ATP-binding cassette G1 membrane transporter-mediated cholesterol efflux capacity influences coronary atherosclerosis and cardiovascular risk in Rheumatoid Arthritis. Issue 136 (April 2023)

• Record Type: Journal Article
• Authors: Karpouzas, George A.; Papotti, Bianca; Ormseth, Sarah R.; Palumbo, Marcella; Hernandez, Elizabeth; Adorni, Maria Pia; Zimetti, Francesca; Budoff, Matthew J.; Ronda, Nicoletta
• Is Part Of: Journal of autoimmunity. Issue 136(2023)
• Publication Date: 2023-04
• Subjects: Rheumatoid arthritis -- Coronary atherosclerosis -- Cardiovascular events -- Cholesterol efflux capacity -- ABCG1; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2023.103029
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Objectives: Cholesterol efflux capacity (CEC) measures the ability of high-density lipoprotein (HDL) to remove cholesterol from macrophages and reduce the lipid content of atherosclerotic plaques. CEC inversely associated with cardiovascular risk beyond HDL-cholesterol levels. CEC through the ATP-binding-cassette G1 (ABCG1) membrane transporter is impaired in rheumatoid arthritis (RA). We evaluated associations of ABCG1-CEC with coronary atherosclerosis, plaque progression and cardiovascular risk in RA. Methods: Coronary atherosclerosis (noncalcified, partially, fully-calcified, low-attenuation plaque) was assessed with computed tomography angiography in 140 patients and reevaluated in 99 after 6.9 ± 0.3 years. Cardiovascular events including acute coronary syndromes, stroke, cardiovascular death, claudication, revascularization and hospitalized heart failure were recorded. ABCG1-CEC was measured in Chinese hamster ovary cells as percentage of effluxed over total intracellular cholesterol. Results: ABCG1-CEC inversely associated with extensive atherosclerosis (≥5 plaques) (adjusted odds ratio 0.50 [95% CI 0.28–0.88]), numbers of partially-calcified (rate ratio [RR] 0.71 [0.53–0.94]) and low-attenuation plaques (RR 0.63 [0.43–0.91] per standard deviation increment). Higher ABCG1-CEC predicted fewer new partially-calcified plaques in patients with lower baseline and time-averaged CRP and fewer new noncalcified and calcified plaques in those receiving higher mean prednisone dose. ABCG1-CEC inversely associated with events in patients with but not without noncalcified plaques, with <median but not higher CRP and in prednisone users but not nonusers (p-for-interaction = 0.021, 0.033 and 0.008 respectively). Conclusion: ABCG1-CEC inversely associated with plaque burden and vulnerability, and plaque progression conditionally on cumulative inflammation and corticosteroid dose. ABCG1-CEC inversely associated with events specifically in patients with noncalcified plaques, lower inflammation and in prednisone users. Highlights: ABCG1-cholesterol efflux capacity predicted less plaque in rheumatoid arthritis. It predicted lower plaque progression contingent on inflammation and steroid dose. It predicted fewer cardiovascular events in patients with noncalcified plaques. ABCG1-CEC associated with fewer events in patients with lower inflammation. ABCG1-CEC associated with fewer cardiovascular events in prednisone users.