Lipoprotein (a): Causes, Testing, and Management

• Lp(a) is not LDL: It’s an LDL-like particle with an extra apolipoprotein(a), making it more harmful and genetically determined.
• Unlike regular bad cholesterol, Lp(a) levels stay high despite diet, exercise, or most medications.
• High Lp(a) = higher risk: Elevated levels increase risk of heart attack, stroke, and aortic valve disease, even with normal LDL.
• Treatment is evolving: Lifestyle changes don’t lower Lp(a), but new drugs like siRNA and oral agents show 70–95% reductions.

Lipoprotein(a) or Lp(a) (pronounced "L-P-little-a") is a type of cholesterol in your blood that's largely determined by your genes. About 1 in 4 people worldwide have high levels, which can greatly increase the chances of heart attacks, strokes, and problems with the aortic valve in the heart.

Unlike regular "bad" cholesterol (LDL), high Lp(a) doesn't improve much with healthy eating, exercise, or most cholesterol medicines. That's why it's often called a "residual risk", meaning it can still cause trouble even if your other cholesterol numbers look good.

How Is Lp(a) Different from Regular Cholesterol?

Lp(a) looks a lot like LDL cholesterol, but it has an extra protein called apolipoprotein(a) attached. This extra part makes Lp(a) "stickier," making the particle more dangerous than regular LDL.

• It is more likely to get trapped in your artery walls, leading to plaque buildup (atherosclerosis).
• Its structure mimics proteins involved in blood clotting, meaning it can interfere with your body’s ability to dissolve clots, increasing the risk of a sudden blockage.
• Pro-inflammatory: It carries oxidized phospholipids that irritate the lining of your blood vessels, accelerating the "hardening" of the arteries.
• Over 90% of Lp(a) variation is determined by the LPA gene. Levels are stable lifelong and minimally influenced by lifestyle.

Why Isn't Lp(a) Routinely Tested?

Standard lipid panels measure total cholesterol, LDL-C, HDL-C, and triglycerides, but not Lp(a). A separate blood test is required. Experts suggest testing if you have:

• Family history of "premature" heart disease (heart attacks or strokes before age 55 in men or 65 in women)
• Very high cholesterol that runs in the family
• LDL that stays high despite treatment
• Other strong risks for heart issues

A "high" level is usually above 50 mg/dL or 125 nmol/L (doctors prefer the nmol/L unit because it's more accurate). Anything over that raises your risk, and very high levels mean even more danger.

Since Lp(a) comes from your genes (mainly the LPA gene), it often runs in families. If one person has it high, checking relatives makes sense.

What Can You Do If Your Lp(a) Is High?

Right now, there are no medicines approved just for lowering Lp(a). But you can still lower your overall heart risk by focusing on everything else:

• Eat a heart-healthy diet (lots of fruits, veggies, whole grains, lean proteins)
• Get regular exercise
• Maintain a healthy weight
• Quit smoking if you do
• Control blood pressure, blood sugar, and other cholesterol

Some common medicines help indirectly:

• Statins, ezetimibe, and others to drop LDL as low as possible
• PCSK9 inhibitors can lower Lp(a) by 20-30% as a side benefit
• Low-dose aspirin might be suggested in some high-risk cases to thin the blood

Exciting New Treatments on the Way

siRNA Drugs (e.g., Lepodisiran)

Recent Phase II trials have shown astounding results:

• A single 400 mg dose reduced Lp(a) by ~94% at 6 months
• Levels remained ~89% lower at one year after one dose, and ~95% after two doses. Well-tolerated with mild injection-site reactions in ~10%, but no serious adverse events. A Phase III cardiovascular outcomes trial (ALPACA/ACCLAIM-Lp(a)) is underway.

Oral Pills (e.g., Muvalaplin)

• Phase II data show 70–85% Lp(a) reduction after 12 weeks, depending on dose.
• Represents a first-in-class oral option that disrupts apo(a) binding to apoB.

What This Means for You

If your Lp(a) is high, work with your doctor to:

• Lower LDL aggressively
• Manage other cardiovascular risk factors like blood pressure and smoking
• Consider new therapies or clinical trials if your Lp(a) remains elevated

For most people, routine screening isn't necessary, but testing can be crucial for those with personal or family heart risk where Lp(a) may be a hidden driver.