Episode 52: Lp(a) Q&A: Testing Kids, The Saturated Fat Debate, and Aspirin Risks

Show Notes

A follow up Q&A to the Lp(a) deep dive earlier in the week. Dr. Ravi Kumar picks five of the most thoughtful listener questions and does a mini deep dive on each, tying together the key themes from the full episode and filling in a few of the practical and biological gaps.

If you listened to the lipoprotein(a) deep dive earlier in the week and walked away with more questions, this is the follow up. Dr. Kumar walks through whether you should test your kids for Lp(a) (and at what age), why exercise still matters even though it does not budge the number itself, the Tokelauan and Maasai data that complicates the conventional saturated fat story, the Women’s Health Study and ASPREE findings showing that low dose aspirin disproportionately benefits Lp(a) carriers, and where the new 90% lowering drugs like pelacarsen and olpasiran stand in the pipeline. He closes with two bonus topics: the meta analysis evidence that cutting saturated fat actually raises Lp(a), and the evolutionary case for why this gene exists in humans, old world primates, and (strangely) the European hedgehog at all.

In this episode, you will discover:

• Why you should test your kids for Lp(a): Lp(a) is one of the most heritable cardiovascular risk factors known. If you have a high level, each of your first degree relatives has roughly a 50% or greater chance of also having an elevated level, driven primarily by a single gene called LPA. The 2024 update from the National Lipid Association formally recommends cascade screening of first degree relatives once you identify an elevated index case
• When to test: Expert consensus is that Lp(a) is essentially stable from around age five onward. A single test in the teenage years is enough for life. A high number gives a 30 to 40 year head start on every modifiable risk factor. A low number takes the worry off the table permanently
• Why exercise is still essential even with high Lp(a): A 2022 review on non genetic influences on Lp(a) confirmed that the direct effect of exercise on the number ranges from no change to minimal change. But Lp(a) only becomes harmful in the presence of chronic endothelial injury and oxidizable fuel. Exercise hits the first condition hard by lowering blood pressure, improving insulin sensitivity, and boosting nitric oxide production
• The right exercise prescription: Three to four resistance training sessions per week, plus 150 to 300 minutes of moderate aerobic activity weekly. Exercise does not change the cards you are dealt, but it dramatically changes the table you are playing on
• The Tokelau Island Migrant Study: The foundational paper in the American Journal of Clinical Nutrition in 1981 documented Tokelauans on their home atolls getting more than 50% of daily energy from coconut, almost entirely saturated fat, while also smoking heavily. Atherosclerotic disease was rare. When those same individuals migrated to New Zealand and shifted toward refined carbohydrates, sugar, and seed oils, their lipid profiles deteriorated and cardiovascular risk climbed
• The Maasai data: A 1964 field survey of 400 Maasai men eating an essentially exclusive diet of meat, milk, and blood from their cattle found low cholesterol levels and almost no clinical or autopsy evidence of atherosclerotic disease. A 1972 follow up paper confirmed the finding
• Why conventional saturated fat dogma persists: Most physicians are trained inside an educational system heavily influenced by pharmaceutical industry messaging. Looking at what the data actually says, with an unbiased lens, takes deliberate effort. Dr. Kumar’s cardiovascular series in Episodes 1 through 5 lays out the full historical and scientific argument
• The Women’s Health Study and aspirin: In nearly 28,000 women followed for 10 years, women carrying high Lp(a) variants had an elevated risk of major cardiovascular events. Among carriers randomized to aspirin, that excess risk was effectively wiped out, with a statistically significant 56% relative risk reduction. Non carriers saw essentially no significant benefit
• The ASPREE confirmation: A more recent analysis from the ASPREE trial found the same pattern in older adults. Carriers of the high Lp(a) variant got disproportionate benefit from aspirin. Non carriers did not
• Why aspirin works specifically for Lp(a) carriers: Lp(a)’s apo(a) protein mimics plasminogen and slows clot breakdown, which made our ancestors better at sealing wounds but makes modern coronary clots more dangerous. Aspirin’s antiplatelet effect specifically counteracts Lp(a)’s tendency to promote stickier, more durable clots. If your Lp(a) is high, your bleeding risk is low, and you are weighing primary prevention, this is a conversation worth having with your physician
• Pelacarsen, the antisense oligonucleotide: Goes into the liver and tells the LPA gene’s messenger RNA to be destroyed before it can make any apo(a) protein. Phase 2 trials in the New England Journal of Medicine showed roughly 80% reductions with monthly injections. Phase 3 results are expected in 2026
• Olpasiran, the siRNA: A similar concept with a different molecular mechanism. Phase 2 trials published in NEJM in 2022 showed greater than 95% Lp(a) reductions at higher doses, dosed every 12 weeks. Both drugs are designed to answer the question we do not yet have an answer to: does lowering Lp(a) reduce heart attacks, strokes, and cardiovascular death?
• Why you should not wait for the drugs: Even if approved, they will likely first be expensive, secondary prevention only, and primary prevention coverage will take years more to sort out. The lifestyle levers (cut seed oils, control blood pressure, lock in metabolic health, move your body, do not smoke) are available right now, free, with no side effects, and address the root cause directly
• Bonus: low saturated fat diets raise Lp(a): A 2024 review and meta analysis found that lower saturated fat diets modestly but consistently increased Lp(a), with the effect most pronounced when saturated fat was replaced with carbohydrates or trans fats. The Delta trials showed Lp(a) increasing 11 to 20% when saturated fat was cut and replaced. This matters disproportionately for South Asian and African American populations, who carry higher baseline Lp(a)
• Bonus: why Lp(a) exists at all: The gene is confined to humans, old world primates, and the European hedgehog. The hedgehog version evolved completely independently from the primate version through convergent molecular evolution. When evolution independently invents the same thing twice in unrelated species over tens of millions of years, that is a design feature being repeatedly selected for, not a random accident

