Validation of Friedewald, Martin, Sampson and Modified Sampson Equations for Estimating LDL Cholesterol in a Pediatric Population

Background: Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is essential for cardiovascular risk assessment in pediatric populations, yet the comparative performance of available estimation equations remains insufficiently characterized. This study evaluated the agreement, systematic bias, and diagnostic performance of the Friedewald, Martin, original Sampson, and Modified Sampson equations for estimating LDL-C and derived low-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol (LDL/HDL-C) and triglyceride-to-low-density lipoprotein cholesterol (TG/LDL-C) ratios. Methods: A prospective cross-sectional agreement study was conducted among 500 pediatric patients. Agreement with laboratory measurements was assessed using the intraclass correlation coefficient (ICC), concordance correlation coefficient (CCC), coefficient of determination (R2), root mean square error (RMSE), mean absolute error (MAE), percentage bias, Bland–Altman analysis, Passing–Bablok regression, and diagnostic accuracy at an LDL-C cut-off of 110 mg/dL. Results: The Modified Sampson equation demonstrated the best overall analytical performance for LDL-C estimation (ICC = 0.931; CCC = 0.930; RMSE = 8.62 mg/dL; MAE = 6.73 mg/dL; bias = −0.805%) and showed no proportional bias. It also provided the highest agreement for LDL/HDL-C (ICC = CCC = 0.962) and TG/LDL-C ratios (ICC = CCC = 0.965), with the lowest estimation errors. The Martin and original Sampson equations showed intermediate performance, whereas the Friedewald equation consistently demonstrated the lowest agreement and greatest systematic bias. All equations showed excellent diagnostic accuracy; the Martin equation achieved the highest accuracy (94.40%), specificity (97.86%), and area under the receiver operating characteristic curve (AUC) (0.980), while Modified Sampson showed the highest sensitivity (78.75%). Conclusions: Overall, the Modified Sampson equation provided the closest analytical agreement with laboratory LDL-C and derived ratios, whereas the Martin equation showed the strongest classification performance. These findings support the use of newer LDL-C estimation equations over the Friedewald equation in pediatric populations for improved lipid assessment and cardiovascular risk stratification.