Vascular Surgeon: What Really Causes Clogged Arteries | Dr. Lily Johnston

I as a vascular surgeon predominantly see people who've had a problem already from plaque. Why do you have plaque? Is this an inflammation problem? Is this a lipid problem? An insulin problem? Where is this coming from? And how are we going to put that fire out?

LP little A is an LDL cousin, an apo molecule, but it has this very sticky long velcro tail. This makes it much more likely to get stuck in the artery wall. We believe that patients who have elevated levels of lipoprotein little a may be less able to break down small blood clots in the arteries. LP little a also has a relationship to the amount of calcium that can deposit for example on the aortic valve, the valve that keeps blood moving out of the heart into the rest of the body.

The most important thing is to understand are you in a high-risk bucket? Because if you are, then we would like to be more aggressive about managing your overall cardiovascular risk. Somebody who's got overweight and visceral fat, we are overnourished. For many people who start with excess inflammation and visceral fat, a low carbohydrate approach actually reduces cardiovascular risk.

>> What actually causes plaque to form in the artery wall?

>> I actually think it is different in different people. Plaque is the end result of a number of different processes. And we know this sort of colloquially because the disease that we treat, for example, in patients who smoke is a kind of different than the disease that we treat in patients who have kidney failure or the patients who have long-standing diabetes. The plaque where it is is a little different. The composition of it is a little different. And you know, patients come in with plaque from all kinds of different ideologies. Again, some people it's diabetes, some people it's smoking, some people it's autoimmune disease and a long-standing history of inflammation. Other people have a strong family history and genetic component to the plaque in the arteries. So plaque is is like the end state of a number of different pathways that I think lead us into damage to the artery wall and the body's desire to repair that damage and seal that off.

Okay, since it is so multifactorial, somebody say middle-aged right now, feeling healthy, they don't know of any issues when it comes to their arteries. How do they begin to navigate all these different variables and get that baseline?

The kind of standard medical answer would be make sure your blood pressure is under good control. Make sure that you've had some regular lab testing done. And you can go so far as to plug those numbers into the risk calculators that have been developed by, for example, the American Heart Association, American College of Cardiology. The current one is called the Prevent equation, and they do an okay job at the population level of helping us understand who is more likely to develop disease than who than others. However, we know that they miss a lot of people, and they will minimize risk for some people and they overestimate risk for others. And so when I think about this at the individual patient level, I don't love the calculators. I would much prefer people got a little more aggressive in terms of screening and got some imaging because if we are just using a risk calculator, we're guessing, right? This is a population average. But if we want to know, then we have to use our eyeballs. And that means getting some kind of imaging test to look at the artery and figure out, is there disease there?

>> Okay. Well, let's give a lay of the land here. Talk about different options in that realm and pros and cons.

>> The far and away the most common is the CAC, coronary artery calcium score. And it is the most accessible to people, meaning it is easy to get, relatively speaking. It is not that expensive. The radiation dose, it's a CT scan based technique, and the radiation dose is pretty low. So for a lot of people, it's a good starting point because it's again, the easiest thing to get, and some imaging is better than no imaging. It has some drawbacks. It only images calcified plaque, which is a little bit older, probably more stable, and ultimately it is that calcium is is a marker for the idea that there is also newer, less stable, lipid-rich soft plaque that might be in the arteries and about to cause trouble.

The other techniques that are available are like ultrasound-based techniques that image usually the femoral arteries and the carotid arteries. So in the groin and in the neck. Uh, and you can get a regular ultrasound or you can get something a little more advanced, CIM or carotid intimal medial thickness testing, and protocols associated with that can be very, very useful, and it's something I lean on heavily in my practice. The other thing that's become very popular in the last several years would be CT angiography of the coronary circulation or the blood vessels around the heart. So CCTA is how we're going to abbreviate that one. And that is like a calcium score, but it uses dye that's injected into the veins that circulates in the body, and it shows us actually the vessels themselves. So it's not just the calcium. Now we can also see the lumen or the flow channel of the arteries around the heart, and we can now visualize the soft plaque as well as the calcified plaque and any areas that are severely narrowed. So that gives us a lot more information, and in younger patients or patients who have a very high calcium score who then need additional triage imaging, potentially the CCTA, that angiogram dye test is very, very helpful.

Somebody that feels like they're healthy though, middle-aged, they have no signs or symptoms, what would they start with and at what age to have that baseline?

That's very individual and it really depends on how worried you are and what you're going to do differently. If you're telling me that you're exercising, you know, four or five hours a week, and your diet is perfect, and uh, you've got no family history of heart attack, stroke, anything like this, and you're not prepared to do anything differently because you're feeling amazing, then I would say, uh, you know, don't do anything because if you're not going to change it, then why are we getting more information? Um, I would say that's the minority of people that I that I see and interact with. Most people have something that we can improve on, do better with, and uh, change in our own lifestyle and potentially in other ways. Therefore, it is about, you know, how old are you? How concerned are you about your history? Are we sure you're not having any symptoms? And then what's available to you, right? I have a lot of people who come to me, it's like, I tried to get a CIMT, but they don't have them near me. Okay, let's start with a calcium test. Just get a calcium score and see what that is. And you know, if you're over 55 years old and you have a zero score, that's pretty reassuring. Uh, it's not perfect, but it's reassuring at least for a low event risk in the next 10 years. And if you're under 55, then I would say, you know, are you willing to pay out of pocket and have a little more radiation for a CCTA or to go out of your way to go elsewhere to get a CIMT test?

>> Okay, let's take this from the metabolic health perspective. A common, unfortunately, thing happening within society today. People are metabolically unhealthy, many of them not knowing it. Let's talk about how plaque develops from that ideology.

>> Yeah.

>> And work our way into the formation of a plaque, and we'll go from there.

We have multiple hits. So if we're talking about metabolic syndrome, right? So uh, if you want to talk about how people are metabolically unwell in the United States, for example, the NHANES data would tell us that this is related to elevations in blood pressure, elevations in our triglycerides, which are fatty particles circulating in our bloodstream, low HDL cholesterol, which is a marker again of metabolic syndrome, elevated fasting blood sugar, and elevated waist circumference or visceral fat, fat that has accumulated around the organs, which is very inflammatory. So for all of those things, we we have a bunch of different insults to our vasculature. The first would be that elevated blood sugar also causes elevated insulin, right? That's that hormone from the pancreas that allows us to try to process our excess energy in the body after we've eaten it. And eventually, if that system is stressed long enough, the insulin levels will rise because there's just an excess energy all the time, and the body is like struggling to process that. That insulin circulating is a problem, right? It causes inflammation in the blood vessels. It impacts our nitric oxide synthesis, and that is a relaxation molecule that's circulating in our bloodstream. Exercise raises nitric oxide. Uh, hyperinsulinemia will decrease that. The sugar itself, if we're having excursions of high blood sugar, can be damaging to that very fragile, delicate inner lining of our blood vessels called the endothelium. We know that sugars can damage that glycoalix and the endothelium there. So that's an insult there. The uh, high blood pressure, if that is the result of, well, for whatever reason, high blood pressure pushes more stress on that artery wall, which again can cause micro damage over time, and that is a problem. The arteries then become stiffened. They don't expand well, and that also can result in plaque formation. And then finally, we have the inflammatory insult of excess visceral fat, and that inflammation will also damage our blood vessels and ultimately potentially result in the formation and generation of plaque.

>> Okay, let's keep the story going from the point of we have damage in the vessel. Let's talk about how the body responds. You know, again, this is where we come back to this idea that everybody responds a little differently. I have seen people with bad metabolic markers who don't have plaque, and it's surprising. So this is why I think the imaging is so important, and it doesn't mean that we are any less worried about people's metabolic health because for all kinds of reasons, it's important, right? We also know that it tracks with cancer risk, which is, if the heart disease doesn't get you, then probably cancer is the next most likely thing. So metabolic health is critically important, no matter what. So let's start with that. But at the individual level, people respond differently. There are people with great blood markers and minimal inflammation who still develop plaque, and vice versa. So at the individual level, we don't know, and this is why imaging is important. But let's just talk broadly at the population level.

What happens is that the lipoproteins in our blood, so these are the LDL particles in particular, or any particle with this apo protein. People may have heard of the apo story before, and this is a little bit of a better marker for overall cardiovascular risk than LDL cholesterol. In the majority of people, they track together. But in patients who are metabolically unwell, we can actually have discordance, meaning they don't totally match up. And if your apo is discordantly high, then uh, again, we're we're talking about misunderstanding your risk. So anyway, these apo particles, these are the ones that get trapped in what we're going to call the subendothelial space, or this is in between the two inner layers of our blood vessels. The particles normally travel in and out routinely, right? That this is just the normal process of how things move in our bloodstream. Those particles typically freely come in and out of the artery wall. But if we have inflammation or we have an injury to the arterial wall from high blood pressure or toxic exposures like nicotine, for example, then that inflammatory cascade starts to transform these areas in the blood vessel wall, and they get sticky, and those lipoproteins then get stuck there because they have this more like velcro situation where they don't, they come in, but now they can't leave. And then our immune system starts taking over. The immune system starts eating up these lipoproteins. And then our macrophages turn into what we call foam cells, right? They get all of this fat in them, and they get this soapy, foamy look to them. And then we get transformation of the muscle cells. So the arteries have muscles in them to pump. The veins don't. But the arterial smooth muscle cells then begin to transform, and slowly this becomes a thickening in the wall of the vessel. And if it progresses, because once we start this cycle, then it becomes a feed-forward process. Now there's this pro-inflammatory kind of toxic soup that's sitting in the arterial wall. As more protein lipoproteins get there, they also like there's more macrophages, there's more inflammatory cells, and so they also get kind of picked up into this um plaque forming situation, and it it becomes this feed-forward process. You you get more plaque, more plaque, more plaque until we do something to put out this fire.

>> Okay, once we have the plaque, what's best-case scenario?

>> This is debatable. The recent literature has discussed plaque regression, meaning the ability to actually begin to take some of the fatty molecules out of the plaque and shrink the size of the plaque. Ultimately, plaque is really not the enemy. The enemy is plaque rupture events that lead to heart attack, stroke, and limb loss. And plaque by itself is the best proxy we have to understand whether plaque rupture is going to happen. But there are many, many, many people who will go their whole lives with some stable plaque in their arteries that never causes an issue. So again, you know, we started out with, well, what's your blood pressure and what's your cholesterol? Now we're into this era where we understand that imaging is very helpful, and imaging shows us plaque, and that is the next best thing we have to understanding your risk for an event, but the event is actually the enemy.

