Table 1.
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.