There is much talk about LDL size playing a role as a more accurate indicator of heart disease than using the traditional LDL cholesterol concentration metric. The claim is that small LDL is more atherogenic (causing plaque in arteries) than large LDL, and that the higher the number of small LDL particles, the more risk there is of developing heart disease. This article will help clear up the confusion.
I will use an analogy to help explain these somewhat confusing concepts.Imagine that your body is a city, with the streets being your arteries. People are being transported throughout the city in buses and taxis. In this analogy the people represent cholesterol, taxis represent small LDL particles, and buses represent large LDL particles. So cholesterol is being delivered via small and large LDL particles throughout your body. Just as taxis tend to have more accidents than buses, small LDL is more damaging to your arteries than large LDL.
There are two types of LDL measures. The tradition LDL count, denoted as LDL-C, is the average concentration of cholesterol in LDL particles per litre of blood. It does not take into account whether the particle is large or small, nor does it consider the actual number of particles involved. The newer LDL count, the LDL-P, is the number of particles in one litre of blood, and so the measure of small LDL-P is the number of small LDL particles per litre of blood.
Another definition before we really get going. The Metabolic Syndrome is a group of risk factors and metabolic abnormalities that has been shown to be an important risk factor for cardiovascular (heart) disease incidence and mortality. Researchers used data from The Framingham Heart Study, a multi-generational study of heart disease, to arrive at the following conclusions about the relationship of small LDL-P and Metabolic Syndrome:
1. Small LDL-P is elevated in The Metabolic Syndrome, and increases with the number of syndrome components.
2. Increased small LDL-P identified the Metabolic Syndrome with high sensitivity.
Interesting, but how does this affect me?
Now here is the problem with using LDL-C. Many patients who have metabolic syndrome have normal LDL-C levels and they are misdiagnosed as being healthy. The measure of LDL-P is a much better predictor of heart disease for those people. So to answer the question in the title, yes, size does matter.
Does this mean that we should throw out the LDL-C measurement and have everyone have their LDL-P measured? Not at all. Whether or not you should ask for the new measurement has been investigated by a panel of experts. The National Lipid Association convened a panel of clinical experts from the American College of Cardiology and the American Diabetes Association to evaluate the use of selected biomarkers in clinical practice as either tools to improve risk assessment or as markers to adjust therapy once a decision to treat had been made. In other words, these are the recommendations for when physicians should ask for the LDL-P test, among others. The chart below gives guidelines based on the Framingham Cardiovascular Risk Score. You can ask your doctor for your score, and then see where you fall in the chart to determine if you should ask for the test.
Evaluation of LDL-P for Initial Risk Assessment
|Low risk (<5% 10-year CHD event risk)||Not recommended
|Intermediate risk (5-20% 10-year CHD event risk)||Reasonable for many patients
|CHD or CHD Equivalent||Consider for selected patients
|Family History||Reasonable for many patients
|Recurrent Events||Reasonable for many patients
Of course, you may have to educate your doctor about all of this, but that’s another topic altogether…
For a complete package including full service and a comprehensive guide to lower cholesterol, please see “E-book”.
 Am J Med. 2006 Oct;119(10):812-9. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis.Galassi A, Reynolds K, He J. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, La 70112, USA.
 Circulation. 2006 Jan 3;113(1):20-9. Epub 2005 Dec 27. Increased small low-density lipoprotein particle number: a prominent feature of the metabolic syndrome in the Framingham Heart Study. Kathiresan S, Otvos JD, Sullivan LM, Keyes MJ, Schaefer EJ, Wilson PW, D’Agostino RB, Vasan RS, Robins SJ. Source: The National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, USA.
 Journal of the American College of Cardiology, Vol. 51, No. 15, 2008, Lipoprotein management in patients with cardiometabolic risk, John D Brunzel et al.