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Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?

BACKGROUND: Cellular 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. Evo...

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Autores principales: Ying, Qidi, Ronca, Annalisa, Chan, Dick C., Pang, Jing, Favari, Elda, Watts, Gerald F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9541635/
https://www.ncbi.nlm.nih.gov/pubmed/35294778
http://dx.doi.org/10.1111/eci.13766
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author Ying, Qidi
Ronca, Annalisa
Chan, Dick C.
Pang, Jing
Favari, Elda
Watts, Gerald F.
author_facet Ying, Qidi
Ronca, Annalisa
Chan, Dick C.
Pang, Jing
Favari, Elda
Watts, Gerald F.
author_sort Ying, Qidi
collection PubMed
description BACKGROUND: Cellular 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). METHODS: We 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. RESULTS: Evolocumab 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). CONCLUSIONS: In 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.
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spelling pubmed-95416352022-10-14 Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments? Ying, Qidi Ronca, Annalisa Chan, Dick C. Pang, Jing Favari, Elda Watts, Gerald F. Eur J Clin Invest Original Articles BACKGROUND: Cellular 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). METHODS: We 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. RESULTS: Evolocumab 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). CONCLUSIONS: In 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. John Wiley and Sons Inc. 2022-03-24 2022-07 /pmc/articles/PMC9541635/ /pubmed/35294778 http://dx.doi.org/10.1111/eci.13766 Text en © 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. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Ying, Qidi
Ronca, Annalisa
Chan, Dick C.
Pang, Jing
Favari, Elda
Watts, Gerald F.
Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?
title Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?
title_full Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?
title_fullStr Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?
title_full_unstemmed Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?
title_short Effect of a PCSK9 inhibitor and a statin on cholesterol efflux capacity: A limitation of current cholesterol‐lowering treatments?
title_sort effect of a pcsk9 inhibitor and a statin on cholesterol efflux capacity: a limitation of current cholesterol‐lowering treatments?
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9541635/
https://www.ncbi.nlm.nih.gov/pubmed/35294778
http://dx.doi.org/10.1111/eci.13766
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