ZACH MOORE: Welcome to On Health with Houston Methodist. I’m Zach Moore. I’m a photographer and editor here, and I’m also a long-time podcaster.

KATIE MCCALLUM: I’m Katie McCallum. I’m a former researcher, turned health writer, mostly writing for our blogs.

TODD ACKERMAN: I’m Todd Ackerman. I’m a former medical reporter, currently an editor for Houston Methodist.

KIM RIVERA HUSTON-WEBER: I’m Kim Rivera Huston-Weber and I’m a copywriter here at Houston Methodist.

ZACH: And Todd, what are we talking about today?

TODD: We’re talking about cholesterol.

ZACH: What is cholesterol, Todd? That’s my question for you.

KATIE: Starting with the basics.

[Chuckling]

TODD: Cholesterol is a waxy substance that the body needs for certain functions, but too much of it can lodge in your arterial walls and form plaque that narrows your arteries and can rupture and lead to heart attacks.

KATIE: That was a fantastic definition.

ZACH: That was really good.

KATIE: I’m giving you, like, ten out of ten on the spot, you just defined it. That was awesome. Nice job.

TODD: Thank you.

ZACH: And my experience with cholesterol has been hearing the terms, “Oh high cholesterol, low cholesterol,” and then seeing, maybe like, diagrams in, like, health books where it’s, like, the cross section of your arm and it says, “if you continue to live an unhealthy lifestyle, then your arteries will just continue to, kinda, close up.” Alright? That’s what my -- That’s where my mind goes when I hear this and that’s pretty much what happens, right?

TODD: That’s right on, yeah.

KATIE: Mine goes to eggs.

ZACH: Why is that?

KATIE: Well, ‘cause you hear eggs are, like, a healthy food but you hear people be like, “Oh, don’t eat too many eggs. They have cholesterol in ‘em. You’re gonna get high cholesterol.” Which I think I’ve also heard recently that, like, that might not really be totally true and that we might be, kinda, villainizing the cholesterol in eggs and other foods a little too much.

TODD: Well, that was the old wisdom.

KATIE: Yeah.

TODD: The thinking has certainly changed, that’s what we’ll be exploring in today’s podcast.

ZACH: Okay.

TODD:  Egg yolks in particular, people.  So, a lot of people --

KATIE: So, the egg whites. It’s like you order an egg white omelette and you’re, like, healthier, it’s because -- Well, there are, like, less calories but it’s oh, there’s no cholesterol now, so the egg whites are healthier than eating a whole egg.

ZACH: Well, I feel like – and that’s the other thing that I, kinda, know about cholesterol, something that I always thought, “Oh, that’s for older, for like, when you grow older, like, you gotta look out for that,” right? And I’m still mid 30’s, I’m still making that mental shift, like, “You’re not a young man anymore.” So, you really gotta start, like, “Wow, that’s, like, 40 years away for me.” But no, it’s like you’re here, you need to start. The things you do now are gonna affect you for the rest of your life. And, you know, you don’t wanna turn around and, “I’m sorry, all your arteries are blocked ‘cause you’ve been drinking seven soft drinks a day for the last 40 years of your life.” That’s where I am right now, so, I’m still making that mental shift.

KATIE: It sounds like it’s very visceral for you right now.

[Chuckles]

ZACH: It’s coming at me fast, y’all.

TODD: You mentioned in the trailer that you didn’t r -- you weren’t really familiar with these matters.

ZACH: No LDL or anything like that, no.

TODD: Yeah, have you -- Did you rush out after that to go have it tested?

ZACH: No.

[Chuckles]

I was hoping that you would inform me, which, you know, this podcast is very important, Todd. Thank you.

TOOD: Maybe you should resolve to do that now.

ZACH: I might.

TODD: You could report back at a future podcast on what your results were.

ZACH: Part of what we’re talking about today, Todd, is what should those numbers be? Like, what range is a good range for, you know, cholesterol and who do we talk to about that today, Todd?

TODD: We talked to Dr. Khurram Nasir, who’s a preventative cardiologist at Methodist. He not only lays out the ideal numbers but also talks about how the thinking about cholesterol has really changed in recent years. It was a pretty enlightening conversation for me.

