What tests should a patient order to assess lipoprotein(a) [Lp(a)] and apolipoprotein B (ApoB) levels?

Laboratory Testing for Lipoprotein(a) and Apolipoprotein B

Order a standard lipoprotein(a) immunoassay and an apolipoprotein B immunoassay as separate tests through any commercial clinical laboratory—both can be measured without fasting and are widely available on conventional autoanalyzers. 1, 2

Specific Test Orders

For Lipoprotein(a) Measurement

• Request a lipoprotein(a) immunoassay using nephelometric, turbidimetric, or ELISA methods—these are the most reliable commercially available assays 3
• The test does not require fasting and can be drawn at any time of day 1, 2
• Results will be reported in either mg/dL or nmol/L—both units are acceptable, though standardization between laboratories remains imperfect 3
• Measure Lp(a) only once in a lifetime for risk stratification, as levels are genetically determined and remain stable throughout life 1, 2

For Apolipoprotein B Measurement

• Request an apolipoprotein B immunoassay—good immunochemical methods are available and easily run on conventional autoanalyzers 2
• This test also does not require fasting and remains accurate regardless of meal timing 1, 2
• Results are reported in mg/dL 1, 2
• ApoB can be measured repeatedly to monitor treatment response, unlike Lp(a) 2

Critical Distinction Between These Tests

Lp(a) and ApoB measure fundamentally different things and are not interchangeable. 1

• ApoB quantifies all atherogenic particles (VLDL, IDL, LDL, and Lp[a]) by counting the single ApoB-100 protein present on each particle 1, 2
• Lp(a) is a specific lipoprotein particle consisting of an LDL-like core with ApoB-100 plus an additional apolipoprotein(a) molecule covalently attached 1
• Every Lp(a) particle contains one ApoB molecule, so Lp(a) contributes to the total ApoB count, but ApoB includes many other particles beyond Lp(a) 4, 5

When to Order Each Test

Order Lp(a) if the patient has:

• Premature cardiovascular disease (men <55 years, women <65 years) 3, 1
• Family history of premature CVD or elevated Lp(a) 1, 2
• Familial hypercholesterolemia 3, 1
• Recurrent CVD despite optimal statin therapy 3, 1
• ≥5% 10-year risk of fatal CVD by risk calculator 1
• Intermediate risk (7.5-20% 10-year ASCVD risk) where reclassification would change management 3

Order ApoB if the patient has:

• Triglycerides ≥200 mg/dL (when LDL-C calculations become unreliable) 1, 2
• Metabolic syndrome or diabetes with normal LDL-C 1, 2
• Uncertainty about cardiovascular risk after calculating 10-year ASCVD risk 2
• Need to assess adequacy of lipid-lowering therapy 1, 2
• Hypertriglyceridemia, obesity, or very low LDL-C levels 6

Interpretation Thresholds

Lipoprotein(a) Risk Thresholds:

• ≥30 mg/dL (or ≥75 nmol/L): Abnormal, approximately 75th percentile 3, 1
• ≥50 mg/dL (or ≥125 nmol/L): Risk-enhancing factor per ACC/AHA guidelines 1, 2
• >180 mg/dL: Very high risk, may further stratify high-risk patients 2

Apolipoprotein B Treatment Targets:

• <80 mg/dL: Target for very high-risk patients (established CVD, diabetes with complications, CKD stage 3-5) 1, 2, 6
• <100 mg/dL: Target for high-risk patients (10-year ASCVD risk ≥7.5-10%, multiple risk factors) 1, 2, 6
• ≥130 mg/dL: Risk-enhancing factor, corresponds to LDL-C ≥160 mg/dL 1, 2

Important Caveats

Measurement Standardization Issues:

• Lp(a) assays lack universal standardization between laboratories, making absolute comparisons difficult 3
• Despite standardization challenges, precision within a single laboratory is sufficient for clinical decision-making 3
• No reliable conversion factor exists between mg/dL and nmol/L units for Lp(a) due to particle size heterogeneity 1

Clinical Interpretation Pitfalls:

• Lp(a) cholesterol is included in measured LDL-C, potentially overestimating true LDL-C by 30-45% of the Lp(a) mass in patients with elevated Lp(a) 1
• Statins may increase Lp(a) levels while lowering LDL-C, complicating interpretation 1
• ApoB underestimates risk in patients with very high Lp(a) because Lp(a) particles are approximately 7-fold more atherogenic than LDL particles on a per-particle basis 5

Practical Ordering Considerations:

• Both tests are more expensive than standard lipid panels but provide superior risk assessment in specific populations 2
• Laboratory reliability varies—ensure your laboratory uses validated immunochemical methods 3, 2
• Non-fasting samples are acceptable for both tests, improving patient convenience 1, 2