| Title: | Triglyceride-rich lipoprotein remnants, low-density lipoproteins, and risk of coronary heart disease: a UK Biobank study |
| Journal: | European Heart Journal |
| Published: | 26 Jun 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37358553/ |
| DOI: | https://doi.org/10.1093/eurheartj/ehad337 |
| URL: | https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad337/50705397/ehad337.pdf |
| Citations: | 35 (35 in last 2 years) as of 8 Aug 2024 |
Publication 10928
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Abstract
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.</p>
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.</p>
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.</p>
7 Authors
- Elias Björnson
- Martin Adiels
- Marja-Riitta Taskinen
- Stephen Burgess
- Aidin Rawshani
- Jan Borén
- Chris J Packard
1 Application
| Application ID | Title |
|---|---|
| 53308 | Predictive Models for Cardio-Metabolic Disease: a Machine Learning Approach |
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