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.


Elevations in ApoC-III Containing Apolipoprotein Complexes Predict Coronary Atherosclerosis Progression in Rheumatoid Arthritis Patients.

Bathon3,  Joan M., Centola4,  Michael, Giles2,  Jon T., Knowlton5,  Nicholas, Wages5,  Joshua, Payne5,  Adam J., Cavet1,  Guy

Crescendo Biosciences, Inc., South San Francisco, CA
Johns Hopkins Univ, Baltimore, MD
Johns Hopkins Univ Ste, Baltimore, MD
Oklahoma Med Research Foundation, Oklahoma City, OK
Oklahoma Medical Research Foundation, Oklahoma City, OK

Purpose:

Higher rates of cardiovascular (CV) associated events and mortality in rheumatoid arthritis (RA) cannot be accounted for with conventional lipid measures. However, alterations in the equilibrium among apolipoprotein complexes that traffic plasma lipids may have atherogenic consequences in RA.

Method:

Apolipoprotein complexes were measured at baseline in RA patients participating in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis (ESCAPE RA) study by precipitation and immunoturbidimetric analysis. Coronary artery calcium (CAC), a measure of coronary atherosclerosis, was assessed by cardiac computed tomography (CT) at two timepoints spanning approximately 3.5 years. Patients with a change in CAC >=1 were designated as progressors, and patients with no change or improvement in CAC were designated as nonprogressors. Univariate comparisons were made using t-tests. To model all the ApoC-III containing complexes together, we combined them using a Principal Component Analysis (PCA). Multivariate analyses were performed using logistic regression.

Results:

Baseline DAS 28 and ethnicity did not differ significantly between the groups (p=0.53 & p =0.419 respectively). However, gender and age distributions were significantly different between the groups, (p=0.011 & p=0.009, respectively). Of the 152 participants who had CAC measurements at two time points, 89 (59%) were progressors and 63 (41%) nonprogressors. Of the 12 apolipoprotein complexes measured, baseline mean values of 7 were statistically significantly higher in the progressors, compared to nonprogressors (see fig. 1). Interestingly, in contrast to the complexes not associated with progression, these 7 complexes all contain ApoC-III, which is predominantly a triglyceride carrier. All 7 complexes, when combined via PCA, were statistically associated with progression, both in crude analyses (OR 1.86; p=0.003) and after adjusting for Framingham Risk Score, age, and gender (OR 1.83; p=0.016).

Conclusion:

Associations between ApoC-III plasma levels and CVD progression were more pronounced in RA patients than outcome associations of conventionally assessed lipoproteins (i.e. LDL-, HDL-cholesterol). Elevated plasma levels of apolipoprotein complexes containing ApoC-III particles were strongly predictive of progression of coronary atherosclerosis in RA. Elevation of these triglyceride rich particles is caused by defects in plasma triglyceride transport and metabolism, which may contribute to accelerated atherosclerosis in RA. These findings provide a means of developing a standardized assay to identify high risk CVD in RA patients and a potential therapeutic target for intervention.

MarkerMean (SD) NonprogressorsMean (SD) ProgressionP-Value
Triglycerides105.57 (54.82)146.07 (99.10)0.002
VLDL21.11 (10.96)27.75 (14.32)0.002
Apo B93.22 (15.33)100.65 (15.87)0.004
LPA-II:B:C:D:E14.65 (6.43)17.37 (7.92)0.021
LpB:C+LpB:C:E8.3 (4.41)10.28 (4.09)0.006
ApoC-III8.97 (2.99)10.38 (4.17)0.019
ApoC-III Heparin Precipitated2.57 (1.02)3.1 (1.60)0.015
Framingham0.05 (0.07)0.09 (0.07)0.002
ApoA1145.34 (20.27)140.88 (22.73)0.206
Cholesterol191.16 (40.23)200 (39.89)0.18
Age57.13 (8.09)60.7 (8.25)0.009
Gender Female*75% (0.44)53% (0.50)0.011
T-test - Nonprogressors (n=63, DCAC<=0), Progressors (n=89, DCAC>0)*Chi-squared Test

To cite this abstract, please use the following information:
Bathon, Joan M., Centola, Michael, Giles, Jon T., Knowlton, Nicholas, Wages, Joshua, Payne, Adam J., et al; Elevations in ApoC-III Containing Apolipoprotein Complexes Predict Coronary Atherosclerosis Progression in Rheumatoid Arthritis Patients. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1030
DOI: 10.1002/art.28797

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