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

Elias Björnson; Martin Adiels; Marja-Riitta Taskinen; Stephen Burgess; Aidin Rawshani; Jan Borén; Chris J Packard

doi:10.1093/eurheartj/ehad337

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

Eur Heart J. 2023 Oct 14;44(39):4186-4195. doi: 10.1093/eurheartj/ehad337.

Authors

Elias Björnson¹, Martin Adiels^{1

2}, Marja-Riitta Taskinen³, Stephen Burgess^{4

5}, Aidin Rawshani¹, Jan Borén¹, Chris J Packard⁶

Affiliations

¹ Department of Molecular and Clinical Medicine, University of Gothenburg, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden.
² School of Public Health and Community Medicine, University of Gothenburg, Medicinaregatan 18A, 41390 Gothenburg, Sweden.
³ Research Program for Clinical and Molecular Metabolism, University of Helsinki, Biomedicum 1, Haartmanninkatu 8, 00290 Helsinki, Finland.
⁴ MRC Biostatistics Unit, University of Cambridge, Robinson Way, Cambridge, CB2 0SR, UK.
⁵ Cardiovascular Epidemiology Unit, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Papworth Road, Cambridge, CB2 0BD, UK.
⁶ Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, G12 8TA Glasgow, UK.

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.

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.

Keywords: Apolipoprotein B; Cardiovascular disease; Genetics; LDL cholesterol; Mendelian randomization; Remnants; Single-nucleotide polymorphisms; Triglyceride; UK Biobank.

MeSH terms

Apolipoproteins B / genetics
Biological Specimen Banks*
Cholesterol
Cholesterol, LDL
Coronary Disease* / epidemiology
Coronary Disease* / genetics
Humans
Lipoproteins / genetics
Triglycerides
United Kingdom / epidemiology

Substances

Cholesterol, LDL
Triglycerides
Lipoproteins
Cholesterol
Apolipoproteins B

Abstract

MeSH terms

Substances

Grants and funding