Lipoprotein(a): Genetic Cholesterol Risk and What You Can Do About It

Most people know about LDL and HDL cholesterol. But there’s another cholesterol particle hiding in plain sight-lipoprotein(a), or Lp(a)-that can silently raise your risk of a heart attack or stroke, even if your other numbers look fine. Unlike regular cholesterol, Lp(a) isn’t affected by diet or exercise. It’s not something you can fix with a salad or a run. It’s genetic. And if you have it, you might never know unless you ask for a specific blood test.

What Exactly Is Lipoprotein(a)?

Lipoprotein(a), or Lp(a), is a type of lipoprotein that carries cholesterol and fat through your bloodstream. It looks a lot like LDL-the "bad" cholesterol-but it has an extra protein attached called apolipoprotein(a). That extra piece makes it dangerous. It sticks to artery walls, helps build plaque, and blocks your body’s natural ability to break down blood clots. Think of it as a double threat: it clogs arteries and makes clots harder to dissolve.

It was first discovered in 1963, but for decades, doctors didn’t test for it. Even today, most routine cholesterol panels don’t include Lp(a). You have to specifically ask your doctor for it. That’s why so many people with high Lp(a) are caught off guard when they have a heart event with no warning signs.

Why It’s a Genetic Time Bomb

Your Lp(a) level is mostly set at birth-70% to 90% determined by your genes. The LPA gene controls how much of this protein your body makes. If one of your parents has high Lp(a), you have a 50% chance of inheriting it. It doesn’t skip generations. It doesn’t fade with age. It’s just there.

And it’s common. About 1 in 5 people worldwide have levels high enough to raise their risk of cardiovascular disease. That’s over 1.4 billion people. Yet most don’t know it. In fact, Lp(a) is the most common inherited cause of high cholesterol-related heart disease.

Some populations are more affected than others. Black individuals tend to have higher Lp(a) levels on average than white, Hispanic, or Asian populations. Women often see a rise in Lp(a) after menopause because estrogen, which helps keep levels down, drops. But no matter who you are, the rule is simple: higher Lp(a) = higher risk.

How High Is Too High?

There’s no single "normal" level, but experts agree on thresholds for concern:

• ≥ 50 mg/dL (or ≥ 125 nmol/L) = increased risk
• ≥ 90 mg/dL (or ≥ 190 nmol/L) = high risk
• ≥ 130 mg/dL (or ≥ 280 nmol/L) = risk equivalent to familial hypercholesterolemia

These numbers aren’t arbitrary. Studies show that people with Lp(a) above 90 mg/dL have the same heart attack risk as someone with inherited high cholesterol. And unlike LDL, which can be lowered with statins, Lp(a) doesn’t budge much with standard treatments.

Testing can be tricky because different labs use different methods. Some report in mg/dL, others in nmol/L. The conversion formula is roughly: nmol/L = 2.18 × mg/dL - 3.83. That’s why it’s important to know which unit your lab uses and to track your results over time using the same test.

What Conditions Does It Cause?

High Lp(a) doesn’t just raise your risk of heart disease-it drives multiple life-threatening conditions:

• Coronary artery disease: Plaque builds up faster in the arteries that feed your heart.
• Heart attack: The sticky nature of Lp(a) makes clots more likely to form and stick.
• Stroke: It can clog arteries in the brain, just like in the heart.
• Peripheral artery disease: Reduced blood flow to legs and arms.
• Aortic valve stenosis: Lp(a) contributes to calcium buildup on the heart’s main valve, making it stiff and narrow.

One study found that people with Lp(a) above 125 nmol/L had nearly twice the risk of needing a heart procedure or dying from heart disease compared to those with low levels-even after adjusting for other risk factors.

Why Statins Don’t Help (And Might Make It Worse)

This is where things get frustrating. If you’re told your cholesterol is high, your doctor will likely prescribe a statin. But statins barely touch Lp(a). In fact, some people see their Lp(a) levels go up slightly when they start taking them.

