Speaker 00: 0:00

Welcome to the Health Pulse, your go-to source for quick, actionable insights on health, wellness, and diagnostics. Whether you're looking to optimize your well-being or stay informed about the latest in-medical testing, we've got you covered. Join us as we break down key health topics in just minutes. Let's dive in.

Speaker 01: 0:26

Welcome to the deep dive. Today we're tackling something really important, but often overlooked in heart health. It's called lipoprotein. LP. Or you'll often just hear it called LPA. And here's the kicker, the thing that really grabs you. You could be doing, well, everything by the book, your normal cholesterol check. LDL, HDL could look absolutely perfect. Pristine, even, but, and this is a big but. You might still have a significantly higher risk, maybe two, maybe three times higher for a heart attack or stroke. And the reason, it often comes down to this one hidden factor, this LPA. So our mission today is to really dive deep into this hidden risk. What makes it different is that it's uh almost entirely genetic, not really about your diet or how much you exercise.

Speaker 02: 1:07

Aaron Powell That's exactly right. And we need to be clear, this isn't some minor detail. LPA is, well, it's recognized now as a strong independent risk factor for atherosclerosis, that's plaque buildup, and also for those sudden events like heart attacks and strokes. The real issue is that standard tests just don't measure it. So you have many, many people walking around completely unaware they have this elevated risk. Often they don't find out until, unfortunately, something actually happens. So awareness, just knowing about it, is really the first step.

Speaker 01: 1:34

Aaron Powell Okay, let's try and unpack this particle then. You mentioned it's like cholesterol. Structurally, it looks a lot like LDL, right? The quote unquote bad cholesterol. So what makes LPA so much more, well, dangerous?

Speaker 02: 1:47

Aaron Powell Yeah, it starts with that LDL-like core, but the crucial difference is this extra protein it carries, something called apolipoprotein. It's sort of hitched onto the LDL particle. And that attachment, that's the key. You can think of it like LDL, sure, but maybe LDL carrying, I don't know, a hidden weapon that causes trouble in your arteries. And the scale of this, it's why we need to talk about it. Around one in five people globally have elevated LPA. That's 20% of everyone, carrying a common but uh very underdiagnosed risk factor for heart disease, often happening much earlier in life.

Speaker 01: 2:21

One in five.

Speaker 02: 2:22

Yeah.

Speaker 01: 2:22

Wow, that's huge. And this is maybe the most important thing for you, the listener, to grasp. Your LPA level is largely fixed. It's set by a specific gene, the LPA gene that you inherit. So, unlike your regular cholesterol, this number doesn't really change much throughout your life. It means basically one single blood test can give you a pretty clear picture of your lifelong risk profile from the specific factor.

Speaker 02: 2:42

Aaron Powell Exactly. That genetic stability is why getting tested at least once is so important, especially if there's any family history of early heart issues. Now, about that hidden weapon part, why is LPA seen as such a problem? It seems to cause damage through multiple ways, not just one like standard LDL, a kind of triple threat.

Speaker 01: 3:01

Aaron Powell Okay, so mechanism number one is pretty straightforward: plaque formation. Just like its cousin LDL, the LPA particle delivers cholesterol into your artery walls. That directly helps build up atherosclerotic plaque. That's the basic cholesterol deposit function.

Speaker 02: 3:14

Okay, so it drops off cholesterol, fuels plaque. Got it, like NDL. But you said triple threat. What else is going on? Where does that extra protein, the epilipoprotein, come into play? Right. So that attached apolipoprotein is where the second mechanism kicks in, thrombosis or clotting. This protein actually looks a bit like another protein involved in breaking down blood clots, plasminogen. It gets in the way, it sort of jams the system your body uses to dissolve clots. So it creates what we call a pro-thrombotic environment. Meaning if a plaque does break open, you're much more likely to form a dangerous clot right then and there. And that sudden clot is what causes a heart attack or a stroke.

Speaker 01: 3:50

Aaron Powell Hold on, so it's not just building the plaque, it's actively stopping your body from cleaning up potential blockages afterwards. That sounds really insidious.

