Challenges in LDL-C measurement in lipemic specimens: a comparative evaluation of four homogeneous assays

Area of Science:

• Clinical Chemistry
• Cardiovascular Diagnostics
• Biomarker Analysis

Background:

• Low-density lipoprotein cholesterol (LDL-C) is a key indicator for atherosclerotic cardiovascular disease (ASCVD) risk.
• Conventional homogeneous LDL-C assays can be inaccurate in patients with hypertriglyceridemia (high triglycerides).
• Accurate LDL-C measurement is vital for effective ASCVD risk stratification and management.

Purpose of the Study:

• To systematically evaluate the performance of four commercial homogeneous LDL-C assays in lipemic (high triglyceride) serum samples.
• To compare these assays against a gold-standard method (β-quantification) to identify the most accurate methodology.
• To assess the impact of triglyceride levels on the accuracy of different LDL-C assays.

Main Methods:

• Analyzed 257 serum samples with triglyceride levels ranging from 0.54 to 27.16 mmol/L.
• Performed parallel β-quantification on 40 of these lipemic samples.
• Compared Roche, Sekisui, JiuQiang, and Mindray homogeneous LDL-C assays using linear regression and bias analysis.

Main Results:

• The Roche assay showed the highest agreement with β-quantification, with a mean bias of -9.47%.
• Roche assay performance remained robust up to TG levels of 16.9 mmol/L, showing minimal deviation (-4.45%).
• Other assays exhibited significant bias (57.31-145.24%) and decreased correlation (R² = 0.013-0.493) with increasing triglyceride levels, with all assays exceeding 20% bias above 19 mmol/L.

Conclusions:

• Homogeneous LDL-C assays demonstrate triglyceride-dependent variability in accuracy.
• The Roche assay offers superior performance in lipemic samples up to TG 16.9 mmol/L compared to Sekisui, JiuQiang, and Mindray assays.
• Standardizing protocols for analyzing hypertriglyceridemia samples is essential to prevent misclassification of ASCVD risk.