Management of Elevated Apolipoprotein B Levels

Introduction to Apolipoprotein B and ASCVD Risk

• The American College of Cardiology recommends statin therapy as the first-line treatment for elevated apolipoprotein B (apoB) levels ≥130 mg/dL, which constitutes a significant risk-enhancing factor for atherosclerotic cardiovascular disease (ASCVD) 1, 2
• An elevated apoB level (≥130 mg/dL) is considered a risk-enhancing factor for ASCVD and corresponds to an LDL-C ≥160 mg/dL, according to the American College of Cardiology 1, 3
• Apolipoprotein B (ApoB) is the primary structural protein of atherogenic lipoproteins, including LDL, VLDL, IDL, and lipoprotein(a), and is directly associated with increased cardiovascular risk, providing a more accurate risk predictor than LDL-C, especially in patients with hypertriglyceridemia, diabetes, and metabolic syndrome 4, 5, 6, 7

Risk Assessment and Calculation

• The American College of Cardiology suggests identifying additional risk factors, including family history of premature ASCVD, primary hypercholesterolemia, metabolic syndrome, chronic kidney disease, and high-risk race/ethnicities, to comprehensively assess ASCVD risk 2
• The Pooled Cohort Equations should be used to calculate 10-year ASCVD risk and categorize patients as low risk (<5%), borderline risk (5% to <7.5%), intermediate risk (≥7.5% to <20%), or high risk (≥20%), as recommended by the American College of Cardiology 1
• Traditional risk factors, such as age, sex, smoking, hypertension, and diabetes, should be considered when assessing overall cardiovascular risk, in addition to lipid parameters, as stated by the European Society of Cardiology 4
• The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) defines very high risk as having established cardiovascular disease, diabetes with target organ damage, severe chronic kidney disease, or SCORE ≥10%, and high risk as having markedly elevated single risk factors, diabetes without target organ damage, moderate chronic kidney disease, or SCORE ≥5% and <10% 4

Treatment Recommendations

• Moderate to high-intensity statin therapy is recommended for patients with elevated apoB, particularly when associated with intermediate or high ASCVD risk, according to the American College of Cardiology 1
• For intermediate-risk patients, an LDL-C reduction of ≥30% is recommended, while for high-risk patients, an LDL-C reduction of ≥50% is recommended, as suggested by the American College of Cardiology 1
• ApoB measurement is particularly valuable when triglycerides are ≥200 mg/dL, as LDL-C calculations become less reliable, according to the American College of Cardiology 1
• First-line therapy for indicated treatment is moderate to high-intensity statin, with ezetimibe as second-line therapy if target is not achieved with maximum tolerated statin, and PCSK9 inhibitors as third-line therapy for very high-risk patients not achieving targets 8
• Lipid profile and ApoB should be rechecked in 4-12 weeks after initiating or changing therapy, and monitored annually or more frequently if clinically indicated, with consideration of measuring non-HDL-C as an alternative target 7

Apolipoprotein B Testing and Target Levels

• The following table summarizes guideline recommendations for ApoB testing:

• The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines recommend target ApoB levels of <80 mg/dL for individuals at very high cardiovascular risk and <100 mg/dL for individuals at high cardiovascular risk, with a strength of evidence rated as moderate 4
• Lowering ApoB (via statins and other lipid-lowering therapies) reduces cardiovascular risk, although its use as a treatment target is not widely recommended by American guidelines 4, 5

Apolipoprotein E and APOA1

• Apolipoprotein E (APOE) exists in three major isoforms: E2, E3, and E4, playing a key role in lipid transport and metabolism, as stated by the European Society of Cardiology 4
• APOE genotyping is more clinically relevant than APOE levels for diagnosing dysbetalipoproteinemia, assessing risk in families with familial hyperlipidemia, and evaluating risk for Alzheimer's disease, as recommended by the European Society of Cardiology 4
• Normal reference values for APOA1 are >120 mg/dL for men and >140 mg/dL for women, according to the European Society of Cardiology 4
• For isolated high APOA1 with otherwise normal lipid profile, generally no specific treatment is needed, and a heart-healthy lifestyle should be continued, as advised by the European Society of Cardiology 4
• For high APOE with lipid abnormalities, treatment depends on overall lipid profile and cardiovascular risk, and should target LDL-C, non-HDL-C, or ApoB levels rather than APOE levels, as recommended by the European Society of Cardiology 4