This document discusses LDL (bad) cholesterol particle size and its role in cardiovascular risk assessment. It notes that while total LDL is routinely tested, LDL particles vary in size, with small, dense particles posing greater risk. Two patients could have the same LDL level but different risks depending on their particle size distribution. Tests are available to measure particle size directly. Having high triglycerides and low HDL is associated with more small, dense LDL particles. Measuring particle size may help further stratify risk, especially for borderline cases, and guide treatment with niacin or fibrates which affect particle size.
This document discusses LDL (bad) cholesterol particle size and its role in cardiovascular risk assessment. It notes that while total LDL is routinely tested, LDL particles vary in size, with small, dense particles posing greater risk. Two patients could have the same LDL level but different risks depending on their particle size distribution. Tests are available to measure particle size directly. Having high triglycerides and low HDL is associated with more small, dense LDL particles. Measuring particle size may help further stratify risk, especially for borderline cases, and guide treatment with niacin or fibrates which affect particle size.
This document discusses LDL (bad) cholesterol particle size and its role in cardiovascular risk assessment. It notes that while total LDL is routinely tested, LDL particles vary in size, with small, dense particles posing greater risk. Two patients could have the same LDL level but different risks depending on their particle size distribution. Tests are available to measure particle size directly. Having high triglycerides and low HDL is associated with more small, dense LDL particles. Measuring particle size may help further stratify risk, especially for borderline cases, and guide treatment with niacin or fibrates which affect particle size.
by Paul E. Lemanski, MD, in mg of LDL particles in a for the LDL receptor2. dense LDL predominate. It MS, director of the Center deciliter of plasma. LDL Observational and epidemi- is seen more commonly in for Preventive Medicine and particles are, however, hetero- ological studies suggest those diabetic patients and those Cardiovascular Health, geneous in size, density, and having a predominance of with established coronary Prime Care Physicians, P.C., composition. A growing body small, dense particles may artery disease (CAD). and assistant clinical professor of evidence suggests that LDL have an increase in risk up Small, dense LDL may of medicine at Albany particles that are small and to 300 percent greater than also be identified in some Medical College those having a predominance situations by routine choles- Cholesterol testing is an A growing body of large and fluffy LDL terol testing. Small, dense integral part of the global of evidence suggests particles. This observed LDL particles are found in risk assessment promoted that LDL particles increase in risk forms the association with high by the National Cholesterol that are small and dense are more basis of the rationale in using triglycerides (TG) and low Education Program (NCEP) atherogenic than particle size as an adjunct to HDL. When TG, in a 12- ATP-3 guideline for clini- those which are the standard proven means hour fasting specimen, are cians. For the majority of large and “fluffy.” of risk assessment. increased in the serum, it is patients, such routine Small, dense LDL may be usually a result of increased cholesterol testing and risk dense are more atherogenic measured directly by various VLDL (very low density assessment will provide a than those which are large means. Berkeley HeartLab, lipoprotein). Under these fairly unequivocal determi- and “fluffy.”1 Thus, two Inc. (www.bhlinc.com) conditions, TG are trans- nation of those needing patients with the same LDL offers an LDL gradient gel ferred from VLDL to LDL pharmacological treatment. measurement in mg/dl may electrophoresis; LipoScience, in exchange for cholesterol However, for borderline have differing levels of cardio- Inc. (www.lipoprofile.com) ester by CETP (cholesterol cases, clinicians have looked vascular risk depending on offers a nuclear magnetic ester transfer protein). These to a variety of new tests to the relative proportions of resonance (NMR) method; TG enriched, cholesterol further stratify risk. One small, dense and large, and Atherotec, Inc. ester depleted LDL particles such new test is LDL fluffy particles. (www.thevaptest.com) has are then acted upon by particle size. The rationale An increase in the propor- their vertical