The plaque itself comes in lots of different forms, right? We have unstable plaque, we have stable plaque, and it does two different things. Eventually, you can have so much plaque burden, just actual physical amounts of it, that it can narrow the artery, and you can prevent oxygen from being delivered. If that happens slowly over time, that tends to cause stable symptoms like angina, which is chest pain with activity. But some people get it when they, you know, walk three miles, but at two miles they're fine. And at three miles they start to get this chest pressure. If they slow down or stop, it gets better. People can have the same issue in the vessels in the legs. It's called claudication. We walk for a while. The leg muscles start to cramp as they are needing more oxygen than they're getting. But if we stop and rest, it gets better. So that is typically a like physical problem, just delivering the amount of oxygen that the body's asking for. The other thing that can happen is that we get a sudden blockage, occlusion, rupture of this plaque that then suddenly blocks off flow. That is most of the time what is causing heart attack, stroke, or sudden acute limb problems. And that is really the enemy here. So that's a soft plaque problem most of the time. And that means that plaque itself could go away. That's probably the best-case scenario. But a and in some studies, we're having early signals that perhaps plaque regression is actually better than just stabilizing our plaque, the existing stuff that we have, and turning it from the vulnerable soft plaque into the hard stable calcified plaque. But up until now, in the kind of mainstream community, the idea has been, let's at least, at the very least, just stabilize the existing plaque we have, turn it into this calcified dormant volcano, right? And prevent it from becoming an erupting volcano. Let's just cool it down, stabilize it, and if that never changes, then we'll call that a win. And let's do everything we can to prevent the formation of new plaque over time.

>> Okay, coming back to our story there where all the cells come in, we have inflammation in the vessel. Is that soft plaque at that time? And then if we don't get a rupture and that eventually progresses over time, does that solidify and become the hard plaque?

>> Yes. To the best of our understanding, that is the progression. And so the the plaque different types of plaque are actually different time points of plaque evolution. And so there are many people who will have like a high calcium score, but if you do a CT angiogram, they actually have minimal soft plaque, either because they have changed everything in their metabolic health milieu that has now evolved and created a stable situation and they've put that fire out, or because they have undergone significant treatment for whatever inherited pathology they may have. And so we can have a fair amount of stable plaque that doesn't really cause trouble. Conversely, you can have people that have not too much calcified plaque but a lot of soft new atheroma or plaque, and uh, that is that situation where, you know, people are saying, I had a calcium score of zero, but then I had a heart attack, or people saying, you know, I had a normal stress test and then I had a heart attack. And so those are situations in which there's a fair amount of vulnerable plaque that may not be blocking blood flow very much yet, but is still very likely to create uh, an event. And our understanding of how to how to capture those people early is a challenge because it's not the majority of the population, but for those particular people, it is, of course, life-changing if this happens. So we're still evolving because overt treatment is probably a is definitely a concern, as well as under detection and under treatment.

Do we have any idea at this point if somebody has soft plaque, it doesn't rupture, eventually becomes the stiffened calcified plaque, what that timeline is to go through the process?

>> I think that the timeline really depends on how aggressive we are in terms of the environment in which things are progressing. So I have used the analogy of weather in a forest before, right? So a forest fire is this unstable uh plaque situation, and you know, whether things continue to smolder in the long run uh versus totally extinguish has a lot to do with how dry is the environment. Is there rain? Is there lush vegetation, or is this all dry tinderbox, and is that ongoing? So I think for people who have some soft plaque and then radically change what they're doing based on that information or based on any kind of impetus to have a new health journey, then uh, that calcification can happen more rapidly. Certainly, we know that certain medications can rapidly stabilize plaque. Uh, but I think it's still on a time frame of months to years. We're not talking about days to weeks.

>> Okay. Got it. But living the lifestyle and adopting the diet we're going to talk about later will speed up that process of getting from A to B.

>> I believe so.

>> Let's come back to our soft plaque unstable. Do we know when there's an event and that ruptures? What makes somebody's plaque more vulnerable to that?

>> The amount of lipid inside the plaque tends to be relevant, and that we know from prior imaging studies. There is a cap over top of the plaque. You can think of this like the the little bit of earth or crust over the top of a volcano before it erupts. And the thickness of that fibrous cap is directly relevant to plaque rupture risk. So the thinner the cap, obviously the more likely you are to have an event. And we know that certain things kind of trigger events. So heart attacks are more common around like daylight savings time changes, uh, when we have a disruption in the circadian rhythm. It's more common around the holidays when people are more stressed out or potentially like feeling more socially isolated, and uh, you know, all kinds of stressful things can trigger this. But I would say spikes in inflammation can absolutely cause a rupture event. Uh, anything that is acutely stressful may trigger that. We we don't know for sure what triggers it in any particular person at any given time. But certainly at the at again, at the population level, we have some indication that acute stressors can do it.

As somebody moves towards that solidification of the plaque, it's now calcified. Are you concerned of an event at that point, or is that person basically the same as somebody without plaque once that's totally solidified?

I based on the population data, they are never the same as somebody who has no plaque. But I think the, for example, the literature in endurance athletes is interesting. Right? We have evidence that suggests that endurance athletes have more calcification in their coronary arteries than you might expect. And for the same level of calcium, if you compare an endurance athlete to the average sedentary person at the same calcium score, call it 300, the endurance athlete is much less likely to have an event, but they don't go all the way down to zero. The risk doesn't translate to somebody with no plaque or a CAC of zero, but it's much less than the CAC, the same CAC of 300 in a sedentary person. So for whatever reason, whether that is that there is still some ongoing other plaque that we haven't detected, whether that is embolization from the calcified plaque, or I don't know exactly. What I can say is your event risk comes way down. We're probably never going to get it to the level where it's zero or no risk or the same as somebody with a CAC of zero, but it's much better.

>> Okay. As somebody is going through the healing process, they're going from a state of a lot of soft plaque to hard plaque, I would assume their calcium score will go up. Does that happen? And then how do you reassure somebody that they're on the right path if that's happening?

This is why I don't love repeat calcium scores by themselves because you can have this in one of two scenarios. The first scenario where your calcium score goes up is that we are transforming soft vulnerable plaque into the calcified more stable plaque. And that's a good thing, right? Overall, the total plaque burden is the same, but more of it is stable and calcified. The alternative situation, which you cannot really distinguish between these if all you're doing is calcium scoring, is you have progression of disease. Whatever we have done in terms of your nutrition, your lifestyle, medications and supplements, sleep and stress, whatever we've done to intervene is not enough, and the calcium score goes up. Well, that in in a person where we're not doing enough is actually the progression of disease. They have more calcified plaque and more soft plaque. But a calcium score doesn't tell you that. So what you need at that point is more advanced imaging, either a CCTA, that coronary angiography with dye, or a CIMT that will talk to you about how much soft plaque there might be and how much inflammation there is in the vessel wall. Both of these are being, you know, in this scenario that I'm discussing, both of these are sort of being used beyond where they've been tested, right? There's not a guideline that says if there's progression in your IMT or there's progression in your soft plaque volume that we're going to do something differently. But intuitively, it makes perfect sense, right? If there's more soft plaque or total plaque volume, uh, then obviously we're not doing well enough controlling the environment around this forest fire, we have not put out the fire. So, for this reason, I don't really recommend repeat calcium scans by themselves to help us understand what's happening because it's one of two things. One's good, one's bad. Um, and the the real way to to get a better handle on that is to get more advanced imaging.

Let's talk more about the CIMT. So, somebody's getting an ultrasound done in the neck. We're looking at the carotid arteries there. How much does that correlate to what's happening in the heart?

It's a great question, and it depends on how you do it. So I will start off by saying in the general medical community, CIMT is not well-liked. It is not recommended, and many classic providers will not do it. If the average person is getting an ultrasound of their carotid arteries, what they're usually getting is a standard regular carotid duplex, which is looking for enough plaque to narrow the artery by 50% or more, which is a lot of plaque if you're thinking about, you know, the grand scheme of things. Um, below 50%, a regular carotid duplex is going to read as normal. Some texts will comment on the presence of soft plaque that or any plaque that is not flow-limiting, but not every tech will. And not every physician who reads that ultrasound will make any mention of plaque if it's less than 50% narrowed. So that's what the average person gets when you get an ultrasound of the neck. That's not super helpful in understanding your coronary risk if it's negative. The CIMT is, if you just say it like that, right? Just a CIMT. That is a measurement that any ultrasound machine can do with a push of a button. And by that standard, it's not super helpful. Um, what it really means is the thickness of the two innermost layers of the artery wall. It's the intima and the media. That's the I and the M in the CIMT. That measurement, if you're only looking at one small piece of a three-dimensional structure, uh, is not super reliable. The IMT measurement is a little bit dependent on the sonographer who's doing the testing and where they're choosing to get that measurement. The way to make this a much more reliable examination is to have a protocol where we're taking multiple images at very high resolution of the common carotid artery on both sides of the neck. We're trying to get, we're trying to take pictures of the entire back wall of the artery. So that requires multiple different angles of the probe to get that, and then making as many measurements as we can, hundreds of measurements on each of these images, and averaging that to try to get a very precise estimate of that IMT. And if we're doing a true IMT high-quality protocol test, we are also looking for the presence of plaque, which is a separate part of this examination. When I think about CIMT in my practice, this is really what I mean is also the detection of plaque. And there is a very well-known preventive cardiologist named Dr. Fooster who has done work imaging middle-aged asymptomatic individuals. And between detecting plaque in the carotid arteries in the neck and the femoral arteries in the leg, we can get about 90% concordance with coronary imaging. So that means 10% of the time we're missing patients. Uh, either they have plaque in the neck and the femorals but don't have it in the heart, or they have it in the heart and we didn't detect anything from the neck and the groin area. But 90% isn't bad considering we're having no radiation. It's a test we could do every year, and uh, it is, you know, pretty pretty reliable.

>> Okay. It sounds like there's a real art to getting this done properly and getting the value from it. How does somebody find a practitioner who's competent at doing it?

>> I think the best thing to do is to go through the two, there there's at least one amazing lab. So, Cardiorisk is the imaging lab that I use to grade and and score my IMT tests. Uh, there may be some others out there, but in in my, you know, research, I haven't found any of them as as dedicated to quality, reliability, and reproducibility as the Cardiorisk team. So, Cardiorisk is a company. They, I send them my ultrasound images, but they have ultrasound techs of their own, and they will fly a tech out to your practice. If you're a clinician and you have like 10 people who you need to get scanned, if you can like get them all together in a day, Cardiorisk will send a sonographer and an ultrasound out to your practice, and they will scan those patients for you. Uh, they are now doing some pop-up scans. So, if you go to the cardiorisk.com website and you look up where can I get scanned, they are now having these pop-up events where they have like one or two days a month in California, Arizona, Hawaii, other places around the country where anybody can sign up and go get a scan. So, Cardiorisk is still a small company. There are not. Again, this is why I still use calcium scoring for some patients because not everybody can get a Cardiorisk CIMT done, but if you can, that is far and away. Uh, the best test.

How do you look at lipid panels? And when you get one of those done, what do you find valuable?

