What is being tested?
Lipoprotein electrophoresis separate the commonly measured lipoprotein fractions LDL (Low Density Lipoprotein, often called the bad cholesterol) – into subfractions based on the size, density, and/or electrical charge. Rarely testing may also identify subfractions of VLDL (Very Low Density Lipoprotein, also considered to be a bad cholesterol) or HDL (High Density Lipoprotein, often called good cholesterol).
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 cholesterol).
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. This may be the main reason is why LDL is referred to as the bad cholesterol. Small dense VLDL particles (known as remnants) are also thought to increase risk of atherosclerosis. However, the data are not clear on whether testing for subfractions provides additional information compared to an ordinary lipid profile about a person’s cardiac risk or whether results from such testing should affect decisions about treatment.
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.
Patient who have diabetes or obesity often have elevated triglycerides and low HDL and these findings are predictive of small dense LDL.
A variety of methods are used to determine lipoprotein subfractions in research laboratories. 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 and in Australia, LDL subfraction testing is not covered by Medicare.
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.”
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.
More clinical research is needed to determine whether there is value in testing for lipoprotein subfractions and how the results may be used.
How is it used?
Lipoprotein electrophoresis is not routinely ordered. LDL electrophoresis is more common than for VLDL or HDL since LDL has been identified as a primary risk factor for heart disease and more research and development has focused on LDL measurement.
When is it requested?
This test is rarely ordered in Australia other than for research purposes.
What does the result mean?
In general, the result is interpreted within the framework of a lipid profile and its associated risk. If the patient has primarily small dense LDL, this finding will add to the risk of developing CAD above and beyond the risk associated with the total LDL. On the other hand, the presence of exclusively large fluffy LDL will add no additional risk. The interpretation of the VLDL subfractions is similar. However the evidence to support use of these tests in clinical practice is weak.
Is there anything else I should know?
It is important to remember that lipoprotein electrophoresis (and other lipid and cardiac risk factor testing) is not diagnostic. It attempts to evaluate a patient’s statistical risk of developing CAD, but it cannot predict the development or severity of CAD in a particular patient.
Results of lipoprotein electrophoresis reflect the method and reporting format used as well as the patient’s total LDL-cholesterol, VLDL, and/or HDL-cholesterol. Since different methods separate the subclasses based on different physical properties (size, density, and/or electrical charge), results may not be directly comparable method to method or laboratory to laboratory.
More information can be obtained from a standard lipid profile by calculating ratios such as the total cholesterol/HDL cholesterol (TC/HDL) or the LDL cholesterol/HDL cholesterol (LDL/HDL). In people with high triglyceride levels the TC/HDL seems to better correlate with other markers of cardiac risk and this ratio is more frequently used as it is also easier to measure. The American Heart Association suggests that this ratio should be less than 5 and optimally should be 3.5. However the absolute levels of total cholesterol and LDL cholesterol are still important and LDL should be as low as possible. Australian guidelines indicate that LDL should be less than 2.0 mmol/L in people at very high risk and less than 2.5 mmol/L in other at-risk people.
Apolipoprotein B (Apo B) and apolipoprotein A-I (Apo A) are the main structural proteins of atherogenic lipoproteins and HDL particles, respectively. Some studies have shown that the Apo B/Apo A ratio is good predictor of cardiovascular risk. The LDL cholesterol/Apo B ratio is an indicator of LDL particle size and is relatively easy and cheap to measure. However the evidence for the utility of these parameters is less than that for the standard lipid markers (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides).
Common questions
Although there is a genetic component, lipoprotein subfractions can be altered by adopting a diet low in saturated fats, losing excess weight, and exercising regularly. The use of lipid-lowering drugs may also affect the subfraction distribution.
Very Low Density Lipoprotein (VLDL) is one of three major lipoprotein particles. The other two are high density lipoprotein (HDL) and low density lipoprotein (LDL). Each one of these particles contains a mixture of cholesterol, protein, and triglyceride, but in varying amounts unique to each type of particle. LDL contains the highest amount of cholesterol. HDL contains the highest amount of protein. VLDL contains the highest amount of triglyceride. Since VLDL contains most of the circulating triglyceride and since the compositions of the different particles are relatively constant, it is possible to estimate the amount of VLDL-cholesterol by dividing the triglyceride value (in mmol/L) by 2.2. At present, there is no simple, direct way of measuring VLDL-cholesterol, so the estimate calculated from triglyceride is used in most settings. This calculation is not valid when the triglycerides are greater than 4.5 mmol/L. Increased levels of VLDL-cholesterol have been found to be associated with increased risk of heart disease and stroke.
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