What does Lpa (Lipoprotein(a)) mean in terms of cardiovascular health?

Lipoprotein(a) and Cardiovascular Health

Lipoprotein(a) [Lp(a)] is a causal mediator of cardiovascular disease (CVD) and calcific aortic valve disease (CAVD), with elevated levels significantly increasing risk of myocardial infarction, stroke, peripheral arterial disease, heart failure, and aortic stenosis. 1

Structure and Prevalence

• Lp(a) is composed of an apolipoprotein B (apoB)-containing low-density lipoprotein (LDL)-like particle covalently linked to the plasminogen-like glycoprotein apolipoprotein(a) (apo(a)) 1
• Circulating plasma Lp(a) levels are primarily determined by the LPA gene locus encoding apo(a), with some influence from the APOE locus and PCSK9 R46L loss of function mutations 1
• Elevated Lp(a) levels affect approximately 20-30% of the global population, representing more than one billion people worldwide 1, 2

Clinical Significance in Cardiovascular Disease

• Lp(a) levels in the atherothrombotic range are generally accepted as >30–50 mg/dL or >75–125 nmol/L 1
• Pathophysiological mechanisms of Lp(a)-mediated cardiovascular damage include:
  • Induction of vascular inflammation 2
  • Promotion of atherogenesis 2, 3
  • Vascular calcification 2
  • Enhanced thrombosis 2, 3
• Evidence from randomized statin and PCSK9 inhibitor trials shows that when Lp(a) is elevated, cardiovascular event rates are higher at any achieved LDL-C level, indicating unaddressed Lp(a)-mediated risk 1

When to Measure Lp(a)

According to guidelines, Lp(a) measurement should be considered in:

• Patients with premature cardiovascular disease 1
• Patients with familial hypercholesterolemia (FH) 1
• Individuals with family history of premature CVD or family history of elevated Lp(a) 1
• Patients with recurrent CVD despite optimal lipid-lowering therapy 1
• Patients with ≥5% 10-year risk of fatal CVD according to the SCORE algorithm 1

Risk Thresholds

• European Society of Cardiology/European Atherosclerosis Society suggests significant risk when Lp(a) levels are >80th percentile, or >50 mg/dL (~100–125 nmol/L) 1
• Canadian Cardiovascular Society Guidelines use a cutoff of Lp(a) >30 mg/dL to define abnormal levels 1
• Risk thresholds in primary care populations are generally >20–30 mg/dL 1

Clinical Challenges

• Lack of standardization in Lp(a) measurement with values reported as either molar (nmol/L) or mass concentrations (mg/dL) by different assays 4
• No ICD-10 code exists for the diagnosis of elevated Lp(a) levels in the United States, limiting documentation and research 1
• Conventional therapies like lifestyle modification and statin therapy are ineffective at lowering Lp(a) 5
• Limited therapeutic options specifically targeting Lp(a) are currently available 1, 5

Management Considerations

• Aggressive management of other modifiable cardiovascular risk factors is essential in patients with elevated Lp(a) 4
• PCSK9 inhibitors provide modest Lp(a) reduction and may be considered in high-risk patients 4, 5
• Emerging nucleic acid-based therapies (antisense oligonucleotides like pelacarsen and small interfering RNA like olpasiran) show promise for potent Lp(a) reduction 2, 5
• For patients with progressive coronary heart disease despite maximum statin therapy and very high LDL-C levels, LDL apheresis may be considered 6

Important Clinical Pitfalls

• Relying solely on LDL-C levels for cardiovascular risk assessment without considering Lp(a) may underestimate total risk in affected individuals 1, 2
• Failure to measure Lp(a) in patients with premature or recurrent cardiovascular events despite optimal therapy may miss an important modifiable risk factor 1, 4
• Assuming that statin therapy adequately addresses Lp(a)-related risk is incorrect, as statins do not effectively lower Lp(a) 5
• Using non-standardized Lp(a) assays may lead to inconsistent risk assessment 4