Liposcale: a novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR spectroscopy

Roger Mallol,Núria Amigó,Miguel A Rodríguez,Mercedes Heras,Maria Vinaixa,Núria Plana,Edmond Rock,Josep Ribalta,Oscar Yanes,Lluís Masana,Xavier Correig

doi:10.1194/jlr.d050120

Abstract

Determination of lipoprotein particle size and number using advanced lipoprotein tests (ALTs) is of particular importance to improve cardiovascular risk prediction. Here we present the Liposcale test, a novel ALT based on 2D diffusion-ordered (1)H NMR spectroscopy. Our method uses diffusion coefficients to provide a direct measure of the mean particle sizes and numbers. Using 177 plasma samples from healthy individuals and the concentration of ApoB and ApoA from isolated lipoprotein fractions, our test showed a stronger correlation between the NMR-derived lipoprotein particle numbers and apolipoprotein concentrations than the LipoProfile(®) test commercialized by Liposcience. We also converted LDL particle numbers to ApoB equivalents (milligrams per deciliter) and our test yielded similar values of LDL-ApoB to the LipoProfile(®) test (absolute mean bias of 8.5 and 7.4 mg/dl, respectively). In addition, our HDL particle number values were more concordant with the calibrated values determined recently using ion mobility. Finally, principal component analysis distinguished type 2 diabetic patients with and without atherogenic dyslipidemia (AD) on a second cohort of 307 subjects characterized using the Liposcale test (area under the curve = 0.88) and showed concordant relationships between variables explaining AD. Altogether, our method provides reproducible and reliable characterization of lipoprotein particles and it is applicable to pathological states such as AD.

Highlights

Determination of lipoprotein particle size and number using advanced lipoprotein tests (ALTs) is of particular importance to improve cardiovascular risk prediction
As an alternative to current NMR methods, here we present the Liposcale test, a novel method for characterizing lipoprotein particles based on 2D diffusion-ordered 1H NMR spectroscopy (DOSY)
Our results indicate that only the area of the lipoprotein fraction that has been spiked-in shows a substantial increment, demonstrating that our NMR functions are correctly assigned to VLDL, LDL, and HDL particles

Summary

Introduction

Determination of lipoprotein particle size and number using advanced lipoprotein tests (ALTs) is of particular importance to improve cardiovascular risk prediction. Cardiovascular events are more likely to occur in patients with diabetes and metabolic syndrome These pathologies share a common phenotype characterized by a high content of triglycerides, a preponderance of small dense LDL particles, and low HDL levels. Journal of Lipid Research Volume 56, 2015 737 lipid panels that measure the cholesterol or triglyceride content of lipoproteins seem to be insufficient to predict risk of CVD To fill this gap, advanced lipoprotein tests (ALTs) [5] that allow for an extensive characterization of lipoprotein particles through a range of additional parameters, such as size and particle number, have been proposed for improving assessment of risk of CVD and for guiding lipid-lowering therapies [6]

Methods

Results

Discussion

Conclusion