What Lp(a) is
Lipoprotein(a), pronounced "L-P-little-a", is a particle similar to LDL but with an additional protein called apolipoprotein(a) attached. The (a) protein has structural similarity to plasminogen (a protein involved in clot dissolution) and may interfere with normal clot biology. The particle is independently atherogenic and pro-thrombotic.
Why it's genetic
Lp(a) levels are about 90% determined by genetic variation in the LPA gene. Lifestyle changes that move LDL, diet, exercise, weight loss, barely move Lp(a). Statins don't lower it (and may slightly raise it). The level you have at age 25 is largely the level you'll have at age 65.
Risk elevation
Elevated Lp(a) (typically defined as >50 mg/dL or >125 nmol/L) substantially raises:
- Cardiovascular disease risk (1.5-2× increase)
- Aortic valve calcification and stenosis
- Atherothrombotic stroke (specific subtype)
- Heart attack at younger ages
- Cardiovascular events in patients with familial hypercholesterolemia (synergistic)
How common it is
Roughly 20% of the global population has elevated Lp(a). Prevalence varies by ancestry, higher in African ancestry, lower in East Asian. Most affected adults have never been tested.
Testing approach
- Test at least once in adulthood
- If normal, repeat testing not generally needed (level is stable)
- If elevated, intensify cardiovascular prevention
- Test in mass units (mg/dL) or molar units (nmol/L), the relationship between them isn't 1:1; nmol is preferred
- Ask for Lp(a) specifically, it's not on standard lipid panels
Interpreting results
- <30 mg/dL or <75 nmol/L: low
- 30-50 mg/dL or 75-125 nmol/L: moderate
- >50 mg/dL or >125 nmol/L: elevated
- >125 mg/dL or >300 nmol/L: very high
Treatment options
Currently:
- Aggressive control of all other cardiovascular risk factors (Lp(a) compounds them)
- Statins to lower LDL/ApoB
- PCSK9 inhibitors lower Lp(a) ~25%
- Niacin lowers Lp(a) ~30% (less commonly used due to other concerns)
- Apheresis for very high levels with established CVD (rare)
Emerging therapies (siRNA-based, antisense oligonucleotides) targeting Lp(a) specifically are in trials and may produce 80-90% reductions. Approval expected within years.
The clinical pearl: Test Lp(a) at least once. If elevated, you'll know to be more aggressive about every other modifiable risk factor, and to monitor for emerging Lp(a)-specific therapies.
Bottom line
Lp(a) is the most common inherited cardiovascular risk factor. Levels are genetic and stable. Standard panels don't include it; specific testing required. Elevated Lp(a) warrants aggressive risk factor control and consideration of PCSK9 inhibitors. Targeted therapies emerging.