What is Lipoprotein(a) (LPA) and what is the significance of elevated Lipoprotein(a) (LPA) levels?

From the Guidelines

Lipoprotein(a), or Lp(a), is a genetically determined risk factor for cardiovascular disease that is largely inherited and present from birth, and an elevated Lp(a) level increases the risk of heart attacks, strokes, and valve calcification independent of other risk factors. When explaining an elevated Lp(a) to patients, it is essential to emphasize the importance of aggressive management of other modifiable risk factors.

Key Points to Discuss with Patients

• Elevated Lp(a) levels are associated with an increased risk of cardiovascular disease, including heart attacks, strokes, and valve calcification 1.
• Lp(a) levels are mainly determined by genetic traits and do not respond well to traditional lifestyle changes like diet and exercise 1.
• Currently, there are no FDA-approved medications specifically targeting Lp(a), though PCSK9 inhibitors and niacin may modestly reduce levels 1.
• The most important approach for patients with elevated Lp(a) is aggressive management of other modifiable risk factors, including:
  • Maintaining optimal LDL cholesterol (often below 70 mg/dL for high-risk patients) 1.
  • Controlling blood pressure and diabetes if present 1.
  • Avoiding smoking 1.
  • Maintaining a healthy weight 1.
  • Following a heart-healthy diet 1.

Importance of Regular Check-Ups and Family Screening

Regular cardiovascular check-ups are essential for patients with elevated Lp(a), and family members should consider getting tested since this is a genetic condition 1. New medications specifically targeting Lp(a) are in clinical trials and may become available in the coming years 1.

Clinical Recommendations

The European Society of Cardiology (ESC) guidelines recommend measuring Lp(a) in patients at high risk of cardiovascular disease and targeting levels below 50 mg/dL 1. Additionally, the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol recommends considering Lp(a) as a risk-enhancing factor, especially at higher levels 1.

From the Research

Definition and Significance of LPA

• 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, calcific aortic valve stenosis, and venous thromboembolism 3, 4.
• Lp(a) is a genetically determined risk factor, with approximately 70% to 90% of interindividual heterogeneity in levels being genetically determined 3.

Explaining Elevated LPA to Patients

• Patients with elevated Lp(a) levels (≥50 mg/dL) are at increased risk of cardiovascular disease, even if they have optimal LDL cholesterol levels 2, 4.
• Elevated Lp(a) levels can contribute to residual cardiovascular risk despite traditional risk factor optimization, including LDL cholesterol reduction 2.
• Patients with a family history of premature cardiovascular disease or elevated Lp(a) may benefit from Lp(a) measurement and targeted treatment 4.

Treatment and Management of Elevated LPA

• Current treatment options for elevated Lp(a) include lipoprotein apheresis, PCSK9 inhibitors, and emerging nucleic acid-based therapies such as antisense oligonucleotides and small interfering RNA agents 2, 5.
• Aspirin may be beneficial for primary prevention in individuals with high Lp(a) levels, particularly given interactions between Lp(a) and the fibrinolytic system/platelets 6.
• Further studies are needed to determine the effectiveness of these treatments and to establish guidelines for Lp(a) measurement and management 3, 4, 5, 6.