Abstract
Objectives
Low-density lipoprotein cholesterol (LDL-C) concentration was calculated for many years using the Friedewald equation, but those from Sampson and extended-Martin-Hopkins perform differently. Their accuracy in fasting hypertriglyceridemia and non-fasting state were compared and the clinical impact of implementing these equations on risk classification and on the setting of lipid treatment goals was assessed.
Methods
Seven thousand six standard lipid profiles and LDL-C concentrations measured after ultracentrifugation (uLDL-C) were retrospectively included. uLDL-C were compared to calculated LDL-C in terms of correlation, root mean square error, residual error, mean absolute deviations and cardiovascular stratification.
Results
In fasting state (n=5,826), Sampson equation was the most accurate, exhibited the highest percentage of residual error lower than 0.13 mmol/L (67 vs. 57 % and 63 % using Friedewald, or extended-Martin-Hopkins equations respectively) and the lowest misclassification rate. However, the superiority of this equation was less pronounced when triglyceride concentration (TG) <4.5 mmol/L were considered. In post-prandial state (n=1,180), extended-Martin-Hopkins was the most accurate equation, exhibited the highest percentage of residual error lower than 0.13 mmol/L (73 vs. 39 % and 57 % using Friedewald and Sampson equation respectively). Overall, the negative bias with Sampson equation may lead to undertreatment. Conversely, a positive bias was observed with extended Martin-Hopkins.
Conclusions
None of the equations tested are accurate when TG>4.52 mmol/L. When TG<4.52 mmol/L both Sampson and Martin-Hopkins equations performed better than Friedewald. The switch to one or the other should take in account their limitations, their ease of implementation into the lab software and the proportion of non-fasting patients.
Acknowledgments
We would like to thank physicians and nurses of endocrinology units for recruiting patients, Mrs. Eléonore DIVRY and Mrs. Jade MAAMI for their contribution in determination of LDL-C after ultracentrifugation. The graphical abstract was created with BioRender.com.
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Research funding: None declared.
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Author contributions: Clinical assessments: SC PM. Experiments: conception and design: JV, AL, MDF. Performed the experiments: CB. Analyzed the data: JV, AL, NM, OM, SC, PM, MDF. Wrote the paper: JV, AL, MDF. Approve the version to be published, agree to be accountable for all aspects of the work: all authors.
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Competing interests: The authors declare that they have no direct or indirect conflict of interest associated with this publication.
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Informed consent: This study was carried put according to the French ethic laws.
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Ethical approval: Data were anonymized but the age and the sex were known. The study was carried out according to The Code of Ethics of the World Medical Association (Declaration of Helsinki) and obtained the agreement of the ethical committee of the Ethics Committee of the Hospices Civils de Lyon (LDL FORMULA CNIL 2185588 – clinical trial: NCT05598216).
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0360).
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