Conclusion
In patients with RA, higher ABCA1-CEC may reflect a proatherogenic state, associated with enhanced cardiovascular risk. Statin use may unmask the protective impact of ABCA1-mediated cholesterol efflux on plaque formation, progression and cardiovascular risk.
Methods
Evaluation with computed tomography angiography was undertaken in 140 patients and repeated in 99 after 6.9 ± 0.3 years. Events comprising cardiovascular death, acute coronary syndromes, stroke, claudication, revascularization and heart failure were recorded. ABCA1-CEC and ABCG1-CEC were evaluated in J774A.1 macrophages and Chinese hamster ovary (CHO) cells respectively and expressed as percentage of effluxed over total intracellular cholesterol. Covariates in all cardiovascular event risk and plaque outcome models included atherosclerotic cardiovascular disease (ASCVD) risk score and high-density lipoprotein cholesterol.
Results
ABCA1-CEC negatively correlated with ABCG1-CEC (r = -0.167, p = 0.049). ABCA1-CEC associated with cardiovascular risk (adjusted hazard ratio 2.05 [95%CI 1.20-3.48] per standard deviation [SD] increment). 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 vulnerable 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). 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).