At a Glance
Why Get Tested?
To help evaluate your risk of developing cardiovascular disease (CVD)
When to Get Tested?
When you have a personal and/or family history of CVD at an early age; when the result of your low-density lipoprotein cholesterol (LDL-C) test is within a healthy range, but your health practitioner thinks that you may have an increased risk of developing heart disease; sometimes to help monitor the effectiveness of lipid-lowering treatment and/or lifestyle changes
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; only water is permitted. Follow any instructions you are given.
The Test Sample
What is being tested?
Low-density lipoproteins (LDL) are particles that transport lipids throughout the body. Each particle contains a combination of protein, 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. 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 are more likely to cause atherosclerosis than fewer light, fluffy LDL particles. Researchers think that the presence of an increased number 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.
However, the data are not clear on whether routine testing for LDL 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 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. This is illustrated with:
- A recommendation from the 2009 guidelines on Emerging Biomarkers of Cardiovascular Disease and Stroke from the National Academy of Clinical Biochemistry that states "Lipoprotein subclasses, especially the number or concentration of small, dense LDL particles, have been shown to be related to the development of initial CHD events, but the data analyses of existing studies are generally not adequate to show added benefit over standard risk assessment for primary prevention." (See Sources)
- 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 cardiovascular disease (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).
The number of small, dense LDL particles (sdLDL) 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.
A variety of methods are used to determine lipoprotein subfractions. These include ultracentrifugation (separation by density), polyacrylamide gradient gel electrophoresis (separation by charge and size), and NMR (nuclear magnetic resonance) spectroscopy, which determines relative quantities of particles of different compositions.
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.
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?
Current standards recommend that lipid testing be done when you are fasting. For 9 to 12 hours before the test, only water is permitted. Follow any instructions you are given.
Ask a Laboratory Scientist
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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
Mackey, R. et. al. (2012 August). High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multi-ethnic study of atherosclerosis). J Am Coll Cardiol. 2012 Aug 7;60(6):508-16. [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/pubmed/22796256 through http://www.ncbi.nlm.nih.gov. Accessed September 2013.
Otvos, J. et. al. (2011 March-April). Clinical Implications of Discordance Between LDL Cholesterol and LDL Particle Number. J Clin Lipidol. 2011 Mar–Apr; 5(2): 105–113. [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070150/ through http://www.ncbi.nlm.nih.gov. Accessed September 2013.
Rosenson RS, and Underberg JA. (2013 July 28). Systematic Review: Evaluating the Effect of Lipid-Lowering Therapy on Lipoprotein and Lipid Values. Cardiovasc Drugs Ther. 2013 Jul 28. Abstract [Epub ahead of print] [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/pubmed/23893306 through http://www.ncbi.nlm.nih.gov. Accessed September 2013.
Cole, T. et. al. (2013 ). Association of Apolipoprotein B and Nuclear Magnetic Resonance Spectroscopy–Derived LDL Particle Number with Outcomes in 25 Clinical Studies: Assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices. Clinical Chemistry May 2013 vol. 59 no. 5 752-770 Abstract [On-line information]. Available online at http://www.clinchem.org/content/59/5/752.abstract through http://www.clinchem.org. Accessed September 2013.
Master, S. and Rader, D. (2013 March 13). Beyond LDL Cholesterol in Assessing Cardiovascular Risk: apo B or LDL-P? Clinical Chemistry 2013; v. 59, p.723-725 Extract. [On-line information]. Available online at http://www.clinchem.org/content/59/5/723.extract through http://www.clinchem.org. Accessed September 2013.
Sniderman, A. and Kwiterovich, PO. (2013 April). Update on the detection and treatment of atherogenic low-density lipoproteins. Curr Opin Endocrinol Diabetes Obes. 2013 Apr;20(2):140-7 Abstract. [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/pubmed/23422241 through http://www.ncbi.nlm.nih.gov. Accessed September 2013.
Mietus-Snyder, M. et. al. (2013 August). Low-Density Lipoprotein Cholesterol versus Particle Number in Middle School Children. J Pediatr. 2013 Aug;163(2):355-362 Abstract. [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/pubmed/23415622 through http://www.ncbi.nlm.nih.gov. Accessed September 2013.
DeGoma, E. and Rader, D. (2012) High-Density Lipoprotein Particle Number. A Better Measure to Quantify High-Density Lipoprotein? Medscape Multispecialty from J Am Coll Cardiol. 2012;60(6) [On-line information]. Available online at http://www.medscape.com/viewarticle/768499 through http://www.medscape.com. Accessed September 2013.
(2013 July 19). A Test in Focus: LDL Particle Concentration NMR, Plasma. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://news.mayomedicallaboratories.com/2013/07/19/a-test-in-focus-ldl-particle-concentration-nmr-plasma-2/ through http://news.mayomedicallaboratories.com. Accessed September 2013.
(© 1995–2013). LDL Particle Concentration NMR, Plasma. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/62186 through http://www.mayomedicallaboratories.com. Accessed September 2013.
Ghassab, R. et. al. (March 2010). Determination of Low Density Lipoprotein Particle Size by Polyacrylamide Gradient Gel Electrophoresis in Patients with Coronary Artery Stenosis. LabMedicine v 41 (3) [On-line information]. Available online at http://labmed.ascpjournals.org/content/41/3/164.full through http://labmed.ascpjournals.org. Accessed September 2013.
Myers, G. Editor (© 2009). Emerging Biomarkers for Primary Prevention of Cardiovascular Disease and Stroke. The National Academy of Clinical Biochemistry, Laboratory Medicine Practice Guidelines, Emerging Biomarkers for Primary Prevention [On-line information]. Available online through http://www.aacc.org. Accessed September 2013.
Pagana, K. D. & Pagana, T. J. (© 2011). Mosby's Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 622-625.
Clarke, W., Editor (© 2011). Contemporary Practice in Clinical Chemistry 2nd Edition: AACC Press, Washington, DC. Pp 285-297.
(June 13, 2009) The New Blood Lipid Tests -- Sizing Up LDL Cholesterol. Heart Health Special Report. Johns Hopkins Medicine. Available online at http://www.johnshopkinshealthalerts.com/reports/heart_health/1886-1.html through http://www.johnshopkinshealthalerts.com. Accessed November 2013.
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 through http://www.4qc.com.
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. Accessed May 2008.