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Evaluation of current indirect methods for measuring LDL-cholesterol

  • Sophia Drobnik EMAIL logo , Hubert Scharnagl , Nilesh J. Samani , Peter S. Braund , Christopher P. Nelson , Tim Hollstein , Ursula Kassner , Alexander Dressel , Wolfgang Drobnik and Winfried März
Published/Copyright: February 19, 2025
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 6

Abstract

Objectives

Accurately quantifying low-density lipoprotein cholesterol (LDL-C) is crucial for precise cardiovascular disease risk assessment and treatment decisions. The commonly used Friedewald equation (LDL-CFW) has faced criticism for its tendency to underestimate LDL-C, particularly at high triglycerides (TG) or low LDL-C, potentially leading to undertreatment. Newer equations, such as those by Martin and Hopkins (LDL-CMH) or Sampson (LDL-CSN), have been proposed as alternatives. Our study aimed to assess the validity of LDL-CFW, LDL-CMH, and LDL-CSN compared to ß-quantification (LDL-CUC), the reference method recommended by the Lipid Research Clinics.

Methods

Using data from three studies comprising 5,738 datasets, LDL-C was determined with the four methods in samples with TG up to 5.65 mmol/L. We calculated median and mean differences, correlations, and used the Passing and Bablok regression for comparisons. Concordance/discordance analyses were conducted.

Results

All equations provided generally accurate LDL-C estimations with slight differences among them. At TG<1.69 mmol/L, no clinically significant divergences were observed. As TG values increased, LDL-CFW offered the most accurate estimation, followed by LDL-CSN, while LDL-CMH exhibited increasingly strong positive bias. LDL-CFW was not inferior to LDL-CSN and LDL-CMH in terms of concordance/discordance.

Conclusions

LDL-CFW generally provided reliable estimates of LDL-C in most samples, showing non-inferiority to LDL-CSN or LDL-CMH, thereby confirming its legitimacy for routine use. Since current treatment recommendations are based on studies employing LDL-CFW, its replacement by alternatives is not justified.

Keywords: low-density lipoprotein cholesterol; beta quantification; Friedewald equation; Martin/Hopkins equation; Sampson equation
Corresponding author: Sophia Drobnik, Medical Clinic I, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany, E-mail:

  1. Research ethics: All studies were conducted in accordance with the Declaration of Helsinki and after approval by the study sites´ Institutional Review Boards.

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors declare the following financial interests/personal relationships that could be seen as potential conflicts of interest: S. Drobnik, U. Kassner, A. Dressel, W. Drobnik have nothing to declare. H. Scharnagl: Abbott Diagnostics, Amgen, Sanofi. C.P. Nelson, P.S. Braund, N.J. Samani: funding by the British Heart Foundation (RG/200004). T. Hollstein: AMGEN, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Novo Nordisk, Sanofi, Science & Stories GmbH, Techniker Krankenkasse, SOBI, Recordati Pharma, W. März: AMGEN, Sanofi, Amryt Pharmaceuticals, Abbott Diagnostics, Akzea Therapeutics, Novartis Pharma, SOBI, employment with SYNLAB Holding Deutschland GmbH.

  6. Research funding: None declared.

  7. Data availability: Data is available from the Corresponding Author upon reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0024).

Received: 2025-01-08
Accepted: 2025-01-29
Published Online: 2025-02-19
Published in Print: 2025-05-26

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2025-0024
Keywords for this article
low-density lipoprotein cholesterol; beta quantification; Friedewald equation; Martin/Hopkins equation; Sampson equation

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. The Friedewald formula strikes back
  4. Liquid biopsy in oncology: navigating technical hurdles and future transition for precision medicine
  5. The neglected issue of pyridoxal- 5′ phosphate
  6. Reviews
  7. Health literacy: a new challenge for laboratory medicine
  8. Clinical applications of circulating tumor cell detection: challenges and strategies
  9. Opinion Papers
  10. Pleural effusion as a sample matrix for laboratory analyses in cancer management: a perspective
  11. Interest of hair tests to discriminate a tail end of a doping regimen from a possible unpredictable source of a prohibited substance in case of challenging an anti-doping rule violation
  12. Perspectives
  13. Sigma Metrics misconceptions and limitations
  14. EN ISO 15189 revision: EFLM Committee Accreditation and ISO/CEN standards (C: A/ISO) analysis and general remarks on the changes
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  16. Evaluation of current indirect methods for measuring LDL-cholesterol
  17. Verification of automated review, release and reporting of results with assessment of the risk of harm for patients: the procedure algorithm proposal for clinical laboratories
  18. Progranulin measurement with a new automated method: a step forward in the diagnostic approach to neurodegenerative disorders
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