Cited by 20Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsCholesterol and Lipid Metabolism

ApoB, LDL-C, and non-HDL-C as markers of cardiovascular risk

Sehayek, Daniel, Cole, Justine, Björnson, Elias, Wilkins, John T., Mortensen, Martin B., Dufresne, Line, Pencina, Karol M., Pencina, Michael J. +2 more·2025·Journal of Clinical Lipidology

Abstract

BACKGROUND Conventional statistical approaches are not designed to compare highly correlated variables such as low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (apoB). Discordance analysis was designed to overcome this limitation by creating groups in which the predictions of 2 markers differ. OBJECTIVE This systematic review compiled all discordance studies that compare the predictive powers of LDL-C and non-HDL-C vs LDL particle number (LDL P) or apoB as markers of atherosclerotic disease risk to determine which is the most accurate marker of cardiovascular risk. METHODS A PubMed search completed September 30, 2024, identified 15 studies involving 593,354 participants. These studies encompassed diverse populations, and included patients with and without statin therapy. Several variations of discordance analysis were used including median-based, percentile-based, residual-based, and variance-based approaches. RESULTS ApoB outperformed LDL-C in 9 of 9 studies whereas LDL P was superior to LDL-C in 2 of 3 comparisons. In 1 study, non-HDL-C was superior to apoB, in 1 study apoB and non-HDL-C were equivalent, whereas in 7 studies, apoB, overall, was a significantly more accurate marker of atherosclerotic cardiovascular disease risk than non-HDL-C. CONCLUSION Discordance analysis provides robust evidence that apoB is a more accurate marker of cardiovascular risk than either LDL-C or non-HDL-C, notwithstanding these variables are highly intercorrelated. Thus, neither LDL-C nor non-HDL-C are adequate clinical surrogates for apoB. Accordingly, apoB should be the primary measure in clinical care to estimate the cardiovascular risk attributable to the apoB lipoproteins and the adequacy of lipid-lowering therapy to reduce this risk.

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Crossref · 10.1016/j.jacl.2025.05.024

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Authors
Sehayek, D., Cole, J., Björnson, E., Wilkins, J. T., Mortensen, M. B., Dufresne, L., Pencina, K. M., Pencina, M. J., Thanassoulis, G., & Sniderman, A. D.
Affiliations
  • McGill University Health Centre (CA)
  • University of Gothenburg (SE)
  • Northwestern University (US)
  • Aarhus University Hospital (DK)
  • Brigham and Women's Hospital (US)
  • Duke University (US)
Corresponding author
Sniderman, Allan D.
Venue
Journal of Clinical Lipidology
Publisher
Elsevier BV
Published
2025-06
Volume
19
Issue
4
Pages
844-859
ISSN
  • 1876-4789 (ISSN-L)
  • 1933-2874
OpenAlex
W4411080977
Cited by
20
References
45
Citations by year
2026: 17 · 2025: 3
FWCI
17.27
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of clinical lipidology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Servier
  • McGill University Health Centre
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
apolipoprotein B, LDL cholesterol, non-HDL cholesterol, cardiovascular risk prediction, LDL particle number, atherosclerotic cardiovascular disease, lipid-lowering therapy, surrogate markers
MeSH terms
Heart Disease Risk Factors, Apolipoproteins B, Cardiovascular Diseases, Humans, Cholesterol, HDL, Cholesterol, LDL, Biomarkers

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