Key result
Calculated LDL-C equations fail at triglycerides >400 mg/dL, with error rates exceeding ~49%.
Why the study?
Do calculated LDL-C equations accurately estimate LDL-C compared to beta-quantification in patients with dyslipidemia?
Cohort (n=32,533)
Do calculated LDL-C equations accurately estimate LDL-C compared to beta-quantification in patients with dyslipidemia?
In patients with triglycerides >400 mg/dL, none of the current LDL-C equations perform adequately compared to beta-quantification, indicating LDL-C should be directly measured rather than calculated in this population.
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.
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Paquette et al. (2026) conducted a cohort in Dyslipidemia (n=32,533). Calculated LDL-C equations vs. β-quantification method was evaluated on Proportion of values outside the National Cholesterol Education Program total allowable error limit of 12%. All calculated LDL-C equations had >49% error rates for triglycerides >400 mg/dL, whereas for TG ≤400 mg/dL, the Enhanced Sampson (8.5%) and Friedewald (11.6%) equations performed best.
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