Lipoprotein Subfraction Testing

Lipoproteins are a group of particles that are responsible for transporting lipids throughout the body. Each particle contains a combination of protein, cholesterol, triglyceride, and phospholipid molecules. The composition of the particles change as they circulate in the blood; some molecules are removed and others are added. The result of this dynamic process is a spectrum of LDL, HDL, and VLDL lipoprotein particles that vary from large and fluffy (those with a high proportion of triglycerides) to small and dense (those with a high proportion of protein).

Some studies have shown that small dense LDL particles are more likely to cause atherosclerosis than light fluffy LDL particles. Researchers think that the presence of small dense LDL could be one of the reasons that some people have heart attacks even though their total and LDL cholesterol concentrations are not particularly high. This is why LDL is referred to as the bad cholesterol. Small dense VLDL particles are also thought to increase risk of atherosclerosis. However, the data are not clear on whether testing for subfractions provides additional information about a person’s cardiac risk or whether results from such testing should affect decisions about treatment. More clinical research is needed to determine whether there is value in testing for lipoprotein subfractions and how the results may be used.

A summary of draft guidelines on Emerging Biomarkers of Cardiovascular Disease and Stroke from The National Academy of Clinical Biochemistry states “Lipid subclasses, especially the number or concentration of small dense LDL particles, have been shown to be related to the development of initial coronary heart disease events, but the data analyses of existing studies are generally not adequate to show added benefit over standard risk assessment. There is insufficient data that measurement of lipid subclasses over time is useful to evaluate the effects of treatments.” (See Sources)

Although less is known about HDL subclasses, some initial studies have shown that large fluffy HDL particles may provide more protection against atherosclerosis than small dense HDL particles.

The number of small dense LDL, VLDL, and HDL particles a person has is partially genetically determined, partially due to gender (males tend to have more small LDL and HDL than females), and partially due to lifestyle and a person’s general state of health. Certain diseases and conditions, such as diabetes and hypertension, are associated with increased levels of small dense LDL.

A variety of methods are used to determine lipoprotein subfractions. These include ultracentrifugation (separation by density), electrophoresis (separation by charge and size), and NMR (nuclear magnetic resonance) spectroscopy (which counts the number of particles in each subfraction). Until recently, these methods were too expensive and technically demanding to be used on a commercial basis, but lipoprotein subfraction testing has begun to be offered in some larger laboratories and reference laboratories.