Lipoprotein(a) — Lp(a)

What it is

Lp(a) consists of an LDL-like particle with an additional apolipoprotein(a) attached. Its plasma concentration is ~90% genetically determined by the LPA gene and stays roughly stable over the lifespan.

Why it matters

• Independent risk factor for atherosclerotic cardiovascular disease and calcific aortic stenosis.
• Approximately 20% of adults have clinically elevated levels (>~125 nmol/L or >50 mg/dL).
• Levels do not respond meaningfully to diet, exercise, or statins.
• Statins may modestly increase Lp(a) in some individuals while reducing overall cardiovascular risk.

Testing

A single lifetime measurement is usually sufficient (since it is genetically determined and largely stable). Test in:

• Family history of premature ASCVD.
• Established ASCVD.
• Recurrent events on standard therapy.
• Calcific aortic stenosis.

What lowers Lp(a)

• Currently approved: PCSK9 inhibitors (~25% reduction), niacin (rarely used due to side effects), lipoprotein apheresis (rare).
• In trials: olpasiran, pelacarsen, muvalaplin — antisense and small molecule agents that dramatically reduce Lp(a). Outcome trials (e.g. HORIZON) pending.

Until outcome trials read out, the standard response to high Lp(a) is aggressive control of every other modifiable risk factor.

Related entries

ApoB, Statins, Cardiovascular disease.