What is the significance of elevated Apolipoprotein B (ApoB) levels?

From the Guidelines

Elevated apolipoprotein B (apoB) levels are a significant risk factor for cardiovascular disease, and levels above 130 mg/dL are considered a risk-enhancing factor for atherosclerotic cardiovascular disease (ASCVD) 1. The clinical significance of apoB lies in its ability to provide a more accurate assessment of atherogenic risk, as it measures the total number of potentially harmful lipoprotein particles, with each atherogenic particle (VLDL, IDL, LDL) containing exactly one apoB molecule.

Key Points to Consider:

• Elevated apoB levels denote high lifetime risk for ASCVD and favor initiation of statin therapy, especially when accompanied by persistently elevated triglycerides 1.
• The presence of elevated apoB, along with other risk-enhancing factors such as family history of ASCVD, premature menopause, and patients of South Asian race, conveys a higher baseline risk and are stronger candidates for statin therapy.
• Treatment for elevated apoB typically includes lifestyle modifications and pharmacological interventions, with target apoB levels generally <80 mg/dL for high-risk patients and <65 mg/dL for very high-risk patients with established cardiovascular disease.
• Regular monitoring every 3-6 months after treatment initiation is recommended to assess response and adjust therapy as needed.

Management Strategies:

• Lifestyle modifications: adopting a Mediterranean or DASH diet, regular exercise (150 minutes weekly of moderate activity), weight management, and smoking cessation.
• Pharmacological interventions: statins (such as atorvastatin 20-80mg or rosuvastatin 10-40mg daily), which can reduce apoB by 30-50%, and for patients not reaching targets or intolerant to statins, ezetimibe 10mg daily, PCSK9 inhibitors, or bempedoic acid may be added. It is essential to note that while apoB is a valuable marker, its measurement is not yet widespread, but if measured, it should be considered in the context of overall cardiovascular risk assessment, as suggested by the 2019 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.

From the FDA Drug Label

Rosuvastatin significantly reduced LDL-C (primary end point), total cholesterol and ApoB levels at each dose compared to placebo. Rosuvastatin 20 mg significantly reduced LDL-C, total cholesterol, ApoB, and non-HDL-C compared to placebo The significance of elevated apolipoprotein B level is that it is a risk factor for cardiovascular disease. Elevated ApoB levels are associated with increased levels of low-density lipoprotein (LDL) cholesterol, which can lead to the development of atherosclerosis and increase the risk of heart attacks and strokes. Reducing ApoB levels, as seen with rosuvastatin treatment, can help to decrease this risk. 2

From the Research

Significance of Elevated Apolipoprotein B Level

• Elevated apolipoprotein B (apoB) levels are a significant risk factor for cardiovascular disease, as apoB is a key component in lipid metabolism and subendothelial retention of apoB-containing lipoproteins is a necessary initiating event in atherogenesis 3.
• ApoB levels predict ischemic cardiovascular events in both genders and are better than LDL cholesterol in this respect 3.
• The 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines concluded that apoB was 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) 4.
• There is now a robust body of evidence demonstrating the superiority of apoB over LDL-C and non-HDL-C as a clinical marker of cardiovascular risk 4.

Comparison with LDL-C

• ApoB is a more reliable indicator of risk than LDL-C, as it measures the number of circulating atherogenic lipoproteins, whereas LDL-C measures the cholesterol content of these particles, which is variable 5.
• LDL-C is not the appropriate marker to assess the benefits of statin/ezetimibe/PCSK9 therapy, and apoB should be the primary metric to guide this therapy 4.
• The addition of apoB measurement to the routine lipid panel for assessing and monitoring patients at risk for cardiovascular disease would enhance patient management 6.

Clinical Implications

• Elevated apoB levels indicate an increased risk of atherosclerotic cardiovascular disease, and reducing apoB levels through lipid-lowering therapy can help reduce this risk 7.
• New therapeutic agents, such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, and antisense oligonucleotide (ASO) therapies, are being developed to target apoB and other lipid profiles to reduce residual cardiovascular risk 7.
• The use of apoB as a therapeutic target in clinical practice is still a topic of controversy, but there is strong evidence that apoB is a more accurate indicator of cardiovascular risk than either total cholesterol or LDL cholesterol 5.