Speaker 02: 4:00

The third element is inflammation. LPA particles tend to carry these things called oxidized phospholipids. Think of them as inflammatory signals. When LPA gets into the artery wall, it brings these signals with it, triggering localized inflammation. And inflammation makes those plaques angrier, less stable, and much more prone to rupturing unexpectedly.

Speaker 01: 4:19

So building plaque, increasing clot risk, and fanning the flames of inflammation. Wow. Looking at the research, this triple threat really translates into a massive risk increase, doesn't it? We're seeing figures like uh two to three times greater risk of premature heart disease for people with high LPA. And crucially, that's even if all their other standard numbers, like LDL, look perfectly fine, that really highlights why just checking standard lipids isn't enough.

Speaker 02: 4:45

Absolutely. And the impact isn't just limited to the coronary arteries either. We now have strong evidence linking high LPA to another serious condition, calcific aortic valve stenosis. That's where the main valve leading out of your heart gets stiff and narrowed. So it seems LPA contributes to problems in heart valves too, not just arteries, it's a systemic issue.

Speaker 01: 5:05

Okay, this brings us to a really practical point: detection. You'd think something this common and this dangerous would be part of every checkup. But the challenge, as you mentioned, is that high LPA doesn't cause any symptoms you can feel. Nothing. And you can't really diet or exercise it away significantly, so you have to actively look for it.

Speaker 02: 5:22

Precisely. We often rely on clues, indirect signs. The biggest red flag that should definitely trigger an LPA test is a strong family history of cardiovascular disease happening early. You know, a parent, sibling, grandparent having a heart attack or stroke before, say, age 55 in men, or maybe 65 in women, that's a major signal. We also know there are genetic variations, and certain ethnic groups, including people of African ancestry, tend to have higher LPA levels more often. That's another factor to consider.

Speaker 01: 5:53

So if it's not on the standard panel and there are no release symptoms, how do people usually find out they have high LPA right now?

Speaker 02: 6:01

Well, sometimes it's picked up if a doctor orders a more advanced lipid panel, but honestly, that's less common. More often it's discovered because of clinical suspicion. You know, a doctor sees someone, maybe relatively young, who's had a heart attack or stroke, they look at the person's chart, see normal LDL and normal triglycerides, and think, wait a minute, this doesn't add up. That mismatch serious heart disease, despite seemingly good standard cholesterol numbers, that's a huge prompt to specifically test for LPA.

Speaker 01: 6:26

It seems like a catch-22. You often don't test for it until after the event you were trying to prevent. If 20% of us have this and the risk is fixed and significant, why isn't it just routine, like checking blood pressure?

Speaker 02: 6:38

Ah, and that leads us straight into the biggest historical challenge, treatment. Or rather, the lack of effective treatment for decades. LPA just doesn't respond well to our usual go-to strategies. Take statins, for example, the most common cholesterol drugs, they generally have little to no effect on LPA levels. In fact, in some people, they might even cause a small increase. And as we've said, lifestyle changes, diet, exercise, while fantastic for overall health, they just don't significantly lower this genetically driven number. So for a long time, doctors thought, well, even if I find it, what can I really do about it? The options were and still are somewhat limited. We have PCSK9 inhibitors. These are powerful injectable drugs, mainly used for very high LDL. They do lower LPA, but only modestly, maybe around 20%, perhaps 30% reduction. Good, but not dramatic for LPA. And then for the absolute highest risk patients, there's something called lepoprotein apharesis. It's basically like dialysis, but it filters lipids, including LPA, out of your blood. Highly effective, but also very invasive, time-consuming, and expensive, reserved for extreme cases.

unknown: 7:38

Aaron Powell Right.

Speaker 01: 7:38

So it sounds like we've mostly been managing around the edges, trying to control all the other risk factors even more aggressively if LPA is high. Because we couldn't directly tackle the LPA itself. But this is where things get really exciting, isn't it? Science often has these moments where the game suddenly changes. What's happening now with targeted therapies?

