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.

Highlights

  • Low-density-lipoprotein cholesterol (LDL-C) is the main target in atherosclerotic cardiovascular disease (ASCVD)

  • Recent American Heart Association/American College of Cardiology (AHA/ACC) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines emphasise the use of aggressive LDL-C targeted therapy for reductions in the level of LDL-C by > 50% if the level is higher than a certain threshold in very high-risk ­patients[2,3,4]

  • LDL-C is widely estimated using the Friedewald equation (FLDL). This equation is associated with very low-density lipoprotein cholesterol (VLDL-C) overestimation and LDL-C underestimation under conditions of low LDL-C and high triglyceride (TG) levels, given the fixed TG:VLDL-C ratio of 5:16,7

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Summary

Introduction

Low-density-lipoprotein cholesterol (LDL-C) is the main target in atherosclerotic cardiovascular disease (ASCVD). 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). LDL-C is widely estimated using the Friedewald equation (FLDL) This equation is associated with very low-density lipoprotein cholesterol (VLDL-C) overestimation and LDL-C underestimation under conditions of low LDL-C and high triglyceride (TG) levels, given the fixed TG:VLDL-C ratio of 5:16,7. Martin et al developed an equation using an adjustable factor (strata-specific median VLDL-C:TG ratio) in place of the fixed TG denominator of ­58 This equation is more accurate than the Friedewald equation, at low LDL-C levels, and shows a much stronger concordance with directly measured LDL-C using the ultracentrifugation method than the Friedewald equation, according to TG l­evel[9]. The new equation, which they deemed favourable for use in patients with low levels of LDL-C and/or hypertriglyceridemia, yielded a misclassification rate lower than 35% in the categorisation of patients with hypertriglyceridemia into different LDL-C treatment g­ roups[5]

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