| Title: | Remnant cholesterol-incorporating dual-axis lipid risk stratification using apolipoprotein B and the LDL-C to total cholesterol ratio: a prospective cohort study from the UK Biobank |
| Journal: | Lipids in Health and Disease |
| Published: | 5 Aug 2026 |
| DOI: | https://doi.org/10.1186/s12944-026-03023-z |
Publication 21074
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Abstract
BackgroundAtherogenic lipid-related risk may not be fully characterized by a single lipid measure. A dual-axis framework combining apolipoprotein B (ApoB), a measure of atherogenic particle number, with the LDL-C to total cholesterol ratio (LDL-C/TC), a derived measure of cholesterol partitioning, has been proposed to characterize lipid-related risk heterogeneity. The position of remnant cholesterol (RC) within this framework remains uncertain.MethodsWe analyzed 288,257 UK Biobank participants free of cardiovascular disease and lipid-lowering therapy. Participants were classified using dual-axis framework. Associations with incident atherosclerotic cardiovascular disease (ASCVD) were assessed using Cox models. RC was evaluated in combination with these axes across strata, including SCORE2-defined low-to-intermediate risk populations.ResultsOver a median follow-up of 13.9 years, the dual-axis framework differentiated ASCVD risk, with the dual-elevated phenotype (ApoB ≥ 90 mg/dL and LDL-C/TC ≥ 0.60) showing the highest risk (adjusted hazard ratio 1.23; 95% CI, 1.17-1.29). RC did not modify associations across dual-axis categories (P for interaction = 0.44), and higher RC levels were associated with attenuation of risk gradients across categories. In low-to-intermediate SCORE2 risk individuals, increasing numbers of elevated markers (ApoB, LDL-C/TC ratio, and RC) were associated with stepwise increases in risk, with absolute risk differences reaching 1.49% at 10 years for individuals with all three markers elevated versus those with none elevated. ApoB and the LDL-C/TC ratio produced small C-index increases (ΔC, 0.0013 and 0.0012), whereas RC produced no further improvement (ΔC, − 0.0001; P = 0.364).ConclusionsRC did not materially modify associations across ApoB-LDL-C/TC phenotypes but identified absolute-risk heterogeneity within ApoB strata. Co-occurring marker elevations characterized higher-risk lipid phenotypes, although gains in discrimination were small and require external validation.Graphical Abstract</p>
2 Authors
- Bin Wang
- Dong Li
1 Application
| Application ID | Title |
|---|---|
| 531547 | Comparison of Lipid-Derived Indices with Conventional Lipoprotein Tests and Apolipoproteins for Cardiovascular Disease Prediction Using UK Biobank Data |
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