What are the benefits of ordering a Lipoprotein(a) (Lp(a)) test?

Benefits of Ordering Lipoprotein(a) Testing

Measuring Lipoprotein(a) [Lp(a)] is strongly recommended for patients with premature cardiovascular disease, those at intermediate cardiovascular risk, and patients with recurrent or progressive vascular disease despite optimal lipid-lowering therapy, as it can identify individuals with elevated residual cardiovascular risk who require more intensive risk factor management. 1

Patient Populations Who Benefit from Lp(a) Testing

Lp(a) testing is particularly valuable in the following patient groups:

• Premature cardiovascular disease (CVD) and stroke patients, especially when other risk factors don't fully explain disease presence 1
• Patients falling into intermediate risk categories using traditional risk calculators (Framingham, PROCAM, ESC Heart Score) 1
• Patients with recurrent or rapidly progressive vascular disease despite being on lipid-lowering medications 1
• Familial hypercholesterolemia (FH) patients or those with other genetic dyslipidemia 1, 2
• Patients with family history of premature CVD or elevated Lp(a) 1, 2
• Patients with ≥5% 10-year risk of fatal CVD according to risk algorithms 1
• Patients with low HDL-C or genetic defects related to hemostasis and homocysteine 1
• Patients with diabetes mellitus or autoimmune diseases 1
• Hemodialysis patients and those with renal disease, as Lp(a) is two to three-fold elevated in these conditions 1

Clinical Value of Lp(a) Testing

1. Risk Stratification and Reclassification

   • Identifies patients with elevated Lp(a) (>50 mg/dL) who should be reclassified into higher risk categories 1
   • Helps identify a significant component of residual cardiovascular risk in patients with well-controlled traditional risk factors 2, 3
   • Reveals a causal genetic risk factor for cardiovascular disease that may be contributing to disease progression 4, 5

2. Treatment Guidance

   • Guides more intensive management of modifiable risk factors, especially LDL cholesterol 1, 2
   • Identifies candidates who may benefit from more aggressive LDL-C targets (<70 mg/dL) 2
   • Helps identify patients who might benefit from specific Lp(a)-lowering therapies like niacin or emerging antisense oligonucleotides 2, 6
   • Informs decisions about adding ezetimibe or PCSK9 inhibitors in high-risk patients 2

3. Disease Mechanism Insights

   • Explains atherosclerotic disease in patients with seemingly well-controlled traditional risk factors 3
   • Helps understand mechanisms of calcific aortic valve disease, which is strongly associated with elevated Lp(a) 6, 5

Thresholds for Elevated Lp(a)

• Traditional threshold: >30 mg/dL or >75 nmol/L (75th percentile in white populations) 1, 2
• European threshold: >50 mg/dL (~100-125 nmol/L) 1
• Risk stratification levels:
  • Low risk: <75 nmol/L (30 mg/dL)
  • Intermediate risk: 75-125 nmol/L (30-50 mg/dL)
  • High risk: ≥125 nmol/L (50 mg/dL) 2

Clinical Implications of Elevated Lp(a)

When elevated Lp(a) is detected, the following clinical actions are recommended:

1. Intensify management of traditional modifiable risk factors:

   • More aggressive LDL-C lowering with high-intensity statins 2, 4
   • Consider adding ezetimibe if LDL-C remains >70 mg/dL 2
   • Optimize blood pressure control, smoking cessation, diabetes management, and weight management 2

2. Consider specific Lp(a)-lowering therapies in high-risk patients:

   • Niacin (extended-release) up to 2000 mg/day for patients with persistent cardiovascular risk and Lp(a) >125 nmol/L 2, 4
   • PCSK9 inhibitors can reduce Lp(a) by 25-30% while significantly lowering LDL-C 2, 6
   • In severe cases with progressive coronary heart disease or very high LDL-C levels (≥160-200 mg/dL), consider LDL apheresis 4

Pitfalls and Caveats

• Lp(a) measurement is not standardized across laboratories, making result interpretation challenging 1
• No ICD-10 code exists specifically for elevated Lp(a) levels in the United States, limiting documentation and research 1
• Lp(a) contributes to the measured "LDL-C" in standard lipid panels, which may be significant in patients with very low LDL-C levels 1
• Currently, no randomized controlled trials have demonstrated that specifically lowering Lp(a) reduces cardiovascular risk, though this is being investigated 4, 5
• Statins may have neutral or even detrimental effects on Lp(a) levels 6

Emerging Therapies

Novel targeted therapies in development show promise for Lp(a) reduction:

• Antisense oligonucleotides (e.g., pelacarsen) can reduce Lp(a) levels by up to 80-90% 2, 5
• Small interfering RNA agents (e.g., olpasiran) can reduce Lp(a) levels by >80% 2, 5
• The ongoing Lp(a)HORIZON study will evaluate whether selective Lp(a) lowering reduces cardiovascular events 6, 7

Lp(a) testing provides valuable clinical information for cardiovascular risk assessment and management, particularly in patients with premature or unexplained cardiovascular disease, or those with residual risk despite optimal treatment of traditional risk factors.