Advanced lipoprotein testing for cardiovascular diseases risk assessment: a review of the novel approaches in lipoprotein profiling

Abstract

Abstract:With the increasing prevalence of cardiovascular diseases (CVD) worldwide, finding reliable and clinically relevant biomarkers to predict acute cardiovascular events has been a major aim of the scientific and medical community. Improvements of the understanding of the pathophysiological pathways of the disease highlighted the major role of lipoprotein particles, and these past decades have seen the emergence of a number of new methodologies to separate, measure and quantitate lipoproteins. Those methods, also known as advanced lipoprotein testing methods (ALT), have gained acceptance in the field of CVD risk assessment and have proven their clinical relevance. In the context of worldwide standardization and harmonization of biological assays, efforts have been initiated toward standardization of ALT methods. However, the complexity of lipoprotein particles and the multiple approaches and methodologies reported to quantify them have rendered these initiatives a critical issue. In this context and to better understand these challenges, this review presents a summary of the major methods available for ALT with the aim to point out the major differences in terms of procedures and quantities actually measured and to discuss the resulting comparability issues.

Particle number analysis of lipoprotein subclasses by gel permeation HPLC in patients with cholesteryl ester transfer protein deficiency

“…Serum lipoproteins were analyzed using the GP-HPLC system as previously described [ 11 ], and recently reviewed[ 12 ]. Briefly, lipoproteins in fresh-frozen serum (4 μl) were separated with tandemly connected Skylight PakLP1-AA gel permeation columns (Skylight Biotech Inc., Akita, Japan, 300 mm × 4.6 mm I.D.).…”

Machine learning modelling of blood lipid biomarkers in familial hypercholesterolaemia versus polygenic/environmental dyslipidaemia

“…The 'Lipoprint' profile was obtained using the 'Lipoprint LDL subfractions test' (Quantimetrix) 16 . This is a semiquantitative method that separates by polyacrylamide gel electrophoresis the different lipoprotein fractions as VLDL, IDL, LDL 1-7 subfractions (LDL subfractions 3-7 considered the sdLDL) and HDL [16][17][18] . For the purpose of this study, ratios that relate lipid parameters were calculated and included as additional variables to explore previous observations suggesting a differential contribution of TG and LDL metabolism and anti-atherogenic/pro-atherogenic factors to FH+ and FH− dyslipidaemic states (Table 1).…”

Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM

“…However, apoB cannot substitute for NMR-or ion mobility-based particle size measurements and does not differentiate between LDLP and VLDL particle numbers [61,62]. A major impediment to LDLP testing is its limited availability in the clinical laboratories, higher cost, and lack of standardization [63], although it does provide additional information on other lipoproteins VLDL and HDL, beyond LDLP.…”

“…Hence, emerging and advanced lipoprotein testing will likely become more and more useful in the future. This underscores the need to standardize and validate advanced lipoprotein tests, such as NMR-or ion mobility-based LDLP and VLDL particle numbers and size [62,63], and multiplexed LC-MSMS apolipoprotein profiles [68], which have the potential to become widely available medical tests [99]. These novel technologies provide complementary diagnostic information regarding the complex molecular basis of dyslipidemias and, as such, can be used to explore and evaluate precision medicine approaches for identifying better and individualized treatment options for patients at high risk of ASCVD [99].…”