Low-density lipoproteins (LDL) are particles that transport lipids throughout the body. Each particle contains a combination ofprotein, cholesterol, triglyceride, and phospholipid molecules. Their composition changes as they circulate in the blood. Some molecules are removed and others are added, resulting in lipoprotein particles whose properties vary from large and fluffy to small and dense. LDL particle testing determines the relative amounts of particles of differing properties in the blood. This is often called subfraction testing.

Traditional lipid testing measures the amount of LDL cholesterol (LDL-C) present in the blood, but it does not evaluate the number of particles of LDL (LDL-P). Some studies have shown that increased numbers of small, dense LDL particles (sdLDL) are associated with inflammation and are more likely to cause atherosclerosis than fewer light, fluffy LDL particles. Researchers think that the presence of an increased number of sdLDL could be one of the reasons that some people have heart attacks even though their total cholesterol and LDL cholesterol concentrations are not particularly high.

Data are not clear on whether routine testing for LDL subfractions provides additional information about cardiac risk or whether results from such testing could impact decisions about treatment. The 2015 report from the National Lipid Association Annual Summary of Clinical Lipidology does refer to potential use of subfraction testing for a select population of patients; however, more clinical research is needed to determine the ultimate value in testing for LDL subfractions and how the results should be used. Recommendations on the use of LDL subfraction testing and LDL-P continue to evolve as a result of ongoing studies and include:

• The results of a clinical study named JUPITER, studying therapies for cardiovascular disease (CVD) and finding an association between disease and LDL subfractions
• A review of multiple studies on exercise, verifying the relationship between exercise and a reduction in both the level of small LDL particles and risk for CVD
• A study illustrating a relationship between disease progression and increases in small LDL particles using multiple methods for measuring the particles, including ultracentrifugation (separation of particles by density), polyacrylamide gradient gel electrophoresis (separation by charge and size) and NMR (nuclear magnetic resonance) spectroscopy, which measures particles according to differences in composition
• A 2013 Assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices, which compared the use of apolipoprotein B (Apo B) with LDL-P as indicators of atherogenic particle numbers; the group concluded that both tests were nearly equivalent in their ability to assess CVD risk and that both were stronger than LDL-C. The group supported the adoption of either Apo B or LDL-P into CVD risk screening and treatment guidelines but expressed a current preference for Apo B because of its availability and several other factors. (See Sources) Note: Apo B is considered a potential substitute for LDL-P because a molecule of Apo B is present in each particle of LDL and very low-density lipoprotein (VLDL).
• An analysis of genetics of LDL subfractions and related therapy in European subjects, illustrating that genetic controls for LDL subfractions differ from genetic controls for total LDL

The number of sdLDL particles a person has is partially genetically determined, partially due to sex (males tend to have more sdLDL 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 sdLDL.

As mentioned above, a variety of methods are used to determine lipoprotein subfractions, including ultracentrifugation, polyacrylamide gradient gel electrophoresis, and NMR spectroscopy.

It is also usually possible to predict whether a person has a high number of sdLDL particles by looking at the person's triglyceride and high-density lipoprotein cholesterol (HDL-C) levels. These tests are typically performed as part of a lipid profile. People who have high triglyceride and low HDL-C tend to have more sdLDL. Specifically, having a triglyceride level above 120 mg/dL and an HDL-C level lower than 40 mg/dL in men and lower than 50 mg/dL in women is associated with having more sdLDL.

Subfraction testing is also available for other lipoprotein particles, such as HDL and VLDL, but these tests are mostly used in research settings and are not addressed in this article.

A blood sample is obtained by inserting a needle into a vein in the arm.

Current standards recommend that lipid testing be done while fasting. For 9 to 12 hours before the test, only water is permitted. Follow any instructions provided by the healthcare practitioner or lab.