Let's start with the very basic lipid panel that most people are going to walk in with from their primary's office. That is your standard total cholesterol, LDL, HDL, and triglycerides. Uh, in most places, you can have this done fasting or non-fasting. A non-fasting lipid panel is not very helpful to me, and I would actually almost always repeat that as a fasting test because the most interesting thing for me in your standard lipid panel is probably your triglycerides. The next thing that's interesting is your non-HDL cholesterol, uh, which is your total cholesterol minus the HDL. And both of those things will be pretty significantly impacted by the triglycerides, which are the most sensitive to being elevated after a meal. So postprandial elevation, which is a normal thing, by the way, but I don't know how to interpret your panel under those conditions because I don't know what you had to eat and how much of it, and how far after your meal were your labs drawn, and all of this. So a fasted lipid panel is the most interesting thing. And if we're just looking at your basic panel, then your triglycerides and HDL, of course, that gives us two pieces of the five for whether you might have metabolic syndrome. And um, I'd love to see triglycerides under 100. 150 is usually what the reference range, like top of the um or the bottom of the normal values in a reference range are, but I really want them under 100. Some people would even say under 90 is optimal. And I'd love to see them actually lower than your HDL cholesterol. And that's kind of the unicorn holy grail scenario. And I have many patients who achieve that. The LDL cholesterol is the next thing. We have to be a little bit careful about how that's calculated and especially if triglycerides are elevated, how we understand that. And at that point, now we're going to talk about sort of more advanced lipid testing and how to get a little bit more value out of your non-HDL or your LDL cholesterol. Right? This comes back to the idea that the cholesterol was the first thing we could measure. Okay? When we started trying to understand lipids in the blood, cholesterol was what originally we could isolate and measure. But cholesterol is actually the cargo. What is being transported are the lipoproteins, the proteins, because cholesterol is a fatty molecule, and our bodies are mostly water. And, you know, that oil and water don't mix. And so how are you transporting these fatty molecules in our water-based ecosystem of the body? The answer is that they are bound to these lipoproteins. And it's the lipoproteins that are actually much more involved in atherogenesis or formation of plaque because the actual cholesterol molecule on HDL particles is the same as the cholesterol molecule on the apo or the LDL particles. So it's not the cholesterol by itself that is so important. It is actually what transports the cholesterol and the proteins or the lipoprotein particles that are doing this. And so the way to think about this, if we want to step back, is just to think about it like a delivery fleet. So you're Amazon, and you have packages that need to go different places. Okay? So all of the cargo in your Amazon Prime delivery truck, that's the cholesterol, but the trucks, the bikes, the little, you know, people who are couriers and doing it from their sedans, the big shipping containers, like how stuff gets around, those are the lipoproteins. And if you want to think about plaque formation, what's much more relevant is about, you know, the the analogy is how do you understand about your risk of getting into an accident on a major highway. Okay? Is it about the amount of cargo in the trunk of any given number of cars, or is it about the number of cars on the road? Your risk for getting into an accident is way more related to the number of cars on the road than the amount of cargo that they are carrying. And if you had nothing else to go on, sure, the amount of cargo is a proxy for the amount of cars on the road, right? If there's a lot of cargo, you imagine there are more cars on the road than if there's a little bit of cargo. But you could also see how it depends on the size of the car, how big the cargo space is, and how full are they, right? This is where we get this distinction between LDL cholesterol, which is what's typically measured, and more interesting measures like LDL particle counts, which is actually now counting the number of cars, or APOB, which is now counting the number of atherogenic cars on the road. And that's why advanced lipid testing can be helpful, especially in patients where AOB and LDLC are not tracking together.

>> Okay, let's make sure we clarify. LDLC, LDLP and APOB.

>> This is something I still get confused on. LDLP is LDL particles, and this is the actual measure of the low-density lipoprotein particles that are circulating in the blood, and those can be, uh, we can assess the sizes of them, and so there are small dense particles, there are larger apo or sorry, larger LDL particles. The lipid community has moved away from thinking too hard about this. They really believe that the particle size for LDL particles is not that relevant, and we shouldn't worry about it. And just because you have large buoyant LDL particles does not mean that you're safe. That said, if you look at again, population-level data, what is most predictive are the small dense particles. So to some approximation, that is helpful information. But I would say if you're just wanting the breadth of perspective, there's definitely a perspective now that says we don't care about particle size anymore. But let's just step back. LDLP is the total number of LDL particles. There are other particles that also carry that APOB 100 protein that can also get stuck in that subendothelial space and cause plaque to form. So triglycerides also carry an APOB, uh, intermediate density IDL particles, very low density particles VLDLDLs also carry this APOB 100. So APOB is a broader measure of all the particles that can cause plaque to form. And so APOB is that more broad measure of all of the cars, trucks, motorcycles on the road that could cause an accident. And LDLC is the cargo. That is just the boxes in the trunk that are being carried by these particles.

>> Okay, so I think I have it. Apo B, you could subdivide that down for LDL. If you're just looking at LDL, that would be the LDLP. If you go up to the APOB, that includes the LDLP plus other lipoproteins. The math won't totally add that way, but yes, I mean, if you're thinking about just big umbrella perspective, yes, LDL particles are a subset of the total APOB particles, and they're the biggest subset by far. As long as triglycerides are relatively normal, uh, APOB is generally pretty concordant with LDLC. Where we start to see discordance is where triglycerides or these remnant particles are very high for some reason.

You mentioned how the large fluffy versus small dense is losing steam at least conventionally. Is that still something you like to look at?

>> I think where we run into issues are patients who don't tolerate lipid-lowering therapies, right? There are a large number of patients who have significant side effects on lipid-lowering therapies, and lots of people who just don't want to take them. That is a valid choice. What you want then is to understand how risky is that compromise or how much risk reduction have we accomplished. And I do think that there is something to be said for, you know, if you still have a large particle count, but your small dense is very low, then I feel better about that than if you still have the same large particle count, elevated particle count, but you have a fairly decent amount of small dense particles. To me, those are still different patients, and I would encourage us to really work on at least getting that small dense count down. Does that mean that if you have, you know, an LDLP of 3,000, which is high, that, you know, you're at no risk if they're all large? I don't think that that's true if you have plaque. Now, we can talk about lean mass hyperresponders, which are kind of a different subset of patients in my opinion. Uh, that is not a conventional perspective, right? The the mainstream community does not really believe that LMHRs are are a separate cohort. Um, in my practice, they do seem to behave differently. So the question for that population is, do you have plaque or not? Really, that is the the bifurcation in my own clinical practice. If you do not, and you still have elevated particle counts, and your small dense particles are low, and your inflammation is low, and there's really nothing else metabolically active with you that we can treat, then at that point, what are what are we how are we helping? Um, we can talk about it, it's possible, right? But I think that that's a different thing than a patient who is still has elevated triglycerides and still has low HDL and still has high blood pressure and this particle count of 3,000,000 and uh, some elevation and small dense particles, like this is all just the big picture. I try really hard not to treat one number. I try really hard to take the whole full picture into perspective, which is not only the lab values, not only the body composition of my patient, not only the blood pressure, but also what's their family history, what's their risk, what does the rest of their lifestyle look like? What did everything up until, you know, their health journey started look like? Were they smoking with a hemoglobin A1C of 12 and, you know, 200 lb overweight? That will cause this fire to smolder even if we have changed everything from a lifestyle perspective and really done a huge 180. We may need to be a little more aggressive in that patient just because the exposure leading up to that was so toxic. And again, that's like nobody's fault, right? We're we're doing our best with what we have today. And that's okay. We are doing what we can and making the best choices. And the last piece of this is what does my patient want? How what is their philosophy about how to manage this? Because I recognize that my bias and my perspective from the hospital side of what I treat is that this is a terrible, miserable disease, and it's miserable if you get it in your 60s, but it's also miserable in your 90s. Right? I treat patients who suddenly end up with plaque and a crusty black toe when they're in their 80s and 90s, and like it's hard. It's a really awful disease. So I know that that's my bias, and I really don't want anybody to suffer with it. But I'm also not the one living their life. And if taking medicine every day is just something that would make life not worth living, then, you know, it's okay. It's okay to make a choice that I wouldn't make. It's okay to have a perspective that says I will have a shorter life. It's fine. I just don't want to be treating this. I don't think that that risk reduction is worth it to me. So that's the last piece of this whole perspective. And it's not my job to bring a medical philosophy to my patients. It's my job to listen when they tell me what matters the most to them and give them the tools, techniques, and resources to try to live that best life.

>> Let's come back to our LMHRs. Talk about what that is and then how you work with somebody in that category.

So uh Dave Feldman, Nick Norwitz, Adrienne Stomod have sort of defined this concept of this lean mass hyperresponder, and this is based on the lipid energy model that they have of lipid trafficking and what the purpose of especially the the low-density lipoproteins or the LDL particles are in circulation. And the LMHR phenotype or the the way that we would define this is somebody with low triglyceride, so under 100 for sure, normal to high HDL cholesterol, and very high LDL cholesterol that started when they went to a high-fat way of eating. Uh, in general, this these are not patients who have always had elevated LDL cholesterol since they were children. This is something that they can demonstrate was normal when they were eating more carbohydrates and had circulating glucose for energy and had, well, we all still have circulating glucose for energy, but glucose was the predominant energy system for their body, and then when they went to a low-carb, high-fat, higher protein way of eating, then the lipid system became the predominant energy system circulating for these people, and their LDL count particles or cholesterol went very high. Um, lean. They are typically quite lean, and we believe that this is related to, again, availability of energy and the body's desire to help process this. Um, I say we, it is not my model, and it's not my uh, not my hypothesis to defend. That being said, I will say I have seen it. I have patients who come to me who have this phenotype, and, you know, just like Nick Norwoods recently shared that he's had this very elevated cholesterol for for many, many years. He's had repeat imaging, and he has no soft plaque. I there are people who have this. I have also seen patients who've had low LC for their whole life who form plaque anyway because they are metabolically unwell for other reasons. So this is very much an individual decision and discussion because again, if you had 50 years of a different lifestyle that led to the formation of plaque, and then you went on a low-carb journey and have gotten that all under control, but you still have a lot of plaque that showed up because of these earlier life choices, I am not necessarily reassured by the fact that you're an LMHR. To me, we have evidence that if you have plaque, you might continue to progress, right? Maybe it's not worse than uh, somebody with a lower LDLC, but it's still progression of plaque, and you are still at risk for events. And the question then is, what do you want to do about it? Because for many people, a low carbohydrate way of eating has fixed something for them that medicine otherwise could not. Whether that is a mental health problem, whether that is a circadian rhythm disorder, whether that is inflammation or food addiction, all kinds of things can be treated dramatically effectively with a ketogenic or a low carbohydrate style of eating that medicine otherwise did not have an answer to or had bad answers to. So, if this way of eating has fixed something for you that otherwise we could not fix, I will never take that away from you. But we might talk about how to mitigate the risk that an elevated particle count may contribute to if you have a plaque burden. Because I think again, there's this risk that once you have the inflammatory process ongoing in the plaque, you may continue to develop more plaque if we are not even more aggressive about stamping that out. But this is a data-free zone. We do not have a study that says one way or the other what we are supposed to do for these patients. Again, everybody who has seen a mainstream physician or cardiologist who's an LMHR has heard up the wazoo that they are going to die tomorrow with their cholesterol numbers. And they have also heard from Nick Norwitz that it's totally well, I I won't put words in Nick's mouth. Um, they may have inferred from what we have learned so far that for some people it's totally irrelevant. I think the answer is individual and somewhere in the middle. There are people for whom that elevated particle count may continue to cause issues, and we should manage it. Uh, I have a patient in particular I'm thinking of that I'm helping manage this. Um, but I also have other patients who seem to have this path, like this phenotype, who don't have plaque, and we're just going to monitor. If they develop plaque, then we'll when then we'll sort that out. You know, the arguer argument is nobody needs this amount of cholesterol circulating. Why wouldn't you just treat it anyway and make it go away? Um, and the answer is you can. And if your patient is open to that, then that's not a crazy idea. And there are risks and benefits to medications. We know this.

