Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol measurement in Familial Dysbetalipoproteinemia

Abstract

Aim: To compare LDL-C concentrations using the Friedewald formula, the Martin-Hopkins formula, a direct assay and polyacrylamide gradient gel electrophoresis (PGGE) to the reference standard density gradient ultracentrifugation in patients with Familial Dysbetalipoproteinemia (FD) patients. We also compared non-HDL-cholesterol concentrations by two methods.

Methods: For this study data from 28 patients with genetically confirmed FD from the placebo arm of the EVOLVE-FD trial were used. Four different methods for determining LDL-C were compared with ultracentrifugation. Non-HDL-C was measured with standard assays and compared to ultracentrifugation. Correlation coefficients and Bland-Altman plots were used to compare the methods.

Results: Mean age of the 28 FD patients was 62 ± 9 years, 43 % were female and 93 % had an ɛ2ɛ2 genotype. LDL-C determined by Friedewald (R² = 0.62, p <0.01), Martin-Hopkins (R² = 0.50, p = 0.01) and the direct assay (R² = 0.41, p = 0.03) correlated with density gradient ultracentrifugation. However, Bland-Altman plots showed considerable over- or underestimation by the four methods compared to ultracentrifugation. Non-HDL-C showed good correlation and agreement.

Conclusion: In patients with FD, all four methods investigated over- or underestimated LDL-C concentrations compared with ultracentrifugation. In contrast, standard non-HDL-C assays performed well, emphasizing the use of non-HDL-C in patients with FD.

Keywords: Cholesterol; Density gradient ultracentrifugation; Direct homogeneous assay; FRIEDEWALD; Familial Dysbetalipoproteinemia; Low-density lipoprotein; Martin-Hopkins; Non-high-density lipoprotein; Polyacrylamide gels; Treatment goal; Type III hyperlipoproteinemia.