[Sound effect signaling beginning of interview]

TODD: Hello, Dr. Nasir, good to have you here to talk with us today.

DR. KHURRAM NASIR: Ah, Todd, thank you so much for having me here today.

TODD: So, where gonna talk about cholesterol, specifically high cholesterol. Generally, is there a consensus that high cholesterol leads to cardiovascular disease?

DR. NASIR: So, over the last -- I would say over the last three decades. Now we have strong consensus and both the medical and scientific communities that bad cholesterol or high cholesterol, specifically called the “Low Density Cholesterol,” LDL, is one of the most important risk factors for that. So, what’s cholesterol? Really, it’s kind of, fat traveling into the body attached to proteins. And a high exposure of over long period of time can increase the risk of those fat deposits happening under the blood lining of the blood vessels. And if they get oxidized with inflammation, they can start building plaques which has many compositions of fat, fiber, calcification, and the consequences of that, that it can start narrowing your arteries. That could lead to some chronic conditions like having chest discomforts or having pain in your leg with exercise. But the most significant consequence is increasing the risk of heart attack or strokes with plaque rupture that -- what happens that the platelets try to block that bleeding, and by doing so can create a clot that blocks the artery, the oxygen, the nutrients to the heart and the brain, and cause the heart attack and stroke.

TODD: So, you mentioned bad cholesterol, LDL, what’s a number that’s sort of, definitely too high, that’s a sign of a problem?

DR. NASIR: It’s, I would say, a moving target. We used to think it was more than 190. The threshold came down to 160, 130 but not --

TODD: That’s total cholesterol or LDL?

DR. NASIR: We’re talking about the LDL. So, the total cholesterol equates to around 200 to 280 in that range. So now, I’m talking about just the bad cholesterol, LDL, which is the most important one. As in general, it’s taught that it’s optimal if it’s less that 100. If it’s 100 to 130 sub-optimal, elevated more than 130. High if it’s more than 160, and very high more than 190. But that’s not the whole story. The cholesterol now we know and especially the bad cholesterol, you cannot take just the numbers into account. It all depends whether you have an underlying heart disease like a prior heart attack, a blocked artery, reduction in the blood flow in the legs, or stroke, and then the levels become much more different because then you may wanna drop your bad cholesterol, or the normal bad cholesterol should be around 70 or lower. Whereas, if you did not have any prior heart attack or stroke, then it all depends how much underlying plaque buildup or atherosclerosis you are harboring, and depending upon what you have, then the thresholds can be decided accordingly.

TODD: So, with new patients that aren’t presenting with issues do you do any sort of scanning?

DR. NASIR: Absolutely. So, if you look at the newer guidelines, they suggest that if you’re uncertain about your risk, for example a 60-year-old male would walk into my clinic and have average LDLs of around 130. And they had a family history, they’re non-diabetic, their blood pressure is well controlled, and the question really is, “What do you do about this cholesterol?” Now, the answer depends upon what’s your risk of having a heart attack or stroke. Now, historically, what we have done is taken these risk factors, all that I mentioned and whether you are a smoker and diabetes and put them in a model. And it would spit out your risk of having a heart attack in the next ten years. The general recommendation is if your ten-year risk is seven and a half, 10% or more of having a heart attack, you should consider therapies apart from lifestyle intervention like statins, that most of us would have heard and similar Lipid-lowering therapies to reduce your risk. What we and others have shown that actually, this mathematical modelling is subpar in the sense that almost half of the individuals that we would recommend committing to lowering cholesterol for their lifetime have no plaque buildup. If you would have done a non-contrast CT scan, commonly known as coronary calcium testing, and they can avoid committing to those therapies. So, in general, in our clinic, most of these decisions are based on whether you have any underlying disease, yes or no, and how much. For the same person who doesn’t have any disease, we have very flexible goals. We engage in conversations about more lifestyle, about modifying their diet, weight reduction, more exercise that can help with 10-15% of cholesterol lowering. We offer them an option if they want to go on a cholesterol lowering pill, but they have flexibility, and the goal is not to dictate. However, if you’re one of those individuals who have tremendous amount of disease, for example, if you have a calcium score more than a hundred which is considered heart disease equivalent, that means you should be treated as intensely as somebody, one of your peers who might have a heart attack. So, in essence, what your cholesterol numbers are, how do you get treated, especially if you don’t have heart disease, at least in 2023 there is a significant movement in the direction not looking at cholesterol in isolation but putting that together how much atherosclerosis plaque buildup that you can see with simple testing like the coronary artery calcium test.