>> Well, let's put the LMHRs aside for now.

>> Okay.

>> And talk to the regular patient and sticking on the lipid lowering therapy. Who would you say that's right for to at least consider?

I think anybody with plaque should consider doing something to lower their particle burden. And again, let

Me, just be very clear. This is not the only thing I manage, right?

If we have a situation where we have like elevated lipids and diabetes with a poor A1C, like far and away the A1C is the thing I would really like to focus on and really get down. And we will worry about that long before we deal with the, not long before, but let's just say my my sense of urgency about managing poorly controlled insulin and sugar is much higher than my urgency about managing a non-optimal lipid panel.

So while we're talking about lipids, like yes, that is something that I incorporate in my practice because most of the patients who come to me have plaque. We are not really talking about the young person who just has an abnormal lipid panel but no plaque. That's a different patient than somebody who has plaque, which is a different patient than somebody who's had plaque and a heart attack, a stroke, a stent, or some complication related to plaque. These are all different buckets, and it's important to distinguish.

I, as a vascular surgeon, predominantly see people who've had a problem already from plaque. So in those patients, yes, lipid-lowering therapy is one of many things that I would recommend, and we have good evidence in that population, especially if it's with your legs, that your chances of keeping your leg are higher if we implement lipid-stabilizing therapy for you. So I feel reasonably secure in that. And again, we're not going to ignore inflammation. We are not going to ignore visceral fat. We are not going to ignore hyperinsulinemia, hypoglycemia, and the other components of metabolic syndrome. Absolutely not. But yes, lipid lowering in those patients is important.

The middle ground are patients with plaque but no events. So this is a bit of a mixed bag because technically they still count as primary prevention, meaning they've not yet had an event, but we know they have the disease. So they are at risk for an event, much higher risk than somebody with no event and no plaque. So that's the kind of gray zone where how much plaque is probably relevant, right? Somebody with a calcium score of 300, we have data that suggests their risk is equivalent to somebody who's already had a heart attack and stroke. So at that level, yeah, I think probably we should work on optimizing all of the risk factors that we have to reduce the chances for that patient to have a heart attack or a stroke. If your calcium score is 12, well, perhaps we're not as urgent, and then we can think about what are the, like, let's understand why do you have risk? Why do you have plaque? Is this an inflammation problem? Is this a lipid problem? Is this an insulin problem? Where is this coming from? And how are we going to put that fire out?

When it comes to pharmaceuticals, when you decide with a patient to go that route, what are the ones at the top of the list? And then pros and cons. There are now a myriad of options, right? Statins are the ones that have been around the longest. There is a very controversial, uh, or, you know, there's a, it's very contentious, right? Statin therapy because of the side effect profile and because of the sort of vocal perspective of people that have had adverse events related to statin therapy. In my practice, statin side effects are dose-dependent. Um, but I want to step back and talk about the fact that while there may be better drugs for the average person who does not have an unlimited income to spend, we are likely to step through these therapies from oldest to newest because it is directly related to your insurance's ability to have these medicines covered for you.

So even though statins are not necessarily my favorite drug among the whole stable of lipid-lowering options, it is typically what I start with because my patients mostly cannot afford to pay out of pocket for the newer drugs like Bempedoic acid that it's still on patent, or the injectables like Repatha, the PCSK9 inhibitors, which are, you know, more powerful drugs and don't cross the blood-brain barrier, and like that's neat and it's awesome, and yes, perhaps we should be more aggressive in using these other drugs. But what I hear in like, you know, social media commentary is like, well, why does anybody use statins anymore at all? And the answer is because they are dirt cheap. And if I can take people through this in a way that is safe and that it, like, acknowledges that they might have issues with them and we'll just stop it if that happens, then at least I can work with them to achieve a strategy that is like not going to break the bank.

So I, I want to just acknowledge that there is a real cost to medications. There is a way to get this done through your insurance, uh, that is, you know, not fraudulent and also, you know, safe. So I've had patients who try a statin for like a week and you're like, I hate it. I'm not doing it. Like, okay, great, great. We just take it off your med list. We say that it's an intolerance. We try one more. If that also causes an intolerance, then we're done with statins and we don't have to go back to it. But I have to be able to say with a clear conscience to your insurance and to every other healthcare provider that they cause side effects. And as long as you're open to hearing that your patient might be having issues, then I think it's a reasonable thing as a shared decision with your patient to at least try them so that then we can move on.

In my personal practice, I prefer to do the lowest possible dose of a statin and Ezetimibe, which is another medication that is fairly inexpensive and prevents cholesterol absorption and reabsorption on the intestinal side. And so they, um, work synergistically in many patients, and especially in people that are hyperabsorbers, to get a pretty decent lowering of our LDL-C with, uh, minimal side effects in most of my patients.

Somebody who's committed to the diet and lifestyle, we're going to get to real soon. Do you ever find that they still need the drugs because of whatever genetic factor or previous history to prevent that plaque from continuing to build?

Yes, for sure. And again, "need" is a strong word, right? I, there are patients for whom I still recommend lipid-lowering therapy for this. And like, I have people in my immediate family who have an amazing lifestyle, who exercise a lot, and they have had sort of ongoing progression in their IMT. And, you know, it's, it's a discussion, right? And we just see what makes the most sense, and everybody will come to a different conclusion for themselves. That's okay. But yes, I, I absolutely have people who have optimized lifestyle to the extent that it is possible, who still, for all kinds of reasons, uh, are choosing to continue to reduce their residual risk by taking low-dose medications.

What are your thoughts on LDL that's been oxidized, and is that different than the small dense?

It's a different thing that's measured. Um, the small dense particles are more likely to be oxidized, but, um, you know, I had this conversation recently with another clinician and a patient who had an oxidized LDL measurement and like wanted that to be optimized. And it's definitely, again, if we look at a population level, oxidized LDL is more predictive than regular LDL-C. And, you know, what is the exact way that we're going to target oxidized LDL versus LDL-C? Well, generally speaking, reducing total LDL burden, ApoB burden, is probably the most efficient way to reduce your oxidized because the less you have available to oxidize, the less will be oxidized. Um, obviously reducing whatever inflammatory component might be a proxidative state is helpful. Uh, but there aren't necessarily a lot of papers or a lot of evidence that would say, well, if you have a like normal LDL-C, but your oxidized LDL is high, then if you just take this one thing, you're going to, like, treat the oxidized LDL. Um, I would love it if we had that. We don't. And I would say not that many people measure oxidized LDL, so it's a thing. And again, at a population level, it's more predictive than just your LDL-C or even your LDL-P, probably. But, um, exactly what to do with it is a little less clear on a patient-by-patient basis.

Let's bring Lp(a) in. Talk about what that is and is it something you find valuable to measure?

I think everybody should have Lp(a) measured at least once in a lifetime. Those are actually the new guidelines. Some people may want it measured more than once for reasons we can talk about. But Lp(a), lipoprotein(a), not to be confused with Lp or or lipoprotein big A, A A1, which is actually the lipoprotein that is on your HDL particles. Lp(a) is an LDL cousin. It is a, it is an Apo molecule, but it has this very sticky, long velcro tail on the end. And this velcro tail makes it much more likely to get stuck in the artery wall. And Lp(a) has a homology, meaning it is structurally similar to plasminogen plasmin, which is a part of our clot breakdown process in the body. And we believe that patients who have elevated levels of lipoprotein(a) may be less able to break down small blood clots in the arteries, which is important. Lp(a) also has a relationship to the amount of calcium that can deposit, for example, on the aortic valve. So this is the valve that keeps blood moving out of the heart into the rest of the body rather [snorts] than going back into the left ventricle. And the aortic valve can get very stiff and calcified over time. And if that happens, you might need the valve replaced. But Lp(a) can track with your risk for developing calcified aortic stenosis.

So the issue with Lp(a) is that it's predominantly genetically determined. So you basically inherit the number of copies of L of this lipoprotein(a) that you're going to get and how long that tail is from mom and dad. It is also a bit of an acute phase reactant, meaning the levels can change with inflammation in the body. But for people who've measured it repeatedly over time, you will notice some difference in your measurements there. We'll talk about, remind me to come back to how it's measured because it's actually different depending on the lab, and so the numbers are not always interchangeable. But most people will notice that they cycle up and down by sometimes even 30, 40%. But most people typically stay in this very low-risk bucket, in the intermediate-risk bucket, or in the high-risk bucket, even if the absolute value changes a little bit from measurement to measurement. And the most important thing is to understand are you in a high-risk bucket? Because if you are, then we would like to be more aggressive about managing your overall cardiovascular risk and your metabolic risk.

And what would that look like differently for that person?

In 2026, it looks like, so the lipidology recommendations would be lower ApoB even further. So that means usually medications and nutritional interventions to get your overall Apo burden down. Uh, there are a number of molecules in clinical trials right now that specifically lower Lp(a). None of the available drugs on the market are targeted for Lp(a) yet. That hopefully we are getting clinical trial data to result. 2026 should be the first trials published. We know right now that they dramatically lower Lp(a). What we don't know yet is whether they reduce the events associated with very high Lp(a). So that hopefully will come out 2026, early 2027. If it's helpful, then, you know, those molecules will be available to those patients hopefully in the next couple of years. In the meantime, the, um, statins keep Lp(a) stable or sometimes even increase up to 20 to 30%. The PCSK9 inhibitors tend to decrease Lp(a) by 20 to 30%. But you cannot, and I've tried, get insurance to approve a PCSK9 inhibitor just because somebody has Lp(a). They still say that, you know, it's not an approved indication for that. So, um, and fortunately, we still have to have this same pathway of failing our cheap generic medication options before we move on. Is that Amil is neutral for Lp(a)? Uh, for women who go through menopause, Lp(a) can increase. So the, you know, couple of outside scenarios where you might check it again would be if you were in an intermediate Lp(a) bucket in your premenopausal years. If you are post-menopausal, you might double-check your Lp(a) again to see if you're now in a high-risk bucket. Does it matter if you change into the high-risk bucket late in life? Nobody knows. Uh, menopausal hormone therapy can reduce Lp(a). It is not a reason by itself to do menopausal hormone therapy, but it's kind of a nice side bonus if you are considering that anyway after menopause.

