Underestimation of Low-Density Lipoprotein Cholesterol (LDL-C) Using the Friedewald Equation at Higher Triglyceride Levels: Evidence From a Method-Comparison Study

Background: In biochemical laboratories, low-density lipoprotein cholesterol (LDL-C) levels are generally measured using the widely accepted Friedewald equation:, where TC represents total cholesterol, and HDL stands for high-density lipoprotein.In the case of high serum triglycerides (TGs), the LDL-C value is underestimated using the Friedewald equation.Our study aimed to assess the reliability of calculated LDL-C (cLDL-C) compared with directly measured LDL-C (dLDL-C) in categorizing dyslipidemia patients across different TG levels.Methods: cLDL-C was estimated using the Friedewald equation, and dLDL-C was measured by the homogeneous method.Bland-Altman plots (BAPs) were plotted to analyze the agreement between dLDL-C and cLDL-C.We used Lind's concordance correlation coefficient to evaluate the correlation between stroke volume and cardiac output between the two methods.Mean bias with standard deviation and 95% confidence interval was determined at different TG strata.Results: BAP between dLDL-C and cLDL across TG levels also showed unacceptable agreement at higher TG levels.Mean bias between cLDL-C and dLDL-C is low; however, it rises to +20.2 mg/dL (-17.0 to 57.5) at 250-300 and +26.5 mg/dL (-17.7 to 70.6) above 300 mg/dL.Whereas, beyond TG values >250 mg/dL, cLDL-C shows poor sensitivity.At high TG concentrations, 58.7% of samples at 250-300 mg/dL and 58.1% above 300 mg/dL are assigned to a lower LDL-C band by the Friedewald equation than by direct measurement.Conclusions: The Friedewald equation shows acceptable agreement with the homogeneous direct LDL-C assay used in this laboratory at lower TG concentrations and unacceptable agreement at higher concentrations.At high TG concentrations (>250 mg/dL), the Friedewald equation misassigns more than half of patients to a lower LDL-C band than the homogeneous direct measurement and puts them at risk for atherosclerosis.Therefore, we recommend estimating LDL-C using Friedewald equation when serum TG is less than 250 mg/dL; beyond these levels, LDL-C should be measured directly.