Lipoprotein(a) and Cardiovascular Health

Introduction to Lipoprotein(a)

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, 2

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

Lp(a) levels in the atherothrombotic range are generally accepted as >30–50 mg/dL or >75–125 nmol/L 1, 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, 4

The American College of Cardiology recommends Lp(a) measurement in patients with premature cardiovascular disease 5, 6
The 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) 6
The Canadian Cardiovascular Society Guidelines use a cutoff of Lp(a) >30 mg/dL to define abnormal levels 7

No ICD-10 code exists for the diagnosis of elevated Lp(a) levels in the United States, limiting documentation and research 5
Limited therapeutic options specifically targeting Lp(a) are currently available 7
Relying solely on LDL-C levels for cardiovascular risk assessment without considering Lp(a) may underestimate total risk in affected individuals 1
Failure to measure Lp(a) in patients with premature or recurrent cardiovascular events despite optimal therapy may miss an important modifiable risk factor 6