Summary
Lipoprotein(a) — Lp(a) — is a unique lipoprotein particle consisting of an LDL-like core attached to a glycoprotein called apolipoprotein(a). Lp(a) levels are 80–90% genetically determined and remain stable throughout life. Elevated Lp(a) is an independent, largely genetic cardiovascular risk factor that doubles the risk of heart attack and aortic stenosis — yet it is rarely tested in routine health checks.
Approximately 20% of the UK population have Lp(a) levels above 75 nmol/L — the threshold commonly used for elevated cardiovascular risk. At this prevalence, Lp(a) is one of the most common genetic cardiovascular risk factors, yet it remains underrecognised.
Lp(a) promotes cardiovascular disease through two mechanisms: (1) atherogenesis — the LDL core deposits in arterial walls; (2) thrombosis — apolipoprotein(a) competitively inhibits plasminogen activation, impairing fibrinolysis and promoting clot formation.
Unlike LDL, Lp(a) is minimally affected by diet, exercise, or standard statin therapy. Knowing your Lp(a) level identifies whether elevated cardiovascular risk requires more aggressive standard risk factor management (lower LDL targets, blood pressure control). Specific Lp(a)-lowering therapies (RNA-based, such as pelacarsen) are currently in advanced clinical trials.
What It Is
Lp(a) is an LDL-like particle in which ApoB-100 is covalently linked to apolipoprotein(a) [apo(a)] via a disulfide bond. Apo(a) is structurally homologous to plasminogen — sharing its kringle domains — but lacks plasminogen’s ability to convert to plasmin. By competing with plasminogen for fibrin binding, Lp(a) impairs fibrinolysis.
Lp(a) is measured in nmol/L (preferred, as it counts particles) or mg/dL (mass-based, less accurate due to variable apo(a) isoform sizes). The LPA gene at chromosome 6q26 determines Lp(a) levels — individuals inherit distinct levels from each parent. Dietary or lifestyle changes have minimal impact ( 125 nmol/L (> 50 mg/dL) are associated with approximately 3× the cardiovascular risk of lower levels.
Functions
Atherosclerosis promotion
The LDL-like core of Lp(a) deposits in arterial walls, contributing to plaque formation independently of standard LDL.
Thrombosis promotion
Apo(a)'s structural similarity to plasminogen allows Lp(a) to inhibit fibrinolysis — promoting clot formation on ruptured plaques.
Aortic stenosis risk
Lp(a) deposits in aortic valve leaflets, promoting the calcification that causes aortic stenosis — a cardiovascular risk distinct from coronary disease.
Genetic cardiovascular risk flag
Elevated Lp(a) identifies individuals who need more aggressive management of other cardiovascular risk factors to compensate for this largely unmodifiable risk.
Reference Ranges
Lipoprotein(a) — Lp(a)
Measured in nmol/L| Status | Range (nmol/L) | Range (mg/dL) | What it means |
|---|---|---|---|
| Low | < 75 | < 30 | Low Lp(a) — no significant additional Lp(a)-related cardiovascular risk. |
| Borderline | 75–125 | 30–50 | Moderately elevated — meaningful additional cardiovascular risk. Optimise all modifiable factors. |
| High | > 125 | > 50 | Elevated Lp(a) — approximately 3× cardiovascular risk increase. Aggressive risk factor management warranted. |
Lp(a) measurements in nmol/L and mg/dL are not interchangeable due to variable particle sizes between individuals. EAS recommends nmol/L as the preferred unit. Lp(a) is stable over time — testing once is sufficient for most people.
Symptoms of Imbalance
Elevated Lp(a) is completely asymptomatic — its consequences are cardiovascular events after decades of plaque accumulation.
- Low Lp(a) is normal and carries no additional risk.
- Elevated Lp(a) is entirely asymptomatic
- Long-term consequences: premature coronary artery disease, stroke, aortic stenosis
- Familial hypercholesterolaemia often co-exists with high Lp(a) — an additive risk combination
Causes of Imbalance
- Genetically low Lp(a) (LPA gene variants producing fewer apo(a) copies) — beneficial
- Genetic inheritance — 80–90% of Lp(a) level is genetically determined
- Smaller apo(a) isoforms (fewer kringle IV repeats) produce higher Lp(a) levels
- Post-menopausal oestrogen loss can raise Lp(a) by 10–20%
- Kidney disease — impaired Lp(a) clearance
- Hypothyroidism — may raise Lp(a)
FAQs
Lifestyle interventions (diet, exercise, weight loss) have minimal effect on Lp(a) — levels change by < 10% with most interventions. This is because Lp(a) production is primarily genetically determined. Niacin reduces Lp(a) by ~20–30% but did not reduce cardiovascular events in clinical trials. PCSK9 inhibitors reduce Lp(a) by ~25%. RNA-targeting therapies (pelacarsen, olpasiran) reduce Lp(a) by 80–90% and are currently in phase III cardiovascular outcome trials — they may become available in the next few years.
Since Lp(a) cannot be easily lowered currently, the strategy is to aggressively reduce all other modifiable cardiovascular risk factors: achieve a lower LDL target (< 1.8 mmol/L rather than the standard < 3.0), optimise blood pressure, stop smoking, control diabetes, and ensure regular exercise. Some cardiologists use high Lp(a) as a reason to start statin therapy at an earlier stage or to intensify treatment.
Lp(a) levels are genetically set and remain stable throughout adult life. Testing once is sufficient for most people. A single test identifies your genetically determined Lp(a) level, which does not need to be repeated unless there is a specific clinical reason (e.g. monitoring a Lp(a)-lowering therapy in a trial, or investigating an unexplained change in cardiovascular risk profile).
Yes, absolutely. If you have a first-degree relative with a heart attack or stroke before age 55 (men) or 65 (women), or if you have been diagnosed with familial hypercholesterolaemia, Lp(a) testing is strongly recommended. High Lp(a) is significantly more common in people with premature cardiovascular disease and those with FH — and identifies an additional treatable risk factor beyond LDL.
Lp(a) is measured in two ways: nmol/L (particle number, preferred) and mg/dL (mass). Because Lp(a) particles vary significantly in size between individuals (due to different apo(a) isoform lengths), the same mass concentration (mg/dL) can represent very different particle numbers in different people. nmol/L is the more accurate measure of true cardiovascular risk and is now recommended by the European Atherosclerosis Society as the preferred unit.
References
- Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69(6):692–711. View source
- Nordestgaard BG, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844–2853. View source
- EAS Consensus Panel. Lipoprotein(a): a genetically determined cardiovascular risk factor with expanding therapeutic possibilities. Eur Heart J. 2022;43(39):3925–3946. View source