Ann Lab Med.  2023 Jan;43(1):29-37. 10.3343/alm.2023.43.1.29.

Intuitive Modification of the Friedewald Formula for Calculation of LDL-Cholesterol

• Hong J
• Gu H
• Lee J
• Lee W
• Chun S
• Han KH
• Min WK

• KMID: 2551577
• DOI: http://doi.org/10.3343/alm.2023.43.1.29

Abstract

Background
High LDL-cholesterol (LDL-C) is an established risk factor for cardiovascular disease and is considered an important therapeutic target. It can be measured directly or calculated from the results of other lipid tests. The Friedewald formula is the most widely used formula for calculating LDL-C. We modified the Friedewald formula for a more accurate and practical estimation of LDL-C.
Methods
Datasets, including measured triglyceride, total cholesterol, HDL-cholesterol, and LDL-C concentrations were collected and assigned to derivation and validation sets. The datasets were further divided into five groups based on triglyceride concentrations. In the modified formula, LDL-C was defined as total cholesterol − HDL-cholesterol − (triglyceride/adjustment factor). For each group, the adjustment factor that minimized the difference between measured LDL-C and calculated LDL-C using modified formula was obtained. For validation, measured LDL-C and LDL-C calculated using the modified formula (LDL-CM), Friedewald formula (LDL-CF), Martin-Hopkins formula (LDL-CMa), and Sampson formula (LDL-CS) were compared.
Results
In the derivation set, the adjustment factors were 4.7, 5.9, 6.3, and 6.4 for the groups with triglyceride concentrations <100, 101–200, 201–300, and >300 mg/dL, respectively. In the validation set, the coefficient of determination (R2) between measured and calculated LDL-C was higher for LDL-CM than for LDL-CF (R²=0.9330 vs. 0.9206). The agreement according to the National Cholesterol Education Program Adult Treatment Panel III classification of LDL-C was 86.36%, 86.08%, 86.82%, and 86.15% for LDL-CM, LDL-CF, LDL-CMa, and LDL-CS, respectively.
Conclusions
We proposed a practical, improved LDL-C calculation formula by applying different factors depending on the triglyceride concentration.

Keyword

Calculation; Friedewald formula; LDL cholesterol; Triglycerides

Figure

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  Fig. 1 Flowchart of the study design. Abbreviations: HDL-C, HDL-cholesterol; LDL-C, LDL-cholesterol; NCEP-ATP III, U.S. National Cholesterol Education Program Adult Treatment Panel III; TG, triglyceride.

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  Fig. 2 (A) The mean of difference between calculated and measured LDL-C for each group of triglycerides and factors in derivation set. The smallest mean differences are observed in factor 4.7, 5.9, 6.3, and 6.4 for the groups with triglyceride concentrations <100, 101–200, 201–300, and >300 mg/dL. (B) The mean of difference between calculated and measured LDL-C for each group of triglycerides and factors in validation set. 95% confidence interval is shown for groups with triglyceride concentrations 301–400 and >400 mg/dL. Abbreviations: CI, confidence interval; LDL-C, LDL-cholesterol.

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  Fig. 3 Scatter plots and regression lines comparing measured and calculated LDL-C using the Friedewald formula (A), modified formula (B), Martin-Hopkins formula (C), and Sampson formula (D). Abbreviation: LDL-C, LDL-cholesterol.

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  Fig. 4 (A) Distribution of LDL-C calculated with different formulae according to the NCEP-ATP III classification. (B) Agreement rate between measured LDL-C and calculated LDL-C using different formulae. Abbreviations: LDL-C, LDL-cholesterol; NCEP-ATP III, U.S. National Cholesterol Education Program Adult Treatment Panel III.

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  Fig. 5 Cases with LDL-C ≤100 mg/dL were analyzed by applying the 2019 ESC/EAS guidelines. (A) Distribution of LDL-C calculated with different formulae according to the 2019 ESC/EAS guidelines. (B) Agreement rate between measured LDL-C and calculated LDL-C using different formulae. Abbreviations: ESC/EAS, European Society of Cardiology and European Atherosclerosis Society; LDL-C, LDL-cholesterol.

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