Lipoprotein(a)
The inherited cardiovascular risk most people have never heard of — unaffected by statins or diet
Lp(a) is 90% genetically determined. Statins don't lower it. Diet barely touches it. About 1 in 5 people carry levels high enough to significantly increase their lifetime heart attack risk — and most have never been tested.
Lipoprotein(a) is an LDL particle with apolipoprotein(a) covalently bound to apoB-100. The apo(a) component has structural homology to plasminogen — allowing Lp(a) to both deposit in arterial walls and inhibit fibrinolysis, creating dual atherogenic and prothrombotic mechanisms. Its plasma level is 80–90% genetically determined by the LPA gene — largely resistant to lifestyle and most current medications, yet 1 in 5 people carry significantly elevated levels.
Reference Ranges
How clinicians interpret Lipoprotein(a) — Lp(a) results — from optimal to concerning.
⚠ Reference ranges vary by laboratory and assay. Always interpret your result in context of your laboratory's own reference intervals and your clinical presentation.
What raises Lipoprotein(a) — Lp(a)
Smaller apo(a) isoforms (fewer KIV-2 repeats) produce more Lp(a). This is largely immutable — explains familial CVD risk.
TSH elevation upregulates hepatic Lp(a) synthesis — treating hypothyroidism can reduce Lp(a) by 15–30%.
Oestrogen suppresses Lp(a) synthesis — levels rise 10–15% after menopause.
Urinary protein loss triggers compensatory hepatic lipoprotein synthesis — Lp(a) rises with declining GFR.
What lowers Lipoprotein(a) — Lp(a)
Evolocumab and alirocumab reduce Lp(a) as a secondary effect alongside primary LDL lowering.
siRNA targeting LPA gene expression — reduces Lp(a) by 70–100%. Phase 3 outcome trials ongoing.
LDL apheresis with Lp(a) filtration — used in severely elevated Lp(a) with recurrent events.
Important: statins do not lower Lp(a) and may modestly raise it. High Lp(a) does not respond to statin intensification.
Conditions this biomarker signals
When Lipoprotein(a) — Lp(a) is outside normal range, these are the most clinically significant possibilities.
Found in 25–40% of patients with premature MI/stroke (< 55 men, < 65 women). Key screening target.
Lp(a) independently accelerates aortic valve calcification — a modifiable risk factor for AVS progression.
Co-existing elevated Lp(a) doubles the already high FH cardiovascular risk — Lp(a) testing is recommended in all FH patients.
Which tests measure this biomarker
Lipoprotein(a) — Lp(a) may be included in or ordered alongside these panels.
One lifetime measurement is sufficient — Lp(a) is genetically stable. Report in nmol/L where possible.
Why Lp(a) is more dangerous than LDL alone
Lp(a) damages arteries through two distinct mechanisms. Like LDL, it enters arterial walls and oxidises — contributing to atherosclerotic plaque. Uniquely, its apo(a) component has 75–95% sequence homology with plasminogen — allowing it to competitively inhibit plasminogen binding to fibrin, impairing thrombolysis and promoting thrombosis. Olpasiran (siRNA targeting LPA), currently in Phase 3 trials (OCEAN(a)-OUTCOMES), reduces Lp(a) by 70–100% — the first therapy that may truly address this inherited risk in 1.4 billion people worldwide.
20% of the population have elevated Lp(a)
Lp(a) > 50 mg/dL affects approximately 20% of the global population — ~1.4 billion people. Levels are significantly higher in people of African descent (median ~30 mg/dL) than European (~10 mg/dL) populations, with similar cardiovascular risk implications across ethnicities.
RNA interference may finally tame Lp(a)
Olpasiran, an siRNA therapy targeting LPA gene expression, reduces Lp(a) by 70–100% in Phase 2 trials. If OCEAN(a)-OUTCOMES confirms CV benefit, this will transform management of elevated Lp(a) — which until now has had no effective pharmacological treatment.
nmol/L is more accurate than mg/dL for Lp(a)
Lp(a) particle size varies between individuals (different KIV-2 repeat counts) — making mg/dL measurements inconsistent. nmol/L measures particle number directly and is a more precise risk metric. 75 nmol/L corresponds approximately to 30 mg/dL but the conversion varies per individual.
Clinical use — when and why this is ordered
How clinicians use Lipoprotein(a) — Lp(a) in practice — the real-world scenarios where it changes decisions.
Premature CVD workup
Screen when MI or stroke < 55y (men) / < 65y (women), or family history of premature CVD. One-time test — results are lifelong.
Borderline ASCVD risk reclassification
In patients with 10-year ASCVD risk 5–20%, Lp(a) > 50 mg/dL upgrades risk and supports earlier statin initiation.
FH patients — always test
All FH patients should have Lp(a) measured — co-existing high Lp(a) may prompt earlier PCSK9 inhibitor use.
Recurrent events on maximal statin therapy
Recurrent MI/ACS despite LDL < 70 mg/dL: test Lp(a) — a commonly missed residual risk factor.