What is the significance of Apolipoprotein B (ApoB)?

From the Guidelines

Apolipoprotein B (ApoB) is a superior marker for cardiovascular risk assessment compared to traditional LDL cholesterol measurements, and its levels should be used to guide treatment decisions for patients at risk of cardiovascular disease. ApoB is the primary protein component of atherogenic lipoproteins, including LDL, VLDL, and lipoprotein(a), and each particle contains exactly one ApoB molecule, making ApoB levels a direct measure of the number of potentially harmful particles circulating in the bloodstream 1. Normal ApoB levels are generally below 100 mg/dL, with optimal levels for high-risk individuals being below 80 mg/dL, as recommended by the European Society of Cardiology and other societies 1. Elevated ApoB levels indicate an increased risk of atherosclerosis and cardiovascular events, even when LDL cholesterol appears normal, particularly in conditions like diabetes, metabolic syndrome, and obesity.

Some key points to consider when using ApoB levels to guide treatment decisions include:

• ApoB levels can be used as an alternative to LDL cholesterol for risk assessment and monitoring treatment 1
• Non-HDL cholesterol, which is calculated by subtracting HDL cholesterol from total cholesterol, is also a useful marker for cardiovascular risk assessment and is highly correlated with ApoB levels 1
• Treatment approaches for high ApoB include lifestyle modifications, such as a Mediterranean diet, regular exercise, and weight management, as well as medications like statins, ezetimibe, PCSK9 inhibitors, and bempedoic acid
• The use of ApoB levels to guide treatment decisions can provide a more accurate assessment of cardiovascular risk and can help guide personalized treatment decisions for patients at risk of cardiovascular disease 1

It's worth noting that while some studies have suggested that ApoB may not provide additional benefit beyond non-HDL-C or traditional lipid ratios 1, more recent and higher-quality studies have consistently shown that ApoB is a superior marker for cardiovascular risk assessment compared to LDL cholesterol 1. Therefore, ApoB levels should be prioritized when making treatment decisions for patients at risk of cardiovascular disease.

From the Research

Apolipoprotein B as a Measure of Cardiovascular Risk

• Apolipoprotein B (apoB) is considered a more accurate measure of cardiovascular risk than low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) 2, 3
• The 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines endorse apoB as a better guide to the adequacy of lipid lowering than LDL-C or non-HDL-C 2
• ApoB can be measured more accurately than LDL-C or non-HDL-C, making it a reliable indicator of risk 2

Comparison of Apolipoprotein B with Other Lipid Markers

• ApoB is a better measure of circulating LDL particle number (LDL-P) concentration than LDL-C 3
• Non-HDL cholesterol is an adequate surrogate of apoB during statin therapy, independent of triglyceride status 4
• The target of apoB of 80 mg/dl correlates with LDL cholesterol of 90 mg/dl and non-HDL cholesterol of 110 mg/dl at baseline, and with LDL cholesterol of 74 mg/dl and non-HDL cholesterol of 92 mg/dl with statin therapy 4

Effects of Lipid-Lowering Therapies on Apolipoprotein B

• Intensive statin therapy can alter the relation of atherogenic lipoprotein cholesterol to apoB 4
• Atorvastatin and rosuvastatin can cause significant decreases in apoB-48 and remnant lipoprotein cholesterol levels 5
• Therapeutic lowering of apoB is associated with reduced cardiovascular outcomes across various lipid-lowering therapies, including statins, ezetimibe, and PCSK9 inhibitors 6

Association of Apolipoprotein B with Cardiovascular Outcomes

• Lowering apoB is associated with reduced all-cause mortality and cardiovascular mortality, with a relative risk of 0.95 for all-cause mortality and 0.93 for cardiovascular mortality for every 10 mg/dL decrease in apoB 6
• Reduction in all-cause mortality is limited to statins, with a relative risk of 0.92 for every 10 mg/dL decrease in apoB 6
• The relative risk of major adverse cardiovascular events (MACE) per 10 mg/dL reduction in apoB is 0.93 for all therapies combined, with significant reductions seen with statin and non-statin therapies that clear apoB by upregulating LDL-R 6