Lipoprotein(a)
Lipoprotein(a), or Lp(a), is an inherited cholesterol-carrying particle that about one person in five has enough of to add substantially to their risk of heart attack, stroke and narrowing of the aortic valve. Its level is set almost entirely by your genes, and statins don't lower it. Experimental drugs that cut it by 70% or more are in trials, but the first one tested for outcomes did not prevent heart attacks or strokes, so no treatment for it has been shown to work yet.
Have Lp(a) measured once in your life. If it is high, no drug is approved to lower it, so control everything else harder, starting with LDL cholesterol, and get your parents, siblings and children tested.
What it is and what it does
Lp(a) is an LDL-like (low-density lipoprotein) particle with one extra feature: a tail of a protein called apolipoprotein(a), which is structurally similar to plasminogen, a clot-dissolving protein. Like LDL, it carries one molecule of apolipoprotein B (apoB) and builds plaque; it also carries oxidised fats that promote inflammation. Because of its resemblance to plasminogen, Lp(a) has long been suspected of promoting clots as well, but the European Atherosclerosis Society judges that role unproven in people.[1]
It raises the risk of both coronary disease and calcific aortic valve stenosis, a narrowing of the main valve out of the heart. In people aged 45–54, aortic stenosis was about three times as common when Lp(a) was in the top fifth.[2]
How much risk it adds
About 20% of people — roughly 1.4 billion worldwide — carry enough Lp(a) to add substantially to their cardiovascular risk.[3] At 125 nmol/L (50 mg/dL), a level about one person in five reaches, risk is about 1.4 times that of someone with a typical level; at 250 nmol/L (100 mg/dL) it is about double. At about 430 nmol/L (180 mg/dL), seen in about 1 in 100 people, risk is about four times that of a typical level, similar to the inherited cholesterol disorder familial hypercholesterolaemia.[4] That means someone with a high value carries more risk than their LDL cholesterol and apoB alone suggest, which is why the 2026 US cholesterol guideline (from the American College of Cardiology and American Heart Association) now recommends that every adult have it measured at least once.
Set by your genes, barely moved by anything else
More than 90% of your Lp(a) level is inherited. Adult levels are usually reached by about age 5 and then stay fairly stable, although they tend to rise in women at menopause. So one test is enough. Lifestyle barely moves it: diet changes shift Lp(a) by about 10–15% at most, in either direction, and exercise has little or no effect.[5]
Standard cholesterol drugs don't help much either:
- Statins don't lower it and may raise it modestly in some people, but the average rise is small — about 1 mg/dL compared with placebo — and no reason to stop a statin.[6]
- Ezetimibe and bempedoic acid have no effect.[7]
- PCSK9 (proprotein convertase subtilisin/kexin type 9) antibodies, injected drugs that make the liver clear more LDL, lower it by roughly 15–30%. Filtering it out of the blood (lipoprotein apheresis) also lowers it but is resource-intensive.[8]
In a large trial of the PCSK9 antibody evolocumab in people with established cardiovascular disease, the drug cut coronary events by about 23% when Lp(a) was above the median, against a non-significant 7% when it was lower — 2.49 against 0.95 fewer events per 100 patients over 3 years.[9] Because that is a subgroup finding, it cannot show whether the extra benefit came from lowering Lp(a) or LDL cholesterol.
The first Lp(a) drug failed its outcome trial
A class of drugs built to block Lp(a) production — most by silencing its gene's messenger RNA in the liver, one by stopping the particle from forming — has been or is being tested in large outcome trials:
| Drug | How it's given | Lp(a) lowering in early trials | Outcome trial |
|---|---|---|---|
| Pelacarsen | Monthly injection | About 72% at a monthly dose[10] | Missed its main goal (topline results, September 2026) |
| Olpasiran | Injection every 12 weeks | More than 95% at doses of 75 mg and above[11] | Expected to finish 2028[12] |
| Lepodisiran | Injection once or twice a year | About 94%, averaged over a year at the highest dose[13] | Expected to finish 2029[14] |
| Muvalaplin | Daily pill | Up to about 86%, or about 70% by a different lab method, at 12 weeks[15] | Expected to finish 2031[16] |
The pelacarsen trial gave 80 mg monthly injections or placebo to 8,323 people with established cardiovascular disease and an Lp(a) of at least 70 mg/dL, on top of their usual cholesterol treatment. It was the first outcome trial of any Lp(a)-lowering drug. Topline results in September 2026 showed that pelacarsen lowered Lp(a) but did not significantly reduce the combined rate of cardiovascular death, heart attack, stroke and urgent procedures to restore blood flow to the heart (stents or bypass) — either in everyone enrolled or in the prespecified group with Lp(a) of 90 mg/dL or more.[17] No effect sizes or event rates have been released; the full data are still to come.
So no trial has yet shown that lowering Lp(a) prevents heart attacks or strokes, and no drug is approved for it. Whether the other drugs can do better is the question for the trials still running. Lp(a) remains an independent risk factor, and a high value is still worth knowing because it is a reason to control everything else harder.[18]
What to do
- Test once. It is cheap and the result is stable; add it to the midlife lab panel.
- If it is high, treat everything else harder. The National Lipid Association advises earlier and more intensive control of the other risk factors — chiefly lowering LDL cholesterol with lifestyle change and, when overall risk is high, cholesterol-lowering drugs — plus Lp(a) testing of parents, siblings and children.[19]
- With cardiovascular disease and LDL cholesterol above goal on the highest statin dose you tolerate, the 2026 US guideline specifically recommends adding a PCSK9 antibody.[20]
- Don't chase Lp(a) with diet. Nothing you eat moves it much; the levers that matter are the ones in Lipid management.
Further reading
- Kronenberg F et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J 2022.[21]
- Lp(a)HORIZON topline results — pelacarsen did not meet its primary endpoint (Novartis, September 2026).[22]
- Blumenthal RS et al. 2026 ACC/AHA/Multisociety guideline on the management of dyslipidemia. J Am Coll Cardiol 2026;87:2624.[23]