Table 1.

Commonly Used LDL Subfraction Tests and Terms

Commonly used tests to measure LDL subfractions

Nuclear magnetic resonance: Clinically available test using a mass spectrometer. Measures the signal from the aggregate number of terminal methyl groups in the lipid within the particle. The number of methyl groups is reflected in the amplitude of the methyl NMR signal. The amplitude of each lipoprotein particle signal serves as a measure of the concentration of that lipoprotein. The NMR data are converted into subfraction concentrations by using assumptions in proprietary software. Size and pattern of LDL can be derived through additional calculations.

LipoPrint gel electrophoresis*: Clinically available test using a specific gel kit, equipment, and method for defining LDL subfractions. Relatively rapid system compared with most gel electrophoresis methods. Separates particles into 7 subfractions by size and to a lesser extent charge. Lipoprotein subfraction profiles can be classified into type A or B. Use of LipoPrint to determine particle sizes or LDL scores or any other form of classification is not recommended by the manufacturer of the kit but is routinely done by researchers.

Berkeley HeartLab segmented gel electrophoresis*: Clinically available test using a specific gel kit together with a proprietary computer algorithm for calculating the number of particles in an LDL subfraction. Separates particles into 7 LDL subfractions (I, IIa, IIb, IIIa, IIIb, IVa, and IVb) on the basis of particle size and shape.

Bench gel electrophoresis†: The principal method used in research laboratories to measure LDL subfractions. The LDL subfractions are separated by electrophoresis across a sodium dodecyl sulfate gradient gel. For the majority of specific gel electrophoresis methods, researchers create their own gels and apply nonstandardized techniques to separate the LDL subfractions. Different compounds are used to create the gels, although polyacrylamide is the most common. Different distributions of gel densities are used. Different approaches are used to define and determine the specific LDL subfractions.

Ultracentrifugation†: Performed only in research laboratories by using a variety of instruments, specific methods, and definitions of LDL subfractions. The LDL subfractions are separated by ultracentrifugation on the basis of density. A variety of arbitrary density cut-points between subfractions has been reported.

Commonly used LDL subfraction terms

Small, dense LDL particles: Considered to be most atherogenic. Generally < 197 Å or < 212 Å, but see Table 4 for other definitions. Reported as the plasma concentration. Considered to be the atherogenic subfraction.

Medium LDL particles: Particles of a size between small and large. Some reports omit this category.

Large LDL particles: Considered to be least atherogenic. Generally > 213 Å, but see Table 4 for other definitions.

LDL particle number (or concentration): The concentration of LDL particles, measured in nmol/L. Determined only by NMR as a calculated value. Higher concentrations are considered to be more atherogenic.

LDL particle size: Absolute measure of the average or peak size of the LDL particles, reported in Å or nm. Smaller size is considered to be more atherogenic.

Pattern A: Predominance of larger, more buoyant LDL particles (“normal”).

Pattern B: Predominance of smaller, denser LDL particles (“abnormal”).

Pattern AB or intermediate: A pattern either intermediate to or of mixed patterns A and B. Often analyzed together with pattern B.

Individual subfractions: Usually divided into 7 subfractions primarily on the basis of density fractions. Various nomenclatures are used, generally with LDL1 (or equivalent) being most buoyant and LDL7 (or equivalent) being most dense.

LDL subfraction score: Based on electrophoretic mobility of the particles. Calculated values are based on areas under the curve of subfraction concentration. Can be divided into pattern A (score < 5.5), B (score > 8.5), and intermediate (score of 5.5–8.5).

LDL low-density lipoprotein; NMR nuclear magnetic resonance.

^*No studies of incidence or severity of cardiovascular disease used this method.

^†Studies using these methods are included only in the section “All Methods of Measuring LDL Subfractions.”