And the last thing I'll say is Lp(a) is measured in two different ways. It is measured in milligrams per deciliter, which is like the, you know, lipid concentration in your in your Lp(a), and that's a similar metric to the way the rest of your lipid panel is measured. It's also measured in nanomoles per liter. And the threshold for what is normal or abnormal is different depending on how it's measured. So I have a number of people who, you know, text me or call me for a consultation like the patient's Lp(a) is 100. I'm like, well, that's really different. If it's milligrams per deciliter, that's very high. If it's nanomoles per liter, that's actually just in the intermediate bucket. It's not that high. So, it's important to know what test you had or how it was measured, and to make sure that you're taking that into consideration if you're getting a repeat test done or if you're trying to communicate that with a clinician.

Do we know population-wide a general idea how many people are in that high bucket?

Yeah, it's about 20%. 20% of the population. It's a variable based on ethnicity and geography, but the G-W wiz figure is about one in five. And if you were in that category, and maybe you are, what would you do differently? Diet, supplements, lifestyle. You've talked about drugs. But on the other end, natural, what would you do differently?

I would do the same thing irrespective of Lp(a). If I had an increased family risk of cardiovascular disease, I would do the same thing as if I didn't have Lp(a) but still had an increased family history risk, which is, you know, make my nutrition as optimal and boring as possible. Exercise like it's a drug because it absolutely is. And I would prioritize my sleep. If I had any concerns about disordered sleep, especially disordered sleep breathing, like sleep apnea, I would absolutely get that checked. Make sure my blood pressure is well controlled, and think about how to manage the chronic stress in my everyday life. If, you know, um, our lives are stressful. I'm never going to say that that's not true, and I would be the biggest hypocrite in the world if I said, well, you just, you know, do something different. Like, I have a stressful job. It's true. And I have a meditation practice, and I have my exercise, and I have my colleagues and friends that I talk to when I'm stressed out. Like, there are strategies to help manage the burden of chronic stress in our everyday lives. And it's really important, right? We actually have really good data that chronic stress is as important a cardiovascular risk factor as disordered sleep, as high blood pressure, as our lipids, right? And it's probably the least acknowledged or managed part of cardiovascular risk.

When it comes to blood pressure, where do you like to see that? And then natural ways somebody can tame that down.

You know, the ideal is like that 120 over 80 number that people talk about. I certainly want it less than 130s, uh, for the top number, the systolic blood pressure. This changes a little if you're getting into an older population, uh, where the risks of dropping their blood pressure too low and having falls is a bigger issue. But let's just say we're talking about the average person in midlife, and we'd definitely like to see it in the 120s or even maybe a little bit lower. Um, if you're not getting lightheaded or dizzy on a regular basis, you're probably not too low. Your body will manage you pretty well, and you're unlikely to be too low without pharmacology. So, unless you have some kind of, you know, orthostatic syndrome, uh, which is totally a thing for many people, but broadly speaking, we would love to see you on 120s or less. And I think the most important thing for people to have at home is a blood pressure cuff so that you can have it measured in sort of real living conditions. Everybody is stressed when they come to the doctor's office. They're like running 3 minutes late. They, you know, almost hit somebody in the parking garage. They ran upstairs to get to the doctor's office. The MA was rushed and trying to get them in the room on time, and they, you know, slapped that blood pressure cuff on them, uh, without a second thought and did it on the way in. And like, yeah, it's likely to be a little elevated. There is some evidence that even if you have white coat hypertension, which is this idea that, you know, you're just stressed at the doctor's office and normally it's low, but now you're high just because you're here and because my white coat stresses you out, um, that may also be relevant medically, right? It may actually still confer some increased risk. But overall, I am much more concerned about you checking your blood pressure at home twice a day for a couple of weeks and sending me that blood pressure log. If that is routinely in the one teens, 12s, then I'm happy. That's pretty great. So, that's probably the most important thing. And the biggest thing people can do is get their insulin under control to help manage blood pressure risk. I am a lot less concerned about the amount of sodium in your diet than I am about, you know, how you got there. So, if you're eating out a lot and you're eating a lot of processed food, yes, you're going to have a lot of sodium in your diet. But why that's a problem is because you also probably have insulin resistance and hypoglycemia that's causing you to retain the sodium. It's causing your kidneys to hang on to that because insulin is high. If you get insulin down, you will pee out all that sodium, and it's a much less, it's much of a less of a concern.

Nitric oxide has come up in the conversation. Let's come back to it. Talk about what that is and then how somebody can go about supporting that in their body in a healthy way.

Nitric oxide is, you can think of it as a relaxation molecule. It's very short-lived in the bloodstream, you know, milliseconds to seconds. So we don't measure it directly, but what we can measure is the relaxation of blood vessels. This is also not very commonly done in the United States, but there are things like flow-mediated dilation, uh, and other ways like that we have measured the ability of a blood vessel to expand and relax, uh, that can show us the impact of nitric oxide indirectly in the body. And what we know is that some people, there are a couple of different pathways, right? We synthesize it and then we break it down. And so you can either reduce the breakdown of it, you can increase the synthesis of it. Things like leafy green vegetables, um, getting sort of your nitrites in can be converted to nitric oxide. Uh, the oral bacteria in our mouth, uh, actually contribute to this. So there's a reason why people will tell you, like, don't use alcohol-based mouthwash all the time. It actually destroys the bacteria in our mouth that begin converting our dietary nitrites into nitric oxide pathways. Um, exercise is far and away the best lever we have for nitric oxide in our body. There are some other ways potentially to, like, improve it. You can use, like, L-arginine and and citrulline to get that up. You can use some of the pharmacologic solutions to prevent breakdown. So those are things like Viagra and Cialis. They're called PDE5 inhibitors, phosphodiesterase 5 inhibitors. They prevent the breakdown of nitric oxide and allow that to relax. That's how they work as erectile dysfunction drugs. They increase the amount of nitric oxide in the blood vessels. They relax the blood vessels and allow more blood to flow where it needs to go to manage the problems associated with erectile dysfunction. So you can imagine that happens everywhere in the body. It's not specific to the pelvis. So that does improve, uh, nitric oxide broadly. There are some people who think we should use this as a cardiovascular health drug, as a longevity drug. Data are not available to support that as a, um, you know, population-level intervention, but it's out there.

How do you think about aspirin? Somebody taking that preventatively if they haven't had an event in the past, and then somebody who has had some kind of heart attack, stroke, stent put in, using that as a long-term strategy.

The job of aspirin is to prevent platelets, which are the little sticky molecules in our blood that start a blood clot process. Uh, aspirin inhibits the platelets from sticking together. There are other antiplatelet medications. Plavix is probably the other one that's most commonly used. It's also clopidogrel is the generic name. There are like Brilinta. There's a few of them. If you have had a heart attack, a stroke, or a stent put in, you are on some kind of antiplatelet medication. And the best evidence we have suggests that you should stay on that, some version of it, whether it's aspirin or Plavix or something, whatever your doctor put you on, if you have had that event, that stent, a reconstruction of your blood vessels anywhere, please stay on your antiplatelet drugs. That is important for you irrespective of your age.

If you have not had any events and we don't know if you have any plaque, and you are just thinking that an aspirin a day keeps the doctor away, you probably should not be taking aspirin. The most recent evidence that we have for primary prevention does not really support the use of aspirin in the broader population just to prevent an event. And that's especially true the older you get because aspirin, even though most of us, uh, think of it as a reasonably safe drug, it's over-the-counter, it's not that dangerous. However, again, at a population level, it's associated with increased bleeding complications, and those increase as patients get older. So over 70, primary prevention, bad idea. Even over 60, primary prevention, not great. Under 60, if you have a couple of specific conditions, we would talk about it. So, let's say you're under 60, you're, you know, a 50-year-old person who got a coronary calcium score because you listened to this conversation with Jesse and you're like, "Oh, I should check out my blood vessels." Got a calcium score and it was 400. But you've not had a heart attack, you've not had a stroke, you don't get any chest pain when you exercise. Um, aspirin for you might be worthwhile, right? Risks might be less than the benefits for you. That's a gray zone. And Lp(a) is another gray zone. There are some people with Lp(a) who get disproportionately better with aspirin therapy. It has to do with one particular mutation in the Lp(a) gene. Um, but in some series, people who have elevated Lp(a) who take an aspirin have an outsized benefit from that particular intervention. Now, again, we're going to weigh the risks of bleeding. We're going to talk about your age. We're going to talk about how likely are you to have this event. What else is going on in your health? But I would say elevated CAC or elevated plaque imaging of any kind and Lp(a) would be those gray zone areas for people taking aspirin.

Can you talk more about the mechanism, what it does in the body physiology-wise? And then for somebody who wants to do it in a natural way, any supplements out there that work in a similar way?

The plaque rupture that we talked about, right? The, um, eruption of this volcano in your arteries where you have this soft lipid-rich, um, magma, molten lava situation. When that ruptures, all of that inflammatory stuff shows up inside your artery all of a sudden, and the body's like, "Whoa, whoa, whoa. This is toxic. We cannot have this. We need to fix this." The way that that starts are the platelets. The inflammatory component of that lava that's just erupted immediately attracts these platelets. And these platelets are just going to cover all of that goo and stuff. And the platelet forms this clot. And it's the clot that blocks the blood flow and causes the heart attack and stroke. But it's your body trying to contain this eruption, and the platelets sticking to it are the f is the first step in this whole process. So if you make the platelets less sticky, then you get less of a reaction to all of that, and you are less likely to completely block off the vessel if this happens. Uh, and again, there are other medicines that also inhibit platelets that can do this, but aspirin is that how it's how it works. It just reduces the stickiness of those platelets to form. So you're less likely to get this complete blockage in a plaque rupture situation. And the platelets are permanently inhibited. So the lifespan of a platelet is 7 to 10 days. So if you take an aspirin every day, then, uh, your platelets are always inhibited. If you take it every other day, you're getting some inhibition, but you're getting some new platelets that are not yet inhibited, and so there's less of an effect.

