What is the use of Lipoprotein(a) (Lp(a)) testing?

Lipoprotein(a) Testing: Clinical Applications and Recommendations

Lipoprotein(a) [Lp(a)] testing should be performed once in a lifetime for individuals with increased cardiovascular risk, particularly those with premature cardiovascular disease (CVD), family history of premature CVD, or those with recurrent cardiovascular events despite optimal lipid-lowering therapy. 1

When to Measure Lp(a)

Lp(a) testing is recommended in the following specific clinical scenarios:

• Individuals with premature atherosclerotic cardiovascular disease (ASCVD)
• Patients with family history of premature CVD or elevated Lp(a)
• Patients with recurrent cardiovascular events despite optimal statin therapy
• Individuals with familial hypercholesterolemia (FH) 2, 1
• Patients with intermediate or high cardiovascular risk according to traditional risk calculators 1
• Individuals of African or South Asian ancestry (who tend to have higher Lp(a) levels) 1, 3

Interpretation of Lp(a) Levels

Lp(a) levels indicate cardiovascular risk according to the following thresholds:

• Elevated risk: >30 mg/dL (75 nmol/L)
• Significantly elevated risk: >50 mg/dL (125 nmol/L) 1

It's important to note that Lp(a) risk is amplified when LDL-C is also elevated, creating a compounding effect on cardiovascular risk 1.

Measurement Challenges

Several important considerations exist regarding Lp(a) measurement:

• Lack of standardization between assays makes comparison between laboratories difficult 2, 1
• Newer assays report Lp(a) in nmol/L (particle number) rather than mg/dL (mass) due to limitations of mass assays 1
• Population means and median levels vary significantly by race/ethnicity 1
• A single lifetime measurement is generally sufficient since Lp(a) levels remain relatively stable throughout life due to genetic determination 3

Clinical Management Based on Lp(a) Results

For patients with elevated Lp(a):

1. Aggressive LDL-C reduction is the primary strategy:

   • High-intensity statin therapy aiming for ≥50% LDL-C reduction
   • Consider PCSK9 inhibitors for additional reduction 1

2. Intensive management of other modifiable risk factors:

   • Hypertension control
   • Smoking cessation
   • Diabetes management
   • Weight reduction in obesity 1

3. Consider Lp(a)-lowering therapies:

   • PCSK9 inhibitors (approximately 27% reduction)
   • Aspirin (10-20% reduction) in select populations
   • Lipoprotein apheresis (up to 80% reduction) for extreme cases 1, 4

Emerging Therapies

Promising targeted therapies currently in clinical trials include:

• Antisense oligonucleotides (e.g., pelacarsen)
• Small interfering RNA agents (e.g., olpasiran)

These can reduce Lp(a) by >80% and are being evaluated in large-scale cardiovascular outcomes trials 1, 3.

Common Pitfalls and Caveats

• Statin therapy may paradoxically increase Lp(a) levels despite cardiovascular benefits 1
• Low-saturated fat diets may also paradoxically raise Lp(a) levels 1
• Different assays may give significantly different results due to lack of standardization 2, 1
• The European Heart Journal notes that many patients may develop CVD despite very low Lp(a) levels, highlighting that Lp(a) is one of many risk factors 2
• Niacin can reduce Lp(a) by up to 35%, but its use has declined due to side effects and questionable cardiovascular benefit in recent trials 1, 4

By identifying individuals with elevated Lp(a), clinicians can implement more aggressive risk factor modification and consider targeted therapies to reduce cardiovascular risk in this high-risk population.