64. LP(a): The Massively Important, But Totally Overlooked Biomarker of Heart Attacks, Strokes, and Heart Disease

In this episode of Extend, we're digging into one of the most dangerous—and most overlooked—drivers of heart disease: LP(a). You could have a clean lifestyle, normal labs, and still be at high risk for a heart attack or stroke. Why? Because LP(a) isn't included in standard cholesterol tests—and 1 in 5 people have elevated levels without knowing it. I break down what LP(a) actually is, why it's more inflammatory and damaging than LDL, and how it contributes to plaque, heart attacks, strokes, and valve disease. You'll learn why lifestyle changes don't lower it, what to do if your levels are high, and how cutting-edge RNA therapies could offer hope. I also share exactly which labs and scans to request so you're not flying blind. ➡️ If you care about preventing cardiovascular disease, this is essential listening. It's time to add LP(a) to the conversation. I Also Discuss: The stealth cholesterol marker no one's testing for Think your cholesterol panel is fine? Here's what it's missing LP(a): the hidden culprit behind "healthy" heart attacks This could be why young people are having strokes The one stat that should have everyone talking Got high LP(a)? Here's your action plan The game-changing drugs that silence LP(a) at the source Thank You for Our Sponsors: Deliverance: Give your liver the care it deserves! Deliverance is a powerful plant-based formula designed to support and restore liver health. Get 10% off your first order with code DRSHAH at loveyourliver.com Timeline: Upgrade your energy from within! MitoPure by Timeline helps power up your cells, supporting muscle strength, mental clarity, and overall vitality. Stay active, sharp, and strong at any age! Claim 10% off your first order now at timeline.com/DrShah Learn more about Dr. Shah: Website: https://www.drshah.com/ Clinic: https://www.next-health.com/ Instagram: https://www.instagram.com/darshanshahmd/

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:03Dr. Darshan Shah?

  Welcome to Extend with me, Dr. Darshan Shah, a podcast dedicated to cutting-edge science, research, tools, and protocols designed to help you extend your health span. Having become one of the youngest doctors in the country at the age of 21, and trained and board-certified at the Mayo Clinic, I've accumulated three decades of practice as a board-certified surgeon and longevity expert. Over that time, I've discovered that a mere 20% of health knowledge yields 80% of the results when it comes to your health span. We're living in a new era where we are creating a new healthcare system, no longer focused on disease management, but achieving optimal health and vitality. Join me as I interview world-renowned experts, offering you a step-by-step guide to proactively avoid disease, and most importantly, extend your health span.

• 0:49Dr. Darshan Shah?

  Hello, everybody. This is Dr. Shah, and this is an extremely important episode that I'm doing today. This is a solo-sode, which is just me, Dr. Shah, talking to you about a very important topic, LP little a. So what is LP little a? If you have never heard of LP little a, you are not alone. This is an overlooked genetic risk factor for heart disease, and it's something that many doctors have not even heard of or test for, to my surprise. LP little a is one of the most important and under-recognized markers for heart disease that we have today. And in this episode, we're going to dive deep on LP little a, what it is, why it matters, how common it is, and what you can do about it. So let's get started.

• 1:34Dr. Darshan Shah?

  LP little a, at its basics, is one of the cholesterol markers that we've never really tested for until the last few years. Another name for this is lipoprotein A, and it's an extremely common variant of LDL cholesterol that has an added protein on it called apolipoprotein A that's attached to it. So it's a protein attached to LDL. And the problem with this LP little a protein is that it's extremely more pro-inflammatory, more pro-thrombotic, and much more likely to infiltrate into

• 2:10Dr. Darshan Shah?

  The wall of your artery and create plaque. So basically, it's one of the worst cholesterol molecules you can have because it causes a lot more damage than any of the other cholesterol particles in most people. What's extremely important to realize about LP little a is that it's typically not picked up in your standard cholesterol panel. So your standard cholesterol panel, one in which you get LDL, HDL, total cholesterol, triglycerides, does not report on LP little a. So it's completely missed in all standard cholesterol panels. And unless you've gotten a functional medicine panel at Next Health or through some other provider or a Boston Heart's diagnostic test, you really wouldn't know that you have an LP little a problem. And LP little a is actually much more common than you think.

