How do you interpret Lipoprotein(a) (LpA) results?

Interpreting Lipoprotein(a) Results

Lipoprotein(a) [Lp(a)] levels above 30 mg/dL (75 nmol/L) indicate increased cardiovascular risk, with levels above 50 mg/dL (125 nmol/L) representing significantly elevated risk requiring more aggressive management. 1, 2

Risk Stratification Based on Lp(a) Levels

Risk Categories:

• Low risk: <30 mg/dL (<75 nmol/L)
• Intermediate risk: 30-50 mg/dL (75-125 nmol/L)
• High risk: ≥50 mg/dL (≥125 nmol/L) 2

Different Guideline Thresholds:

• European Atherosclerosis Society: >50 mg/dL (~100-125 nmol/L) 1
• Canadian Cardiovascular Society: >30 mg/dL 1
• Traditional threshold: >30 mg/dL (>75 nmol/L) 2

Clinical Significance of Elevated Lp(a)

Elevated Lp(a) is associated with:

• Increased risk of coronary heart disease (risk ratio 1.13 per standard deviation increase) 2
• Calcific aortic valve stenosis 3
• Residual cardiovascular risk despite optimal LDL-C lowering therapy 3
• Increased all-cause mortality (hazard ratio 1.20 for Lp(a) >93 mg/dL vs <10 mg/dL) 4

The relationship between Lp(a) and cardiovascular disease risk may not be strictly continuous, with significant risk increases observed once Lp(a) exceeds 30 mg/dL, with further risk increases at higher concentrations 1.

Important Considerations in Lp(a) Interpretation

1. Measurement standardization issues:

   • Historically, lack of standardized assays has complicated interpretation 1
   • Newer assays report values in nmol/L (apo(a) particle number) rather than mg/dL (mass) 1
   • Mass assays are being phased out due to inherent limitations 1

2. Genetic and racial/ethnic variations:

   • Lp(a) levels show several-hundred-fold interindividual variability 5
   • Population means and median levels vary by race/ethnicity 1
   • African-Americans and Asian-Indians typically have higher Lp(a) levels than Caucasians 5

3. Relationship with other lipids:

   • Lp(a) risk is amplified when LDL-C is also elevated 1, 6
   • Lp(a) contributes to measured "LDL-C" (30-45% of Lp(a) is cholesterol) 1
   • Consider calculating risk-weighted ApoB: Risk-weighted ApoB = ApoB + (Lp(a) × 6) 2

Clinical Management Based on Lp(a) Results

For patients with elevated Lp(a):

1. Aggressive LDL-C reduction:

   • Target ≥50% LDL-C reduction from baseline 2
   • High-intensity statin therapy as first-line treatment
   • Consider PCSK9 inhibitors for additional reduction 2

2. Intensive management of other modifiable risk factors:

   • Hypertension control
   • Smoking cessation
   • Diabetes management
   • Weight reduction in obesity 2

3. Consider Lp(a)-lowering therapies:

   • PCSK9 inhibitors (reduce Lp(a) by ~27%) 2
   • Niacin therapy (reduces Lp(a) by up to 35%) 2
   • Lipoprotein apheresis for very high Lp(a) levels (>60 mg/dL) with progressive cardiovascular disease 2
   • Emerging therapies (antisense oligonucleotides, small interfering RNA) in clinical trials 3

Common Pitfalls in Lp(a) Interpretation

1. Assay variability: Different assays may give different results due to lack of standardization 1

2. Statin effect: Statins may actually increase Lp(a) levels despite their cardiovascular benefits 2

3. Diet effect: Low-saturated fat diets may paradoxically raise Lp(a) levels 2

4. Frozen sample issues: Measurements from long-term frozen samples may be unreliable 1

5. Small study limitations: Due to the extremely wide range of plasma Lp(a) levels and skewed distribution, studies with small numbers of cases are prone to random findings 1