What is Lipoprotein(a) (Lp(a))?

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Last updated: April 5, 2025 • View editorial policy

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From the Guidelines

Lipoprotein(a) levels should be managed by aggressively treating all other cardiovascular risk factors, particularly LDL cholesterol, and considering the use of high-intensity statins, PCSK9 inhibitors, or other therapies to reduce overall cardiovascular risk. Lipoprotein(a), or Lp(a), is a specialized type of LDL cholesterol particle that can significantly increase cardiovascular risk when present at elevated levels in the bloodstream. The European Society of Cardiology (ESC) guidelines recommend measuring Lp(a) in patients at high risk of cardiovascular disease (CVD) and to target levels below 50 mg/dL 1.

Key Recommendations

  • High-intensity statins, such as atorvastatin 40-80mg or rosuvastatin 20-40mg daily, should be used to reduce overall cardiovascular risk.
  • PCSK9 inhibitors, such as evolocumab or alirocumab, can modestly reduce Lp(a) by 20-30% while significantly lowering LDL.
  • Niacin (1-3g daily) can lower Lp(a) by 20-30% but has fallen out of favor due to side effects and limited outcome benefits.
  • Lp(a) levels are primarily determined by genetics and remain relatively stable throughout life, which is why testing is typically only needed once in adulthood.

Patient Selection for Lp(a) Measurement

  • Patients with premature CVD and premature stroke.
  • Patients who fall into an intermediate risk group when classical risk algorithms are used.
  • Patients with recurrent or rapidly progressive vascular disease, despite being on lipid-lowering medication.
  • Patients with familial hypercholesterolemia (FH) or other forms of genetic dyslipidaemias.
  • Patients with low HDL-C, genetic defects related to haemostasis and homocysteine, diabetes, and auto-immune diseases.

Future Directions

  • Novel therapies specifically targeting Lp(a), including antisense oligonucleotides, are currently in clinical trials and show promise for the future management of this important cardiovascular risk factor 1.
  • The NHLBI working group recommends testing of the "Lp(a) hypothesis" in patients with elevated Lp(a) levels to determine the effectiveness of Lp(a) lowering agents in reducing cardiovascular risk 1.

From the Research

Lipoprotein(a) Overview

  • Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a) 2
  • Elevated Lp(a) levels are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis 2
  • Lp(a) is considered a causal risk factor for ASCVD, with a potentially causal association between high Lp(a) levels and atherosclerotic cardiovascular disease 2

Measurement and Screening

  • Current guidelines recommend measuring Lp(a) levels in patients with an intermediate-high risk of ASCVD, familial hypercholesterolemia, a family history of early ASCVD or elevated Lp(a), and progressive ASCVD despite receiving optimal therapy 3
  • The European Atherosclerosis Society notes that Lp(a) levels of 50 mg/dL or higher confer increased cardiovascular risk 2
  • Universal measurement of Lp(a) is recommended, with a focus on population screening 4

Treatment and Therapies

  • Traditional lipid-modifying therapies, such as statins and ezetimibe, do not lower Lp(a) levels 5, 3
  • Emerging nucleic acid-based therapies, such as antisense oligonucleotides (ASO) and small interfering RNAs (siRNAs), have shown significant reductions in Lp(a) levels, with up to 90% reductions in some studies 5, 3, 6, 2
  • Lipoprotein apheresis (LA) efficiently lowers Lp(a) levels and has been associated with a reduction in incident CV events 6
  • Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors) can reduce Lp(a) levels by up to 30% 6

Future Directions

  • Ongoing clinical trials, such as the Lp(a)HORIZON study, aim to determine whether selective Lp(a) lowering with ASO reduces the risk of major CV events 6
  • Phase 3 trials will establish whether emerging nucleic acid-based therapies improve cardiovascular outcomes 2
  • Targeted apolipoprotein(a) [apo(a)]-lowering therapies are in phase 3 clinical development, with a focus on reducing Lp(a) levels in patients with high Lp(a) 4

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

4
Research

High lipoprotein(a): Actionable strategies for risk assessment and mitigation.

American journal of preventive cardiology, 2024

5
Research

Lipoprotein(a): cardiovascular risk and emerging therapies.

Expert review of cardiovascular therapy, 2023

6
Research

Lipoprotein (a): When to Measure and How to Treat?

Current atherosclerosis reports, 2021

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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