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Do Triglyceride-Rich Lipoproteins Equal Low-Density Lipoproteins in Risk of ASCVD?

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Abstract

Purpose of Review

Recent large clinical trials have failed to show that triglyceride-rich lipoprotein-lowering therapies decrease the risk of atherosclerotic cardiovascular disease (ASCVD). In this review, we reconcile these findings with evidence showing that elevated levels of triglyceride-rich lipoproteins and the cholesterol they contain, remnant cholesterol, cause ASCVD alongside low-density lipoprotein (LDL) cholesterol.

Recent Findings

Results from observational epidemiology, genetic epidemiology, and randomized controlled trials indicate that lowering of remnant cholesterol and LDL cholesterol decrease ASCVD risk by a similar magnitude per 1 mmol/L (39 mg/dL) lower non-high-density lipoprotein cholesterol (remnant cholesterol+LDL cholesterol). Indeed, recent guidelines for ASCVD prevention recommend the use of non-high-density lipoprotein cholesterol instead of LDL cholesterol.

Summary

Current consensus is moving towards recognizing remnant cholesterol and LDL cholesterols as equals per 1 mmol/L (39 mg/dL) higher levels in the risk assessment of ASCVD; hence, triglyceride-rich lipoprotein-lowering therapies should also lower levels of non-HDL cholesterol to reduce ASCVD risk.

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Acknowledgements

We thank the staff and participants from the Copenhagen General Population Study for their valuable contributions.

Employment

Recent, present, and anticipated employment is The Capital Region (Danish: Region Hovedstaden) in Denmark for all authors, all paid through tax-generated money without any influence from private companies.

Funding

Independent Research Fund Denmark (grant 1030-00168B), Novo Nordisk Foundation (grant NNF21OC0071977), Johan and Lise Boserup Fund, Aase and Ejnar Danielsen Fund, and Herlev and Gentofte Hospital provided funding. The funders had no role in the design of the study or in the collection, analysis, interpretation of data, writing the manuscript, or the decision to submit the article for publication.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 73, entrance 7, 4th floor, N5, DK-2730, Herlev, Denmark

    Benjamin N. Wadström, Anders B. Wulff, Kasper M. Pedersen & Børge G. Nordestgaard

  2. The Copenhagen General Population Study, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 73, entrance 7, 4th floor, M3, DK-2730, Herlev, Denmark

    Benjamin N. Wadström, Anders B. Wulff, Kasper M. Pedersen & Børge G. Nordestgaard

  3. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b 33.5, DK-2200, Copenhagen, Denmark

    Benjamin N. Wadström, Anders B. Wulff, Kasper M. Pedersen & Børge G. Nordestgaard

Authors
  1. Benjamin N. Wadström
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  2. Anders B. Wulff
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  3. Kasper M. Pedersen
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  4. Børge G. Nordestgaard
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Contributions

BNW performed literature search and wrote the first draft of the manuscript. ABW, KMP, and BGN revised the manuscript for critical scientific content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Børge G. Nordestgaard.

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BGN reports consultancies and talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Ionis, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Esperion, Abbott, Silence Therapeutics, and Mankind. BNW, ABW, and KMP do not have any financial competing interests.

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Wadström, B.N., Wulff, A.B., Pedersen, K.M. et al. Do Triglyceride-Rich Lipoproteins Equal Low-Density Lipoproteins in Risk of ASCVD?. Curr Atheroscler Rep 25, 795–803 (2023). https://doi.org/10.1007/s11883-023-01153-8

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