 (6.8)6 (4.6)0.2
Total plaque burden score1.5 ± 2.14.3 ± 3.80.001
  Non-calcified/mixed1.4 ± 2.13.9 ± 3.70.001
  Calcified0.7 ± 2.41.8 ± 3.10.09
Linear Regressionsr (NC plaque burden)r2b (95% CI)p
Cor Risk F (composite)0.370.142.9 (1.04–5.7)0.04
B2 GPI IgA0.410.162.5 (1.2–3.9)0.003
DAS28-3v0.230.061.2 (1.05–3.7)0.04
CRP (mg/dl)0.040.0021.04 (0.31–1.2)0.6
ESR0.160.030.03 (-0.01–0.07)0.16
TNFi therapy-0.25-0.07-1.63 (-3.1–-0.3)0.03
Relative Risk Regression*b2GP1-IgA (-) b2GP1-IgA (+)p
  Total plaque burden score1 (ref) 1.47 (CI=1.06–4.76)0.01
  Non-calcified/mixed1 (ref) 1.52 (CI=1.18–3.34)0.004
  Calcified1 (ref) 1.09 (CI=0.72–3.71)0.09
* Adjusted for age, gender, all traditional CRF, RA duration and DAS28-3v.

To cite this abstract, please use the following information:
Karpouzas, George A., Ahmadi, Naser, Choi, Tae-Young, Hajsadeghi, Fereshteh, Munoz, Silvia, Budoff, Mathew; Anti-b2-Glycoprotein-1 (b2GP1) IgA Ab Are Highly Prevalent and Predict Vulnerable Coronary Plaque in Asymptomatic Patients with Rheumatoid Arthritis (RA). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2165
DOI: 10.1002/art.29929

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