Should LDL-Cholesterol Particle Concentrations Replace LDL Levels to Assess Risk?

November 8 - 12, 2008, New Orleans, Louisiana

Linda Brookes, MSc


February 16, 2009

In This Article


Until very recently, guidelines for the assessment of coronary heart disease (CHD) risk, such as the third report Adult Treatment Panel of the National Cholesterol Education Program (NCEP ATP III),[1] focused on low-density lipoprotein cholesterol (LDL-C) as the primary target for preventive therapy, based on the assumption that cholesterol is the most important lipoprotein-related proatherogenic risk factor. However, CHD risk is more directly related to the number of atherogenic lipoprotein particles circulating in the serum than it is to the total volume of cholesterol. The total volume of LDL-C is used as a surrogate for measuring LDL particles, although the same LDL-C volume can correspond with a widely varying LDL particle number; it fails to account for the possibility that an extremely atherogenic level of small, dense LDL particles might be measured as a "normal" LDL-C level.

Recently there has been growing emphasis on the fact that each LDL particle contains a single molecule of the atherogenic apolipoprotein (apo) B, meaning that measuring the concentration of apoB provides a direct measure of the number of circulating atherogenic lipoprotein particles. Increasing evidence from clinical and epidemiologic studies indicates that measurement of apoB is superior to measuring LDL-C for predicting probability of fatal and nonfatal CHD. In addition, therapy with statins has been shown to reduce LDL-C content more than LDL particle concentration, which may explain the observation that so many patients on optimum statin therapy will still experience CHD events and also emphasize that apoB may provide a better assessment of residual risk for patients on statin therapy.

On the basis of all this evidence, it has been recommended that assessment of apoB should be included in all guidelines as an indicator of cardiovascular risk.[2] Measurement of apoB has been incorporated into both the last Canadian guidelines for the management of dyslipidemia and prevention of cardiovascular disease[3] and the recent consensus conference report for management of lipoproteins in patients with cardiometabolic risk recently issued jointly by the American Diabetes Association (ADA) and the American College of Cardiology Foundation (ACCF).[4] Both reports note that increased apoB levels and triglyceride concentrations are prevalent in patients with the metabolic syndrome and type 2 diabetes mellitus and that apoB measurement is warranted in patients at risk for determining cardiovascular risk and monitoring statin treatment. It is in this context that several reports at the American Heart Association (AHA) 2008 Scientific Sessions have important implications for clinicians treating dyslipidemic patients.


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