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.
- 1Medical Data Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, China. [email protected].
- 2Medical Data Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, China. [email protected].
Abstract
Background
Atherogenic 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.Methods
We 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.Results
Over 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).Conclusions
RC 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.
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BibTeX
@article{wang2026remnant,
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.}},
author = {Bin Wang and Dong Li},
journal = {Lipids in health and disease},
year = {2026},
month = aug,
doi = {10.1186/s12944-026-03023-z},
url = {https://europepmc.org/article/MED/42968168},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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.
AU - Bin Wang
AU - Dong Li
PY - 2026
DA - 2026/08/05
JO - Lipids in health and disease
DO - 10.1186/s12944-026-03023-z
UR - https://europepmc.org/article/MED/42968168
AB - Background Atherogenic 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.Methods We 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.Results Over 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).Conclusions RC 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.
SN - 1476-511X
ER -