Poor Performance of LDL-Cholesterol Equations versus Beta Quantification in a Very Large Cohort of Patients with Dyslipidemia

Clin Chem. 2026 Apr 28:hvag038. doi: 10.1093/clinchem/hvag038. Online ahead of print.

ABSTRACT

BACKGROUND: Accurate estimations of low-density lipoprotein cholesterol (LDL-C) is important to guide clinical decisions concerning lipid-lowering treatment. The Friedewald formula has been used for the past 50 years, but its limitations compared to the reference β-quantification method have led to the development of several newer equations. The objective of this study was to evaluate and compare the performance of calculated LDL-C equations using a real-world β-quantification dataset from a very large cohort of dyslipidemic patients.

METHODS: A total of 32 533 LDL-C results from β-quantification were available for this study. The β-quantification procedure was performed by qualified technicians according to the NIH reference method. LDL-C was calculated using the following equations: Modified Sampson, Enhanced Sampson, Extended Martin-Hopkins, Sampson, Martin-Hopkins, and Friedewald.

RESULTS: In patients with triglycerides (TG) concentrations between 401 and 800 mg/dL, the proportion of values outside the National Cholesterol Education Program total allowable error limit of 12% was >49% for every equation, whereas it was >79% for every equation in patients with TG concentration >800 mg/dL. In patients with TG concentrations ≤400 mg/dL, the Enhanced Sampson equation had the lowest proportion of values outside the error limit (8.5%), followed by the Friedewald equation (11.6%).

CONCLUSIONS: In patients with TG <400 mg/dL (≤4.52 mmol/L), the Friedewald equation performed well and was not inferior to the Sampson or the Martin-Hopkins equations. However, in patients with TG >400 mg/dL none of the formulas performed adequately and LDL-C should not be calculated in these patients.

PMID:42047357 | DOI:10.1093/clinchem/hvag038

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