Why check lipoprotein(a) (Lp(a)) levels if there is no specific treatment for elevated levels?

Measuring Lipoprotein(a): Purpose and Clinical Utility Despite Limited Treatment Options

Measuring lipoprotein(a) [Lp(a)] is valuable despite limited specific treatments because it identifies patients at higher cardiovascular risk who require more aggressive management of other modifiable risk factors and may benefit from emerging therapies.

Why Measure Lp(a)?

Risk Stratification

• Elevated Lp(a) (≥50 mg/dL or ≥125 nmol/L) is an independent, causal risk factor for atherosclerotic cardiovascular disease (ASCVD), present in approximately 20% of the population 1
• Individuals with elevated Lp(a) have approximately 2.5-fold increased risk of ASCVD compared to those with normal levels 2
• Patients with both elevated Lp(a) and LDL cholesterol have a 10-fold or higher risk of myocardial infarction 3

Identification of Specific Patient Groups

Lp(a) testing is recommended for:

• Patients with premature cardiovascular disease (CVD) or stroke without evident risk factors 3, 1
• Intermediate CVD risk groups (according to Framingham, PROCAM, ESC Heart Score) 3
• Patients with recurrent or rapidly progressive vascular disease despite treatment 3
• Familial hypercholesterolemia, genetic dyslipidemia, or low HDL-C 3, 1
• Patients with genetic defects of hemostasis, homocysteine metabolism, diabetes mellitus, or autoimmune diseases 3

Management Options for Elevated Lp(a)

Current Treatment Approaches

1. Aggressive LDL-C reduction:

   • Primary focus should be on intensive LDL-C lowering with high-intensity statins 1
   • Target LDL-C reduction of ≥50% from baseline 1
   • Consider more aggressive LDL-C targets (<70 mg/dL or even <55 mg/dL) for patients with elevated Lp(a) 1, 2

2. Available Lp(a)-lowering options:

   • Niacin (extended-release): Most established therapy for Lp(a) reduction, can lower levels by 30-35% 3, 1
   • Aspirin: May reduce Lp(a) by 10-20% 3, 1
   • PCSK9 inhibitors: Can reduce Lp(a) by 25-30% while significantly lowering LDL-C 1
   • Lipoprotein apheresis: For severe cases with progressive CVD despite optimal therapy, can reduce Lp(a) by up to 80% 3, 1

Emerging Therapies

• Antisense oligonucleotides and small interfering RNA agents targeting Lp(a) production can reduce levels by >80% and are currently in clinical trials 1, 4
• These targeted therapies may provide definitive evidence of the benefit of Lp(a) reduction 3

Clinical Approach to Lp(a) Testing

When to Test

• Measure Lp(a) at least once in adults at intermediate or high cardiovascular risk 1, 5
• Consider cascade testing in families with history of premature ASCVD or known high Lp(a) 1, 5

Interpretation of Results

• Risk stratification based on Lp(a) levels 1:
  • 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)

Common Pitfalls and Caveats

• Lp(a) assays vary between laboratories; values should be interpreted with caution 1
• Statins may have neutral or slightly elevating effects on Lp(a) levels 1, 4
• Lp(a)-C content is included in standard LDL-C measurements, potentially making LDL-C targets harder to achieve in patients with elevated Lp(a) 3
• Patients with elevated Lp(a) may require combination lipid-lowering therapy (statins plus ezetimibe and/or PCSK9 inhibitors) to achieve LDL-C goals 2

Conclusion

While specific Lp(a)-targeted therapies with proven cardiovascular outcomes are still in development, measuring Lp(a) provides valuable information for risk stratification and guides more aggressive management of modifiable cardiovascular risk factors. The identification of elevated Lp(a) should prompt consideration of more intensive lipid-lowering therapy and closer monitoring for cardiovascular disease.