To check for hyperlipidemia, should I measure lipoprotein(a) (Lp(a)) or Apolipoprotein B (Apo B)?

Apolipoprotein B vs Lipoprotein(a) for Hyperlipidemia Screening

For routine hyperlipidemia screening and cardiovascular risk assessment, measure Apolipoprotein B (ApoB), not Lipoprotein(a) [Lp(a)]—ApoB quantifies the total burden of all atherogenic particles and serves as both a diagnostic and therapeutic target, while Lp(a) is reserved for specific clinical scenarios as a risk-enhancing factor only. 1

Primary Screening: Why ApoB is Superior

ApoB represents the total concentration of all atherogenic lipoprotein particles (LDL, VLDL, IDL, and remnants) because each particle contains exactly one ApoB molecule, making it a direct particle count rather than an estimate of cholesterol content. 1, 2

Clinical Advantages of ApoB:

• Does not require fasting, unlike standard lipid panels where LDL-C calculations become unreliable in non-fasting states 3
• Remains accurate with hypertriglyceridemia (triglycerides ≥200 mg/dL), where Friedewald-calculated LDL-C becomes unreliable 1, 3
• Superior risk prediction compared to LDL-C both before and during lipid-lowering therapy 4
• Resolves discordance: When LDL-C and ApoB disagree, cardiovascular risk aligns better with ApoB 4

ApoB Thresholds and Targets:

• Risk-enhancing factor: ApoB >130 mg/dL (corresponds to LDL-C ≥160 mg/dL) 1
• High-risk target: <100 mg/dL 5, 6
• Very high-risk target: <80 mg/dL 6
• Particularly valuable when triglycerides ≥200 mg/dL to determine if hypertriglyceridemia is atherogenic 1

When to Measure Lp(a): Specific Indications Only

Lp(a) is NOT a screening test for hyperlipidemia—it serves as a risk-enhancing factor in select populations and should be measured once in a lifetime for risk stratification, not for routine diagnosis of dyslipidemia. 1

Specific Indications for Lp(a) Measurement:

• Family history of premature ASCVD (atherosclerotic cardiovascular disease) 1
• Personal history of ASCVD not explained by major risk factors 1
• Very high Lp(a) levels (>180 mg/dL) may help further risk stratify patients already in high-risk categories 1
• Consider once in each adult's lifetime to identify those at very high lifetime risk 1

Lp(a) Risk-Enhancing Thresholds:

• ≥50 mg/dL or ≥125 nmol/L constitutes a risk-enhancing factor 1
• In women: Only consider measuring if hypercholesterolemia is already present, as risk prediction improvement is minimal 1
• Note: Lp(a) is NOT a treatment target—no randomized trials show that lowering Lp(a) reduces cardiovascular risk 1

Critical Distinction: Diagnosis vs Risk Enhancement

ApoB diagnoses and quantifies hyperlipidemia by measuring the actual atherogenic particle burden, making it both a diagnostic tool and therapeutic target. 1, 4

Lp(a) does not diagnose hyperlipidemia—it identifies an additional genetic risk factor that modifies cardiovascular risk independently of cholesterol levels. 1

Practical Algorithm for Clinical Use:

Initial Evaluation:

1. Standard fasting lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) for all patients 1
2. Add ApoB measurement if:
   • Triglycerides ≥200 mg/dL 1
   • Family history of premature ASCVD or genetic hyperlipidemia 1
   • Discordance suspected between LDL-C and actual particle burden 4
   • Non-fasting sample obtained 3

Risk Stratification:

1. Measure Lp(a) once if:
   • Family history of premature ASCVD 1
   • Personal ASCVD unexplained by traditional risk factors 1
   • Considering it as part of lifetime risk assessment 1

Common Pitfalls to Avoid:

• Do not use Lp(a) to diagnose hyperlipidemia—it does not reflect cholesterol metabolism and is genetically determined 1
• Do not rely solely on LDL-C when triglycerides are elevated—ApoB is more accurate in this setting 1, 3
• Lp(a) measurement standardization remains problematic—different assays use mg/dL (mass) or nmol/L (molar) with no reliable conversion factor 1, 6
• ApoB measurement carries extra expense and may not be reliable in all laboratories, but when available, provides superior information 1
• Non-HDL-C (calculated as total cholesterol minus HDL-C) can serve as an alternative to ApoB when the latter is unavailable, as it correlates highly with ApoB and captures remnant lipoprotein risk 1, 5