Niacin (vitamin B3) can lower Lp(a) by 20-30%, but it causes flushing, liver problems, and high blood sugar. Most doctors won’t recommend it unless there’s no other option.

PCSK9 inhibitors, powerful injectable drugs used for severe cholesterol, can lower Lp(a) by about 25-30%. That’s helpful-but not enough for people with very high levels. And they’re expensive.

Right now, lifestyle changes-eating well, exercising, quitting smoking-don’t reduce Lp(a). But they still matter. Lowering your overall cardiovascular risk by controlling blood pressure, managing diabetes, and avoiding tobacco can help offset the danger from Lp(a). Think of it like wearing a seatbelt: you can’t change the fact that you’re driving fast, but you can reduce the damage if something goes wrong.

The New Hope: Drugs That Actually Lower Lp(a)

There’s real excitement in cardiology right now. A new class of drugs called antisense oligonucleotides (ASOs) is showing dramatic results. One drug, called pelacarsen, has been shown in early trials to reduce Lp(a) by up to 80%.

The big news? A phase 3 trial called the Lp(a) HORIZON Outcomes Trial is currently underway. It’s testing whether lowering Lp(a) with pelacarsen actually prevents heart attacks, strokes, and death in high-risk patients. Results are expected in 2025. If the trial succeeds, this could be the first treatment ever approved specifically to target Lp(a).

Other drugs in development include small interfering RNA (siRNA) therapies like olpasiran, which also show promise in early studies. These aren’t available yet, but they’re coming fast.

Who Should Get Tested?

Because Lp(a) is genetic and dangerous, testing isn’t just for people with heart disease-it’s for prevention. Experts now recommend screening for:

• Anyone with a family history of early heart disease (before age 55 in men, 65 in women)
• Anyone diagnosed with familial hypercholesterolemia
• People who’ve had a heart attack or stroke with no clear cause
• Those with aortic valve stenosis
• Anyone with a strong family history of high Lp(a)

Even if you feel fine, if you have any of these risk factors, ask your doctor for an Lp(a) test. It’s a simple blood draw. No fasting required. And one test gives you a lifetime of insight.

What to Do If You Have High Lp(a)

If your test comes back high, don’t panic. You’re not doomed. But you do need a plan:

1. Confirm the result: Get tested again. Levels can vary slightly between tests.
2. Check your family: Tell your siblings and children. They should get tested too.
3. Lower your other risks: Control blood pressure, keep LDL cholesterol low (aim for under 70 mg/dL if you’re high risk), manage diabetes, don’t smoke.
4. Consider a statin: Even if it doesn’t lower Lp(a), it helps with overall plaque buildup.
5. Ask about PCSK9 inhibitors: If your LDL is still high despite statins, these can help reduce total risk.
6. Stay informed: Watch for updates on pelacarsen and other Lp(a)-targeting drugs. They may be available within the next few years.

There’s no magic pill yet-but there’s a clear path forward. The goal isn’t to eliminate Lp(a). It’s to reduce your overall risk so much that Lp(a) doesn’t decide your future.

The Bottom Line

Lp(a) isn’t your fault. You didn’t eat too much butter. You didn’t skip the gym. You were just born with it. But now that we know it’s out there, ignoring it is no longer an option. It’s not a "maybe" risk. It’s a confirmed, genetic, independent driver of heart disease.

Testing for Lp(a) is simple. Knowing your level gives you power. And with new drugs on the horizon, the future for people with high Lp(a) is finally looking brighter.

If you’ve had early heart disease, a stroke with no clear cause, or a family history of sudden cardiac events-ask your doctor for an Lp(a) test. Don’t wait for a crisis. Get the facts. Take control.

Next Steps

If you’re over 40 and have a family history of early heart disease, ask your doctor for an Lp(a) test today. If you’ve already been diagnosed with high Lp(a), work with your cardiologist to build a risk-reduction plan. Focus on keeping your LDL low, your blood pressure under control, and your lifestyle healthy.

And keep an eye on 2025. That’s when we might get the first treatment that actually targets Lp(a)-not just the symptoms, but the root cause. This isn’t just science fiction anymore. It’s coming.