Uh, there is no supplement or like intervention that is a medically appropriate substitute for aspirin or an antiplatelet. So, if you have a stent, if you have had a bypass of some kind, and somebody's like, "Hey, you should take some nattokinase instead of your Plavix." Uh, I'm going to tell you that's a bad idea. Now, nattokinase is probably the one that comes up the most often in this context, and nattokinase has a small amount of antiplatelet activity. It also has some anti-fibrinolytic properties or some, uh, excuse me, some pro-fibrinolytic properties. So, fibrinolysis is the pro is the process of breaking down, uh, clot that has already formed. So our body has this beautiful, very complex pathway where we make clot, but we also break it down because we know that we don't want to bleed to death, but we also don't want to block off every pathway in our body for blood flow. So the body has this beautiful like ebb and flow of like making clot and then breaking it down. So fibrinolysis is the breakdown of clot that's already formed. The Lp(a) molecule we talked about earlier is partly impacting this clot breakdown side of the equation. Nattokinase is favorably going to potentially help break down clots. Nattokinase is an very interesting molecule, right? It's derived from the fermented soy product natto. We know that people in Japan who eat a lot of natto tend to have lower risks of heart disease and stroke than people who don't. That doesn't necessarily mean that nattokinase as an isolated enzyme is going to help. We don't know how much nattokinase gets absorbed. The data for nattokinase are actually best for blood pressure, and like why it impacts blood pressure preferentially is a little un, is a little interesting. There have been some show studies that show that it reduces lipids, others that show that it increases lipids. There is one one study that was not randomized, was not placebo-controlled, that showed plaque reduction using high doses of nattokinase. There have also been a couple of case reports that showed, uh, bleeding events associated with nattokinase related to this. So while it's an option and it's an interesting molecule, I am not, I actually tried it in a couple of patients. I had one patient who took it for a year. We repeated her CINT and it went up, which is not good, u more than would be expected just based on age, and we quit, uh, because I didn't think it was helpful and it was potentially harmful. So I am, I was really excited about it when I first read this study that showed plaque regression. As I have reread the study and thought about it more, it's not a particularly strong study in a lot of ways, and it's the only one. There's been a randomized controlled trial that showed no change in CINT at a much lower dose, you know, acknowledging that, but, you know, we don't know yet. I would say that it's possible that someday we will be using nattokinase. Whether we're doing it because it has anti-inflammatory properties, anti, um, clotting properties, whether we're doing it for lipid properties or blood pressure, like, we don't know why it's working. And there have been people that have tried taking nattokinase instead of their blood thinners. So somebody clotted off their brand new heart valve doing that. So I would be very, very careful using that without the blessing of your clinical team, and if you are on a blood thinner for a blood clot, for if you're on an antiplatelet for a stent, please don't stop any of that before you talk to your clinician. And, um, please don't take nine on top of that because there are also some case reports of bleeding issues. So it's interesting. I am open to patients using it. Like, we just have to be very thoughtful about it.

Somebody young, healthy, no plaque, no heart events. Can you see any value in using that low dose preventatively to prevent plaque?

We don't know. We just don't know. I mean, the, the randomized control trial would say no. Um, does that mean the dose was wrong? We're not sure, right? Uh, I would say, you know, in, in my younger patients, what I want is a clear understanding of what their pathway to plaque would be. Are we having problems with overweight and in visceral fat and causing inflammation? Are we having issues with toxic exposures like tobacco, nicotine, um, even cannabis if it's smoked can cause cardiac issues? Are we having issues with blood sugar and hyperinsulinemia? Like, what is the thing that's going to really reduce our risk for that patient? Because I feel much better that if I have a tangible pathway to plaque, then that is something I can intervene on. If it's high blood pressure, then there may be some role for lower dose nattokinase for that. The, the blood pressure data for nattokinase are actually okay, and that would be something to think about if, if for whatever reason somebody would prefer to do that than, um, other mechanisms to lower blood pressure. Sure, we can talk about that.

Somebody coming to you, hypothetical patient, they're overweight, they have visceral fat, they're metabolically unhealthy, they're not sure yet where their vessels are at in their heart, but they want to change their diet and start there and be proactive to fixing their metabolic health and in turn preventing any vascular issues. How do you begin with them?

Let's think about, I mean, somebody who's got overweight and visceral fat, we are overnourished. So we have to think about how are we going to reduce total energy in, in a way that is meaningfully, in a way that doesn't disrupt our patients' lives. And so there are a lot of options for this. Low carbohydrate way of eating is one, and it is the one that I offer to most of my patients. But I have to be very clear, it is not the only way to manage this problem, and it is not the one that works for absolutely everybody. There are people who do not do well on a low, or who don't feel well on a low-carbohydrate diet. And if you don't feel well doing it, and then let's just acknowledge, right, past the, um, fat adaptation window, right? You give it a shot for you. We're, we're two months in, we're three months in, and you still don't feel well. Um, and yes, we've double-checked that we're doing everything right. Yeah. Yeah. Yeah. Um, if it's not working for you, I have people who don't correct A1C that way. I've had a physician who went very low carb. She was like, all in. She really, you know, read the research and thought this was going to work for her, and her A1C didn't drop enough. She was still pre-diabetic, and she went whole food plant-based and felt much better, and her A1C did come down. So, yeah, there's a lot of, you know, I don't want to say trash talk, but like, there's a lot of hate in in all of these dietary tribes against the others for whatever reason. And I think that how you come to your own way of eating is very personal. And there are all kinds of considerations, right? Are you hungry? Are you eating foods that work for you? Do you feel well? Um, what else are we managing? Right? So, you know, for many people who start overweight with excess inflammation and visceral fat, a low-carbohydrate approach actually reduces cardiovascular risk. And the Verta study has shown us that. So, I don't necessarily say it's a bad diet or a bad way of eating for cardiovascular health, but it is not the intervention that is likely to lower your blood lipids. If you want to manage your LDL cholesterol with nutrition, that is possible, but it's a little bit of a different dietary strategy. Um, and we have to make some accommodation for it. That's okay. We just need to talk about all of the trade-offs that we make when we choose a way of eating. There is not a dogma, a religion. I don't, you know, again, I do find the low-carbohydrate approach works for most patients, but not all. And I think just being humble and curious and helping patients figure out what is a healthful, sustainable way of eating for them going forward that minimizes what we could all agree are junk foods, right? Um, highly processed is a is a loaded term. We can debate that, but I think whole foods, we can kind of figure out intuitively what those should be. And if we get a plan that focuses on that, whether that is predominantly animal-based products, whether that is a mix of animal and plant products, whether that is plant-based products, I, there are [snorts] a lot of ways to skin this cat.

Okay. Well, let's again stick with our hypothetical here. You're going to try a low-carb diet with somebody. How do you practically explain that to them and what does that transition look like? How low carb do you like to see them go?

A little bit depends on how they react to the suggestion, right? Um, we talk about readiness for change. If people come to me and they've already done some research and they're like, I think I want to try this. I just don't know how. Then I say, sure, let's do this. And here's what a carbohydrate is. I, it starts with education, right? Um, and explaining to people that yes, like sugar and things that are sweet are absolutely carbohydrates. Most people get that already. They don't need to be told that. But the number of patients I have who don't recognize that starches are also carbohydrates. And that, you know, so flour-based products, they'll, they can usually get there pretty quick, but like rice tends to surprise some people. Uh, potatoes tend to surprise some people. And the starchy ve, you know, other starchy vegetables tend to, um, throw people, like turnips and whatever. So just describing, right, what is energy? So what do we eat? What are our macronutrients? We have protein, we have fats, we have carbohydrates. Protein is a structural building block. It is repair and it is synthesis of muscle in our body, but it probably should not be an energy source. Then we have our energy sources, which are either fats or carbohydrates. And some people use one preferentially to the other. Some people run efficiently on one versus the other. If you've been on a glucose-based metabolism for a long time, it's going to take your body a while to adapt to a fat-based metabolism, but that is something that can be done. And the fastest way to do that is to drop our carbohydrates, um, certainly below 50. That would be a very low carbohydrate diet. Uh, and some for some people it's even less than 20 total grams of carbs a day for an induction phase. I know Dr. Westman tends to advocate for that about that level of daily carbohydrate, total carbohydrate. Uh, at which point we're really just talking about mostly proteins and fats and a very small amount of maybe leafy green vegetables or maybe not. Um, but that's a pretty restricted amount. And that's again, one approach. For me, I try to read the room and figure out some people do better cold turkey and just like going whole hog into this. Other people do best slowly and like getting, like, let's just start with breakfast, right? Can we just start with getting rid of cereal or like waffles or something that is a high starch bad way to to start your day? And maybe we just start with breakfast. Either we cut it out entirely and we work on time-restricted eating, or we think about eggs, or we think about, um, leftover protein from dinner last night, right? We can talk about lots of ways, and we just do one meal at a time. And for some people, the slower approach feels less disruptive and like they can then slowly buy into this. And so I don't do it the same way every time. I wish I could just, you know, be like Dr. Westman, like this is the page four and like this is what you eat and this is what you don't eat and here's that. Um, it's probably ultimately, uh, as effective or more than what I do. But I try to meet people where they are and figure out what's going to get them there without breaking trust, without having a huge speed bump where they're like, "Oh, I can't do this. It's too hard." Right? I try to like build their confidence and and allow people to get there. And if it's one meal at a time, great. We can do it that way. If it is throw out everything in your house that is a carbohydrate in a box or a starchy thing, great. We can do it that way, too.

When it comes to lowering the carbs like that, it sounds like depending on how low they went, you'd be bordering on ketosis. Is that ever part of the goal when you're working with somebody?

It sure can be. And I think, you know, the, the low-carb community is a little split on this. There are people like Dr. Bos who think that ketosis is essential and an essential part of of this strategy for everybody. And I appreciate that her clinical experience tells her that that is true. Um, for me, I think the data strongly support therapeutic ketosis for the brain-based diseases. Uh, so anything mental health related, epilepsy, um, any brain disorder, right? The ketones seem to be a particularly useful, efficient fuel for the brain. And I think for cancer malignancy, therapeutic ketosis seems to have very strong data. The rest of my patients, I don't know whether chasing ketones is really helpful for them or if it is, um, something to focus and drive them, but is not necessarily truly physiologically moving the needle. I don't know. Uh, and I think for many people, it, it can be a distraction. So I don't chase ketones in my patients personally, but I know that there are other people in our space who do, and, um, I respect their experience for sure. I am not asking my patients to check ketones or drive that unless we are really targeting brain diseases or or cancer, and truthfully, I am not generally managing those patients just based on who I see in my practice most of the time.

What does your current diet look like and talk about what led you there?

