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Cited by 359Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsCholesterol and Lipid Metabolism

Apolipoprotein B and Non-HDL Cholesterol Better Reflect Residual Risk Than LDL Cholesterol in Statin-Treated Patients

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Johannesen, Camilla Ditlev Lindhardt, Mortensen, Martin Bødtker, Langsted, Anne, Nordestgaard, Børge Grønne·2021·Journal of the American College of Cardiology
DOI 10.1016/j.jacc.2021.01.027
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Abstract

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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Crossref · 10.1016/j.jacc.2021.01.027

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  • Type 2 diabetes dyslipidemia is marked by elevated triglyceride-rich lipoproteins (VLDL), intermediate-density lipoprotein, and remnant particles, which metabolically lead to low HDL-C and increased small dense LDL-C.

    “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]

    The Sensitivity Analyses passage (page not supplied) describes triglyceride-rich apoB-containing particles and says apoB and non-HDL cholesterol include VLDL. Another passage notes that diabetes affects lipoprotein levels, but our copy does not establish the claimed type 2 diabetes pattern of elevated VLDL, IDL, and remnants, or the proposed progression to low HDL-C and increased small, dense LDL-C. (LLM, conf=0.82)

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  • ApoB was identified as a more accurate marker for the risk of myocardial infarction than LDL cholesterol.

    “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]

    The Conclusions state that apoB is a more accurate marker of myocardial infarction risk than LDL cholesterol in statin-treated patients. The citing sentence omits that population restriction, so the source does not establish the comparison for patients generally. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • apoB is a more accurate measure of the adequacy of lipid-lowering therapy than LDL-C or non-HDL-C.

    “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]

    The Conclusions report that, in statin-treated patients, apoB was a more accurate marker of all-cause mortality risk than LDL-C or non-HDL-C. They find apoB more accurate for myocardial infarction risk than LDL-C, but do not establish superiority over non-HDL-C for that outcome. The broader claim that apoB measures the adequacy of lipid-lowering therapy more accurately than both markers exceeds these residual-risk findings. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • All reports since 2019, with one exception, including observational studies and randomized clinical trials, have confirmed that apoB is a more accurate marker of cardiovascular risk than LDL-C or non-HDL-C.

    “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]

    The Conclusions report that, among statin-treated patients, apoB was a more accurate marker of all-cause mortality risk than LDL-C or non-HDL-C, and of myocardial infarction risk than LDL-C. The paper is an observational study; it does not establish the sentence’s broader claim about all reports since 2019, and it does not find apoB superior to non-HDL-C for myocardial infarction risk. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Prior work shows that apoB concentration is the most predictive parameter of CV risk.

    “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]

    The Conclusions report that apoB was a more accurate marker of all-cause mortality risk than LDL or non-HDL cholesterol in statin-treated patients, and of myocardial infarction risk than LDL cholesterol. The claim broadens those comparisons to call apoB the most predictive parameter of cardiovascular risk generally; the cited paper does not establish that broader ranking. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Johannesen, C. D. L., Mortensen, M. B., Langsted, A., & Nordestgaard, B. G.
Affiliations
University of Copenhagen (DK)
Corresponding author
Nordestgaard, Børge Grønne
ORCID
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)
DOI
10.1016/j.jacc.2021.01.027
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 · 2019: 1
FWCI
52.35
Type
journal article
Language
en
Open access
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 › 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, 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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