43. Lipoprotein (a) | Inherited, Overlooked & Finally Understood

In this episode of Mohivate, Dr Mohi Sarawgee explores Lipoprotein(a), a tiny particle carried in the blood, inherited almost entirely through our genes, and largely unchanged by diet, exercise, or most current cholesterol-lowering treatments. For more than sixty years, medicine knew it was there but rarely spoke about it. Now, that is beginning to change.

We look at what Lipoprotein(a) is, why high levels can raise the risk of heart attack, stroke, and aortic valve disease, who may be more likely to carry it, and why a single blood test can sometimes reveal something important about an entire family.

The conversation also turns to what “high” really means, whether you should be tested, and why the guidelines have suddenly shifted, with the 2026 US guidelines now recommending Lipoprotein(a) be measured at least once in every adult. I share whether I’d test myself, and why knowing a number you can’t change can still be a kind of power.

And finally, the hopeful horizon: a new generation of medicines designed to switch Lp(a) down at the source, and the landmark trials, unfolding right now, that may finally tell us whether lowering it saves lives.

This is also an episode about inheritance, uncertainty, and the difference between what we are given and what remains within our hands. Because we may not choose every card we are dealt, but we can still choose how we play the rest of the hand.

References:

1. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia. Journal of the American College of Cardiology.2026 May 19;87(19):2624–2757. (The guideline that, for the first time in the US, recommends measuring Lp(a) at least once in every adult — a Class I recommendation.) https://www.jacc.org/doi/10.1016/j.jacc.2025.11.016

2. American Heart Association newsroom summary of the 2026 guideline (plain-language overview, March 2026). https://newsroom.heart.org/news/accaha-issue-updated-guideline-for-managing-lipids-cholesterol

3. HEART UK — Lipoprotein(a): what it is, why it matters, and testing. https://www.heartuk.org.uk (search “Lp(a)”)

4. British Heart Foundation — Lipoprotein(a) and your heart. https://www.bhf.org.uk

5. Lp(a) HORIZON trial (pelacarsen) — design and rationale. American Heart Journal, 2025. The first-ever cardiovascular outcomes trial for an Lp(a)-lowering drug (~8,300 patients). https://www.sciencedirect.com/science/article/pii/S0002870325001012

6. OCEAN(a)-Outcomes trial (olpasiran) — ClinicalTrials.govlisting. https://clinicaltrials.gov (search “OCEAN(a) Outcomes olpasiran”)

7. ACCLAIM-Lp(a) trial (lepodisiran) — ClinicalTrials.gov listing. https://clinicaltrials.gov (search “ACCLAIM-Lp(a) lepodisiran”)

8. Enas EA, et al. Lipoprotein(a) and its role in the disproportionate burden of cardiovascular disease in South Asians. (Reviews the ~25% high-Lp(a) prevalence and earlier-onset heart disease.) Search via PubMed: https://pubmed.ncbi.nlm.nih.gov

Just a gentle reminder: this episode is for information, education, and inspiration only. It’s not a substitute for your doctor’s advice. For any personal health concerns, always seek guidance from your doctor.

