[OP0171] ELEVATIONS IN APOC-III CONTAINING APOLIPOPROTEIN COMPLEXES PREDICT PROGRESSION OF CORONARY ATHEROSCLEROSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS
N. Knowlton1, J.T. Giles2, J. Wages1, A. Payne1, G. Cavet3, M. Centola1, P. Alaupovic1, J.M. Bathon2. 1OMRF, Oklahoma City, OK; 2Johns Hopkins University School of Medicine, Baltimore, MD; 3Crescendo Bioscience, S. San Francisco, United States
Background: Conventional lipid measures do not account for higher rates of cardiovascular (CV) associated events and mortality in rheumatoid arthritis (RA). However, alterations in the equilibrium among apolipoprotein complexes that traffic cholesterol, triglycerides, and fatty acids may lead to atherogenic consequences in RA.
Objectives: Assess associations of apolipoprotein complexes to subclinical arthrosclerosis progression to identify prognostic and mechanistic biomarkers of CVD pathogenesis in RA.
Methods: The study population consisted of 196 RA patients participating in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis (ESCAPE RA) study. Apolipoprotein complexes were measured at baseline by precipitation and immunoturbidimetrometric 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. Multivariate analyses were performed using logistic regression.
Results: Of the 152 participants who had CAC measurements at two time points, 89 were progressors and 63 nonprogressors. DAS 28 and race composition didn't differ significantly between the groups, p-0.53 & p -0.419. Mean DAS28 scores and racial distribution did not significantly differ between groups; however, progressors were significantly more likely to be male (p=0.001) and older (p=0.009) than non-progressors. Of the 12 apolipoprotein complexes measured, mean values of 7 were statistically significantly higher in the progressors, compared to nonprogressors (Table 1). Interestingly, in contrast to the complexes not associated with progression, these 7 complexes all contain ApoC-III, which is predominantly a triglyceride carrier. For multivariate modeling, we performed Principal Component Analysis on the significant terms to allow collinear terms to contribute maximally. In these analyses, the first principal component was statistically associated with progression, both with (OR=1.83; p=0.016) and without (OR=1.86; p=0.003) adjustment for Framingham Risk Score, age, and gender.
Conclusion: Elevations in apolipoprotein complexes containing ApoC-III particles were strongly predictive of progression of coronary atherosclerosis in RA, suggesting that defects in apolipoprotein complex metabolism and triglyceride transport may contribute to accelerated atherosclerosis in RA, over and above the effects of conventionally assessed lipoproteins (i.e. LDL-, HDL-cholesterol). Moreover, these complexes could form the basis of a standardized assay to identify patients at high risk for CVD, thus targeting them for therapeutic intervention.
Disclosure of Interest: N. Knowlton Consultant for: Crescendo Bioscience, J. Giles: None Declared, J. Wages Consultant for: Crescendo Bioscience, A. Payne Consultant for: Crescendo Bioscience, G. Cavet Employee of: Crescendo Bioscience, M. Centola Consultant for: Crescendo Bioscience, P. Alaupovic Grant/Research Support from: Crescendo Bioscience, J. Bathon: None Declared
Citation: Ann Rheum Dis 2010;69(Suppl3):111
Session: Abstract Session: Cardiovascular comorbidity in rheumatic diseases