Lipoprotein(a), often written as Lp(a), is a cholesterol-carrying particle in your blood that raises the risk of heart attack, stroke, and aortic valve disease. Unlike regular cholesterol, Lp(a) levels are almost entirely determined by your genes, not your diet or exercise habits. About one in five people has elevated levels, defined as greater than 50 mg/dL (or 125 nmol/L).
How Lp(a) Differs From Regular Cholesterol
You’re probably familiar with LDL cholesterol, the so-called “bad” cholesterol. Lp(a) is essentially an LDL particle with an extra protein attached to it. That extra protein, called apolipoprotein(a), is what makes Lp(a) uniquely dangerous. It gives the particle properties that standard LDL doesn’t have.
Lp(a) does everything LDL does: it deposits cholesterol directly into artery walls, where it builds up as plaque. But Lp(a) is actually more prone to oxidation than regular LDL. When oxidized, it gets gobbled up by immune cells called macrophages, which then turn into “foam cells,” the building blocks of atherosclerotic plaque. This process happens more aggressively with Lp(a) than with ordinary LDL particles.
Why Lp(a) Is a Triple Threat
Lp(a) causes damage through three distinct pathways, which is part of what makes it such a potent risk factor.
First, it accelerates plaque buildup in arteries. Beyond simply depositing cholesterol, elevated Lp(a) impairs the ability of blood vessels to relax and expand normally. It also triggers the release of inflammatory signals that recruit more immune cells to the artery wall and promote the growth of smooth muscle cells, thickening the vessel lining.
Second, Lp(a) promotes blood clots. The extra protein on Lp(a) closely resembles plasminogen, a molecule your body uses to dissolve clots. Lp(a) competes with plasminogen for binding spots on blood vessel cells, essentially blocking your body’s built-in clot-dissolving system. The result is that clots are more likely to form and less likely to break down on their own. It also promotes platelet clumping, which further increases clotting risk.
Third, Lp(a) drives inflammation. It’s associated with higher levels of several inflammatory molecules that damage blood vessel walls and accelerate the progression of heart disease.
The Link to Aortic Valve Disease
One risk that surprises many people: Lp(a) is an independent driver of calcific aortic stenosis, a condition where the heart’s aortic valve stiffens and narrows due to calcium deposits. In the large EPIC-Norfolk study, people with Lp(a) levels at or above 50 mg/dL had roughly double the risk of developing aortic stenosis compared to those with lower levels. People with the highest levels saw their valve disease progress about 1.5 times faster than those with the lowest levels, and they faced about twice the risk of needing valve replacement or dying from cardiac causes.
This connection is strong enough that genetic studies confirm it’s causal, not just a correlation. Certain gene variants that raise Lp(a) levels also independently increase aortic stenosis risk, which is powerful evidence that Lp(a) itself is doing the damage.
Genetics Control Your Levels
More than 90% of the variation in Lp(a) levels between people comes down to the LPA gene. That’s an unusually high degree of genetic control. Your diet, exercise routine, weight, age, and sex have minimal impact on where your Lp(a) sits. This is a sharp contrast to LDL cholesterol, which responds meaningfully to lifestyle changes. Lp(a) levels are essentially set by your DNA and remain relatively stable throughout your life.
This genetic determination is why major cardiology organizations now recommend that every adult have their Lp(a) measured at least once. Since your level doesn’t change much over time, a single test generally tells you what you need to know. The European Society of Cardiology, the Canadian Cardiovascular Society, and several other bodies recommend universal screening. The American College of Cardiology and American Heart Association take a more targeted approach, recommending testing for people at intermediate cardiovascular risk, those with a family history of early heart disease or elevated Lp(a), those with calcific aortic valve disease, or those whose LDL cholesterol doesn’t drop as expected on medication.
Why Standard Treatments Fall Short
Here’s the frustrating part: the most common cholesterol-lowering medications, statins, don’t reliably lower Lp(a). In fact, several studies and meta-analyses indicate that statins may slightly increase Lp(a) levels in some people. One study found that in people with a specific genetic variant affecting the size of the Lp(a) particle, statin therapy raised Lp(a) from a median of about 66 mg/dL to 97 mg/dL. Other studies show no significant change. The effect varies depending on individual genetics, but the takeaway is clear: statins are not a solution for high Lp(a).
This doesn’t mean statins are harmful for people with elevated Lp(a). Statins still lower LDL cholesterol effectively, and reducing LDL remains beneficial for overall cardiovascular risk. But they don’t address the Lp(a) piece of the puzzle.
New Therapies in Development
The good news is that several drugs specifically designed to lower Lp(a) are in advanced clinical trials. These work by targeting the liver’s production of the Lp(a) particle at the genetic level, either by blocking the messenger RNA that tells cells to make Lp(a) or by preventing the particle from assembling in the first place.
The furthest along is pelacarsen, currently in a large phase 3 trial called Lp(a) HORIZON that will determine whether lowering Lp(a) actually reduces heart attacks and strokes. Olpasiran is in a similar phase 3 outcomes trial for patients with Lp(a) levels above 200 nmol/L and high cardiovascular risk. Lepodisiran is another injectable option entering phase 3 testing. All three are given as periodic injections, similar to how some existing cholesterol drugs work.
An oral option, muvalaplin, has completed phase 2 testing. It works differently, preventing the Lp(a) particle from forming rather than reducing production of its components. Taken once daily as a pill, it could be a more convenient alternative if it proves effective in larger trials. Gene-editing approaches are also in early clinical testing, which could theoretically offer a one-time treatment.
None of these are available yet outside of clinical trials. The outcomes data, which will show whether lowering Lp(a) translates into fewer cardiovascular events, is expected in the coming years. Until then, people with high Lp(a) are generally advised to aggressively manage every other modifiable risk factor: keeping LDL cholesterol as low as possible, maintaining healthy blood pressure, not smoking, and staying physically active. These steps won’t budge your Lp(a) number, but they reduce the overall burden on your cardiovascular system.