Speaker 02: 7:56

Aaron Ross Powell This really is the breakthrough era for LPA. We finally have tools that can directly target the root cause, the production of LPA, dictated by that LPA gene. We're seeing incredible results coming out of late-stage clinical trials for brand new types of drugs. These are genetic silencing therapies, things like antisense oligonucleotides or ASOs. There's one called pelicarsin, and also SIRINA drugs like alpacarin and SLN360. These basically tell the liver to stop making so much LPA.

Speaker 01: 8:25

Genetic silencing. That sounds pretty advanced. And what kind of results are they seeing? You mentioned TCSK9 inhibitors give maybe a 20-30% reduction. How do these new drugs compare?

Speaker 02: 8:35

It's a completely different league. We're talking about potentially huge reductions. The early and ongoing studies are showing these therapies can lower LPA levels by 80 to 90 percent, sometimes even more. That's what is potentially transformative. If these trials continue to show benefit and safety, the expectation is that these drugs could become available in the next few years. It would fundamentally change how we manage this high-risk condition.

Speaker 01: 8:58

Wow. 80 to 90 percent. It's a genuine game changer on the horizon.

Speaker 00: 9:02

Yeah.

Speaker 01: 9:02

Okay, so that's the future, and it looks incredibly promising. But let's bring it back to right now. For you listening, while we wait for these amazing new treatments, what can you actually do? What are the proactive steps?

Speaker 02: 9:13

Okay. The absolute first thing, and let's be crystal clear. LPA is not typically included in a standard cholesterol test or lipid panel. You almost always have to ask for it specifically. So talk to your doctor. If you have concerns, especially that family history, ask for the LPA blood test by name. When you get the result, it'll likely be reported in either milligrams per deciliter MGDL or nanomoles per liter NGL. The key threshold to be aware of is generally around 50 milligdl. Or if it's an N mole, that's roughly 125 nelomoles. Levels above that mark are typically considered elevated risk.

Speaker 01: 9:47

So 50 milligdl is the number to watch. Is that the only thing? Or are there other tests that help paint a fuller picture, especially if that LPA number comes back high?

Speaker 02: 9:54

That's a great question. Yes, usually we look at it in context. Two other tests are often very helpful. First, measuring apolipoprotein B, APOB. APOB gives you the total count of all the potentially plaque-causing particles, including LDL and LPA. If your LPA is high, your doctor might set a much lower, more aggressive target for your APOB level. Second, checking inflammatory markers like high sensitivity C reactive protein, HSCRP. This tells you if there's underlying inflammation in your body, which could make the high LPA even more dangerous. And sometimes, particularly if the risk seems high based on LPA and other factors, imaging can be useful. A coronary artery calcium score, or CAC score, is a CT scan that looks for existing hardened plaque in your heart arteries. Finding calcium even a little bit when you also have high LPA really signals a need for very aggressive management of everything else.

Speaker 01: 10:44

Okay, putting it all together for right now, while we wait for those 80-90% reduction therapies, the strategy is clear. Step one is early detection. Find out your LPA number. And if it is high, then step two is relentless aggressive control of every other modifiable risk factor. That means getting your LDL cholesterol, or APOB, way down, keeping blood pressure perfectly controlled, managing inflammation, not smoking, basically compensating for the fixed risk of LPA, but optimizing everything else you can control.

Speaker 02: 11:14

That sums it up perfectly. LPA is this potent genetically determined risk factor that's been hiding in plain sight for too long. Identifying your level empowers you and your doctor to personalize your prevention strategy, control what's controllable today, and be ready for the targeted therapies that are just around the corner.

Speaker 01: 11:30

Absolutely. Knowing your LPA number really is power, especially since it's usually a one-time test that tells you about a stable lifelong risk. If you have that family history or just want to know your full picture, it's definitely a conversation worth having with your clinician. And maybe we could leave you with this final thought to chew on. We've talked about LPA being largely genetic, something diet and exercise don't substantially change. If one in five people carry this fixed risk, does knowing this shift how we think about health, risk, and maybe even accountability? And how long will it be realistically until checking LPA stops being something you have to specifically ask for and becomes as standard as routine as getting your blood pressure checked? Something to consider. Thanks for joining us for this deep dive.

Speaker 00: 12:14

See you next time.quicklabmobile.com. Stay informed, stay healthy, and we'll catch you in the next episode.