Key Takeaways

• If you have high Lp(a), get your kids tested. A single teenage measurement is enough for life and gives a 30 to 40 year head start on prevention. Cascade screening of first degree relatives is now formally recommended by the National Lipid Association
• Exercise does not move the Lp(a) number, but it dramatically changes the vascular environment that Lp(a) needs to cause harm. Aerobic training plus resistance training is non negotiable even for high Lp(a) carriers
• The Tokelauan and Maasai data show that traditional populations on high saturated fat diets had rare cardiovascular disease. The damage shows up when refined carbs and industrial seed oils enter the picture
• Low dose aspirin appears to specifically benefit Lp(a) carriers and not non carriers, in both the Women’s Health Study and the ASPREE trial. If your Lp(a) is high, bleeding risk is low, and you are weighing primary prevention, talk to your physician about it
• Pelacarsen and olpasiran can lower Lp(a) by 80 to 95%, but outcomes data is still pending and coverage will be slow. Lifestyle protection starts today and addresses the root cause
• Cutting saturated fat and replacing it with carbohydrates or seed oils raises Lp(a), an inversion of the conventional cardiology playbook that disproportionately affects South Asian and African American patients
• The Lp(a) gene was conserved across tens of millions of years and re evolved independently in the European hedgehog. High Lp(a) is a survival adaptation, not a defect. Your job is to give that adaptation the right environment so it stays a wound healing superhero rather than a cardiovascular villain

If you have not yet listened to this week’s main episode, Lipoprotein(a): Genetic Risk, Seed Oils & 5 Steps to Protect Your Heart, start there. This Q&A builds directly on those concepts.

Transcript

[00:00 –> 00:20] Dr. Ravi Kumar: Hey, everyone. Welcome back to The Dr Kumar Discovery podcast. Earlier in the week, I did a solo deep dive on lipoprotein(a), and I got a flood of really thoughtful questions in the comments and DMs. So I picked five of the best ones to do mini deep dives on. I think this will tie together most of what we talked about earlier in the week.

[00:20 –> 00:30] Dr. Ravi Kumar: Okay. First question. My Lp(a) just came back at 180 nanomoles per liter. Should I get my kids tested? They’re 14 and 17 years old.

[00:30 –> 00:59] Dr. Ravi Kumar: Okay. So this is a really good question, and the answer to this is yes. And this is one of the most practical things you can do with your result. Lp(a) is one of the most heritable cardiovascular risk factors that we know of. If yours is elevated, your kids have roughly a 50% or greater chance per child of also having an elevated level because it’s largely driven by a single gene called LPA passed down from each parent.

[00:59 –> 01:35] Dr. Ravi Kumar: So that being said, the 2024 update from the National Lipid Association also formally recommends cascade screening of first degree relatives once you identify an elevated index case. So this is no longer fringe advice, it’s mainstream lipidology now. So to the person who asked this question, your 14 and 17 year old can absolutely be tested. The expert consensus is that Lp(a) is essentially stable from around age five onward. So you basically get a single test in the teenage years, and they never need to be tested again in their whole lives.

[01:35 –> 01:58] Dr. Ravi Kumar: And the practical value is enormous. If their number is high, you have a 30 to 40 year head start on every modifiable risk factor we talked about in the main episode. And if it’s low, that’s also useful information that takes worry off the table. So get them tested, get your siblings tested, get your parents tested if they’re still living. In this situation, information is the whole game.