Transcript

SPEAKER_00 0:08

Hi everyone, welcome back to Mohivate. I'm Dr. Mohi Saraugi, a GP by profession, but here I'm swapping prescriptions for perspective. We are in Leo season, and of all the signs, Leo is the one, the old traditions tied to the heart. The warm, the bold, the lion-hearted center of everything. Leo is strength. Leo is that confident, healthy glow. And the heart is lovely, isn't it? A muscle that starts beating before you have a name and simply keeps going through every ordinary day. You never think about it. It races when you're afraid. It lifts when you're in love. It even aches a little when it breaks. We weren't entirely wrong to hang all those feelings on it. It's been with you the whole way. And there are things about that heart even more extraordinary than the feelings we give it. Here's one. We tend to think of our health as something we author. We eat, we move, we live a certain way, and we write the story as we go. And so much of it we truly do write. But the first page was already there when we arrived. Some of the most important lines about your heart were set down before your first meal, your first walk, your first breath in the world. Today is about one of those lines. Something estimated to sit in the blood of roughly one in five people. An inherited part of the story that the strongest, healthiest, most lion-hearted person can carry over a lifetime without ever knowing it's there. It has an unglamorous name, lipoprotein A. For a long time, almost no one had heard of it, and medicine barely spoke of it either, myself included. That's beginning to change now, and now it's a good time to talk about it. So today let's talk about lipoprotein A, what it is, why it matters, what you can and can't do about it, and how I've come to think about this particular quirk of being human with real curiosity and maybe a little wonder. This episode is also part of our ongoing metabolic health series. So let's begin. Let's start with what this thing actually is because the name makes it sound far more complicated than it really is. First, cholesterol itself. It has a bad reputation, but your body actually needs it. It helps build your cells and it's completely normal to have it in your blood. The catch is that cholesterol can't travel through the blood on its own. So the body packs it into tiny parcels to carry it around, and it's the parcels that matter because some are helpful and some cause harm. When you have a blood test, you get a single number for all of it, your total cholesterol. But underneath that one number sit these different parcels doing different jobs. You may have seen their names on a test result HDL, LDL, triglycerides. So total cholesterol was never really one thing to raise or lower. What matters is the balance inside it. The troublemaker of the group is the one you've probably heard called bad cholesterol. Picture an LDL parcel travelling through your blood carrying its cargo of fat and cholesterol in the right amount, useful. But when there are too many of them, these parcels lodge in the wall of your arteries and slowly build up the fatty deposits that narrow them over the years. This is the LDL we try to keep low with diet, with exercise, and with statins. Now, lipoprotein A is a close cousin of that LDL parcel. Take one ordinary LDL parcel and wrap an extra protein around it. A long looping strand called apolipoprotein A. I know nobody in that lab was hired for their poetry. That ribbon coiled around the outside is the whole story because underneath lipoprotein A is still an LDL parcel, so it does everything LDL does. But the ribbon gives it a second trick that plain LDL doesn't have. Two ways to cause trouble, where LDL has only one. The first is the one you'd expect. Like any LDL parcel, it's rich in cholesterol, so it burrows into the artery wall and drives that same slow furring up. The deposits doctors call atherosclerosis. The second is the sinister one. That ribbon happens to look remarkably like another protein in your body called plasminogen. And plasminogen has an important job. It's part of your cleanup crew, the system that dissolves small blood clots before they can cause harm. Because lipoprotein A looks so much like plasminogen, it gets in the way. Think of a fake key that fits the lock but jams it, sitting in the space where the real key should go. So when there's a lot of lipoprotein A around, the body becomes a little slower at clearing clots. Now put those two together. On one side, it helps clog the artery. On the other, it makes a clot in that artery harder to clear. It builds the problem and then it blocks the solution. And that is exactly why high levels are so closely tied to heart attacks and strokes the moment a clot forms on top of a narrowed artery. There's one more place its reach extends. Lipoproteina also seems to play a part in the slow stiffening of one of the heart's valves, the aortic valve, something we tend to see more with age. So its reach goes a little beyond the arteries. And let me reassure you here, because this can all sound alarming. We all have some lipoproteina. It's a completely normal part of human blood. The trouble only comes when the level runs high. And as we'll see, whether it runs high or not was mostly decided long before you were born. So where does that number come from? Almost entirely from your genes. And that's what makes lipoprotein A unusual. Your LDL cholesterol responds to your life. Eat differently, move more, take a statin, and it shifts. Lipoprotein A, on the other hand, holds still. Your level is set almost entirely