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

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

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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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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
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
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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