[01:58 –> 02:18] Dr. Ravi Kumar: Okay. So next question. You said exercise doesn’t lower Lp(a). So if I have a high level, is exercise even worth it for cardiovascular protection? So the answer is yes, and I want to make sure I was clear on this in the main episode because I don’t want anyone thinking they shouldn’t be exercising.

[02:18 –> 02:54] Dr. Ravi Kumar: It is true that the direct effect of exercise on the Lp(a) number itself is essentially negligible. There was a thorough review of non genetic influences on Lp(a) published in 2022 that summarized the evidence on this. They concluded that across studies, the effect of exercise on Lp(a) ranges from no change to minimal change. And what little signal exists depends heavily on the type, intensity, and duration of exercise. So if your goal is to move the number on the lab report, exercise is not going to do that.

[02:54 –> 03:19] Dr. Ravi Kumar: But that’s not the goal. Remember the framework. Lp(a) only becomes harmful in the presence of two things, chronic endothelial injury and oxidizable fuel loaded onto those particles. Exercise hits the first one of those two conditions hard. Regular aerobic exercise lowers blood pressure, which directly reduces mechanical shear injury to your vessel walls.

[03:19 –> 03:43] Dr. Ravi Kumar: It improves insulin sensitivity, which reduces the chronic glycation and inflammation of your endothelium, and it boosts nitric oxide production from your endothelial cells, which is the master signaling molecule that keeps your vessels healthy and pliable. I did a whole episode on nitric oxide last week with Dr. Nathan Bryan. Please listen to it if you haven’t already. You’ll definitely be glad you did.

[03:43 –> 04:11] Dr. Ravi Kumar: Okay, so back to this question. I really like this analogy when thinking about exercise and Lp(a). Exercise doesn’t change the cards you’re dealt, but it dramatically changes the table you’re playing on. A vascular system that’s getting daily exercise is fundamentally less receptive for Lp(a) to deposit cholesterol and start a plaque. That’s how you should be thinking about it if you live with high Lp(a).

[04:11 –> 04:31] Dr. Ravi Kumar: So here’s my advice to you. You should be doing both aerobic exercise and resistance training. Do three to four resistance training sessions per week and 150 to 300 minutes of moderate aerobic activity every week as well. If you do that, you’ll be doing your vascular system a big solid.

[04:31 –> 04:56] Dr. Ravi Kumar: Okay, next question. The Tokelauans and Maasai thing blew my mind. Is this for real or is it cherry picked? Because every cardiologist I’ve seen says saturated fat is the problem. Okay, so this is a topic of debate for sure, because pretty much all doctors are trained in traditional and conventional ways of thinking that is largely dictated by pharmaceutical company influence on medical education.

[04:56 –> 05:15] Dr. Ravi Kumar: That’s just the truth of it, guys. I’m one of them. I went through the same educational system. So I know that it takes bucking of the conventional system, it takes being identified as an outlier, and it takes thinking creatively to actually look at what the data really says. And not many doctors do that.

[05:15 –> 05:54] Dr. Ravi Kumar: This is one of those examples where conventional dogma still has the minds of most doctors and patients trapped in flawed thinking because they haven’t opened their minds and actually looked at the data with an unbiased lens. I have a whole cardiovascular disease series. It’s episodes one through five where I talk about the history and science behind cardiovascular disease and the misconceptions and the misunderstanding that determine conventional dogma. So if you want to learn more about it, those are some fantastic episodes to listen to. Okay, so the Tokelauan data that you’re asking about comes from a long running series of studies called the Tokelau Island Migrant Study.

[05:54 –> 06:41] Dr. Ravi Kumar: The foundational paper was published in the American Journal of Clinical Nutrition in 1981, and the Tokelauans on their home atolls were getting more than 50% of their daily energy from coconut, which is overwhelmingly saturated fat. They also smoked like chimneys because they traded coconut for cigarettes as their primary currency. By any conventional logic, they should have had catastrophic rates of heart disease, but they didn’t. Atherosclerotic disease was rare. What’s even more telling is that when those same Tokelauans migrated to New Zealand and shifted toward a more Western diet with more refined carbohydrates, sugar, and seed oil exposure, their lipid profiles deteriorated and cardiovascular risk climbed.

