LPA Gene

What it determines

The LPA gene’s coding region contains a variable-number tandem repeat (kringle IV-2 domain) that strongly modulates the resulting protein’s size and plasma concentration. Fewer repeats produce shorter apo(a) and higher plasma Lp(a).

This explains ~90% of inter-individual Lp(a) variation. Plasma Lp(a) is essentially set at birth and stable over life.

Clinical implications

• Single lifetime Lp(a) measurement informs ASCVD risk forever.
• High Lp(a) (>~125 nmol/L or >50 mg/dL) ~20% adults.
• Independent CV risk factor; doesn’t respond to diet or statins.
• Drives accelerated calcific aortic stenosis.

Treatment landscape

• Approved: PCSK9 mAbs lower Lp(a) ~25%; lipoprotein apheresis for very severe cases.
• In trials: olpasiran (siRNA), pelacarsen (antisense oligonucleotide), muvalaplin (oral small molecule). Outcomes data expected later this decade.

Until Lp(a)-specific outcome trials read out, the standard response to elevated Lp(a) is aggressive control of every other modifiable risk factor — particularly apoB.

Family screening

LPA-high individuals often have multiple affected relatives. First- degree relative screening (one lifetime measurement each) is high-value.

Related entries

Lp(a), ApoB, PCSK9 inhibitors, Cardiovascular disease.