Quantification of high-density lipoprotein particle number by proton nuclear magnetic resonance: don't believe the numbers.

Abstract

Proton nuclear magnetic resonance (NMR) can rapidly assess lipoprotein concentrations and sizes in biological samples. It may be especially useful for quantifying high-density lipoprotein (HDL), which exhibits diverse particle sizes and concentrations. We provide a critical review of the strengths and limitations of NMR for quantifying HDL subclasses. Recent studies using NMR have shed light on HDL's role in various disorders, ranging from residual cardiovascular risk to host susceptibility to infection. However, accurately quantifying HDL particle number, size, and concentration (HDL-P) remains a challenge. Discrepancies exist between NMR and other methods such as gel electrophoresis, ion mobility analysis and size-exclusion chromatography in estimating the abundance of HDL species and the ratio of apolipoprotein A-I (APOA1) to HDL particles. NMR is a low-cost method for quantifying HDL-P that is readily applicable to clinical and translational studies. However, inconsistencies between the results of NMR quantification of HDL-P and other independent methods hinder the interpretation of NMR results. Because proton NMR apparently fails to accurately quantify the sizes and concentrations of HDL, the relevance of such studies to HDL biology poses challenges. This limits our understanding of pathophysiological implications of HDL-P as determined by NMR, particularly in determining cardiovascular disease (CVD) risk.