[06:41 –> 07:09] Dr. Ravi Kumar: The Maasai data, which is a group of nomadic herders in Africa, is even more striking. The original field survey was published in 1964. They examined 400 Maasai men who were eating an essentially exclusive diet of meat, milk, and blood from their cattle. Despite that, the men had low cholesterol levels and almost no clinical or autopsy evidence of atherosclerotic heart disease. A follow up paper in 1972 confirmed those findings.

[07:09 –> 08:00] Dr. Ravi Kumar: Okay. So next question is about aspirin. You mentioned the Women’s Health Study showed aspirin specifically helps people with high Lp(a). Can you go a little deeper on that finding? Yeah, this is one of the most fascinating things in the entire Lp(a) literature, and it’s still underused clinically. So the Women’s Health Study was a large, randomized, placebo controlled trial. They had nearly 28,000 women who they followed for 10 years and randomly assigned them to either low dose aspirin or placebo. And the original goal was just to look at primary prevention of cardiovascular disease in general. But then about a decade after the trial ended, researchers went back and analyzed the data through a genetic lens. They identified women who carried high Lp(a) gene variants and compared them to non carriers. And the result was, in my opinion, striking. Women carrying the high Lp(a) gene had an elevated risk of major cardiovascular events.

[08:00 –> 09:13] Dr. Ravi Kumar: That’s the part we already knew. But here’s the part that changed the clinical thinking on this. Among carriers who got randomized to aspirin, that excess cardiovascular risk was effectively wiped out. The relative risk reduction in cardiovascular events with aspirin on board in the setting of this Lp(a) gene was 56%, and it was statistically significant. Among non carriers, aspirin allocation gave essentially no significant benefit. A more recent analysis from the ASPREE trial found a similar pattern in older adults. Carriers of the high Lp(a) variant got disproportionate benefit from aspirin, and non carriers didn’t.

[09:13 –> 10:40] Dr. Ravi Kumar: What this means in plain English is that for the subset of people with genetically high Lp(a), aspirin’s antiplatelet effect appears to specifically counteract Lp(a)’s tendency to promote stickier, more durable clots. It’s a beautiful example of mechanistic alignment. So the same structural features that made Lp(a) good at sealing wounds in our ancestors, mimicking plasminogen, and slowing clot breakdown, is also what makes a clot in the coronary artery more dangerous today if you have high Lp(a) levels. Aspirin tilts that back the other way. So the clinical takeaway is, if your Lp(a) level is high, your bleeding risk is low, and you and your physician are weighing primary prevention strategies, this is a worthwhile conversation to have.

[10:40 –> 11:04] Dr. Ravi Kumar: The evidence is not yet at the level of guideline mandate, but it’s far better than guesswork. Okay, question number five. I keep hearing about new drugs that can lower Lp(a) by 90%. When are those going to be available, and should I just wait for them? Okay, so that’s a great question, and the pipeline here is genuinely exciting.

[11:04 –> 11:45] Dr. Ravi Kumar: In about a decade, we’ve gone from having essentially nothing that meaningfully lowers Lp(a) to having multiple drugs in late stage development that can drop it by more than 90%. The two leading candidates are pelacarsen and olpasiran. Pelacarsen is an antisense oligonucleotide. Think of it as a tiny molecule that goes into your liver and tells the LPA gene’s messenger RNA to get destroyed before it can make any apo(a) protein, which is the main protein that defines Lp(a)’s characteristics. The phase 2 trials published in the New England Journal of Medicine showed reduction in Lp(a) at around 80% with monthly injections.

[11:45 –> 12:37] Dr. Ravi Kumar: Pelacarsen is now in large phase 3 trials with final results expected in 2026. Now, olpasiran, the other drug, is a small interfering RNA, which is a similar concept but slightly different molecular mechanism. And the phase 2 trials here were published in the New England Journal of Medicine in 2022, and they showed reductions of greater than 95% of your Lp(a) levels at higher doses, and they dosed it every 12 weeks instead of monthly. Both of these trials I just talked about are designed to answer the most important question we don’t yet have an answer to, and that is, does specifically lowering Lp(a) reduce heart attacks, strokes, and cardiovascular death? We have very strong genetic and mechanistic evidence to think the answer is yes, but until we have a randomized outcomes trial showing it, we don’t truly know.

[12:37 –> 12:55] Dr. Ravi Kumar: We know these drugs lower Lp(a), don’t know if that reduces death or injury from cardiovascular outcomes. Okay, so now back to this question you asked. Let me give you a practical answer here. Should you wait for these drugs? My honest answer is no, and here’s why.

