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Some studies suggest the Martin/Hopkins equation is the most accurate for calculating LDL-C, especially with elevated triglycerides, while other studies highlight the Sampson and modified Friedewald formulas as more accurate in specific conditions like high triglycerides and low LDL-C levels.
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Low-density lipoprotein cholesterol (LDL-C) is a critical marker for cardiovascular disease risk assessment. Traditionally, LDL-C is calculated using the Friedewald equation, which estimates LDL-C based on total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) . However, this method has limitations, particularly in patients with high triglyceride levels (>4.5 mmol/L or 400 mg/dL) .
The Friedewald equation assumes a fixed ratio of TG to very low-density lipoprotein cholesterol (VLDL-C), which can lead to inaccuracies, especially in non-fasting states or in patients with hypertriglyceridemia . Studies have shown that the Friedewald equation often underestimates LDL-C in these scenarios, leading to potential misclassification of cardiovascular risk .
The Martin/Hopkins equation adjusts the TG:VLDL-C ratio based on TG and non-HDL-C levels, providing more accurate LDL-C estimates, particularly in patients with low LDL-C and elevated TG levels . This equation has been validated in large datasets and has shown higher accuracy compared to the Friedewald equation .
The Sampson equation, developed using β-quantification, is designed for patients with TG levels up to 9 mmol/L (800 mg/dL). It performs well in high TG, postprandial, and low LDL-C samples, similar to direct LDL-C measurements . This equation has demonstrated better accuracy in patients with hypertriglyceridemia compared to the Friedewald and Martin/Hopkins equations .
A modified version of the Friedewald equation has been proposed to improve accuracy. This version adjusts the TG factor based on TG concentration ranges, resulting in better agreement with directly measured LDL-C values . However, it still shows a total percentage error above the recommended limit of 12%.
A comprehensive study comparing 23 LDL-C equations found that the Martin/Hopkins equation had the highest accuracy, correctly classifying LDL-C in 89.6% of cases, followed by the Sampson equation at 86.3%. The Friedewald equation, while widely used, had a lower accuracy rate of 83.2%. The study also highlighted that many alternative equations performed worse than the Friedewald equation, emphasizing the need for careful selection of calculation methods.
Given the limitations of the Friedewald equation, especially in patients with high TG levels, the Martin/Hopkins and Sampson equations offer more reliable alternatives for LDL-C calculation . Clinical laboratories should consider implementing these equations to improve the accuracy of LDL-C estimation and better manage cardiovascular disease risk .
Accurate calculation of LDL-C is essential for effective cardiovascular risk management. While the Friedewald equation has been the standard for decades, its limitations necessitate the use of more accurate alternatives like the Martin/Hopkins and Sampson equations. These newer methods provide better accuracy, particularly in patients with high triglyceride levels, and should be adopted in clinical practice to enhance patient care.
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