What is Apolipoprotein B (Apo B)?

Apolipoprotein B (Apo B): A Key Marker of Cardiovascular Risk

Apolipoprotein B (Apo B) is the major structural protein of atherogenic lipoprotein particles, providing a direct measure of the total number of circulating atherogenic lipoproteins in plasma, and serves as a superior marker of cardiovascular risk compared to traditional lipid measurements. 1, 2

Definition and Structure

• Apo B is the major apolipoprotein of atherogenic lipoprotein families including very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) 2
• Each atherogenic lipoprotein particle contains exactly one Apo B molecule, making Apo B concentration a direct measure of the number of these particles in plasma 3, 4
• There are two major isoforms: apoB48 (found in chylomicrons and chylomicron remnants) and apoB100 (found in VLDL, IDL, LDL, and lipoprotein(a)) 3

Clinical Significance

• Apo B provides a good estimate of the number of atherogenic particles in plasma, which is particularly important when there are high concentrations of small dense LDL particles 2
• Multiple studies have shown Apo B to be equal or superior to LDL-C in cardiovascular risk prediction 2, 5
• Apo B more accurately reflects the atherogenic burden of lipoproteins compared to LDL-C, especially in patients with diabetes, metabolic syndrome, or hypertriglyceridemia 6, 7

Technical Advantages of Apo B Testing

• Apo B can be measured using good immunochemical methods that are easily run on conventional autoanalyzers 2, 8
• Unlike LDL-C calculation, Apo B measurement does not require fasting conditions and remains accurate even with moderately elevated triglyceride levels 8, 2
• The analytical performance of Apo B testing is generally good and reliable 2, 8

Comparison with Traditional Lipid Markers

• While LDL-C has been the traditional target for cardiovascular risk assessment, there is growing evidence that Apo B is a more accurate indicator of cardiovascular risk 4, 5
• When there is discordance between LDL-C and Apo B levels, cardiovascular risk generally aligns better with Apo B 6, 1
• Non-HDL-C (total cholesterol minus HDL-C) relates well to Apo B levels and can provide a better risk estimation compared to LDL-C in certain conditions like hypertriglyceridemia, diabetes, or metabolic syndrome 2

Clinical Applications

• For patients at very high cardiovascular risk, the target Apo B level should be <80 mg/dL 1
• For patients at high cardiovascular risk, the target Apo B level should be <100 mg/dL 1
• The ratio between Apo B and Apo A1 (the major protein of HDL) has been used in large prospective studies as an indicator of cardiovascular risk 2

Limitations and Considerations

• Despite its advantages, Apo B is not included in algorithms for calculation of global cardiovascular risk 2
• Apo B has not been evaluated as a primary treatment target in controlled statin trials, although post-hoc analyses suggest it may be a better treatment target than LDL-C 2
• Traditional measures of risk such as total cholesterol and LDL-C remain robust and supported by a major evidence base 2, 1
• There is conflicting evidence regarding the superiority of Apo B over non-HDL-C, with some meta-analyses showing Apo B to be superior and others showing equivalent predictive value 1, 2

Future Directions

• The National Lipid Association and other organizations are working to improve access and reimbursement for Apo B testing 6
• There is an ongoing debate about whether Apo B should replace LDL-C as the primary metric to guide lipid-lowering therapy 5, 6
• Routine measurement of both LDL-C and Apo B may be important to properly estimate global cardiovascular risk and determine residual risk in patients receiving therapy 7