What is the clinical significance of elevated Lipoprotein(a) (Lp(a))?

From the Guidelines

Elevated lipoprotein(a), or Lp(a), is a significant independent risk factor for cardiovascular disease, particularly atherosclerosis, heart attacks, and strokes, and levels above 50 mg/dL (or 125 nmol/L) are generally considered elevated and concerning. The clinical significance of elevated Lp(a) lies in its dual harmful properties: it promotes cholesterol deposition in arterial walls like LDL cholesterol and has pro-thrombotic effects that increase blood clot formation 1.

Key Points

• Lp(a) levels are primarily determined by genetics and remain relatively stable throughout life, unaffected by diet or exercise 1.
• 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.
• Management of elevated Lp(a) focuses on aggressively controlling other cardiovascular risk factors, including using statins, maintaining optimal blood pressure, achieving good diabetes control if applicable, smoking cessation, and adopting a heart-healthy lifestyle 1.
• PCSK9 inhibitors (evolocumab, alirocumab) and niacin can modestly reduce Lp(a) levels, though they're not prescribed primarily for this purpose 1.
• Several promising therapies specifically targeting Lp(a) are in clinical trials, including antisense oligonucleotides 1.

Recommendations

• Patients with elevated Lp(a) should undergo more vigilant cardiovascular monitoring and may benefit from earlier, more aggressive preventive interventions 1.
• Lp(a) measurement is recommended in patients with premature CVD, premature stroke, and those who fall into an intermediate risk group when classical risk algorithms are used 1.
• Treatment with statins is recommended for older adults with established CVD in the same way as for younger patients 1.

Future Directions

• Further research is needed to understand the mechanisms of Lp(a) biology and to develop effective therapies for reducing Lp(a) levels and associated cardiovascular risk 1.
• Collaborative, patient-level meta-analysis should be performed to define the role of baseline and on-treatment Lp(a) and CVD risk in secondary prevention settings 1.

From the Research

Clinical Significance of Elevated Lipoprotein(a) (Lp(a))

Elevated Lipoprotein(a) (Lp(a)) is a causal genetic risk factor for cardiovascular disease 2, 3, 4, 5, 6. The clinical significance of elevated Lp(a) can be summarized as follows:

• Elevated Lp(a) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) and calcific aortic stenosis 2, 3, 4, 5, 6.
• The risk associated with elevated Lp(a) persists even in the presence of guideline-recommended LDL-C levels and adherence to lifestyle modifications 5.
• Lp(a) is the most prevalent inherited dyslipidemia and strongest genetic ASCVD risk factor 5.

Screening and Management of Elevated Lp(a)

The following points highlight the current recommendations for screening and management of elevated Lp(a):

• Candidates for Lp(a) screening include patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, recurrent cardiovascular events, or inadequate LDL cholesterol (LDL-C) responses to statins 2.
• 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 with residual LDL-C elevations despite maximum-potency statins or combination statin therapy, the clinician may consider adding niacin (up to 2 g/d) 2.
• Emerging therapies, including targeted apolipoprotein(a) [apo(a)]-lowering therapies, are in phase 3 clinical development and may provide new options for managing elevated Lp(a) 5, 6.

Therapeutic Options for Elevated Lp(a)

The current therapeutic options for elevated Lp(a) include:

• Statins, which lower LDL-C but may elevate Lp(a) levels 3.
• Proprotein convertase subtilisin/kexin-type 9 (PCSK9) inhibitors, which reduce plasma Lp(a) levels but have unknown mechanisms and clinical limitations 3.
• Lp(a) apheresis, which reduces plasma Lp(a) by approximately 20%-30% on average, but has limited clinical efficacy in reducing cardiovascular events 4.
• Novel apolipoprotein (a) [apo(a)] antisense oligonucleotide therapy, which has shown promise in decreasing plasma Lp(a) levels but requires further testing in clinical trials 4.