Concerns Regarding Lipoprotein Particle Measurement by Ion Mobility Analysis

We read with interest the report by Caulfield et al. (1) describing a new method for measuring lipoprotein particle concentrations by ion mobility (IM)1 analysis. There is growing evidence that the LDL particle concentration, as assessed by apolipoprotein B (apo B) or nuclear magnetic resonance (NMR) measurements, is a better discriminator of cardiovascular risk than the LDL cholesterol concentration, and measures of VLDL and HDL particles have also been suggested to have clinical advantages over analyses of their lipid counterparts. For these reasons, methods capable of quantifying lipoprotein particle concentrations accurately and efficiently are of considerable interest, and we congratulate the authors on their efforts. As part of the validation of the IM method, Caulfield and colleagues present several plots that compare IM-measured particle concentrations with corresponding lipid or apolipoprotein measurements. The results of some of these comparisons do not agree with expectations and raise concerns in our minds about the accuracy of the measured particle concentrations. As the authors point out, only a moderate association is expected between VLDL, LDL, and HDL particle concentrations and the corresponding lipid measurements, given that the cholesterol and triglyceride contents of these lipoproteins are …