Comparison of the effectiveness of Martin's equation, Friedewald's equation, and a Novel equation in low-density lipoprotein cholesterol estimation

Abstract

Low-density-lipoprotein cholesterol (LDL-C) is the main target in atherosclerotic cardiovascular disease (ASCVD). We aimed to validate and compare a new LDL-C estimation equation with other well-known equations. 177,111 samples were analysed from two contemporary population-based cohorts comprising asymptomatic Korean adults who underwent medical examinations. Performances of the Friedewald (FLDL), Martin (MLDL), and Sampson (SLDL) equations in estimating direct LDL-C by homogenous assay were assessed by measures of concordance (R², RMSE, and mean absolute difference). Analyses were performed according to various triglyceride (TG) and/or LDL-C strata. Secondary analyses were conducted within dyslipidaemia populations of each database. MLDL was superior or at least similar to other equations regardless of TG/LDL-C, in both the general and dyslipidaemia populations (RMSE = 11.45/9.20 mg/dL; R² = 0.88/0.91; vs FLDL: RMSE = 13.66/10.42 mg/dL; R² = 0.82/0.89; vs SLDL: RMSE = 12.36/9.39 mg/dL; R² = 0.85/0.91, per Gangnam Severance Hospital Check-up/Korea Initiatives on Coronary Artery Calcification data). MLDL had a slight advantage over SLDL with the lowest MADs across the full spectrum of TG levels, whether divided into severe hyper/non-hyper to moderate hypertriglyceridaemia samples or stratified by 100-mg/dL TG intervals, even up to TG values of 500-600 mg/dL. MLDL may be a readily adoptable and cost-effective alternative to direct LDL-C measurement, irrespective of dyslipidaemia status. In populations with relatively high prevalence of mild-to-moderate hypertriglyceridaemia, Martin's equation may be optimal for LDL-C and ASCVD risk estimation.

Figure 1

Flowchart of study design. N number; HDL-C high-density lipoprotein cholesterol; Non-HDL-C non-high-density lipoprotein cholesterol; TC total cholesterol; LDL-C low-density lipoprotein cholesterol; dLDL direct LDL-C; TG triglyceride; GSHC Gangnam Severance Hospital Check-up; KOICA Korea Initiatives on Coronary Artery Calcification.

Figure 2

Scatter plots showing the correlation of direct LDL-C values with estimated LDL-C values using the Friedewald, Martin/Hopkins, and Sampson equations. RMSE root mean square error; GSHC Gangnam Severance Hospital Check-up; KOICA Korea Initiatives on Coronary Artery Calcification; LDL-C low-density lipoprotein cholesterol; dLDL direct LDL-C; TG triglyceride.

Figure 3

Residual error plots for LDL-C by different equations. (a) Severe hyperTG/ TG < 400 mg/dL; (b) High/Low LDL-C. MAD mean absolute difference; RMSE root mean square error; LDL-C low-density lipoprotein cholesterol; dLDL direct LDL-C; TG triglyceride; GSHC Gangnam Severance Hospital Check-up; KOICA Korea Initiatives on Coronary Artery Calcification.

Figure 4

Comparison of the mean absolute difference scores between direct LDL-C and different estimated LDL-C values for various TG and LDL-C levels. TG triglyceride; LDL-C low-density lipoprotein cholesterol; GSHC Gangnam Severance Hospital Check-up; KOICA Korea Initiatives on Coronary Artery Calcification.