Abstract
Background/Objectives: The currently established equations for calculating low-density lipoprotein cholesterol (LDLc) do not reflect the sex-specific differences in lipid metabolism. We aimed to develop a sex-specific LDLc equation (SSLE) and validate it with three established equations (Friedewald, Sampson-NIH, and ext-Martin-Hopkins) against direct LDLc measurement in Korean adults. Methods: This study included 23,757 subjects (51% male; median age, 51 years) from the 2009-2022 Korean National Health and Nutrition Examination Survey. We developed the SSLE through multiple linear regression incorporating total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), triglycerides (TG), and sex. The validation metrics included Bland-Altman analysis for mean absolute percentage error (MAPE) and agreement of the categorization based on the NCEP ATP-III guidelines, assessed by sex and lipid subgroups. Results: The derived SSLE equation was as follows: for TG < 200 mg/dL, LDLc = 0.963 × TC - 0.881 × HDLc - 0.111 × TG + 0.982 × Sex - 6.958; for TG ≥ 200 mg/dL, LDLc = 0.884 × TC - 0.646 × HDLc - 0.126 × TG + 3.742 × Sex - 3.214 (male = 1, female = 0). The MAPE was similar between males and females for the SSLE (4.6% for both) and ext-Martin-Hopkins (5.0% vs. 4.9%) but higher in males for the Sampson-NIH (5.4% vs. 4.9%) and Friedewald (7.6% vs. 5.7%). In the TG ≥ 400 mg/dL group, the MAPE increased progressively: SSLE (10.2%), ext-Martin-Hopkins (12.0%), Sampson-NIH (12.7%), and Friedewald (27.4%). In the LDLc < 70 mg/dL group, the MAPE was as follows: SSLE (8.0%), Sampson-NIH (8.6%), ext-Martin-Hopkins (9.7%), and Friedewald (12.8%). At TG 200-400 mg/dL, the SSLE revealed very good agreement (κ = 0.801) versus good agreement for other equations (ext-Martin-Hopkins κ = 0.794, Sampson-NIH κ = 0.782, Friedewald κ = 0.696). Conclusions: The novel SSLE demonstrated superior accuracy and agreement in Korean adults. Further validation studies across different ethnic populations are warranted.