by a single gene, the LPA gene. One copy inherited from each of your parents. It's decided early, it settles in childhood, and it stays remarkably steady across your whole life. The number you carry at 20 is more or less the number you'll carry at 60. It's less like a reading that goes up and down and more like a fixed feature of who you are, closer to your eye colour or your height. Now, this is the part I find striking. All the usual advice we give for cholesterol, the healthy diet, the exercise, losing a little weight, even most of the standard cholesterol tablets, the statins, barely move this number. Some of those things are absolutely worth doing for a hundred other reasons, but they don't really change your lipoprotein A. Now that steadiness is actually useful in two ways. The first is practical because the number barely moves, you only ever need to measure it once. One test at any point in adult life tells you your lifelong risk. And that's what the science says today. If that ever changes, we'll talk about it right here on Mohivate. And second, because lipoprotein A runs in families, your number is never only about you. If yours is high, your parents, your brothers and sisters, your children may carry it too. So a single test can become information for a whole family. A conversation that ripples outward from one small vial of blood. And there's something bigger here too, the one that's really the heart of this episode. We live in a world that keeps telling us our health is entirely in our hands. That if we just eat well enough, train hard enough, optimize enough, we control every last bit of it. And so much of it we genuinely do. But lipoprotein A is a humbling reminder, and I think a freeing one that some of the story was handed to us, written in before we had any say in the matter. And a risk you were born with is not a moral failing. It isn't something you did, it's simply something you carry, like so much of what we inherit from the people who came before us. Now for the part I most want you to take from today. Lipoprotein A is written into your genes and it stays loyal to your genes. It largely ignores the things we usually reach for. A healthy diet keeps it where it is, exercise keeps it where it is. The superfoods, the supplements, the powders, the detoxes, they keep it exactly where it is. And I say that plainly because there's a growing industry very happy to suggest otherwise, very happy to sell you a plan or a powder to bring your lipoprotein A down. If anyone ever offers you that, I'd really invite you to keep your money. The science simply isn't there yet. Even our trusted medical tools leave this alone. Statins, the medicines we rely on so heavily to lower ordinary cholesterol, don't lower lipoprotein A. If anything, they can nudge it up a little by perhaps 10 to 20%. Now, this is easy to hear the wrong way. So let me be clear. None of this is a reason to abandon good habits. Remember, lipoprotein A is an LDL parcel at its core, and everything you do for your ordinary cholesterol still works on all the rest of it. A healthy diet, movement, a statin where it's needed, these matter enormously for your blood pressure, for your weight, your arteries, your whole risk of a heart attack or stroke. It's simply an honest acknowledgement that this one particular number sits outside our usual reach, which raises a very fair question. If I can't change it, why would I ever want to know it? Hold that thought because it has a good answer and we'll come to it. But first, a step back. We haven't just discovered lipoprotein A. We've known about it for over 60 years, and for most of that time, we look the other way. The story begins in 1963 in Norway. A geneticist named Koreberg was studying the small natural differences between people's blood, not disease, just the ordinary variation from one person to the next, and he found a factor that some people carried and others didn't. He simply called it the LP system, LP for lipoprotein, and he noticed something troubling. The people who carried it seemed to turn up more often among patients with heart disease. He had stumbled onto a particle, passed down through families that travelled hand in hand with heart attacks. Two decades later, in the 1980s, another scientist carried the story forward. Gerd Atterman worked out why this particle varies so widely from one person to the next. The answer was in the gene itself. It comes in many different forms, and that single piece of inheritance is why one person carries almost none and another carries a great deal. It was the moment lipoprotein A stopped being a mystery in the blood and became a story written in our genes. And yet, for a long time, it was simply hard to measure and easy to overlook. So it slipped into the background, a curiosity, while attention went to its far more famous cousin, LDL. Now there's a part of the story that shapes who carries more of it and who carries less, and it comes back to those genes. Because lipoprotein A is inherited, how much you tend to have varies from one population to another. High levels turn up everywhere in every community on earth. This is not one group's problem, but the average does run higher in some than in others. It's highest on average in people of African heritage. It's raised too in people of South Asian heritage and lower on average in many European and East Asian groups. No community sped, but the dice are loaded a little differently depending on where your family comes from. Let me take the South Asian thread for a moment, partly because it's my own. South Asians tend to develop