Is there utility in ordering lipoprotein(a) (Lp(a)) and apolipoprotein B (ApoB)?

Utility of Ordering Lipoprotein(a) and Apolipoprotein B

Yes, there is clear clinical utility in ordering both Lp(a) and ApoB, but only in specific patient populations—not for general screening—with ApoB being more broadly useful than Lp(a) for risk assessment and treatment monitoring.

Apolipoprotein B (ApoB): When and Why to Order

Primary Indications for ApoB Testing

ApoB measurement is reasonable in adults aged 40-75 years with borderline (5-7.4%) or intermediate (7.5-19.9%) 10-year ASCVD risk, particularly when triglycerides are persistently ≥200 mg/dL. 1 An ApoB level ≥130 mg/dL constitutes a risk-enhancing factor that favors statin initiation or intensification. 1

• ApoB is particularly valuable in patients with metabolic syndrome, chronic kidney disease, or diabetes, where discordance between LDL-C and actual atherogenic particle number is common. 1
• Each atherogenic particle (LDL, VLDL, IDL) contains exactly one ApoB molecule, making it a direct measure of total atherogenic particle burden. 2
• ApoB is superior to LDL-C for risk assessment both before and during treatment with lipid-lowering therapy. 3

ApoB as a Treatment Target

• For very high-risk patients, target ApoB <80 mg/dL; for high-risk patients, target ApoB <100 mg/dL. 1
• ApoB should be measured 4-12 weeks after initiating or intensifying therapy to assess response. 1
• When there is discordance between LDL-C and ApoB, atherosclerotic cardiovascular disease risk generally aligns better with ApoB. 3

When NOT to Order ApoB

• Do not order ApoB for routine screening in asymptomatic adults without additional risk factors. 1 The 2010 ACC/AHA guideline assigns a Class III (No Benefit) recommendation against measuring ApoB for cardiovascular risk assessment in asymptomatic adults without established coronary artery disease. 1
• Standard fasting lipid profiles remain the first-line assessment tool. 1

Lipoprotein(a): When and Why to Order

Primary Indications for Lp(a) Testing

Measure Lp(a) once—not repeatedly—in patients with premature CVD, familial hypercholesterolemia, family history of premature CVD or elevated Lp(a), recurrent CVD despite optimal lipid-lowering therapy, or ≥5% 10-year risk of fatal CVD. 4

• Traditional thresholds for elevated Lp(a) are >30 mg/dL or >75 nmol/L, which approximate the 75th percentile in white populations. 4
• The European Society of Cardiology suggests risk becomes significant when Lp(a) is >50 mg/dL (~100-125 nmol/L). 4
• Lp(a) is genetically determined and stable throughout life, so it only needs to be measured once. 1

Clinical Significance of Elevated Lp(a)

• Elevated Lp(a) adds independent prognostic value for CAD even after adjusting for ApoB particle count. 5
• In patients with elevated Lp(a) (>30-50 mg/dL), standard ApoB measurements may underestimate total cardiovascular risk. 1
• Lp(a) comprises on average 3% of apoB-containing particles but can reach 15% at the highest Lp(a) deciles. 6

When NOT to Order Lp(a)

• There is no justification for screening the general population for Lp(a). 4
• No randomized intervention has shown that reducing Lp(a) decreases CVD risk, and no evidence supports any value as a treatment target. 4

The ApoB/ApoA1 Ratio: Limited Clinical Utility

Do not routinely order ApoA1 or the ApoB/ApoA1 ratio. 1 While the ApoB:ApoA1 ratio is one of the strongest risk markers, it is not established as a treatment goal. 4

• The evidence base for lowering ApoB is substantially stronger than for raising ApoA1. 1, 2
• Drug-induced increases in HDL/ApoA1 have not been shown to improve outcomes, making the ApoB/ApoA1 ratio a problematic treatment target. 1
• ApoA1 measurement has minimal role in routine clinical practice. 1

Practical Clinical Algorithm

1. Start with a standard fasting lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides) for all patients. 1

2. Consider ApoB testing if:

   • Age 40-75 with intermediate ASCVD risk (5-19.9%) 1
   • Persistent triglycerides ≥200 mg/dL 1
   • Metabolic syndrome, diabetes, or chronic kidney disease 1
   • If ApoB ≥130 mg/dL, treat as a risk-enhancing factor 1

3. Consider Lp(a) testing once if:

   • Premature CVD or family history of premature CVD 4
   • Familial hypercholesterolemia 4
   • Recurrent CVD despite optimal therapy 4
   • ≥5% 10-year fatal CVD risk 4

4. Do NOT order:

   • ApoA1 or ApoB/ApoA1 ratio in routine assessment 1
   • Lp(a) for general population screening 4

Important Caveats

• ApoB testing adds extra expense and inter-laboratory variability. 1 However, when indicated, it provides superior risk assessment compared to LDL-C alone. 3
• Lp(a) levels are genetically determined and do not change with standard lipid-lowering therapy (though PCSK9 inhibitors do lower Lp(a) by 20-30%). 1
• Young women (<40 years) with low LDL-C but elevated Lp(a) ≥40 mg/dL may have higher apoB and sdLDL-C levels, suggesting increased cardiovascular risk that would be missed by LDL-C alone. 7
• The most recent high-quality evidence (2025) demonstrates that lipid-related atherosclerotic risk is most accurately reflected by the total count of apoB particles, with elevated Lp(a) adding independent additional risk. 5 Adequate assessment of atherogenic risk from dyslipidemia is best accomplished by consideration of both apoB and Lp(a) concentrations in appropriate clinical contexts. 5