Towards Accurate Low-density Lipoprotein-cholesterol Estimation: Retrospective Comparison of 26 Equations Against the Friedewald Equation in Indian Laboratories

A BSTRACT Background: The Friedewald equation, developed over 50 years ago from a small fasting North American cohort, remains the dominant low-density lipoprotein-cholesterol (LDL-C) estimator worldwide. Its validity in Indian patients – who exhibit distinctly elevated triglycerides (TG), lower high-density lipoprotein cholesterol, and high metabolic syndrome burden – has not been rigorously evaluated at scale. Objective: To subject all 26 available LDL-C estimation equations to head-to-head evaluation against a validated enzymatic direct assay across the full triglyceride spectrum in Indian laboratory practice. Materials and Methods: Retrospective cross-sectional analysis of 17,379 patients at a tertiary care referral hospital (October 2023– December 2024). Direct LDL-C was measured by the Beckman Coulter selective protection enzymatic assay. All 26 equations were evaluated for clinical concordance, mean bias, standard deviation of differences, and R 2 , stratified by LDL-C category and triglyceride stratum. Results: Among 1269 fasting patients with TG <400 mg/dL, Sampson-NIH showed the closest agreement with direct LDL-C measurement ( r = 0.948, R 2 = 0.899, mean bias = 2.17 mg/dL, mean absolute error = 4.63 mg/dL), followed by Jeong et al . ( r = 0.942, R 2 = 0.888). Friedewald’s formula had the weakest agreement ( R 2 = 0.813, concordance 51.9%), with a substantial systematic mean bias of − 178 mg/dL at TG ≥1000 mg/dL. Agreement with direct LDL-C deteriorated progressively above TG 400 mg/dL ( R 2 < 0.25 for all equations). Conclusions: Sampson-NIH and Jeong are meaningfully superior to Friedewald’s in Indian patients, particularly at TG >200 mg/dL and low LDL-C values. Direct LDL-C measurement is essential when TG exceeds 400 mg/dL.