Small dense low-density lipoprotein: Analytical review

Background: The causal relationship between low-density lipoprotein (LDL) and atherosclerotic cardiovascular disease (CVD) has been firmly substantiated. LDL consists of a heterogeneous group of particles with different physicochemical and metabolic properties. Among them, small dense LDL (sdLDL) particles are considered an emerging CVD risk factor and a promising CVD risk biomarker. This paper reviews published analytical and calculation-based methods for sdLDL determination in plasma, present their principles, strengths, and weaknesses, and examine the challenges arising from method comparison. Methods: A literature survey was conducted using the PubMed database. Subject headings and keywords facilitated the search strategy. Titles and abstracts were initially assessed, and the full-text article of the pre-selected ones was reviewed. Results: A range of methods is currently available for the analysis of LDL subfractions and the measurement of sdLDL particle size, number, and cholesterol concentration. Ultracentrifugation (UC), vertical auto profile, gradient gel electrophoresis (GGE), nuclear magnetic resonance (NMR) spectroscopy, high-performance liquid chromatography, ion mobility analysis, and a homogeneous assay are the most prevalent. To date, there is no gold standard. UC and GGE are the most established techniques, albeit significantly sophisticated. NMR and the homogeneous assay are options with potential clinical use as they yield results rapidly and can be highthroughput. None of the proposed equations for the calculated sdLDL determination has been sufficiently validated to serve as a clinical tool. Conclusions: Many analytical procedures have been developed for the study of sdLDL particles. Their use remains largely restricted to research laboratories since their analytical and clinical performance, along with the clinicaland cost-effectiveness of sdLDL determination have not been fully established.

Automated summary

Various methods exist for the analysis of LDL subfractions and the measurement of sdLDL particle characteristics, with ultracentrifugation, gradient gel electrophoresis, NMR spectroscopy, and homogeneous assay being common. While there is no gold standard, ultracentrifugation and GGE are established techniques, while NMR and homogeneous assay are rapid and high-throughput options. However, none of the proposed equations for calculated sdLDL determination have been sufficiently validated for clinical use.