I was keto for a while, and then I have evolved into what I would call a low-carb way of eating. Um, I am reasonably certain that I am not in ketosis, although I haven't checked in probably years. And I still have my keto mojo, but I don't, I don't check it very regularly. And that has evolved for me just based on, uh, my training, right? I, I am more physically active and doing more, uh, exercise than I have before. And so, a small additional amount of carbohydrates. I still think I'm probably under 100 grams a day. Um, but I'm meaning just a little bit more in terms of some berries, uh, with my, um, you know, as my treat for the day. I have some more vegetables, and I have leaned out my protein sources. So, I am not chasing fat in my diet as much anymore, again, because I've boosted my carbs just a little bit, mostly again from, um, whole food sources. And that has given me sort of the place where I feel best and I'm managing my own energy intake optimally. But again, I, I think everybody comes to a way of eating for a certain time frame, and then you can change, right? We can, we come to this idea that, well, keto worked for me for a period of time, and so it's the thing that's going to work for me forever, or carnivore worked for me and it got rid of my IBS, and so now I have to be carnivore forever. Well, maybe. And if it's going to work for you, and if it's still working, that's great. Like, if it's working, don't change it. But I do think that our bodies evolve, right? It's possible to heal your gut and perhaps be able to reintroduce some other foods from time to time, or your ch your training changes, and you might want something to support that. I didn't change my nutrition out of dogma because somebody said I had to have more carbs. I did it because I actually felt a little better and I thought that I was making more progress with my lifting with a small amount of additional carbohydrate on my lifting days. So for me, it was empiric. It was not, um, you know, based on somebody shaking their finger at me and saying, you have to have this for your for your performance. No, I tried it and I tested it, and for me, this is what's working. And it may be different in five years. I completely acknowledge that I may change my protocol based on how I'm feeling and how my body is evolving and changing over time. So, I really push back against this idea that one diet is right for everybody forever. It can be right for a time, and then maybe it's not anymore. That's okay. Let's just experiment, be curious, be humble, and figure out how to evolve with our bodies over time and keep doing what is working.

Riffing off of what you just said there, are changing over time. It's clear part of the reason you're including more carbs right now is for your fitness, but your keto days and your past diet history, was that part of getting metabolically healthy and now allowing for yourself to include more carbs?

I think so. I absolutely think so. It also helped teach me what carbs I can and can't. Like, carbs are just carbs, right? They're an energy source. My decision to avoid grains as a general rule for myself is that I cannot, I still have a food addiction issue and I cannot regulate the amount of baked goods that I consume. So I choose not to eat them because I can't moderate that. I can moderate a piece of dark chocolate, but I cannot moderate scones or pie or bread or anything like that. Um, that's just my personal knowledge, and it took going keto, low carb, and you know, stumbling along the way to understand what were my triggers and what are things that I can do in moderation, what are things that I cannot. Uh, so yeah, for me, that has been a very helpful thing to understand. And then again, right, nobody in the athletic world would say that 100 grams of carbs a day is a lot by any stretch. Like, that's still a very low carbohydrate diet, and I'm not an athlete, right? I, I train, but I'm not competing in anything. Nobody would accuse me of being a high-level athlete, but I want my performance to continue to improve and I want to achieve my goals. So, I think we just get to a point where we are trying things out. And, you know, I was doing some cycling for a while. I'm doing less of that, but when I was cycling, I would have to take just, again, like 10 to 20 grams of carbs with me on that ride because I would bonk. And like, I know that there are endurance athletes who can completely just run on ketones, who do fine, and there are others who supplement on race day. It just depends on your body and like whether that is necessary or not. Nobody knows. But, uh, I do think that we are all our own unicorn and have to just acknowledge what is working for us at any given time.

If you're open to it, I'd love for

You to walk me through a typical day. What you're eating, when you're eating.

Today I am training. I have had uh this is my second cup of black coffee this morning. I will probably train fasted um just because my training today is at around noon. I will take a shake with me after that because I am on call for the hospital and uh eating a meal is is probably asking too much of the universe. So that's going to be some eggs, uh some berries. I put some chia seeds in there. Again, I am working on increasing my fiber slowly because that's what's working for my body. Does everybody need it? Probably not. But um we can talk about that later. And it has um a combination of some beef protein, some egg protein, and some whey and some quazine in it.

Then uh I will have probably a salad with protein for dinner. Um I have a bunch of salad mixes. I also have uh a bunch of like chicken that's in my refrigerator that's already cooked that I can toss in with some curry sauce that I have. I have some like Indian curry mixes that are like mostly coconut milk based that are delicious and I might do that over some shiatakei noodles and I might throw some uh frozen roasted veggies in there or roast some of my own depending on time frame. And um yeah, that's mostly my day of eating. If I want some snacks, I might do some roasted edamame in there uh after my shake with my lunch. I'm trying to limit the like between meal snacking. So typically I'm doing two meals a day. Um, some days that's mo most of the time I would say that's like a lunchtime meal and a dinner time meal. Occasionally I'll do like breakfast and a really late lunch that's almost dinner, something like that. Uh, because of my work schedule, you know, I am frequently eating within 3 hours of bedtime. But if it were a perfect world, I would really try hard not to be eating after the sun went down and within three hours of bedtime. I am not great about that, admittedly. Um, but that's what I do. I do have some uh dark chocolate available as a treat and um I just bought some like organic raspberries the other day that were delicious. That was also uh my my evening treat.

How do you feel about longer fasts for you and for patients?

I think they can be good. I um I have not really done extended fasting beyond about uh like 48 hours. Um, I've been a little curious about it, but I just haven't really done it. I don't have a specific autophagy goal in mind for myself right at the moment, and I don't know how to measure whether it's working or not for me. Like, I don't know what lab test or what thing I'm doing just to see if it's helping. Um, if people want to fast, I think that's an excellent tool. I think timerestricted eating is a little different, but can also help manage total energy intake and hyperinsulinemia. Um I think my consideration about fasting is also very much related to muscle mass and whether we have a strong desire to be maintaining or building muscle. Um it is hard to do that with a lot of prolonged fasting. It is possible. Um but we have to be pretty careful about that. What I don't want is especially for my older patients to be losing a lot of lean mass. Now again if we are overweight and under muscled that's a tough place to be. we have to be trying to manage the excess ataposity or the excess fat especially the visceral fat and work on building the muscle. So in those patients yes fasting can absolutely be helpful. Um I think it's one of many tools I I'm not strongly you know asking all of my patients to do it. If they are interested in doing it on their own or curious about trying it we can do we can talk about it but it's not a tool that I am uh really aggressive about in my practice.

Coming back to autophagy. Have you seen any research on plaque in autophagy and any impact on that?

Not off the top of my head. It's an interesting question.

Let's talk supplements now. Given what you're eating, anything you take on a regular basis to enhance that.

I think of supplements like medications. They are an exogenous substance that we are putting in our body to try to achieve a specific goal or target of some kind. That said, uh, and so for most of my patients, I supplement based on either lab values or specific symptoms or particular, you know, goals and targets. That being said, there are a couple that I think most people can benefit from irrespective of their lab values or what's going on in their life. The first of those is magnesium in the evenings to help support rest and sleep and muscle recovery. Um, I think magnesium is great and I think most people should probably take some and that has, you know, even if your diet's pretty clean, right? Our soil has been depleted and so, um, and it's hard to test for magnesium. We can test blood serum levels, which are almost always normal because your body will prioritize maintaining the level in our circulating blood above everything else. So, you can be depleted in the muscle, depleted in the bones, depleted in the brain, and still have a normal serum level. uh you can measure it in the membrane of a red blood cell, but it's hard to know how well validated that test is. So, I don't think that that's super reliable. The most efficient way or like the the best described way to test for magnesium deficiency has been done for experiments, but it's not done clinically, which is a magnesium repletion where you give people a bunch of IV magnesium and you see how much of it they absorb. Uh and if they absorb a lot, then they were deficient. That's the assumption. Uh so that's not something that's really ever tested clinically, but it's pretty harmless to take. So uh as long as you're taking kind of a chelated version, so that's a bislycinate or glycinate, a 3en8ate, a torate. Um the ones that are a little harder on our digestive system would be mag oxide, mag citrate. Those ones are uh likely to cause some GI upset. So I tend to avoid those and stick with the chilated ones. But if you're if you take too much, you'll pee it out. it's not a huge um concern. So, I think magnesium is a great thing for anybody who's got leg cramps at night, anybody who's got some uh muscle soreness from excess training, and anybody who wants a little bit better support for restful sleep. So, magnesium is a big one for me. And then creatine is the other one. If anybody is doing resistance training, and everybody should be doing resistance training, then I want you on at least five grams of creatine a day to help you support that. Um, the higher doses of creatine that have been discussed for brain health are interesting. I think there's much less data for that, but I anecdotally have tried it for myself after periods of sleep deprivation or jet lag, and I think it seems to be helping. I can't rule out a placebo effect there, but uh I do double or triple up my my creatine on days where I um you know if I've been up all night operating or um severely jetlagged, something like that.

One of the supplements you often hear connected to the blood is fish oil and in terms of thinning the blood. So any truth there and then any value there?

This is a complicated story and it's very interesting. The omega-3 fatty acids that we are trying to improve are the DHA and EPA. And that is what is delivered in in sort of fatty fish. It's what is in the krill oil and the fish oil supplements. And there are a bunch of different stories here. So one is cardiovascular health. And there have been some studies that have looked at a prescription version of EPA, which is the one that's most associated with um cardiovascular inflammation and vascular health. And for patients with elevated triglycerides, that four grams a day of EPA was in a a randomized clinical trial shown to be helpful in reducing cardiovascular events. The uh couple of issues with that study were the sham version or the placebo controlled arm was perhaps it was like I think it was corn oil. So was perhaps a little pro-inflammatory. So we can't rule out that that was actually like maybe the EPA didn't help but actually the corn oil hurt. So that's one option. The other thing is that it increased risk for atrial fibrillation which is an abnormal heart rhythm that can be pretty serious for people who develop it. it might require them to be on blood thinners or have procedures to try to restore a normal heart rhythm. So, at higher doses, the fish oil or the the omega-3 fatty acids in particular seem to increase the risk for atrial fibrillation. So, we have to be a little bit careful about who we're using it in. And of course, we in this space will know that um many people can manage elevated triglycerides with a different nutritional strategy and perhaps u medicating that is like the least effective way to deal with that problem. So, that's another point I will say about that. Um, most people, even if you're taking four fish oil capsules a day, are not going to get four grams of EPA. The DHA component of your omega-3 capsules, whatever they are, can also increase the LDL cholesterol, which is why the lipid people went with EPA only. But the one that's important for brain health, the one that's in our neuron membranes, is the DHA. And so DHA is actually what people who are APOE4 positive are thinking about supplementing more of. And people who are interested in the brain health component are actually preferentially interested in the DHA of those two, you know, primary omega-3 fatty acids. And um it seems to be important how we deliver these fatty acids as well. So your average supplement can be the fatty acids can be packaged in different ways. Okay, so just think of it like different envelopes that you're sending stuff to your friend across the country, right? You have your little postcard, you have a regular mail envelope, you have one of those padded mailers, or you have a big box, right? So there's just different packaging, but you can put the same letter to your friend in all of those different packages. So fish oil capsules can be as an ethylester, they can be a monoglyceride or a triglyceride form, they can also be in a like um like a phosphatilylcholine form. And for people who have brain issues like an APOE4 that may have damaged the bloodb brain barrier, this PC version of phosphodilcholine version, which is also more common in eaten foods like the fatty fish that we eat, uh, seems to go better into the central nervous system. So, you know, if you're getting an omega check or you're getting a lab value that's measured by your doctor for your omega-3 levels, that's what's in your blood, but we don't know that that's actually getting into the brain. So, if brain health is your consideration, you may want to think about more DHA. You may want to think about how it is packaged to try to get into the central nervous system more effectively. Um the guidelines are no longer recommending fish oil supplementation for people for cardiovascular health. Partly because um of the risk for atrial fibrillation, partly because the commercial supplement products are very unreliable in terms of dosing and they are trying to drive people to the very dose controlled prescription versions. Um aabanthyl is the is the one that was in the trial that we talked about earlier. So, that being said, um if you're interested in supplementing, then you just need to be very conscientious about how you're getting your omega-3s and making sure that they're not oxidized, making sure that they've been tested for heavy metals and all of these things. Um or you're doing sardine fasting or, you know, supplementing with sardines and fatty fish in your diet. Perhaps that's uh the most effective way if we can do it.

