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Evaluation of low-density lipoprotein cholesterol equations by cross-platform assessment of accuracy-based EQA data against SI-traceable reference value

  • Hwee Tong Tan , Sharon Yong , Hong Liu , Qinde Liu ORCID logo EMAIL logo , Tang Lin Teo and Sunil Kumar Sethi
Published/Copyright: April 4, 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 61 Issue 10

Abstract

Objectives

Low-density lipoprotein cholesterol (LDLC) is the primary cholesterol target for the diagnosis and treatment of cardiovascular disease (CVD). Although beta-quantitation (BQ) is the gold standard to determine LDLC levels accurately, many clinical laboratories apply the Friedewald equation to calculate LDLC. As LDLC is an important risk factor for CVD, we evaluated the accuracy of Friedewald and alternative equations (Martin/Hopkins and Sampson) for LDLC.

Methods

We calculated LDLC based on three equations (Friedewald, Martin/Hopkins and Sampson) using the total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDLC) in commutable serum samples measured by clinical laboratories participating in the Health Sciences Authority (HSA) external quality assessment (EQA) programme over a 5 years period (number of datasets, n=345). LDLC calculated from the equations were comparatively evaluated against the reference values, determined from BQ-isotope dilution mass spectrometry (IDMS) with traceability to the International System of Units (SI).

Results

Among the three equations, Martin/Hopkins equation derived LDLC had the best linearity against direct measured (y=1.141x − 14.403; R2=0.8626) and traceable LDLC (y=1.1692x − 22.137; R2=0.9638). Martin/Hopkins equation (R2=0.9638) had the strongest R2 in association with traceable LDLC compared with the Friedewald (R2=0.9262) and Sampson (R2=0.9447) equation. The discordance with traceable LDLC was the lowest in Martin/Hopkins (median=−0.725%, IQR=6.914%) as compared to Friedewald (median=−4.094%, IQR=10.305%) and Sampson equation (median=−1.389%, IQR=9.972%). Martin/Hopkins was found to result in the lowest number of misclassifications, whereas Friedewald had the most numbers of misclassification. Samples with high TG, low HDLC and high LDLC had no misclassification by Martin/Hopkins equation, but Friedewald equation resulted in ∼50% misclassification in these samples.

Conclusions

The Martin/Hopkins equation was found to achieve better agreement with the LDLC reference values as compared to Friedewald and Sampson equations, especially in samples with high TG and low HDLC. Martin/Hopkins derived LDLC also enabled a more accurate classification of LDLC levels.

Keywords: beta-quantitation; Friedewald equation; isotope-dilution mass spectrometry; low-density lipoprotein cholesterol (LDLC); Martin/Hopkins equation; Sampson equation
Corresponding author: Qinde Liu, Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, 117528, Singapore, Phone: +65 6775 1605, Ext. 102, Fax: +65 6775 1398, E-mail:

  1. Research funding: None declared.

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

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: This study was based on the results from a local external quality assessment program with the effort to assess the performance of the measurement procedures of the local clinical laboratories. Such quality assessment program is exempted from local institutional ethics review.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2022-1301).

Received: 2022-12-21
Accepted: 2023-03-20
Published Online: 2023-04-04
Published in Print: 2023-09-26

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2022-1301
Keywords for this article
beta-quantitation; Friedewald equation; isotope-dilution mass spectrometry; low-density lipoprotein cholesterol (LDLC); Martin/Hopkins equation; Sampson equation

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Laboratory Medicine: from just testing to saving lives
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