• Qidi Ying, Annalisa Ronca, Dick C Chan, Jing Pang, Elda Favari, and Gerald F Watts.
• Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.
• Eur. J. Clin. Invest. 2022 Jul 1; 52 (7): e13766.

BackgroundCellular cholesterol efflux is a key step in reverse cholesterol transport that may impact on atherosclerotic cardiovascular risk. The process may be reliant on the availability of apolipoprotein (apo) B-100-containing lipoproteins to accept cholesterol from high-density lipoprotein. Evolocumab and atorvastatin are known to lower plasma apoB-100-containing lipoproteins that could impact on cholesterol efflux capacity (CEC).MethodsWe conducted a 2-by-2 factorial trial of the effects of subcutaneous evolocumab (420 mg every 2 weeks) and atorvastatin (80 mg daily) for 8 weeks on CEC in 81 healthy, normolipidaemic men. The capacity of whole plasma and apoB-depleted plasma, including ATP-binding cassette transporter A1 (ABCA1)-mediated and passive diffusion, to efflux cholesterol, was measured.ResultsEvolocumab and atorvastatin independently decreased whole plasma CEC (main effect p < .01 for both). However, there were no significant effects of evolocumab and atorvastatin on apoB-depleted plasma, ABCA1-mediated and passive diffusion-mediated CEC (p > .05 in all). In the three intervention groups combined, the reduction in whole plasma CEC was significantly correlated with the corresponding reduction in plasma apoB-100 concentration (r = .339, p < .01). In the evolocumab monotherapy group, the reduction in whole plasma CEC was also significantly correlated with the corresponding reduction in plasma lipoprotein(a) concentration (r = .487, p < .05).ConclusionsIn normolipidaemic men, evolocumab and atorvastatin decrease the capacity of whole plasma to efflux cellular cholesterol. These effects may be chiefly owing to a fall in the availability of apoB-100-containing lipoproteins. Reduction in circulating lipoprotein(a) may also contribute to the decrease in whole plasma cholesterol efflux with evolocumab monotherapy.© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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