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Apolipoprotein B and Non-HDL Cholesterol Better Reflect Residual Risk Than LDL Cholesterol in Statin-Treated Patients
Open accessAbstract
Background In cholesterol guidelines, low-density lipoprotein (LDL) cholesterol remains the primary target while apolipoprotein B (apoB) and non-high-density lipoprotein (non-HDL) cholesterol are secondary targets.Objectives This study sought to determine if elevated apoB and/or non-HDL cholesterol are superior to elevated LDL cholesterol in identifying statin-treated patients at residual risk of all-cause mortality and myocardial infarction.Methods In total, 13,015 statin-treated patients from the Copenhagen General Population Study were included with 8 years median follow-up. Cox regressions among apoB, non-HDL cholesterol, and LDL cholesterol, respectively, and all-cause mortality or myocardial infarction were examined on continuous scales by restricted cubic splines and by categories of concordant and discordant values defined by medians.Results High apoB and non-HDL cholesterol were associated with increased risk of all-cause mortality and myocardial infarction, whereas no such associations were found for high LDL cholesterol. Compared with concordant values below medians, discordant apoB above the median with LDL cholesterol below yielded hazard ratios of 1.21 (95% confidence interval [CI]: 1.07 to 1.36) for all-cause mortality and 1.49 (95% CI: 1.15 to 1.92) for myocardial infarction. Corresponding values for high non-HDL cholesterol with low LDL cholesterol were 1.18 (95% CI: 1.02 to 1.36) and 1.78 (95% CI: 1.35 to 2.34). In contrast, discordant high LDL cholesterol with low apoB or non-HDL cholesterol was not associated with increased risk of all-cause mortality or myocardial infarction. Also, discordant high apoB with low non-HDL cholesterol yielded hazard ratios of 1.21 (95% CI: 1.03 to 1.41) for all-cause mortality and of 0.93 (95% CI: 0.62 to 1.40) for myocardial infarction. Furthermore, dual discordant apoB and non-HDL cholesterol above the medians with LDL cholesterol below presented hazard ratios of 1.23 (95% CI: 1.07 to 1.43) for all-cause mortality and 1.82 (95% CI: 1.37 to 2.42) for myocardial infarction.Conclusions In statin-treated patients, elevated apoB and non-HDL cholesterol, but not LDL cholesterol, are associated with residual risk of all-cause mortality and myocardial infarction. Discordance analysis demonstrates that apoB is a more accurate marker of all-cause mortality risk in statin-treated patients than LDL cholesterol or non-HDL cholesterol, and apoB in addition is a more accurate marker of risk of myocardial infarction than LDL cholesterol.
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“T2D dyslipidemia is characterized by increased levels of triglyceriderich lipoproteins (VLDL), intermediate-density lipoprotein, and remnant particlesdall apo Becontaining particlesd which metabolically lead to low levels of HDL-C and increased levels of small, dense LDL-C.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [310]
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“Additionally, apoB was identified as a more accurate marker for the risk of myocardial infarction than LDL cholesterol [42].”
From Residual Cardiovascular Risk: Role of Remnants Cholesterol, Monocyte/HDL Ratio and Lipoprotein Ratios on Personalized Cardiovascular Prevention (2024) · cites this paper as [42]
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“given that apoB is a more accurate measure of the adequacy of lipid-lowering therapy than LDL-C or non-HDL-C,1,3–13,27”
From Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention (2024) · cites this paper as [6]
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“Moreover, all reports since then, with one exception,2 including observational studies and randomized clinical trials,3–13 have confirmed that apoB is a more accurate marker of cardiovascular risk than LDL-C or non-HDL-C, reinforcing the validity of the evaluation by the 2019 EAS/ESC Guidelines as to the superiority of apoB.”
From Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention (2024) · cites this paper as [6]
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“This study builds on prior work showing that apoB concentration is the most predictive parameter of CV risk,13,14,15”
From Association of Apolipoprotein B–Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis (2022) · cites this paper as [14]
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“Johannesen et al. conducted a study which revealed that in patients undergoing statin treatment, elevated levels of apolipoprotein B (apoB) and non-HDL cholesterol, rather than LDL cholesterol, are correlated with residual risk of all-cause mortality and myocardial infarction.”
From Residual Cardiovascular Risk: Role of Remnants Cholesterol, Monocyte/HDL Ratio and Lipoprotein Ratios on Personalized Cardiovascular Prevention (2024) · cites this paper as [42]
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“Their discordance analysis indicated that apoB serves as a more precise marker of all-cause mortality risk in statin-treated patients compared to LDL cholesterol or non-HDL cholesterol.”
From Residual Cardiovascular Risk: Role of Remnants Cholesterol, Monocyte/HDL Ratio and Lipoprotein Ratios on Personalized Cardiovascular Prevention (2024) · cites this paper as [42]
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“This is particularly relevant given the growing body of evidence indicating that non–HDL cholesterol and ApoB are important predictors of ASCVD risk [38, 39].”
From The Efficacy and Safety of Plozasiran on Lipid Profile in Dyslipidemic Disorders: A Systematic Review and Meta-Analysis (2026) · cites this paper as [39]
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“Additionally, apoB was identified as a more accurate marker for the risk of myocardial infarction than LDL cholesterol [42].”
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Metadata
- Authors
- Johannesen, C. D. L., Mortensen, M. B., Langsted, A., & Nordestgaard, B. G.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Nordestgaard, Børge Grønne
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 77
- Issue
- 11
- Pages
- 1439-1450
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W3139070968
- Semantic Scholar
- c048cafbb84a1b51c0efb41514223f4c3011f674
- Cited by
- 359
- References
- 26
- Citations by year
- 2026: 72 · 2025: 62 · 2024: 76 · 2023: 77 · 2022: 43 · 2021: 27
- FWCI
- 52.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Scopus (Elsevier) (submittedVersion)
- Funders
- Gentofte Hospital
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein B, non-HDL cholesterol, LDL cholesterol, residual cardiovascular risk, statin-treated patients, all-cause mortality, myocardial infarction, lipid targets, cardiovascular risk prediction, Copenhagen General Population Study, secondary prevention of cardiovascular disease, dyslipidemia, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia
- MeSH terms
- Heart Disease Risk Factors, Aged, Apolipoproteins B, Denmark, Female, Humans, Hypercholesterolemia, Cholesterol, LDL, Male, Mortality, Myocardial Infarction, Registries, Biomarkers, Causality, Risk Assessment, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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