Season 1 Episode 8: Lipoprotein (a)

LDL may get all the blame — but there’s a darker twin hiding in the shadows.
Same cholesterol core. Same ApoB backbone.
But with one sinister twist: a sticky tail called apolipoprotein(a).
That extra piece transforms an ordinary LDL particle into something far more dangerous. 

Meet Lipoprotein(a) — or Lp(a) — one of the strongest, most under-recognized genetic drivers of premature cardiovascular disease.
It’s pro-atherogenic, pro-thrombotic, and pro-inflammatory — a triple threat that can quietly turn even the healthiest-looking lipid panel into a ticking time bomb. 

In this episode of LipidCurious, we’ll uncover 

1.    What is Lp(a)? 

2.    How and when to test for it? 

3.    What to do when Lp(a) is high?

We’ll walk through genetics, testing strategy, and real-world management — plus a glimpse into the promising therapies now in late-phase trials.
By the end, you’ll understand why Lp(a) is the ghost in the lipid story — invisible on a standard panel, but capable of haunting even the fittest hearts. 

Bonus: For the full collection of visuals across episodes, visit the Podcast page.

Download the Free LipidCurious Starter Kit here

Questions or feedback? Reach out at hello@lipidcurious.com 

Disclaimer: This podcast is for educational purposes only. It is NOT medical advice.

Transcript

SEASON 1 EPISODE 8: Lipoprotein (a)

In the spirit of spooky season — let’s talk about one of the scariest things in lipidology: lipoprotein(a).
 Totally unplanned that we’re doing this on Halloween, but honestly… kind of perfect.

Most people don’t even know it exists.
 And yet, it’s the hidden culprit behind stories like this:
 A healthy, non-smoking, 45-year-old marathoner ends up in the cath lab with severe coronary disease.
 Everything else looked fine — except Lp(a).

So this Halloween, when you think of scary things, remember: sometimes the most dangerous things are the ones you can’t see on a standard lipid panel.

Here’s what we’ll unpack today:

1.    What is Lp(a)?

2.    How and when to test for it.

3.    What to do when Lp(a) is high.

You’ll find a bonus visual handout in the show notes, and if you want everything in one place you can check out www.lipidcurious.com. There you’ll find the full visual set for Season 1 plus the free Starter Kit: a collection of practical clinical guides, cheat sheets, and quick references you can actually use in your clinical practice.

And a quick reminder — this podcast is for educational purposes only and not medical advice.

Let’s get started.

What is Lp(a)?

Lp(a) — or lipoprotein(a) — is one of the most potent independent risk factors for heart attack, stroke, aortic valve disease, and overall cardiovascular mortality.

I like to think of it as the evil twin of LDL.
 It has the same cholesterol core and ApoB-100 backbone — but with one sinister twist: a tail called apolipoprotein(a) attached to ApoB by a single bond.

Picture a tennis ball with a slinky or a spring coil hanging off it.
 That extra coil completely changes the story, giving Lp(a) a set of powers that make it far more dangerous.

Apo(a) is a sticky, rope-like structure with repeating loops called kringles.
Here’s the key part: one of those kringle sections (kringle IV type 2) varies from person to person. And it is what makes your Lp(a) level unique.
Some people have just a few repeats, others have forty — and the fewer you have, the higher your Lp(a) tends to be.

More kringle repeats make the protein bulkier, and your liver produces less of it.
 Same gene, different expression — like identical twins of different heights.

And it gets worse. Apo(a) evolved from plasminogen, the protein that dissolves blood clots.
 Because it still looks like plasminogen, it competes with it — blocking normal clot breakdown.
 That’s why Lp(a) is pro-thrombotic. 

So in one particle, you get the worst of all worlds:

1.     The LDL-like core drives plaque formation — pro-atherogenic.

2.     The plasminogen mimicry blocks clot dissolution — pro-thrombotic.

3.     And it carries oxidized phospholipids that trigger inflammation and plaque instability.

Pro-atherogenic. Pro-thrombotic. Pro-inflammatory.
 A triple threat — as terrifying as anything you’ll see this Halloween.

All this is coded right into your DNA.
 The LPA gene on chromosome 6 decides how much Lp(a) your liver makes.

Each person inherits one copy from each parent — both expressed in an autosomal codominant pattern.
 If even one parent carries a high-output variant, your Lp(a) can skyrocket. If both do, levels can be extreme.

That’s why families with premature heart disease — heart attacks or strokes in their 30s or 40s — often share this trait, even when LDL looks “normal.”

And here’s the kicker: lifestyle barely touches it.
 Diet, exercise, and weight loss have almost no effect, because production is genetically hard-wired.
 Your Lp(a) level is set by age five and stays remarkably stable for life.

How and when to test for Lp(a)?

Now that we know what Lp(a) is, let’s talk about something just as important — testing.
 Because what you don’t measure, you can’t manage.

Labs report Lp(a) in one of two ways —
 either mass units (mg/dL) or particle number (nmol/L).
 Here’s the problem: these aren’t interchangeable.
 Different apo(a) sizes carry different amounts of cholesterol, so conversion tables don’t work well.
 That’s why nmol/L, which reflects actual particle count, is preferred.

As a rough guide:
 Values above 30–50 mg/dL or 75–100 nmol/L fall above the 75th–80th population percentile and signal higher risk.

In a large U.S. study of over half a million individuals, Lp(a) levels above 30 mg/dL were found in roughly one-third of people.
 So this is not rare — just rarely measured.

