Lipoprotein(a): The Hidden Genetic Risk for Heart Disease and What You Can Do

Most people know about LDL cholesterol - the so-called "bad" cholesterol - and how it clogs arteries. But there’s another cholesterol particle hiding in plain sight, quietly raising your risk of heart attack and stroke, even if your LDL is perfect. It’s called lipoprotein(a), or Lp(a). And unlike other cholesterol types, you can’t fix it with diet, exercise, or statins. It’s not your fault. It’s your genes.

What Is Lipoprotein(a), Really?

Lipoprotein(a) is a unique particle that looks like LDL cholesterol but carries an extra protein called apolipoprotein(a). This extra piece makes it dangerous. It doesn’t just deliver cholesterol to artery walls - it also sticks to damaged areas, promotes inflammation, and blocks your body’s natural ability to break down blood clots. Think of it as a double threat: it builds plaque and makes clots harder to dissolve.

It was discovered in 1963, but for decades, doctors didn’t test for it. Why? Because standard cholesterol panels don’t include it. You need a specific blood test - and your doctor has to order it. Most people never get tested unless they’ve had a heart event young, have a strong family history, or were diagnosed with familial hypercholesterolemia.

Here’s the kicker: about 1 in 5 people worldwide have elevated Lp(a) levels. That’s 20%. And for many, it’s the reason they had a heart attack at 45 - even if they never smoked, never ate fast food, and ran 5Ks every weekend.

Why Your Genes Are the Main Culprit

Your Lp(a) level is 70% to 90% determined by your DNA. More than any other heart risk factor - more than high blood pressure, diabetes, or obesity - it’s inherited. If one of your parents has high Lp(a), you have a 50% chance of inheriting it. It’s that simple.

The gene responsible is called LPA. Variations in this gene control how many "kringle IV" repeats you have. The fewer repeats, the higher your Lp(a) levels. This genetic quirk is one of the most powerful known drivers of heart disease risk in humans.

And unlike LDL, which can be lowered by lifestyle, Lp(a) barely budges. You can eat kale, run marathons, and meditate every day - your Lp(a) won’t drop much. That’s why so many people are confused when their doctor says, "Your cholesterol is fine," but they still had a heart attack.

What Levels Are Dangerous?

Not all Lp(a) is bad. But when levels go above 50 mg/dL (or 105 nmol/L), your risk of heart disease, stroke, and aortic valve stenosis starts climbing. At 90 mg/dL (190 nmol/L) or higher, your risk matches that of someone with familial hypercholesterolemia - a condition known to cause early heart disease.

There’s a formula to convert between units: Lp(a) in nmol/L = 2.18 × Lp(a) in mg/dL - 3.83. But most labs report in mg/dL. Ask your doctor which unit they use.

Levels between 130-391 mg/dL are especially concerning. These aren’t rare outliers. They’re common enough that the American College of Cardiology now says people with these levels have risk equivalent to inherited high cholesterol.

Who Should Get Tested?

Testing isn’t routine - but it should be. Experts like Dr. Gregory Schwartz from the University of Colorado recommend everyone get tested once in their lifetime. But if you fall into any of these groups, testing is non-negotiable:

• You’ve had a heart attack, stroke, or peripheral artery disease before age 55 (men) or 65 (women)
• You have a family history of early heart disease (parents, siblings, grandparents under 60)
• You’ve been diagnosed with familial hypercholesterolemia
• You have high LDL despite being on statins
• You have aortic valve stenosis - especially if you’re under 70

And if you’re Black, you’re more likely to have higher Lp(a) levels than white, Hispanic, or Asian populations. That doesn’t mean it’s more dangerous - just more common. The risk threshold is the same for everyone: higher level = higher risk.

How Lp(a) Damages Your Heart

Lp(a) doesn’t just sit there. It actively attacks your arteries in three ways:

1. Plaque Builder: Like LDL, it drops cholesterol into artery walls, forming fatty deposits.
2. Clot Promoter: Its kringle domains bind to fibrin - the protein that forms clots - making them bigger and harder to break down.
3. Anti-Fibrinolytic: It blocks your body’s natural clot-busting system, increasing the chance of a heart attack or stroke.

This is why people with high Lp(a) often have sudden, unexpected events - even if their other risk factors look good. It’s not about lifestyle. It’s about biology.

Current Treatments: What Works and What Doesn’t

Here’s the frustrating part: traditional heart meds barely touch Lp(a).

Statins - the go-to cholesterol drug - don’t lower Lp(a). In fact, they can raise it slightly. That’s why some people on statins still have heart attacks: their LDL is down, but Lp(a) is still high.

Niacin (vitamin B3) can reduce Lp(a) by 20-30%. But it causes flushing, liver damage, and high blood sugar. The benefits don’t outweigh the risks for most people.

PCSK9 inhibitors (like evolocumab) lower LDL by 60% and may reduce Lp(a) by 25-30%. They’re expensive and require injections, but for someone with both high LDL and high Lp(a), they’re a good option.

So what’s the future? A new class of drugs called antisense oligonucleotides (ASOs) is showing promise. Pelacarsen - the most advanced - cuts Lp(a) by up to 80% in trials. The big phase 3 trial, called Lp(a) HORIZON, is tracking whether lowering Lp(a) with pelacarsen reduces heart attacks and strokes in people with levels above 430 nmol/L (90 mg/dL). Results are expected in 2025.

If successful, this could be the first treatment ever approved specifically to target Lp(a). It wouldn’t replace statins or lifestyle - it would add to them.

What You Can Do Right Now

Even without a targeted drug, you’re not powerless. Here’s what actually helps:

• Lower your LDL. Since Lp(a) rides on LDL particles, the less LDL you have, the less Lp(a) you have circulating. Statins, ezetimibe, or PCSK9 inhibitors can help.
• Control blood pressure. High blood pressure damages arteries, giving Lp(a) more places to stick.
• Don’t smoke. Smoking increases inflammation and clotting - both of which Lp(a) exploits.
• Maintain a healthy weight. Obesity raises inflammation and worsens overall cardiovascular risk.
• Manage diabetes. High blood sugar damages blood vessels. If you have diabetes, tight control is critical.
• Ask your doctor about aspirin. Some experts suggest low-dose aspirin for high-risk Lp(a) patients to reduce clotting. But this isn’t for everyone - talk to your doctor.

And yes - diet and exercise won’t lower Lp(a), but they’ll lower your other risks. That’s still vital. Think of it like this: if Lp(a) is your genetic risk, everything else is the environmental risk. You can’t change your genes. But you can control the rest.

The Bigger Picture

Lp(a) has been ignored for too long. It’s not rare. It’s not mysterious. It’s not your fault. But it’s real - and it’s deadly.

Doctors are finally catching up. Guidelines from the American Heart Association, the American College of Cardiology, and the European Atherosclerosis Society now recommend testing. But until every doctor orders it, you have to be your own advocate.

If you’ve had early heart disease, or your family has, ask for an Lp(a) test. Don’t wait for symptoms. Don’t assume your normal cholesterol is enough. Ask for the specific test. Get the number. Know your risk.

And if you’re waiting for the new drugs? You don’t have to wait to act. Lower your LDL. Control your blood pressure. Stop smoking. Get moving. You’re not powerless. You just need to know what you’re fighting.