Lipoprotein Subfraction Testing

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Also known as: LDL Subclasses; LDL Subfractions; HDL Subclasses; HDL Subfractions
Formal name: Lipoprotein Subfraction Profile
Related tests: HDL; LDL; DLDL; Lipid Profile; Cholesterol; Apo A; Apo B; Lp(a); Triglyceride; Homocysteine; hs-CRP; VAP

At a Glance

Why Get Tested?

To help evaluate your risk of developing coronary artery disease (CAD)

When to Get Tested?

If you have a personal and/or family history of CAD or peripheral vascular disease at an early age; if your doctor is trying to assess your risk of developing heart disease; sometimes to help monitor the effectiveness of lipid-lowering treatment and/or lifestyle changes

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

You may need to fast for 9-12 hours before this test.

The Test Sample

What is being tested?

Lipoprotein subfraction tests separate two of the commonly measured lipoprotein fractions – HDL (High Density Lipoprotein, often called the good cholesterol) and LDL (Low Density Lipoprotein, often called the bad cholesterol) – into subfractions based on their size, density, and/or electrical charge. Some testing may also identify subfractions of VLDL (Very Low Density Lipoprotein, also considered to be a bad 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 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.

How is the sample collected for testing?

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

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

Fast for 9-12 hours prior to the test or as requested by your doctor.

The Test

How is it used?

Lipoprotein subfraction testing is not routinely ordered, but its use is growing. It may offer useful information in assessing risk in patients who have a personal or family history of early heart disease, especially if their total and LDL cholesterol values are not significantly elevated. LDL subfraction testing is more common than VLDL or HDL subfraction testing since LDL has been identified as the primary risk factor for heart disease and more research and development has focused on LDL measurement.

Subfraction testing is typically done along with a lipid profile. The subfractions are usually expressed as relative proportions or percents of the LDL, VLDL, and/or HDL.

Since subfractions may be affected by lipid treatment and/or lifestyle changes, LDL subfraction testing may also be occasionally ordered to monitor the effectiveness of treatment in decreasing the number of small dense LDL particles.

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When is it ordered?

Lipoprotein subfraction testing may be ordered as part of an overall evaluation of cardiac risk when someone has a personal or family history of early CAD, especially when they dont have typical cardiac risk factors, such as high cholesterol, high LDL, high triglyceride, low HDL, smoking, obesity, inactivity, diabetes, and/or hypertension.

When a patient with a large proportion of small dense LDL particles has undergone lipid lowering treatment or lifestyle changes, his doctor may order LDL lipoprotein subfraction testing, along with other lipid tests, to monitor the effectiveness of treatment.

Although it is not generally recommended as a screening test, a few doctors are ordering lipoproteins subfraction testing along with a battery of other cardiac risk tests when they are attempting to determine a patients overall risk of developing CAD.

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What does the test 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 subfraction is similar. The picture is more complex with HDL subfractions, however, and there is no consensus on how to include the findings in risk assessment, but in general the presence of large fluffy HDL is thought to offer more protection than small dense HDL.

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Is there anything else I should know?

It is important to remember that lipoprotein subfraction testing (and other lipid and cardiac risk factor testing) is not diagnostic. It attempts to evaluate a patients statistical risk of developing CAD, but it cannot predict the development or severity of CAD in a particular patient.

Results of lipoprotein subfraction testing reflect the method and reporting format used as well as the patients 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.

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Common Questions

1.  How can I change my lipoprotein subfractions?

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.

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2.  What is VLDL?

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 mg/dL) by 5. 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 triglyceride is greater than 400 mg/dl. Increased levels of VLDL-cholesterol have been found to be associated with increased risk of heart disease and stroke.

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Article Sources

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Most Recent Review

Pagana, Kathleen D. & Pagana, Timothy J. (© 2007). Mosby’s Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 602-605.

Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. 253-258.

Mudd, J. et. al. (2007 October 29). Beyond Low-Density Lipoprotein Cholesterol -- Defining the Role of Low-Density Lipoprotein Heterogeneity in Coronary Artery Disease. Journal of the American College of Cardiology 50(18):1735-1741. Available online through http://www.medscape.com/. Accessed on 3/8/08.

Navab, M. et. al. (2006 October 20). Mechanisms of Disease: Proatherogenic HDL-An Evolving Field. Nat Clin Pract Endocrinol Metab. 2006;2(9):504-511. Available online through http://www.medscape.com/. Accessed on 3/8/08.

CCMDweb.org. Clinical Insights. Available online through: http://www.ccmdweb.org/clinicalinsights. Accessed May 2008.

The National Academy of Clinical Biochemistry. Laboratory Medicine Practice Guidelines, Emerging Biomarkers of Cardiovascular Disease and Stroke, Draft Guidelines, Version 0906, summary. PDF available for download.Acrobat-Reader_logo.gif Accessed May 2008.

Sources Used in Previous Reviews

Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

Landray, M. et. al (2002 January 2). Abnormal low-density lipoprotein subfraction profile in patients with untreated hypertension. Association of Physicians Q J Med 2002; 95: 165-171. Available online at http://qjmed.oupjournals.org/cgi/content/full/95/3/165 through http://qjmed.oupjournals.org

Bioletto, S. et. al. (2000 February). Acute hyperinsulinemia and very-low-density and low-density lipoprotein subfractions in obese subjects. American Journal of Clinical Nutrition, Vol. 71, No. 2, 443-449. Available online at http://www.ajcn.org/cgi/content/full/71/2/443 through http://www.ajcn.org

(Winter 2004). The Fats of Life, 7 Articles. Lipoproteins and Vascular Diseases Division, AACC, Volume XVIII, Vol 1. PDF available for download at http://www.aacc.org/divisions/lipids/winter04.pdf through http://www.aacc.org

(2002). LDL Subfractions. Specialty Laboratories [On-line test information]. PDF available for download at http://laboratory.specialtylabs.com/education/download_PDF/TN_LDLsub.pdf.

(2004). LDL Subclasses. ARUP’s Guide to Clinical Laboratory Testing. Available online at http://www.arup-lab.com/guides/clt/tests/clt_a34b.jsp through http://www.arup-lab.com

Warnick, G. and Cheung, M. (2000). Measurement and Clinical Significance of High-density Lipoprotein Cholesterol Subclasses. Chapter 15 (Handbook of Lipoprotein of Lipoprotein Testing, AACC Press). Available online at http://www.warnick.biz/dextransulfate/Chapter15.htm through http://www.warnick.biz

Muniz, N., et. al. (2000). A New Tool for the Automated Analysis of LDL Subfraction Patterns Generated by the Lipoprint™ LDL System. Paper presented at The Frontiers in Lipoprotein and Vascular Disease, St Louis, MO. PDF available for download at http://www.4qc.com/pdf/frontiers.pdf.