Here’s a twist many overlook:
 The cholesterol inside Lp(a) actually adds to your LDL-C measurement.
 So if LDL-C seems stubbornly high despite statins, part of that “LDL” might actually be Lp(a) hiding in plain sight.

So, who should we test?
 According to the National Lipid Association, check Lp(a) in patients with:

1.     A personal or family history of premature ASCVD or ischemic stroke. 

2.     First-degree relatives with elevated Lp(a)

3.     Familial hypercholesterolemia or LDL-C ≥ 190 mg/dL

4.     Recurrent or progressive ASCVD despite optimal therapy

5.     Calcific aortic valve stenosis

6.     When LDL-C reduction on statins seems less than expected.

A few practical notes:
 Testing doesn’t require fasting.
 It’s widely available and inexpensive.
 Levels stay stable over time — but inflammation can temporarily bump them, so confirm unusually high results after things settle.

The American Heart Association notes that Lp(a) ≥ 50 mg/dL or ≥ 125 nmol/L is a risk-enhancing factor, one that may tip the scale toward statin therapy for adults 40 to 75 years old.

The European Society of Cardiology goes further — recommending every adult be tested once in a lifetime.
 Very high inherited levels — above 180 mg/dL — carry a lifetime ASCVD risk similar to familial hypercholesterolemia.

Since Lp(a) is almost entirely genetic, one test is usually enough.
 If it’s high, repeat it once to confirm — especially if the patient has inflammatory disease or acute illness.
 Lp(a) testing isn’t just another lab — it’s a risk revelation.
 One test, done once, can uncover hidden genetic risk that standard lipids miss — and that insight can change a patient’s entire prevention strategy.

What to do when Lp(a) is high?

So you’ve identified high Lp(a) — now what?
 Here’s the truth: we can’t directly lower it much yet, but we can absolutely lower the risk it drives.

First, lifestyle still matters.
 A heart-healthy diet, regular activity, blood pressure control, and smoking cessation don’t reduce Lp(a) itself, but they strengthen the foundation.

Next, go after what you can modify — the LDL-related risk.
Aggressively lower LDL-C and non-HDL-C to guideline targets.
High-intensity or maximally tolerated statin therapy remains the cornerstone — even though statins don’t reduce Lp(a), and can slightly raise it, their benefits far outweigh that small bump.

If LDL-C remains above goal, add ezetimibe or a PCSK9 inhibitor.
 PCSK9 inhibitors not only cut LDL-C by 50–60 percent but also lower Lp(a) by about 25 percent.
 In the FOURIER and ODYSSEY trials, patients with high baseline Lp(a) saw the biggest drop in events — suggesting part of the benefit came from lowering Lp(a).

The twice-yearly inclisiran, also reduces Lp(a) by roughly 20 percent.

For the rare patient with recurrent ASCVD despite optimal therapy — think progressive disease, high Lp(a), LDL already near goal — lipoprotein apheresis can temporarily cut Lp(a) by up to 70 percent.
 It’s invasive, expensive, and reserved for select cases, but it can help when everything else has failed.

What not to use:
 Niacin, hormone therapy, mipomersen, and lomitapide can lower Lp(a) on paper — but none have shown outcome benefit and all carry side effects.

And despite its pro-thrombotic nature, a high Lp(a) alone isn’t a reason to start aspirin for primary prevention.

So, for now, our strategy is simple but powerful:

• Maximize LDL-C reduction.
• Address every other modifiable risk factor — hypertension, diabetes, smoking, inflammation.
• Flag family members for screening and education.

And stay tuned — targeted Lp(a)-lowering drugs are on the horizon: Pelacarsen (an antisense oligonucleotide) and Olpasiran (a small-interfering RNA) are both in phase 3.
 If these trials confirm clinical benefit, it could redefine preventive cardiology.

Until then, treat Lp(a) for what it is — a fixed gene, but a modifiable risk story.

So as we wrap up this spooky episode, remember —
 Lp(a) may be invisible on a standard lipid panel, but it’s no myth.
 It’s the quiet genetic ghost haunting even the healthiest hearts.
 One simple test can uncover it — and while we can’t silence it yet, we can outsmart it.
 Because when it comes to cardiovascular prevention, knowledge isn’t just power — it’s protection.

Here are the take-home points:

1.     Lp(a) is genetic and stable — your level is set early in life and barely changes.

2.     Test it once — that single result can reveal hidden cardiovascular risk that LDL alone might miss.

3.     We can’t lower it directly (yet) — but we can lower the danger it creates by targeting LDL, lifestyle, and every other modifiable factor.

Alright folks, our next episode drops in two weeks — we’ll be diving into atherosclerosis and how these lipoproteins actually start plaque formation.

Thanks for tuning in to LipidCurious.
If today’s episode was helpful, share it with a friend or colleague.
I’d love to hear your feedback or topic suggestions — you can always reach me at hello@lipidcurious.com.

Be sure to subscribe or follow so you don’t miss what’s next.
And don’t forget — you can grab the free Starter Kit and Season 1 Visual Guide at www.lipidcurious.com.

Until next time — stay curious, and stay confident.
Signing off, Dr. Pulipati.

Bonus: For the full collection of visuals across episodes, visit the Podcast page.

Download the Free LipidCurious Starter Kit here

Questions or feedback? Reach out at hello@lipidcurious.com