LDL Particle Testing (LDL-P)
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 healthcare provider 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.
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 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 Article Sources below) 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.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?
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.
How is it used?
Low-density lipoprotein particle (LDL particle or LDL-P) testing evaluates LDL particles according to their number, size, density, and/or electrical charge. It may provide useful information for assessing cardiac risk in people who have a personal or family history of heart disease at a young age, especially if their total cholesterol and LDL cholesterol (LDL-C) values are not significantly elevated. LDL subfraction testing is typically done along with or following a lipid profile.
While for many people, the LDL-C test is a good indicator of risk of cardiovascular disease (CVD), research has found that some people with healthy levels of LDL-C still have increased risk of CVD. Similarly, individuals with some chronic conditions such as diabetes may have increased risk even though their LDL-C is at a healthy level. For these populations, it has been suggested that the number of LDL particles and/or their size might be an additional factor to consider when determining their CVD risk. In these cases, lipoprotein subfraction testing may be used to further evaluate an individual's CVD risk.
LDL-P may also be occasionally ordered to monitor the effectiveness of treatment in decreasing the number of small, dense LDL particles (sdLDL).
LDL subfraction testing has been used in clinical settings, while VLDL or HDL subfraction testing is currently used mostly for research purposes. This is because LDL cholesterol has been identified as the primary risk factor for heart disease and more research and development has focused on LDL measurement.
When is it ordered?
This testing may be ordered as part of an overall evaluation of cardiac risk when someone has a personal or family history of early cardiovascular disease (CVD), especially when the person doesn't have typical cardiac risk factors, such as high cholesterol, high LDL cholesterol, high triglyceride, low HDL cholesterol, smoking, obesity, inactivity, diabetes, and/or hypertension.
When a person with an increased LDL-P and/or a large proportion of small, dense LDL particles has undergone lipid-lowering treatment or lifestyle changes, the healthcare practitioner 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 healthcare providers are ordering LDL-P along with a battery of other cardiac risk tests when they are attempting to determine someone's overall risk of developing CVD.
What does the test result mean?
Results of an LDL-P test reflect the method and reporting format used as well as the person's total cholesterol, LDL-C, VLDL, and/or HDL cholesterol. Since different methods separate the subclasses based on different physical properties (particle number, size, density, and/or electrical charge), results may not be directly comparable method to method or laboratory to laboratory.
In general, the result is interpreted within the framework of a lipid profile and its associated risk:
- If a person has a large number of primarily small, dense LDL (sdLDL) and an increased LDL-P, this finding will add to the individual's risk of developing cardiovascular disease above and beyond the risk associated with the total LDL.
- If a person has exclusively large, fluffy LDL and a lower LDL-P, this finding will add no additional risk.
Is there anything else I should know?
It is important to remember that lipoprotein subfraction and LDL subfraction testing (as well as other lipid and cardiac risk factor testing) is not diagnostic. It attempts to evaluate a person's statistical risk of developing CVD, but it cannot predict the development or severity of disease in a particular person.
How can I change my LDL subfractions and decrease my LDL-P?
Although there is a genetic component, lipoprotein subfractions and LDL-P 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 and LDL-P.
How long will it take for my results?
It depends on the laboratory performing the test. Not every lab performs LDL-P testing as it requires specialized instruments. Your sample may be sent to a reference laboratory for testing, so it may take several days before results are available.
On This Site
Conditions: Cardiovascular Disease, Heart Disease
Elsewhere On The Web
American Heart Association: About Cholesterol
American Heart Association Interactive Library: Cholesterol and CAD
National Heart, Lung, Blood Institute: What is Atherosclerosis?
National Cholesterol Education Program: High Blood Cholesterol—What You Need to Know
Sources Used in Most Recent Review
2016 review performed by Rose Romeo, PhD, DABCC, FACB.
Yan Zhang, Sha Li, Rui-Xia Xu, Cheng-Gang Zhu, Yuan-Lin Guo, Na-Quiong Wu, Jing Sun and Jian-Jun Li. System Inflammatory Markers Are Closely Associated with Atherogenic Lipoprotein Subfractions in Patients Undergoing Coronary Angiography. Mediators of Inflammation (2015):2015 Article ID 235742 (9 pages). Available online at http://www.hindawi.com/journals/mi/2015/235742/abs/. Accessed February 7, 2016.
Harold E. Bays, Peter H. Jones, W. Virgil Brown and Terry A. Jacobson. National Lipid Association Annual Summary of Clinical Lipidology 2015. Journal of Clinical Lipidology; 2014 (8) S1-S36. Available online at http://nlaresourcecenter.lipidjournal.com/Content/PDFs/Summary-Revised.pdf as. Accessed February 7, 2016.
Samia Mora, Michael P. Caulfield, Jay Wohlgemuth, Zhizong Chen, Robert Superko, Charles M. Rowland, Robert J. Glynn, Paul M. Ridker, Ronald M. Kraus. Atherogenic Lipoprotein Subfractions Determined by Ion Mobility and First Cardiovascular Events After Random Allocation to High Intensity Statin or Placebo. The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial. Circulation (2015); 132:2220-2229. Abstract available online at http://circ.ahajournals.org/content/132/23/2220.abstract. Accessed February 7, 2016.
Mark A. Sarzynshi, Jeffrey Burton, Tuomo Rankinen, Steven N. Blair, Timothy S. Church, Jean-Pierre Despres, James M. Hapberg, Rian Landers-Ramos, Arthur S. Leon, Catherine R. Mikus, D.C. Rao, Richard L. Selp, James S. Skinner, Cris A. Sientz, Paul D. Thompson, Kenneth R. Wilund, William E. Kraus, Claude Bouchard. The effects of exercise of the lipoprotein subclass profile: A meta-analysis of 10 interventions. Atherosclerosis (2015) 243: 364-372. Abstract available online at http://www.ncbi.nlm.nih.gov/pubmed/26520888. Accessed February 7, 2016.
Paul T. Williams, Xue-Qiao Zhao, Santica M. Marcovina, James D. Otvos, B. Greg Brown, Ronald M. Krauss. Comparison of four methods of analysis of lipoprotein particle subfractions for their association with angiographic progression of coronary artery disease. Atherosclerosis (2015) 233: 713-720. Abstract available online at http://www.atherosclerosis-journal.com/article/S0021-9150(14)00060-4/abstract. Accessed February 7, 2016.
Heejung Shim, Daniel I. Chasman, Joshua D. Smith, Samia Mora, Paul M. Ridker, Deborah A. Nickerson, Ronald M. Krauss, Matthew Stephens.. A Multivariate Genome-Wide Association Analysis of 10 LDL Subfractions, and Their Response to Statin Treatment, in 1868 Caucasians. PLOS ONE 10(4):1-20. Available online at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120758. Accessed February 7, 2016.
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.
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.
(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.
(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.
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.
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.
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.
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. 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/. 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. 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. 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. 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. 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. 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. 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/. 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. 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. 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. Accessed November 2013.