You alluded to the fact that the diet would look a little bit different from the low carb recommendation for somebody trying to bring certain markers down on the lipid panel. What would the diet be and what would be the impact?

Again, this is a controversial topic especially in the low carb space and uh before anybody comes for me. Yes, of course I have read Nina Titrosa's book and I know what our issues with Ancel Keys are and I will say that um there is a relationship between intake of dietary saturated fat and LDL cholesterol. So we can argue about whether changing that marker with dietary interventions is worthwhile. But if you're just asking me from a scientific perspective, you know, you're just a patient who comes to me and says, "Doc, I want to do this naturally. What can I do?" Reducing your saturated fat will reduce your LDLC and increasing your soluble fiber will also reduce your LDLC. So there is something called the portfolio diet which is higher in fiber soluble fiber in particular much lower in saturated fats. And if you are asking what is the dietary strategy that would reduce LDLC that is it now is that the best diet for everybody? Of course not. Is keto the best diet for everybody? Of course not. Right? We'd already talked about this. Your diet choice is comprised of so many more things than one single biioarker or one single diagnosis. So don't misunderstand me. I am not telling everybody to reduce saturated fat. I am not telling everybody that they have to have fiber in their diet. But if you're asking what will move that needle naturally, that is one answer. And what you replace it with is important. So, I'm not telling you to reduce your saturated fat and replace it with refined carbohydrates from Twinkies and Pop-Tarts, right? Obviously, that is not what I am after here. But if you want to replace some of your fatty ribe eyes with some fatty fish that has more omega-3 fatty acids in it, and we are doing a swap, you know, whole food for whole food, protein for protein, and we're just changing the fatty acid composition. Is that a reasonable choice you might make if you're trying to move your LDLC needle? Maybe.

To me, as you share this, it relates to what a conventional doc used to probably most still do recommend to people to bring the LDL down, which is vegetable oils. So, let's bring those in. Talk about what they do to LDL and then how you feel about them in general.

also a super controversial topic and we are there is there's a lot of data for this on on all sides and I think we are we are still in a place to use our common sense above above all else. So again conventional wisdom will say that if you replace saturated fat with polyunsaturated fatty acids whatever wherever those come from that yes you will reduce your LDLC. We had some older trials that did that and in fact lowered cholesterol but had a same or increased risk of cardiac events. So we're talking about the Minnesota coronary experiment and the Sydney heart health study and those were done in a time where we are confounded a little bit by the fact that the polyunsaturated fats they used were probably contaminated with a fair amount of trans fats. and we can still understand the point that cholesterol came down and events went up. Um, a lot of the current trials are also confounded by the omega-3 fatty acids which are potentially a little bit protective like we discussed earlier. So, all of our oil trials are are fraught. Um, they are, you know, different populations. They are different dietary compositions. the carbohydrate content is not controlled for, the other things are not controlled for. So, you're at the end of the day coming back to what makes good sense for you. And I think that whole foodbased approaches, whether that is animals or plants or both, is a good place to start versus the standard American disaster or standard American diet. Um, and how you choose to prioritize those may depend a lot on what you're eating for, what your goals are. Do you care about your lipid panel or not? You may not be convinced by anything that is said in the lipidology space or in the cardiology space or you have no plaque and so you don't really care. Fine. Totally get it. What I'll say is, you know, animal products in 2026 are not what they were when we were roaming the earth hunting for animals, right? They are much fattier now than they used to be. Um, probably including the fish, right? And fish is not without its perils. We have farmed fish, we have microplastics, we have heavy metal contamination. like there is a problem with every approach no matter which approach you want to take. So I think we're all doomed. Um sorry, no, never mind. We are all empowered to make good choices that make sense to us. Um I personally do not choose to replace any of my saturated fat with uh canola oil or soybean oil. If I am cooking with oils, I am cooking with avocado oil or I am cooking with olive oil if I'm low temperature cooking. And um you know I am not afraid to use a small amount of butter or ghee or tallow. I don't spoon it out and eat it by itself. If you're doing if you're chasing ketones for cancer for brain health, you might. I get it. Okay. Like we are we are we have lots of options and lots of different strategies for different people. Um that is my personal choice and that is my understanding. I personally noticed a difference as I went down on my omega-6 fatty acids. So, those are the polyunsaturated fatty acids that are not the beneficial ones like the omega-3s. Um, the sort of mechanistic data on oxidation is again a little bit fraught, but I personally found that I was less sensitive when I cut those out. And so, I am not militant about avoiding them. Right? If I go out to a restaurant, I am not demanding that they never use oil to cook, but I don't eat [laughter] out very often. So, for me, that's a dose issue, and I I will take it on a one-time basis. I'm also trying really hard not to order things that are fried. I'm trying not to like if I get salad dressing, I'll put it on the side and dip my fork into it. I don't drench everything in it. Um, so I think the dose makes the poison. And many of us in Western society are getting a lot of omega-6. And I think we would probably do better with some monounsaturated and some omega-3s and all of that.

Somebody coming to you and they're going to switch up the diet to protect the heart. They're going to lower the carbs because again, this is just a general person. You've made it clear. It depends on the person, their situation. Naturally, they're going to have more animal products, more saturated fat, more cholesterol in the diet. How do you navigate that conversation when they worry about clogging up their arteries, increasing bad cholesterol, because conventionally that's what they've been told?

I say, let's get data. Let's measure it because not everybody who goes on a low carb diet ends up with elevations in their LDLC. Right? We know especially if you're not lean, you're less prone to having a significant elevation in your LDLC. Your triglycerides may come down, right? That's what the Verta Health data show us that overall if you look at the grand picture for those patients who came in with type two diabetes with metabolic syndrome their cardiovascular risk markers overall were better after the after the dietary intervention. Their LDLs were largely stable. Uh and we can also acknowledge right that there is more than one way to do a low carbohydrate diet. And I tell most of my patients like you can call it a Mediterranean style approach if you want. It does not have to be all meat. If you don't love meat, that's fine. If you do like meat, that's cool. You can do that, right? But you can do lean meats, you can do fish, you can do plant-based protein if you feel well that way, right? We can achieve a fair amount of of reduction in carbohydrates with any strategy. So, it just depends on, you know, and I think the um like the metabolic mind group has shown this. There are people who are doing a ketogenic diet who are vegetarian. There are people who are even vegan who are doing this. It takes a lot more work, takes a lot more effort to get there, but you know the carbohydrates that that's just an energy marker. How we get there, you know, people assume that it's always like the Atkins, eggs, bacon, and and steak. Um, and that's what a lot of people choose to do. Okay, it's fine. But it's not the only way to get there.

In closing, somebody comes to you saying, "Over the next year, I want to dramatically reduce my cardiovascular risk. Lily, give me the guidance. Where do I start?"

We start with the lifestyle foundation. So, first of all, we check, let's look at your arteries and see where are we starting so that we know how far we have to go. Then, let us figure out a nutritional strategy that maximizes healthful foods in your diet and reduces sources of inflammation. Let us work on your exercise like it's a drug because it absolutely is. And that is a combination of cardiorespiratory fitness, resistance training, and mobility work. Let us make sure that your sleep is as optimal as we can make it. Let's prioritize that as a lifestyle intervention because sleep is like a third or more of our lives and if we are ignoring that, it's at our peril. Let's think about our stress and let's think about our social connection because these are actually also proven interventions to reduce our risks of cardiac events of stroke and of other diseases, chronic diseases. And if we get all of that in line, we have done 80 to 90% of the work. The last 10% is what we can talk about with supplements, with medications, um other advanced techniques. But I do think that that lifestyle foundation, you know, people come at me about, well, you prescribe statins and you're a shill for pharma. I'm like, I I have sick patients who have a lot of plaque. Yes, I do use lipid lowering therapy in some of my patients, but if you're just coming to me because you're interested in prevention, that is not where we start. Like, let us figure out the metabolic piece first and the lifestyle things that will improve your quality of life. So much, right? People come to me and like, I don't know if my risk is any lower, but I feel great. I am sleeping better. I am going out. I am playing pickle ball with all these new friends that I made because you made me go join a club. Like, I'm doing all these things and I feel great. Guess what? That's amazing. And that is probably the best thing I can do for anybody's health. And yeah, maybe because of genetics or something, we have a little more work to do, but if I can get you that far through your lifestyle, then we are all in better shape.

Somebody who's made it to this point of the conversation, they're excited about all this new information but overwhelmed. They want some handholding. Are you working with people online?

I am working with people online a little. I will say most of my practice is still in person and um I am not licensed in every state. So if you're in California, that is the easiest thing for me. If you are in a couple of the other states where I am licensed, I actually have a separate practice and I am on a wait list for that right now because unfortunately I am uh pretty busy with a bunch of my other projects and I am not able to give people as much time and attention as they deserve. Um so mostly you're going to come see me in Southern California. If you are in California anywhere, I can absolutely do tele medicine with you. And beyond that, there are a few other states where I have a license and we can we can discuss that, but um my practice is a little bit limited that way right now.

All right. Well, we're going to link everything up in the show notes, including your wonderful YouTube channel.

Thank you.

Your website, your social media, Lily, really enjoyed this. Thank you.

Thanks for having me, Jesse. Have a great day.

Thanks for watching the episode. I got another great one lined up for you right here. Don't miss it. I'll see you over there.

High blood glucose is one part of the problem. High insulin levels [music] is a bigger part of the problem. High glucose causes swelling, micro vessel damage, blindness. [music]