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. 2020 Nov 30;67(1):143–153. doi: 10.1093/clinchem/hvaa252

Table 1.

Laboratory tests for triglyceride-rich lipoprotein measures, lipoprotein(a), and inflammatory markers.

Measures Assay features Pros Cons
Total TGs Measures circulating concentrations of total TGs based on quantification of glycerol following lipolytic conversion of TGs

Automated chemistry assay

Standardized methodology via traceable SRMs

High-throughput/low-complexity method

Does not measure TG concentrations of individual lipoprotein classes/subfractions

Non–glycerol blanked TG assays can result in a free glycerol error

Calculated RC Total cholesterol – ( HDL-C + directly measured LDL-C)

Cost effective: can be calculated using standard lipid profile

High-throughput/low-complexity method

May be inaccurate when calculated LDL-C is used instead of directly measured LDL-C

Does not measure cholesterol concentrations of lipoprotein classes/subfractions

RLP-C by homogeneous assay (Denka Seiken) Measures cholesterol concentration in remnant lipoproteins using specific surfactants and enzymes

Automated chemistry assay

Standardized against density gradient ultracentrifugation method

Directly measures cholesterol concentration in remnant lipoproteins

High-throughput/low-complexity method

Novel assay with limited data available from clinical studies
LDL-TG by homogeneous assay (Denka Seiken) Measures TG concentration in LDL using specific surfactants and enzymes

Automated chemistry assay

Standardized against density gradient ultracentrifugation method

Directly measures TG concentration in LDL

High-throughput/low-complexity method

Novel assay with limited data available from clinical studies
Density gradient ultracentrifugation/ precipitation (beta quantification) Can be used to measure cholesterol and TG concentrations in VLDL, IDL, LDL, HDL, and Lp(a) by density ultracentrifugation/precipitation and subsequent enzymatic methods for cholesterol and TGs Gold standard reference method for LDL-C and HDL-C High-complexity method/low-throughput method
NMR (LipoScience/ LabCorp) Measures lipoprotein particle concentrations (VLDL, IDL, LDL, HDL) and size in 11 lipoprotein subfractions

LDL-P assay is US FDA approved

High-throughput assay

Directly measures lipoprotein concentrations and sizes

High-complexity method

Does not measure cholesterol or TG concentration in lipoprotein subfractions

Issues regarding standardization of lipoprotein subfractions and instrument sensitivity

NMR (Nightingale Health) Measures lipoprotein particle concentrations (VLDL, IDL, LDL, HDL) and size in 14 lipoprotein subfractions as well as their TGs, cholesterol (free and esterified), phospholipids, and fatty acids

High-throughput assay

Directly measures lipoprotein concentrations and sizes in addition to their lipid constituents

High-complexity method

Specific software and data analysis tools required

Issues regarding standardization of lipoprotein subfractions and instrument sensitivity

ES-DMA (Quest) Measures lipoprotein particle concentrations (VLDL, IDL, LDL, HDL) and size in lipoprotein subfractions in the range of 17.2–540.0 Å based on ion mobility

High-throughput assay

Directly measures lipoprotein concentrations and sizes

High-complexity method

Does not measure cholesterol or TG concentration in lipoprotein subfractions

Issues regarding standardization against other methodologies

Lp(a) (immuno turbidimetric assays; Denka Seiken, Roche, Randox) Measures circulating Lp(a) concentration using antibodies directed against apo(a)

Automated immunoturbidimetric assay

Assay standardization possible via traceable SRMs (WHO/IFCC)

High-throughput/low-complexity method

Assays using monoclonal antibodies that are kringle IV type 2 repeat insensitive allow for assay standardization (values expressed in nmol/L)

Lp(a) cut off values for ASCVD risk unresolved (older guidelines suggest >30 mg/dL or >50 mg/dL)

Global assay standardization issues related to general acceptance of nmol/L units of measurement

Most currently available Lp(a) assays are affected by apo(a) size heterogeneity

hs-CRP (immuno turbidimetric assays) Widely accepted surrogate marker for chronic low-grade inflammation

Automated immunoturbidimetric/nephelometric assay

Assay standardization via traceable SRMs (ERM/IFCC)

High-throughput/low-complexity method

Cost-effective

Large intraindividual biological variability requires serial measurements for accurate risk classification

Abbreviations: apo, apolipoprotein; ASCVD, atherosclerotic cardiovascular disease; ERM, European Reference Material; ES-DMA, electrospray-differential mobility analysis; FDA, U.S. Food and Drug Administration; HDL, high-density lipoprotein; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; IDL, intermediate-density lipoprotein; IFCC, International Federation of Clinical Chemistry and Laboratory Medicine; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; LDL-TG, low-density lipoprotein triglycerides; Lp(a), lipoprotein(a); NMR, nuclear magnetic resonance; RC, remnant cholesterol; RLP-C, remnant-like particle cholesterol; SRM, U.S. Standard Reference Material; TG, triglyceride; VLDL, very-low-density lipoprotein; WHO, World Health Organization.