heart disease earlier and more severely than many other groups, suffering heart attacks nearly 10 years earlier on average than people of European descent. For years, that's been blamed on the usual suspects diabetes, diet, less exercise, and those matter truly, but they never quite explained the whole gap. Lipoproteinae looks like one of the missing pieces. Around 1 in 4 South Asians, roughly 25%, carry it at high levels. And because South Asians make up such a large share of the world's population, they carry close to a third of all the high lipoproteina on Earth. Now I want to be careful here because this is delicate. And it is not destiny. Plenty of people who carry high levels live long, full, healthy lives. But if you come from one of these backgrounds and you've watched heart trouble arrive early in your family, this may be one of the missing threads. And now it has a name. And if that's you, sit with it for a moment because a single inherited particle may carry folded inside it a small fragment of your family's history. And if that's not your background, if your family comes from somewhere, the average runs lower, the lesson doesn't change. Your ancestry is one thread in this, never the whole cloth. It's simply that some of us start with the dice weighted a little more heavily, and it helps to know which way. So the world of heart medicine has in a real sense turned a corner. For decades, lipoprotein A was treated as a curiosity. Now the guidelines are catching up and quickly. In the United States this year, 2026, the major cholesterol guidelines were rewritten from the ground up. And for the first time, they recommend that every adult have their lipoprotein A measured at least once. Their strongest year of recommendation. In Europe, the advice has been similar for a while. Measure it at least once in a lifetime. And here in the UK, expert groups have recommended for some years now that we measure it in people at higher risk, a strong family history of early heart disease or a personal history of it. Now, what counts as high? As a rough guide, risk starts to climb above about 50 milligrams per deciliter or around 125 nanomoles per liter, depending on how your lab reports it. But the important part is this labs and units differ, so the number that matters is yours read against your own lab's reference range. Not a figure you heard on a podcast, including this one. Take your result to your doctor and read it there. A genuinely important word here because I'm a GP and I don't want half of you booking blood tests before breakfast tomorrow. Whether you personally should be tested is a conversation to have with your own doctor. It depends on your history, your family, and where you live because access and rules differ from country to country, and the picture in the UK is not the picture in the US or in India. This episode isn't here to diagnose you. It's here so that this particle has a name for you now, so that if it's right for you, you can ask a good question and so that you're not frightened by anyone who isn't qualified to read a blood result or anyone selling something that claims to lower your lipoprotein A. Please always speak to your own doctor about what's right for you. Which brings us back to the question I asked you to hold. If I can't change the number, why would I ever want to know about it? And because this is a podcast about perspective, let me be honest with you about my own. I've asked myself the obvious question, would I get myself tested? And sitting here today, I'm not sure I would. For two personal reasons. One, I already know I carry other risks I can actually work on, and that's where my energy wants to go first. And two, if I'm honest, there's a part of me that's at peace, not knowing a number, I couldn't change. That's not the medical answer. The guidelines would tell me to measure it. It's just my answer today, and yours might be completely different for reasons just as good. That's rather the point. This is a decision to make with your own doctor, with your own thought process, your own temperament. Not one I can make for you. And who knows, I might change my mind next year. If I do, you'll be the first to know. That's the fun of doing this together. So, on that note, let's understand what we can actually do. Knowing your lipoprotein A doesn't hand you a lever to pull on the number itself. What it hands you is context, and context changes everything about how you play the rest of the game. So let me put it as a game. Imagine you're at a card table and your heart's future depends on the hand you're playing. Lipoprotein A is one card you were dealt at birth, face up on the table, and you can't swap it. If it's a high card, that's not the hand you'd have chosen. But here's the thing every good player knows the cards are only half of it. What matters is how you play everything else because that dealt card sits alongside others, and most of those you can absolutely change your LDL cholesterol, your blood pressure, what you eat, how much you move, whether you smoke, how much alcohol you drink, your weight, your blood sugar, your stress, your sleep. Doctors call these your modifiable risk factors, and modifiable is the hopeful word. It simply means these you can change. Not one of those touches the lipoprotein A card itself, but every single one of them improves the hand you're holding, and that's the heart of all of this. A high lipoprotein A isn't a reason to throw the cards in, it's a reason to play the rest of the hand better than ever, to take every other card seriously, because now you know the stakes