auto profile hepatic lipase which cleaves for the use of this test and tion of small, dense LDL may out the TG leaving choles- suggestions for how clinical Small, dense increase risk for any given terol ester depleted LDL management may be altered LDL particles level of LDL. This increased particles. The depleted LDL are reviewed below. are found in risk may be due in part to association with particles are physically The NCEP ATP-3 iden- increased deposition in the high triglycerides smaller and because of the tifies LDL as the primary sub-endothelial space where and low HDL. resultant relative increase in target of treatment not only plaque forms. It may be due protein also denser. The because it has been shown also to increased uptake by (VAP) test. All measure small, association of TG with small, to be predictive of clinical macrophages and increased dense LDL and thus may dense LDL suggests a pos- events and angiographic susceptibility to oxidation, identify patients as belonging sible means of establishing disease progression but also both early steps in athero- to LDL subclass “phenotype the presence of predominant because of ease of measure- genesis. It may be due in B.” Phenotype B is termi- small, dense LDL by use of ment and low cost. The LDL part to decreased clearance nology used to describe the TG measurement. Indeed, value reported to clinicians because of reduced affinity LDL pattern in which small, (continued on next page) is the summed contribution
As published in the CDPHP Medical Messenger, May 2004
Beyond Routine Cholesterol Testing: The Role of LDL Particle Size Assessment (continued from previous page) Individuals with TG below measuring LDL particle Please see CDPHP such an association exists 70 do not have small, dense size before the addition of resource coordination policy and proves helpful in deter- LDL. It would not be niacin or fibric acid deriv- “LDL Particle Size mining those for whom the necessary to measure LDL atives. The higher risk of 1370/20.000404” for test may best be applied. particle size in these indi- combination therapy may coverage guidelines for Austin has shown that viduals. For individuals with suggest documenting the particle size testing. those with TG above 140 TG between 70 and 140, TG need for a second agent, 1. Gardner CD, Fortmann SP, have small, dense LDL and cannot be used to predict especially if the lipid profile Krauss RM. Small low density may be classified as LDL those with small, dense LDL was already normalized by lipoprotein particles are phenotype B on the basis of and a test of LDL particle NCEP guideline criteria. associated with the incidence TG alone3. Consequently, a size may be useful. In summary, the mea- of coronary artery disease in separate test of LDL particle As a class, statin drugs do surement of LDL particle men and women. JAMA 1996; size to identify individuals not change particle size size may be of benefit for 276:875-881. at increased risk from small, appreciably. Thus, once cardiovascular risk stratifi- 2. Lamarche F, Tchernof A, dense LDL would be gen- patients achieve their NCEP cation as an adjunct to Moorjani S, et al. Small, dense erally unnecessary for these LDL targets on statin treat- routine cholesterol testing low-density lipoprotein individuals. TG may also be ment, if they also need and global risk assessment particles as a predictor of used to track response to pharmacological treatment for selected populations. the risk of ischemic heart treatment because the of TG to achieve NCEP Identification of small, dense disease in men. Circulation. 1997;95:69–75. approaches which lower TG TG target (<150), then a LDL may alter pharmaco- 3. Austin MA, King MC, also convert small, dense test of LDL particle size logical management. TG Vranizan KM, Krauss RM. LDL to large, fluffy, less would not be needed. If the may be used to identify the Atherogenic lipoprotein atherogenic LDL. Thus, TG were between 70 and majority of individuals with phenotype. A proposed weight loss, exercise, niacin, 140 and the individual was small, dense LDL. Individuals genetic marker for coronary and fibrates which, inde- a CAD risk equivalent, or with TG between 70 and heart disease risk. Circula- pendently, have been shown had established CAD and, 140 may require a direct tion. 1990;82:495–506. to reduce TG, also convert more so, if he or she had measurement of particle size small, dense LDL to larger, progressing CAD, consid- to establish the presence of Dr. Lemanski may be reached at fluffy LDL. eration may be given to small, dense LDL. paul.lemanski@primecarepc.com
As published in the CDPHP Medical Messenger, May 2004