University of Oulu

Simonen, P., Öörni, K., Sinisalo, J., Strandberg, T. E., Wester, I., & Gylling, H. (2023). High cholesterol absorption: A risk factor of atherosclerotic cardiovascular diseases? Atherosclerosis, 376, 53–62.

High cholesterol absorption : a risk factor of atherosclerotic cardiovascular diseases?

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Author: Simonen, Piia1; Öörni, Katariina2,3; Sinisalo, Juha1;
Organizations: 1Heart and Lung Center, Cardiology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
2Wihuri Research Institute, Helsinki, Finland
3Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland
4Helsinki University Hospital and University of Helsinki, Helsinki, Finland
5Center for Life-Course Health Research, University of Oulu, Oulu, Finland
6Raisio Group plc., Raisio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.4 MB)
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Language: English
Published: Elsevier, 2023
Publish Date: 2023-08-25


Lowering elevated low-density lipoprotein cholesterol (LDL-C) concentrations reduces the risk of atherosclerotic cardiovascular diseases (ASCVDs). However, increasing evidence suggests that cholesterol metabolism may also be involved in the risk reduction of ASCVD events. In this review, we discuss if the different profiles of cholesterol metabolism, with a focus on high cholesterol absorption, are atherogenic, and what could be the possible mechanisms. The potential associations of cholesterol metabolism and the risk of ASCVDs are evaluated from genetic, metabolic, and population-based studies and lipid-lowering interventions. According to these studies, loss-of-function genetic variations in the small intestinal sterol transporters ABCG5 and ABCG8 result in high cholesterol absorption associated with low cholesterol synthesis, low cholesterol elimination from the body, and a high risk of ASCVDs. In contrast, loss-of-function genetic variations in another intestinal sterol transporter, NPC1L1 result in low cholesterol absorption associated with high cholesterol synthesis, elevated cholesterol elimination from the body, and low risk of ASCVDs. Statin monotherapy is not sufficient to reduce the ASCVD risk in cases of high cholesterol absorption, and these individuals need combination therapy of statin with cholesterol absorption inhibition. High cholesterol absorption, i.e., >60%, is estimated to occur in approximately one third of a population, so taking it into consideration is important to optimise lipid-lowering therapy to prevent atherosclerosis and reduce the risk of ASCVD events.

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Series: Atherosclerosis
ISSN: 0021-9150
ISSN-E: 1879-1484
ISSN-L: 0021-9150
Volume: 376
Pages: 53 - 62
DOI: 10.1016/j.atherosclerosis.2023.06.003
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Copyright information: © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (