0390: Statins Influence the Relationship Between ATP-binding Cassette Transporter A1 (ABCA1)-mediated Cholesterol Efflux and Coronary Atherosclerosis in Rheumatoid Arthritis

George Karpouzas¹, Bianca Papotti², Sarah Ormseth³, Marcella Palumbo², Elizabeth Hernandez³, Maria Pia Adorni⁴, Francesca Zimetti², Matthew Budoff¹ and Nicoletta Ronda², ¹Harbor-UCLA Medical Center, Torrance, CA, ²University of Parma, Department of Food and Drug, Parma, Italy, ³The Lundquist Institute, Torrance, CA, ⁴Department of Medicine and Surgery, Unit of Neuroscience, University of Parma, Parma, Italy

Background/Purpose: Cholesterol efflux capacity (CEC) is the main antiatherogenic function of high-density lipoprotein (HDL). ATP-binding-cassette A1 (ABCA1) membrane transporter initiates cholesterol export from arterial macrophages to pre-β HDL particles fostering their maturation; in turn, those accept cholesterol through ABCG1-mediated export. Impaired pre-βHDL maturation may disrupt the collaborative function of the two transporters and adversely affect atherosclerosis. Statins exert atheroprotective functions systemically and locally on plaque. We here evaluated associations between ABCA1-CEC, coronary atherosclerosis and cardiovascular risk and the influence of statins on those relationships in rheumatoid arthritis (RA).

Methods: Atherosclerosis (noncalcified, partially or fully calcified, low attenuation plaques) was evaluated with coronary computed tomography angiography in 140 patients without cardiovascular disease and reassessed in 99 after 6.9±0.4 years. ABCA1-CEC and ABCG1-CEC were measured in J774 macrophages and Chinese hamster ovary cells respectively as previously described. Cox regression evaluated the association between ABCA1-CEC and cardiovascular risk. Multivariable negative binomial and robust logistic regression tested associations of ABCA1-CEC and its interactions with statin therapy on coronary plaque burden at baseline and its progression respectively.

Results: ABCA1-CEC inversely correlated with ABCG1-CEC (Pearson r= -0.167, p=0.049). ABCA1-CEC (per SD increment) associated with long-term cardiovascular event risk after adjustments for cardiovascular risk score and baseline plaque burden [HR 2.05 (95% CI 1.20-3.48), Figure 1]. There was an interaction of ABCA1-CEC with time-varying statin use (p=0.038) such that current statin use inversely associated with risk only in patients with ABCA1-CEC below the upper tertile. ABCA1-CEC had no main effect on plaque or plaque progression; instead, ABCA1-CEC (per SD) associated with fewer baseline total plaques (adjusted rate ratio [aRR] 0.81, [95%CI 0.65-1.00]), noncalcified plaques (aRR 0.78 [95%CI 0.61-0.98]), and low attenuation plaques (aRR 0.41 [95%CI 0.23-0.74]) in statin users, and more low attenuation plaques (aRR 1.91 [95%CI 1.18-3.08]) in nonusers (p-for-interaction=0.018, 0.011, 0.025 and < 0.001 respectively, Figure 2). Moreover, ABCA1-CEC (per SD) associated with greater partially/fully-calcified plaque progression (adjusted odds ratio 3.07 [95%CI 1.20-7.86]) only in patients not exposed to statins during follow-up (p-for-interaction=0.009, Figure 3).

Conclusion: In the context of inflammation and impaired pre-β HDL maturation typical of RA, higher ABCA1-CEC may reflect a proatherogenic rather than atheroprotective state, associated with greater coronary atherosclerosis burden, vulnerability and cardiovascular risk. Statin use, by reducing cell cholesterol overload and restoring pre-β HDL maturation may unmask and promote the atheroprotective effect of ABCA1-CEC.








G. Karpouzas: Janssen, 1, Pfizer, 5, Scipher, 1; B. Papotti: None; S. Ormseth: None; M. Palumbo: None; E. Hernandez: None; M. Adorni: None; F. Zimetti: None; M. Budoff: None; N. Ronda: None.