Derivation of a Modified Friedewald's equation for LDL cholesterol estimation in Sub-Himalayan population: A comparative study

Background: Despite the availability of alternative homogenous assays for LDL-C measurement, most of the laboratories still use Friedewald Equation (FE). However, various novel equations have shown better performance than FE specific to a particular population. Besides, no equation has been devised for use in Sub-Himalayan population. Methods: A cross-sectional laboratory data-based study was conducted by recruiting lipid profiles of 1851 samples to validate 10 different equations for calculating LDL and to devise a novel Modified Friedewald Equation (MFE) specific for Sub-Himalayan population. Results: The novel MFE is presented as: LDL-C = -2.421 + (0.752 × TC) - (0.047 × TG) - (0.350 × HDL). A significant difference was observed between direct LDL-C (118.84 ± 40.39 mg/dL) and all other equations except MFE (118.84 ± 37.96 mg/dl, P > 0.999) and Puavilai Equation (117.99 ± 49.05 mg/dL, P = 0.138). Additionally, MFE showed lowest mean percentage bias of 0.14% with 95% limits of agreement within ± 2SD on Bland-Altman analysis. On ROC analysis at cut-offs of clinical decision limits of 100 mg/dl, 130 mg/dl, 160 mg/dl, and 190 mg/dl, MFE outperformed all other equations with highest AUC (0.974, 0.978, 0.982, and 0.995) respectively with specificity >95% at higher levels. MFE also showed highest correlation (r = 0.954, P < 0.001) and least rMSE (13.8) with direct LDL although all the equations showed significant positive correlation with direct LDL (p < 0.001). Conclusion: MFE derived in this study showed a better diagnostic performance as compared to other 10 equations taking Direct LDL-C as gold standard for Sub-Himalayan Population and may be used as a substitute for FE in the study population.