Key result
Dual-elevated ApoB and LDL-C/TC phenotype linked to ~23% higher incident ASCVD risk.
Why the study?
Does a dual-axis lipid risk stratification framework combining ApoB, LDL-C/TC ratio, and remnant cholesterol improve prediction of incident ASCVD in individuals free of cardiovascular disease?
Cohort (n=288,257)
Yes
Does a dual-axis lipid risk stratification framework combining ApoB, LDL-C/TC ratio, and remnant cholesterol improve prediction of incident ASCVD in individuals free of cardiovascular disease?
Hazard Ratio: 1.23 (95% CI 1.17–1.29)
A dual-axis lipid framework using ApoB and LDL-C/TC ratio identifies higher-risk ASCVD phenotypes, though the addition of remnant cholesterol provides minimal improvement in risk discrimination.
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. 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. 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 interactio n = 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). 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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Wang et al. (2026) conducted a cohort in Atherosclerotic cardiovascular disease risk (n=288,257). Dual-elevated lipid phenotype (ApoB ≥ 90 mg/dL and LDL-C/TC ≥ 0.60) vs. Non-elevated phenotype was evaluated on Incident atherosclerotic cardiovascular disease (ASCVD) (HR 1.23, 95% CI 1.17-1.29). A dual-elevated lipid phenotype (ApoB ≥ 90 mg/dL and LDL-C/TC ≥ 0.60) was associated with the highest risk of incident ASCVD (HR 1.23; 95% CI, 1.17-1.29).
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