Correcting for small-HDL disks and small-LDL dimers reduced measurement discrepancies between AF4-LC-MS/MS and NMR from 20% to 4.9% for HDL-P and from -47% to -5.7% for LDL-P.
Correcting for the presence of small-HDL disks and small-LDL dimers improves the accuracy of lipoprotein particle number determination by AF4-LC-MS/MS compared to NMR.
Absolute Event Rate: 0% vs 0%
High-density and low-density lipoproteins (HDL and LDL) are established analytical targets for diagnosis and risk stratification of numerous chronic diseases. This study investigates potential sources of bias in lipoprotein particle counting (HDL-P and LDL-P), focusing on the most atheroprotective small-HDL and most pro-atherogenic small-LDL. Plasma samples were fractionated using asymmetric-flow field-flow fractionation (AF4), coupled with hydrodynamic size measurement and comprehensive liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of each fraction. Concentration-size profiles were deconvoluted into 10 HDL and 8 LDL Gaussian subspecies. Molecular volume ratios were used to evaluate proposed particle models, providing evidence for the presence of s-HDL disk and s-LDL dimers, as sources of bias in calculated HDL-P and LDL-P when spherical particle geometry is assumed. Matching apoA1/HDL-P and apoB/LDL-P to consensus values enabled correction of mass diameters (k*dm), with k≈1.2 for s-HDL disks, and k≈0.8 for s-LDL dimers. These corrections resulted in closer agreements of the calculated HDL-P and LDL-P values with those reported by nuclear magnetic resonance spectroscopy (n = 666). After corrections, average AF4-LC-MS/MS versus NMR differences decreased from 20 to 4.9% for HDL-P and from −47% to −5.7% for LDL-P; x-y correlations improved from 0.83 to 0.85 and 0.51 to 1.03, respectively; and both platforms showed a dominant presence of s-HDL and s-LDL subclasses. Overall, the results support standardization of clinical methodologies for lipoprotein subclass measurement around apoA1 and apoB, and harmonization of HDL and LDL subclass definitions based on composition and structural characteristics rather than strictly enforced size cutoffs.
Kuklenyik et al. (Fri,) reported a other. Correcting for small-HDL disks and small-LDL dimers reduced measurement discrepancies between AF4-LC-MS/MS and NMR from 20% to 4.9% for HDL-P and from -47% to -5.7% for LDL-P.