[12:55 –> 13:34] Dr. Ravi Kumar: Even if the trials succeed and the drugs hit the market in the late 2020s, they will likely be expensive, and they’ll likely first be approved for people with established cardiovascular disease as secondary prevention. And primary prevention coverage will probably take years longer to sort out. More importantly, the lifestyle levers we talked about in the main episode are available right now. They cost nothing, they have no side effects, and they directly address the root cause of how Lp(a) causes harm. Get the seed oils out of your body, control your blood pressure, lock in your metabolic health, move your body, don’t smoke.

[13:34 –> 13:56] Dr. Ravi Kumar: If you do those things, your high Lp(a) becomes a much less interesting number on your lab report. So, the drugs are coming, and if you have high cardiovascular risk with elevated Lp(a), you may end up on one of those drugs. But your real protection can start today with the lifestyle changes I just mentioned. Okay. So now on to some bonus topics.

[13:56 –> 14:32] Dr. Ravi Kumar: These weren’t questions I received, but they were things I thought were worth talking about. The first one is a saturated fat finding I didn’t get into in the main episode. If you listened to my seed oils episode, you know I’m pretty firmly in the camp that the war on saturated fat has been one of the most consequential nutritional mistakes of the last 50 years. So here’s an extra piece of the puzzle. When you reduce dietary saturated fat and replace it with carbohydrates or with monounsaturated fat or polyunsaturated fats, your Lp(a) number goes up, not down.

[14:32 –> 15:20] Dr. Ravi Kumar: A 2024 review and meta analysis pulled together the randomized control trials on this question. They found that lower saturated fat diets modestly but consistently increased Lp(a) compared to high saturated fat diets. The effect was more pronounced when saturated fats were replaced with carbohydrates or trans fats, but the direction was the same across different replacement strategies. The most detailed data on this comes from a series of metabolic feeding trials called the Delta trials, where Lp(a) increased by 11 to 20% when saturated fat was cut and replaced with carbohydrates or monounsaturated fats. And remember, African American populations and South Asian populations on average have higher baseline Lp(a) levels when compared to European populations.

[15:20 –> 15:49] Dr. Ravi Kumar: So this matters a lot for that community in particular. So what does this mean? It means that the standard cardiology playbook of cut your saturated fat, replace it with whole grains and vegetable oils, may be actually raising one of the most important cardiovascular risk factors. You might be lowering your LDL number while simultaneously cranking up your Lp(a) level. And someone who already has elevated Lp(a), that could be a net negative trade.

[15:49 –> 16:19] Dr. Ravi Kumar: So this doesn’t mean go pour butter on everything. It means the simplistic narrative around saturated fats needs to go away. Real, whole food saturated fats from quality sources are not the enemy they’ve been painted as. And if you’ve got high Lp(a), people telling you to swap out your eggs and butter for industrial seed oils or margarines may be making your underlying risk much worse. Okay, so here’s the next bonus topic.

[16:19 –> 16:38] Dr. Ravi Kumar: I thought it would be nice to briefly review why this LPA gene even exists in the first place. And I want to bring this up because I think it’s fascinating. We know that Lp(a) is essentially confined just to humans, old world primates, and weirdly, the European hedgehog. And that’s it. No other mammals have it.

[16:38 –> 17:19] Dr. Ravi Kumar: And the hedgehog version actually evolved completely independently from the primate version by something called convergent molecular evolution. So here we have two different mammalian lineages independently duplicating and modifying the same gene, plasminogen, to produce the apo(a) molecule. So why does that matter? Well, when evolution independently invents the same thing twice in two unrelated species over tens of millions of years, that’s not a random accident. That’s a design feature being selected for repeatedly because it confers a survival advantage.

[17:19 –> 17:51] Dr. Ravi Kumar: It’s one of the strongest pieces of evidence we have that Lp(a) was protective in the ancestral world. So the modern story, where we treat it purely as a disease gene, just doesn’t fit the evolutionary record. So if you’ve got high Lp(a), you’re not broken. You inherited a survival adaptation from your ancestors who needed it to live long enough to reproduce. Your job is just to give that adaptation the right environment where it doesn’t end up causing you harm.

[17:51 –> 18:25] Dr. Ravi Kumar: So stop chronically injuring your endothelium, stop loading your lipoproteins with oxidizable fuel, and Lp(a) remains a wound healing superhero rather than a cardiovascular villain. Okay, so that’s it for this week, folks. If you found this helpful, do me a favor and share it with someone in your life who’s been told they have high Lp(a) and doesn’t know what to do about it. This information changes how people think about their cardiovascular future, and there’s still way too little about it out there. Okay, so that wraps it up.

[18:25 –> 18:27] Dr. Ravi Kumar: I’ll see you next week. Cheers.