Harmonisation of Low-Density Lipoprotein Cholesterol Results Obtained with Different Direct Methods: A Study Based on an External Quality Assessment Program

<b>Objectives:</b> Low-density lipoprotein cholesterol (LDL-C) is a primary lipid cardiovascular risk factor, for which universal decision cut-off values are applied. The aim of our study was to assess the current harmonisation status of LDL-C results obtained with direct methods. <b>Methods:</b> We analysed LDL-C results obtained in an international external quality assessment (EQA) programme 'Lipids and Lipoproteins, Lp(a)' within the period of January 2020 to October 2025. The samples were fresh liquid unprocessed human sera obtained from single donors. The inter-laboratory coefficient of variation (CV), the intra-method CV, and the concentration difference (mmol/L) between the method-specific mean and consensus LDL-C values were analysed. <b>Results:</b> The median of inter-laboratory CV was 8.7% (Q1-Q3: 7.3%-9.9%). The medians of intra-method CV were from 3.3% (Q1-Q3: 2.6%-4.0%) for 'Roche' to 8.6% (4.9%-13.7%) for 'Siemens (Advia & Attelica)'. The median concentration of LDL-C for individual method groups was as follows: 3.45 (Q1-Q3: 2.47-4.59) mmol/L for 'Abbott', 3.31 (2.15-4.11) mmol/L for 'Roche', 3.50 (2.02-4.47) mmol/L for 'Siemens (Advia & Attellica)', and 3.25 (2.27-4.19) mmol/L for 'Thermo Scientific'. The greatest differences between the method groups were observed for serum samples with high LDL-C and high triglyceride levels, for which the medians of concentration difference between the method-specific mean and consensus LDL-C values were from -0.20 (-0.37-(-0.13)) mmol/L to 0.39 (0.30-0.52) mmol/L. <b>Conclusions:</b> Harmonisation of LDL-C results remains a challenge. Healthcare professionals and patients should be aware of possible differences between LDL-C results obtained from different analysers/manufacturers.