• 2:55Dr. Darshan Shah?

  Many clinicians don't even realize that elevated LP little a, which is typically defined as over 50 milligrams per deciliter, affects one in five people worldwide. That's 20% of people have this and we're not even checking for it. There are certain populations that have an even higher incidence of LP little a. Those can be of African or South Asian descent. And unlike LDL or Apo B, LP little a is largely genetically determined and remains relatively stable throughout your life. That means lifestyle changes like diet, exercise, really don't have an impact on lowering LP little a. So if you have a level of LP little a that's in the high category, no matter how hard you try, you're not going to be able to lower LP little a

• 3:40Dr. Darshan Shah?

  using lifestyle interventions. So in other words, LP little a is like LDL's more dangerous stealthy cousin that's resistant to any type of interventions that you can do. So that's what makes it particularly dangerous. In the last episode, I talked to you a little bit about Apo B. Apo B in my mind is the number one cholesterol marker that we all need to be following. What's great about Apo B is it's just one number that you have to follow. But the problem with Apo B is that you could have a normal Apo B, but a large proportion of them could also have that LPA molecule on it, that protein on it. And that's a major risk factor for heart disease that even Having a normal APB won't catch a loan.

• 4:22Dr. Darshan Shah?

  So this is why it's extremely important to check an LP little a level at least once in your life. Now, I say once in your life because once you check it, remember this is genetically determined. So if it's normal, it's highly unlikely that it's going to be high later on in your life. So go ahead and get the check once, ask your doctor for this blood test, LP little a or lipoprotein A. So you know, once and for all, whether or not this is a problem. However, if you're the one in five people that has a high LP little a, remember that's defined as over 50 milligrams per deciliter. You need to start doing some investigations. I'd like to make a quick segue here because there's actually two different ways of reporting LP little a.

• 5:04Dr. Darshan Shah?

  Now, milligrams per deciliter is what I see on most blood panels, but sometimes I do see nanomoles per liter. And so anything above 125 nanomoles per liter is considered abnormal for LP little a. So make sure you're looking at the right units of measurement as well. So let's talk a little bit about what type of investigations you need to do if you have LP little a and what you need to be concerned about. Large scale studies have confirmed that elevated LP little a is an independent risk factor for getting plaque in your arteries called atherosclerotic cardiovascular disease. What does that mean? It means that you can have a completely great lifestyle. You can not smoke, you can be exercising.

• 5:44Dr. Darshan Shah?

  And if you have LP little a, you're still at risk for getting plaques in your arteries. So sometimes really bad plaques in your arteries and it is causal. That means it's not just associated with plaques. LP little a causes the plaques. So remember it has a high propensity to break through that wall of your blood vessel and create plaques. So let's talk about how LP little a can present clinically. Number one, premature myocardial infarctions. What does that mean? That means having an MI or a heart attack at an early age, sometimes even as early as your 40s. So if you heard of someone that had a heart attack out of nowhere and they're super young, or maybe you have a family history of people in your family having early heart attacks, that should raise an

• 6:30Dr. Darshan Shah?

  Alarm bell to you that perhaps LP little a has been a genetic issue in your family for a long time. Also, strokes, remember you there are blood vessels that go to your brain and these can also get plaque and can also form blockages going to your brain and this can cause strokes. And then finally, LP little a also can deposit plaque in your valves. So a lot of people have aortic valve stenosis from LP little a being high. And so if you know anyone that has a murmur or valve disease, it might also be due to LP little a causing that valve disease. So when I see a patient with a high LP little a, I highly recommend doing a coronary calcium score, or even better, a clearly exam that we talked about in a

• 7:12Dr. Darshan Shah?

