What is the management for elevated lipoprotein(a) (Lp(a)) levels?

Management of Elevated Lipoprotein(a)

For patients with elevated lipoprotein(a) [Lp(a)], aggressive LDL-cholesterol reduction should be the primary management strategy, with lower LDL-C goals for these high-risk patients. 1, 2

When to Measure Lp(a)

Lp(a) measurement is recommended in:

• Patients with premature cardiovascular disease (CVD) without evident risk factors 3, 1
• Individuals with a family history of premature CVD or elevated Lp(a) 1, 2
• Patients with familial hypercholesterolemia (FH) 1
• Patients with recurrent cardiovascular events despite optimal lipid-lowering therapy 1, 3
• Patients with ≥5% 10-year risk of fatal CVD according to risk algorithms 1
• Patients with intermediate CVD risk according to Framingham, PROCAM, ESC Heart Score, or Australian/New Zealand risk scores 3

Interpreting Lp(a) Levels

• Traditional thresholds for elevated Lp(a) are >30 mg/dL or >75 nmol/L (approximately the 75th percentile in white populations) 1, 2
• European guidelines define significant risk at Lp(a) >50 mg/dL (approximately 100-125 nmol/L) 1, 2
• Canadian Cardiovascular Society uses a cutoff of >30 mg/dL to define abnormal Lp(a) levels 1
• Risk increases progressively with higher Lp(a) levels, with particularly high risk at >100 mg/dL 3, 4

Management Approach

First-Line Strategy: Aggressive LDL-C Reduction

• Lower LDL-C goals should be targeted in patients with elevated Lp(a) 2, 5
• Important caveat: Statins and ezetimibe may actually increase Lp(a) mass and Lp(a)-C levels 1, 6
• Note that Lp(a)-C content is included in standard "LDL-C" laboratory measurements, potentially affecting achievement of LDL-C targets 1, 3

Pharmacological Options for Lp(a) Reduction

1. PCSK9 inhibitors (alirocumab, evolocumab):

   • Reduce Lp(a) levels by 20-30% 4, 6
   • Consider in high-risk patients not reaching LDL-C goals with statins 2

2. Niacin:

   • Reduces Lp(a) by 30-35% 3
   • Currently most recommended drug specifically for Lp(a) reduction 3
   • Limited by side effects and uncertain clinical benefit 6

3. Other medications with modest effects:

   • Fibrates: Up to 20% reduction (highest effect with gemfibrozil) 3
   • L-Carnitine: 10-20% reduction 3
   • Acetylsalicylic acid: 10-20% reduction (effective even at low doses) 3

Lipoprotein Apheresis

• Most effective currently available treatment for patients with very high Lp(a) levels 4, 6
• Reduces Lp(a) by up to 80% 3
• Consider in patients with:
  • Elevated Lp(a) >60 mg/dL 3
  • Controlled LDL-C 3
  • Recurrent events or progression of CVD despite optimal therapy 3
• Has been shown to reduce cardiovascular events by approximately 80% in patients with elevated Lp(a) 3
• Particularly beneficial for patients with refractory angina and elevated Lp(a) 3

Special Populations

Children and Young Adults with Elevated Lp(a)

• Children with elevated Lp(a) have a fourfold increased risk of acute ischemic stroke 1, 3
• Risk of recurrent ischemic strokes is increased by more than 10-fold in patients with Lp(a) >90th percentile 1, 3
• Consider more aggressive preventive measures in pediatric patients with elevated Lp(a) and history of stroke 3

Patients with Chronic Kidney Disease

• Lp(a) levels are substantially increased in persons with end-stage renal disease and chronic kidney disease 1
• Lp(a) is an independent predictor of incident coronary heart disease events and mortality in CKD patients 1

Emerging Therapies

Several promising therapies are in development:

• Antisense oligonucleotides (pelacarsen): Reduces Lp(a) by up to 80-90% 4, 7
• Small interfering RNAs (olpasiran, SLN360): Can reduce Lp(a) by >95% 7, 6
• These RNA-targeting therapies aim to genetically silence LPA, reduce apo(a) production, and lower serum Lp(a) levels 7

Common Pitfalls to Avoid

• Failing to measure Lp(a) in high-risk patients, particularly those with premature or recurrent cardiovascular disease 1
• Relying solely on LDL-C targets in patients with elevated Lp(a) 1, 2
• Overlooking the contribution of Lp(a)-C to measured LDL-C levels 1, 3
• Not recognizing that statins may increase Lp(a) levels while lowering LDL-C 1, 6
• Assuming lifestyle modifications will significantly impact Lp(a) levels, which are primarily genetically determined 4, 6