Beyond LDL Cholesterol in Assessing Cardiovascular Risk: apo B or LDL-P?

Abstract

Plasma concentrations of LDL cholesterol (LDL-C)4 are positively associated with increased risk of atherosclerotic cardiovascular disease. There is a variety of robust evidence indicating that this association is causal in nature. First, rare and common genetic variants that specifically influence LDL-C concentrations are also strongly associated with cardiovascular risk (1). Second, interventions that reduce LDL-C, especially but not exclusively statin therapy, reproducibly reduce cardiovascular events (2). In fact, the data with statins are so strong that they are often used in patients whose LDL-C concentrations are not particularly increased, a setting in which statins have still been shown to reduce cardiovascular risk. Thus there is substantial interest in lipoprotein-related biomarkers that provide information about future cardiovascular risk above and beyond LDL-C itself. LDL contains a core of hydrophobic lipid, mostly cholesteryl ester, a shell of phospholipids, and single molecule of the large protein apolipoprotein B-100 (apo B). It has long been appreciated that LDL particles vary in size and density, which is largely due to variation in the amount of cholesteryl ester in the particle (3). Because the LDL-C measurement is a measure of the amount of cholesterol being carried in LDL, it is not a reliable measure of LDL particle concentration: small, dense LDL particles have much less cholesterol than large, buoyant LDL particles. Interestingly, however, there is evidence that small, dense LDL may be more atherogenic, which has led to the concept that the overall number of LDL particles may be more predictive of cardiovascular risk than the LDL-C concentration itself (3). Several methods have emerged that allow a more direct quantification of the number of LDL particles. Because an LDL particle contains a single molecule of apo B, it is possible to directly estimate the number of particles through a simple measurement of apo B …