  previous podcast. That's the CAT scan of your heart where we can look at every blood vessel and see what level of plaque you have developed. And we also get a Doppler ultrasound of their neck vessels to assess how they look. And finally, we'll also sometimes get an echocardiogram to look at the valves of their heart as well. At the bare minimum, someone needs to put a stethoscope on your neck and your heart and listen for sounds that can indicate either blockages in the arteries or valve dysfunction. There's a 2019 meta-analysis that was done in the Journal of the American Medical Association Cardiology that showed for every 50 nanomole increase in LP little a, there was a 10 to 15% higher risk of cardiovascular events. And this

• 7:54Dr. Darshan Shah?

  was independent of whether or not you had a high LDL or not. A meta-analysis is a type of study where you're combining the results from many other studies. So it's typically considered one of the best ways to look at results of studies with a lot of data. And this has shown that there is definitely a causal risk between LP little a being high and a higher risk of cardiovascular events. And that's why it's really important that you do all of this testing and closely follow your LP little a levels if your LP little a is elevated.

• 8:30Dr. Darshan Shah?

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• 9:12Dr. Darshan Shah?

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• 9:35Dr. Darshan Shah?

  At my practice at Nex Health, I'm often amazed by how many of my patients have liver health issues. It turns out that 38% of Americans have fatty liver disease and most people have no idea. You wouldn't really know until you do something like a liver scan using ultrasound shear wave technology, which we offer to all of our patients at Nex Health to get a good idea of how much damage has been done from metabolic disease and alcohol consumption. This is where a new product called Deliverance comes in. Invented by Siggi Clavien, it uses natural plant extracts that you drink as a liquid shot, which have been shown in studies to prevent and reverse fatty liver disease. I personally have a history of metabolic disease, which I work really hard to keep at bay. I use Deliverance myself three times a day

• 10:20Dr. Darshan Shah?

  to proflactively make sure that my liver stays healthy. It's super easy to use and actually tastes good, too. You can save 10% on your first order when you use the code DRSAH, that's D-R-S-H-A-H, at the website loveyourliver.com.

• 10:41Dr. Darshan Shah?

  Let's talk about one more reason that LP little a is particularly dangerous. LP little a actually inhibits the dissolution of blood clots. So it inhibits the dissolving of clots in your arteries. And why is that important? Well, a lot of people have studied heart attacks and strokes because that plaque forms a clot in it. And that clot completely blocks the artery very quickly. And so now LP little a, not only does it deposit more cholesterol in your blood vessels, but it's also inhibiting that clot from being dissolved. So you have a much higher likelihood of having a sudden stroke or a sudden heart attack. Another reason why it's really important to get evaluated for LP little a. So you can be more careful and understand what your risk factors are.

• 11:24Dr. Darshan Shah?

  So now, even though that all sounds really bad, let's talk about what are some things that you can do if you have an LP little a that's elevated. So number one, everyone needs to get tested. Whether you're in your twenties or thirties, just get your LP little a tested. Even if you're older, you just want to know. And once you know, we can put into some aggressive strategies to keep that LP little a at bay. Remember, LP little a is a genetic trait. So if it's elevated, it's going to stay elevated. And you only need to measure it one time. Then you know whether or not you're at risk for having all the negative effects of LP little a. Number two, you should know your risks of family history of premature heart disease, even a personal history of cardiovascular events.

• 12:09Dr. Darshan Shah?

  Despite having normal blood lipid values, if anyone had aortic stenosis in your family, then you really want to make sure that you get your LP little a tested because these are all indicators that you have a genetic risk of LP little a in you. Number three, this is how you treat it. You want to manage your other risk factors aggressively. So since we can't directly target LP little a right now, what we can do is manage all the other risk factors, really lower the other risk factors so that LP little a, whatever damage it does, is not as significant because it's not building on top of other risk factors. So what does that mean? You want to keep your APOB Really, really low. Remember, Apo B is all your bad forms of cholesterol.

• 12:53Dr. Darshan Shah?

