Apolipoprotein B Quest

Clinical background

Low-density lipoprotein–cholesterol (LDL-C) level is a well-established marker for CVD risk and is routinely used to set lipid-lowering treatment goals. However, LDL-C provides an incomplete risk assessment, and many individuals with lowered LDL-C still experience CVD events or progression.1 LDL-C levels alone can underestimate CVD risk in individuals with elevated triglycerides and metabolic disorders because their lipid profiles tend to contain an increased number of small, cholesterol-poor LDL particles.1

Apolipoprotein B (apo B), a major protein component of atherogenic lipid particles (including LDL and others), represents the total particle number because each particle contains 1 apo B molecule.1,2 Apo B level is superior to LDL-C and non–high-density lipoprotein–cholesterol (HDL-C) levels as a predictor of CVD events.2,3 Apo B level is also associated with residual risk of CVD events and all-cause mortality in patients receiving lipid-lowering therapy, though this association may be limited to therapies that upregulate LDL receptor expression (eg, statins).3-5

In addition to CVD risk assessment, apo B is used to diagnose certain lipid disorders, including familial dysbetalipoproteinemia and FCHL.6 Familial dysbetalipoproteinemia is characterized by elevated non–HDL-C but normal apo B levels, resulting in high total cholesterol/apo B and non–HDL-C/apo B ratios.7 FCHL is a complex, multigenic disorder that causes premature CVD.8 The combination of elevated apo B and triglyceride levels with a family history of premature CVD identifies individuals most likely to have FCHL.8

Apo B measurement is included in clinical guidance from several professional societies (Table 1).