Key result
Triglyceride-rich lipoproteins are associated with ~4 times greater CHD risk per particle than LDL.
Why the study?
Triglyceride-rich lipoproteins and remnants have a causal relationship with coronary heart disease that has not yet been quantified.
Are triglyceride-rich lipoproteins and remnants more atherogenic than LDL on a per-particle basis, and does this impact the causal association of non-HDL-C with CHD?
Observational
Are triglyceride-rich lipoproteins and remnants more atherogenic than LDL on a per-particle basis, and does this impact the causal association of non-HDL-C with CHD?
Odds Ratio: 3.9 (95% CI 2.8–5.4)
TRL/remnants are approximately 4 times more atherogenic than LDL per particle, suggesting that risk prediction models may need adjustment for percentage TRL/remnant-C.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Studies consistently demonstrate that triglyceride-rich particles are more atherogenic than LDL, maybe even four times more atherogenic, meaning particle for particle, they're more likely to cause heart disease than LDL themselves.”
May support TRL/remnant-adjusted CHD risk models; leaves open whether this refines non-HDL-C predictions in trials.
Background Triglyceride-rich lipoproteins and remnants (TRL/remnants) have a causal but not yet quantified relationship with coronary heart disease (CHD - myocardial infarction plus revascularisation). Objectives To estimate TRL/remnant per-particle atherogenicity, investigate causal relationships with inflammation, and determine whether difference in the atherogenicity of TRL/remnants and LDL impact the causal association of non-HDL-C with CHD. Methods Single nucleotide polymorphisms (SNPs) (n=1357) identified by genome-wide association in the UK Biobank were ranked into 10 clusters according to the effect on TRL/remnant-C versus LDL-C. Mendelian randomisation analysis was used to estimate for each SNP cluster CHD odds ratios per 10 mg/dL apoB and per 0.33 mmol/L non-HDL-cholesterol, and to evaluate association of TRL/remnants with biomarkers of systemic inflammation. Results SNPs in cluster 1 predominantly affected LDL-C while SNPs in cluster 10 predominantly affected TRL/remnant-C. CHD risk per genetically predicted increase in apoB and in non-HDL-C rose across clusters. Odds ratio per 10 mg/dL higher apoB was 1.15[95%CI:1.11-1.19] in cluster 1 versus 1.70[95%CI:1.52-1.90] in cluster 10. Comparing odds ratios between these TRL/remnant predominant- and LDL predominant-clusters, we estimated that TRL/remnants were at least 3.9[95%CI:2.8-5.4] times more atherogenic than LDL on a per-particle basis. For non-HDL-C, CHD odds ratios per 0.33 mmol/L rose from 1.15[1.11−1.19] for cluster 1 to 1.40[1.30−1.50] for cluster 10. TRL/remnants exhibited causal relationships with inflammation, but this did not explain their greater atherogenicity. Conclusion TRL/remnants are about 4 times more atherogenic than LDL. Variation in the causal association of non-HDL-C with CHD indicates that adjustment for percentage TRL/remnant-C may be needed for accurate risk prediction.
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Björnson et al. (2024) conducted an observational in Coronary heart disease. Triglyceride-rich lipoproteins and remnants (TRL/remnants) vs. LDL was evaluated on Coronary heart disease (myocardial infarction plus revascularisation) (OR 3.9, 95% CI 2.8-5.4). Triglyceride-rich lipoproteins and remnants were estimated to be at least 3.9 times more atherogenic than LDL on a per-particle basis for coronary heart disease (OR 3.9; 95% CI 2.8-5.4).
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