  So if your LP little a is high, keeping your Apo B low reduces the damage from other forms of cholesterol. So a lot of people will say, get your Apo B down to less than 50. You will might need to be on cholesterol lowering medication to make that happen. And if that's the case, I think it's very beneficial to be on cholesterol lowering medication. While we wait for a treatment for LP little a to come out. Number two, you want to keep your inflammation at bay. Remember, inflammation is another additive cause to heart disease. So you want your H S C R P, which is a measure of inflammation as close to zero as possible. And you want to look at your homocysteine level, which is directly tied to cardiac heart attacks. And so keeping that normalized as well.

• 13:36Dr. Darshan Shah?

  How do you lower your inflammation? Well, first you want to make sure you have inflammation. If you do, most inflammation starts somewhere in the gut or in your oral cavity. And so you want to take a look at those areas. And if your homocysteine is high, you might have a methylation problem. And you might want to be taking a methylated B vitamin. Number three, keep your metabolic disease under control. The biomarker of metabolic disease, remember, is hemoglobin A1C. You want your hemoglobin A1C as close to 5.2 as possible. And there's lots of ways of doing that. Obviously, you want to control your intake of sugar. But also you want to get a continuous glucose monitor and really learn how you keep your metabolic disease managed. And finally, other life cell interventions, like having a diet rich in omega threes.

• 14:21Dr. Darshan Shah?

  You want to be doing resistance exercise and also aerobic exercise. You want to improve your VO2 max and your strength. You want to have lots of plants in your diet so your gut stays healthy. And finally, you want to be sleeping well and you want to manage your stress levels, obviously. All of these things are contributory to having heart disease and you want to keep all of these at bay. Number four, do not forget about high blood pressure. So high blood pressure is also contributory to high risks of heart disease and strokes. And so if you have high blood pressure, especially if you have LP little a, you want to make sure it's managed to be as close to 120 over 70 as possible. So these are all of the techniques that you can use to manage your risk of heart

• 15:03Dr. Darshan Shah?

  disease while you're waiting for therapies for LP little a to come out. And the good news is we're only a few years away from emerging therapies that are coming out that are going to help solve the problem of LP little a. One of these therapies is called lipodiserin. And this is incredibly novel drug. It's incredibly exciting what they're doing with this drug. This is a drug where they're targeting the messenger RNA that tells your cells to make LP little a. So this drug works essentially by shooting the messenger. It doesn't allow that RNA message to get to your protein forming mechanisms in your cell. So your cell literally does not have the instructions to make LP little a.

• 15:47Dr. Darshan Shah?

  Another drug called olpisiran, which is by Amgen here in California, makes a small interfering RNA that also can shut down the production of LP little a in the liver. The preliminary results of this shows up to a 95% drop in LP little a. And what's crazy about these drugs is just one dose can lead to a complete wiping out of LP little a in what we're seeing in research trials. And this can be a long lasting effect. So incredible treatments are on the horizon for LP little a. And your job is to stay healthy long enough until these treatments come out. If you do have LP little a. And we went over some of the ways to do that. Please make sure if you don't know your LP little a level, take a look at your recent

• 16:32Dr. Darshan Shah?

  blood work and see if it's in there. If it's not in there at your next doctor's visit, get it measured. Everyone should be doing this, especially like I said, if you have a high risk of heart disease in your family history. And there's hope out there. So stay healthy, get tested, and I hope that this is not a problem for you. But if it is, there is hope. So stay alive long enough to be able to take advantage of incredible treatments on the horizon. Thanks so much for tuning into this solo show about LP little a on the Extend podcast. If you know someone that might be diagnosed with LP little a, or someone that you feel has a high risk of getting heart disease, make sure you send them this episode because this episode can really save their life.

• 17:14Dr. Darshan Shah?

  It's really important and it's something that's been somewhat missed in current risk factor assessment for cardiac disease. Thanks again for joining the Extend podcast.

• 17:26Dr. Darshan Shah?

  Thank you so much for listening to the podcast today. Please remember to subscribe if you liked this episode and give us a good review and share a link with your friends. It really helps to support all of our efforts. I also want to remind you that the information shared on this podcast is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Please consult with your healthcare provider or physician before making any decisions or taking any action based on what you hear today, especially if you have any underlying health conditions or on any medications. Your doctor knows your personal health situation the best and it's always important to seek their guidance.