What is the role of Apolipoprotein B (Apo B)?

From the Guidelines

Apolipoprotein B (Apo B) levels should be measured and targeted to be below 80-90 mg/dL for high-risk patients to reduce the risk of atherosclerosis and cardiovascular disease. The measurement of Apo B levels in the blood provides a direct count of atherogenic particles and is considered by many experts to be a more accurate predictor of cardiovascular risk than traditional LDL cholesterol measurements 1. Apo B is the main protein component of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), which are particles that transport cholesterol and triglycerides through the bloodstream. Elevated Apo B levels indicate an increased risk of atherosclerosis and cardiovascular disease, even when LDL cholesterol levels appear normal.

Key Points

• Apo B testing is particularly valuable for patients with diabetes, metabolic syndrome, or family history of premature cardiovascular disease, as these conditions often feature discordance between LDL cholesterol and actual atherogenic particle numbers 1.
• Management of high Apo B typically involves lifestyle modifications (diet low in saturated fats, regular exercise, weight management) and may require medications such as statins, ezetimibe, or PCSK9 inhibitors.
• The target level for Apo B is generally below 80-90 mg/dL for high-risk patients, though optimal levels may vary based on individual risk factors 1.
• Non-HDL cholesterol is highly correlated with Apo B levels and can be used as a surrogate marker for Apo B in clinical practice 1.

Clinical Considerations

• Apo B measurement carries extra expense, and its measurement in some laboratories may not be reliable 1.
• A relative indication for Apo B measurement would be triglyceride >200 mg/dL 1.
• A persistent elevation of Apo B can be considered a risk-enhancing factor 1.

From the Research

Apolipoprotein B (Apo B) and Cardiovascular Risk

• Apolipoprotein B (apoB) is considered a more accurate measure of cardiovascular risk and a better guide to the adequacy of lipid lowering than low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (HDL-C) 2
• The 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines endorse apoB as a central role in cardiovascular risk assessment, while the 2018 American College of Cardiology/American Heart Association Multisociety Guidelines retain LDL-C as the primary metric to guide statin/ezetimibe/Proprotein convertase subtilisin/kexin type 9 (PCSK9) therapy 2

Apo B and Lipid Lowering Therapy

• Using LDL-C to guide the adequacy of lipid lowering therapy represents an interpretive error of the results of the statin/ezetimibe/PCSK9 inhibitor randomized clinical trials, and apoB should be the primary metric to guide statin/ezetimibe/PCSK9 therapy 2
• There is a robust body of evidence demonstrating the superiority of apoB over LDL-C and non-HDL-C as a clinical marker of cardiovascular risk 2

Alternative Therapies for Dyslipidemia

• Elevation in apolipoprotein B-containing lipoproteins in the blood is a cause of atherosclerosis, and therapies beyond statins and monoclonal PCSK9 inhibitors are being developed to further reduce pro-atherogenic lipoproteins and prevent cardiovascular events 3
• Ezetimibe, lomitapide, bempedoic acid, and inclisiran are alternative therapies that have been shown to reduce LDL-C levels and may be useful in patients who are intolerant of statins or require additional lipid lowering therapy 3, 4, 5

Comparison of Therapies

• PCSK9 inhibitors and ezetimibe are alternative treatment options for patients who cannot tolerate statins, and PCSK9 inhibitors have been shown to lower LDL-C levels significantly more than ezetimibe in patients not on statins 6
• Bempedoic acid, an inhibitor of adenosine triphosphate-citrate lyase, has been shown to add LDL-C reduction on top of statins and ezetimibe, and may be an alternative for statin intolerant patients 3, 5