are a little higher for you. The one card is fixed. How you play the table is entirely yours. So a high lipoprotein A is not a losing hand. It's a reason to pay closer attention, to work with your doctor, and in some cases to be dealt a little extra help earlier. Here, knowing really is a kind of power. And finally, this is where the story turns toward hope, which is a beautiful thing to say about a particle we spent 60 years unable to touch because hope in medicine often arrives silently in a lab years before any of us feel it, and it's expected to arrive now, but before the horizon. A word about today because if you learn your lipoprotein A is high right now, there is already something to be done. There's no drug on the market yet for the lipoprotein A itself. So instead, your doctor turns to everything around it. All those modifiable risk factors we just talked about. Keeping your LDL cholesterol as low as possible becomes a priority, usually with a statin, often at a higher dose. If your LDL stays above target, we add a second drug called azetamib. And if it's needed beyond that, a newer class of injectable medicines called PCSK9 inhibitors. Names like alleroQMAP or EvoloQMAB. They are initiated by specialists and they can cut LDL by a further 60 to 70%. Interestingly, in trials so far, these PCSK9 inhibitors have also been shown to lower lipoprotein A modestly by around 20 to 25%, though that isn't what they are licensed for. And here in the UK, if your level is very high or heart disease has run early in your family, before 55 in a father or brother, or before 65 in a mother or sister, your GP may refer you to a specialist lipid clinic. So even now, a high number is never a dead end. It's a reason to protect everything else well. Now the horizon. For all those decades, the frustration of lipoprotein A was simple. We could see it, but we couldn't touch it. That is expected to change in our lifetime. Your lipoprotein A is made in the liver. The liver builds it, releases it into the blood, and does so at a rate your genes set long ago. And that is exactly where this new generation of medicines aims to go to work. Instead of chasing the particle around the bloodstream after it's made, these drugs are designed to travel upstream to the source and tell the liver to make far less of it in the first place. And these medicines have names now, which truly feels like a small miracle in itself. The furthest along is one called pelacarsin, a monthly injection from Novartis. Behind it, alparserin from Amgen, given just once every three months in trials, and lepodyceran from Eli Lili, longer acting still. All three are in phase 3 trials, the final stage of testing, the one that decides whether a medicine reaches patients at all. And in the early results, these treatments have pushed lipoprotein A down dramatically by 80, even 90% and more from a small injection given only a handful of times a year. But here is the honest caveat, and as a doctor, I have to be clear about it. These medicines are still in trials, they are not on the shelf, not yet, and lowering the number is not the same as saving lives, not until it's proven. So far, the company's own results show these drugs can bring lipoprotein A right down. What we don't know yet for certain is whether bringing it down actually prevents heart attacks and strokes. And that, to my mind, that is the single biggest open question in this entire field. The remarkable thing is we are about to find out. The biggest of these trials is following more than 8,000 people with heart disease and high lipoprotein A. And it's the first trial ever built to answer exactly that question. Does lowering the number actually save lives? It was expected to report by the middle of this year. That window closed at the end of June and the result still hasn't landed. So as I record this, the world's cardiologists are waiting a little impatiently for the first big answer. This is a real cliffhanger in medicine unfolding in real time. Depending on when you're hearing this, that answer may be days away or it may already be in. And if those trials succeed, then a particle discovered in 1963 and overlooked for most of a lifetime will finally have an answer to go with the question. And you know, if that day comes and it makes me reconsider testing myself, you'll be the first to know right here. After 60 years in the shadow, that is a rather beautiful place to have arrived. So here we are, a tiny particle written into you before you drew your first breath, carried perhaps unknowingly for an entire lifetime, and only now, more than 60 years after it was discovered, finally finding its rightful place in the story of heart health. I found something strangely comforting while preparing this episode. So much of what we are handed we never choose. The colour of our eyes, the curl of our hair, the face that looks back at us in the mirror. A single line of DNA written long before any of us arrived. We spent so much of life trying to author every word of ourselves, and some of it was never ours to write, it was simply given. But what we do with it, how we carry it, how we play the hand, how we care for the heart that has carried us all this time, that part has always been ours, and perhaps that's enough. I hope something today stirred a thought gave you a smile or simply made you pause. Thank you for listening. I'm Dr. Mohi. Until next time, remember this not everything we carry is something we choose, but understanding what we carry and caring well for the body that carries us is one more step towards coming home to ourselves.