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Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study

AIMS: The strength of the relationship of triglyceride-rich lipoproteins (TRL) with risk of coronary heart disease (CHD) compared with low-density lipoprotein (LDL) is yet to be resolved. METHODS AND RESULTS: Single-nucleotide polymorphisms (SNPs) associated with TRL/remnant cholesterol (TRL/remnant...

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Autores principales: Björnson, Elias, Adiels, Martin, Taskinen, Marja-Riitta, Burgess, Stephen, Rawshani, Aidin, Borén, Jan, Packard, Chris J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576615/
https://www.ncbi.nlm.nih.gov/pubmed/37358553
http://dx.doi.org/10.1093/eurheartj/ehad337
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author Björnson, Elias
Adiels, Martin
Taskinen, Marja-Riitta
Burgess, Stephen
Rawshani, Aidin
Borén, Jan
Packard, Chris J
author_facet Björnson, Elias
Adiels, Martin
Taskinen, Marja-Riitta
Burgess, Stephen
Rawshani, Aidin
Borén, Jan
Packard, Chris J
author_sort Björnson, Elias
collection PubMed
description AIMS: The strength of the relationship of triglyceride-rich lipoproteins (TRL) with risk of coronary heart disease (CHD) compared with low-density lipoprotein (LDL) is yet to be resolved. METHODS AND RESULTS: Single-nucleotide polymorphisms (SNPs) associated with TRL/remnant cholesterol (TRL/remnant-C) and LDL cholesterol (LDL-C) were identified in the UK Biobank population. In a multivariable Mendelian randomization analysis, TRL/remnant-C was strongly and independently associated with CHD in a model adjusted for apolipoprotein B (apoB). Likewise, in a multivariable model, TRL/remnant-C and LDL-C also exhibited independent associations with CHD with odds ratios per 1 mmol/L higher cholesterol of 2.59 [95% confidence interval (CI): 1.99–3.36] and 1.37 [95% CI: 1.27–1.48], respectively. To examine the per-particle atherogenicity of TRL/remnants and LDL, SNPs were categorized into two clusters with differing effects on TRL/remnant-C and LDL-C. Cluster 1 contained SNPs in genes related to receptor-mediated lipoprotein removal that affected LDL-C more than TRL/remnant-C, whereas cluster 2 contained SNPs in genes related to lipolysis that had a much greater effect on TRL/remnant-C. The CHD odds ratio per standard deviation (Sd) higher apoB for cluster 2 (with the higher TRL/remnant to LDL ratio) was 1.76 (95% CI: 1.58–1.96), which was significantly greater than the CHD odds ratio per Sd higher apoB in cluster 1 [1.33 (95% CI: 1.26–1.40)]. A concordant result was obtained by using polygenic scores for each cluster to relate apoB to CHD risk. CONCLUSION: Distinct SNP clusters appear to impact differentially on remnant particles and LDL. Our findings are consistent with TRL/remnants having a substantially greater atherogenicity per particle than LDL.
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spelling pubmed-105766152023-10-15 Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study Björnson, Elias Adiels, Martin Taskinen, Marja-Riitta Burgess, Stephen Rawshani, Aidin Borén, Jan Packard, Chris J Eur Heart J Clinical Research AIMS: The strength of the relationship of triglyceride-rich lipoproteins (TRL) with risk of coronary heart disease (CHD) compared with low-density lipoprotein (LDL) is yet to be resolved. METHODS AND RESULTS: Single-nucleotide polymorphisms (SNPs) associated with TRL/remnant cholesterol (TRL/remnant-C) and LDL cholesterol (LDL-C) were identified in the UK Biobank population. In a multivariable Mendelian randomization analysis, TRL/remnant-C was strongly and independently associated with CHD in a model adjusted for apolipoprotein B (apoB). Likewise, in a multivariable model, TRL/remnant-C and LDL-C also exhibited independent associations with CHD with odds ratios per 1 mmol/L higher cholesterol of 2.59 [95% confidence interval (CI): 1.99–3.36] and 1.37 [95% CI: 1.27–1.48], respectively. To examine the per-particle atherogenicity of TRL/remnants and LDL, SNPs were categorized into two clusters with differing effects on TRL/remnant-C and LDL-C. Cluster 1 contained SNPs in genes related to receptor-mediated lipoprotein removal that affected LDL-C more than TRL/remnant-C, whereas cluster 2 contained SNPs in genes related to lipolysis that had a much greater effect on TRL/remnant-C. The CHD odds ratio per standard deviation (Sd) higher apoB for cluster 2 (with the higher TRL/remnant to LDL ratio) was 1.76 (95% CI: 1.58–1.96), which was significantly greater than the CHD odds ratio per Sd higher apoB in cluster 1 [1.33 (95% CI: 1.26–1.40)]. A concordant result was obtained by using polygenic scores for each cluster to relate apoB to CHD risk. CONCLUSION: Distinct SNP clusters appear to impact differentially on remnant particles and LDL. Our findings are consistent with TRL/remnants having a substantially greater atherogenicity per particle than LDL. Oxford University Press 2023-06-26 /pmc/articles/PMC10576615/ /pubmed/37358553 http://dx.doi.org/10.1093/eurheartj/ehad337 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Research
Björnson, Elias
Adiels, Martin
Taskinen, Marja-Riitta
Burgess, Stephen
Rawshani, Aidin
Borén, Jan
Packard, Chris J
Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study
title Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study
title_full Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study
title_fullStr Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study
title_full_unstemmed Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study
title_short Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study
title_sort triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a uk biobank study
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576615/
https://www.ncbi.nlm.nih.gov/pubmed/37358553
http://dx.doi.org/10.1093/eurheartj/ehad337
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