From the Guidelines
Management of elevated Lipoprotein(a) (Lp(a)) levels should focus on aggressive control of other cardiovascular risk factors, with consideration of novel therapies targeting Lp(a) directly, such as antisense oligonucleotides, which have demonstrated an ability to lower plasma Lp(a) levels by up to 90% or more 1.
Key Considerations
- The first-line approach includes lifestyle modifications such as a heart-healthy diet low in saturated fats, regular physical activity, weight management, and smoking cessation.
- Statins are commonly prescribed to lower LDL cholesterol, though they don't significantly reduce Lp(a) levels.
- For patients with very high Lp(a) levels (>50 mg/dL or >125 nmol/L) and established cardiovascular disease or multiple risk factors, more aggressive LDL-lowering therapy may be warranted, including high-intensity statins (atorvastatin 40-80mg or rosuvastatin 20-40mg daily), ezetimibe (10mg daily), and possibly PCSK9 inhibitors (evolocumab 140mg every 2 weeks or alirocumab 75-150mg every 2 weeks) 1.
Emerging Therapies
- Novel therapies targeting Lp(a) directly, such as antisense oligonucleotides, are in clinical development and have shown promising results in reducing Lp(a) levels 1.
- Lipoprotein apheresis may be considered in extreme cases with recurrent cardiovascular events despite optimal therapy.
Rationale
- The rationale for management stems from Lp(a)'s role in promoting atherosclerosis, inflammation, and thrombosis, contributing to cardiovascular risk independently of other lipid parameters 1.
Important Notes
- 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.
- Lp(a) levels are mainly determined by genetic traits, and it is postulated that Lp(a) particles have pro-atherogenic and pro-thrombotic properties 1.
From the Research
Management of Elevated Lipoprotein(a) (Lp(a)) Levels
The management of elevated Lp(a) levels involves a combination of lipid-modifying therapies and other interventions.
- Reducing LDL-C to the lowest attainable value with a high-potency statin should be the primary focus of lipid-modifying therapies 2.
- If the Lp(a) level is 30 mg/dL or higher in a patient who has a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, recurrent cardiovascular events, or inadequate LDL-C responses to statins, the clinician may consider adding niacin (up to 2 g/d) 2.
- If, after these interventions, the patient has progressive coronary heart disease (CHD) or LDL-C levels of 160-200 mg/dL or higher, LDL apheresis should be contemplated 2.
- Emerging nucleic acid-based therapies, such as the antisense oligonucleotide pelacarsen and the small interfering RNA olpasiran, are generating interest because of their potent Lp(a)-lowering effects 3.
- PCSK9 inhibitors have been shown to lower Lp(a) levels, although the extent of the reduction may not be sufficient to achieve a cardiovascular benefit 4.
Identification of High-Risk Patients
High-risk patients who may benefit from Lp(a) screening include:
- Those with a personal or family history of premature cardiovascular disease 2, 5.
- Those with familial hypercholesterolemia 2.
- Those with recurrent cardiovascular events 2.
- Those with inadequate LDL-C responses to statins 2.
- Those with moderate elevations in LDL-C (135-159 mg/dL) and high Lp(a) levels 6.
Lp(a) Threshold Values
- An Lp(a) level of 30 mg/dL or higher may be considered high-risk 2.
- An Lp(a) level of 50 mg/dL or higher is noted by the European Atherosclerosis Society to confer increased cardiovascular risk 3.
- An Lp(a) level of 100 nmol/L or higher is associated with a high absolute risk of incident cardiovascular disease 6.