TODD: I think most people know, LDL, bad cholesterol and HDL, good cholesterol, but you never hear much abouts triglycerides, what -- how important are they?

DR. NASIR: They’re an important part of the composition, so they are the ones that store the energy. So, think about triglycerides are you’re having calories, and when there are excess calories, the body try to convert that into fat and that’s how the triglycerides are stored, either in the belly, the liver and the blood. Now, historically, of course, LDL are considered the more important. So, I can give you an analogy for the general public to understand. So, LDL can be considered as the fuel or the gas, whereas, things like triglycerides and HDL, and inflammation can be thought as the triggers. So, both have different mechanism of inciting the actual disease, which is the plaque buildup under the blood vessels. However, the mechanisms are entirely different. So, as far as LDL is concerned, most of the time they are not impacted as much as with lifestyle intervention. But for triglycerides which are critically important, the key things are addressing your insulin resistance, by weight loss, cutting back on sugars, carbs, saturated fats, trans fats, aerobic exercises, and if needed then there are some medications that can be used. However, the most important focus for the triglycerides is it’s a great barometer for your actual cardiometabolic health. Whereas, the LDL has a more genetic predisposition and because that’s how much your liver produces and clears. Both critically important different mechanisms, but the most important piece still remains the bad cholesterol.

TODD:  And what’s the current thinking on HDL? I can remember when there was a lot of excitement about this, how protective it was, there were drugs in the pipelines that will raise people’s HDL. As I recall, they were, like, some deaths with one of those trials. And after that I never heard much about HDL. It seemed like people were saying to me, “We don’t really know what to make of HDL.” Did that kill off all the research with it?

DR. NASIR: Actually, as far as increasing HDL, so historically, what’s HDL? HDL is considered the so called “Good cholesterol.” What it means, if your numbers are high, it indicates that you may have a better proportion of bad versus the good cholesterol. So, it means that HDL is clearing as much as possible. For my patients and colleagues, I like to give an analogy, think about HDL as a dump truck. The liver secretes those dump trucks. It goes into the blood vessels, pick up the garbage, which is the bad cholesterol and dump it back into the liver. Now, what we have also learned over the last two decades, and especially over the last five years is, a very high HDL may not be a good thing. Actually, what we have seen a phenomena of a U shaped curve, that means had the very low level of HDL’s which had more indicator of insulin resistance, naturally there is a higher risk of having a heart attack and stroke. But even among individuals who have the highest levels of HDL, which goes belo -- above 90 or 100, there is an increased risk of having a heart attack. So, why is that? Now, we’re learning that it’s not the amount of good cholesterol in the body, but it’s the function of good cholesterol in the body. So, again, as I said, these are dump trucks. If rather than dumping back into the liver, if they just keep on hanging in the blood, there is more transfer of the bad cholesterol back to the vessels and cause of the plaque buildup. Actually, at Houston Methodist, we have one of our prominent biochemists, Henry Pownall, who have identified a test that can look at the HDL functionality and his group. And we just receive a major NIH grant to study this whole phenomenon of HDL function which has been, I would say, plagued with controversies. So, we are very hopeful of now identifying where the real issue is, is going to be around the function of HDL but not how much HDL you have.

TODD: For the average lay person out there, is there a window that they should wanna see their HDL within?

DR. NASIR: Yes, absolutely. So, for an average person, you know, you should try to have your HDL more than 40. Now, less than 40 is more of an indication of your poor cardio metabolic health. And now, what are the things that are going to increase your HDL? There are about four or five major things, one is an optimal diet, high in fiber, low in trans fats and saturated fats, cutting back on carbs, sugars. Again, the same things that are going to affect the triglycerides. Of course, some studies suggest one to two glasses of red wine may also help with the HDL, but losing weight, aerobic exercises, and quitting smoking, all of these things improve HDL. So, in essence, HDL is a great marker that can tell me what your lifestyle is. If it’s going in the wrong direction, it's time to put a lock on the fridge and bring out your running shoes.

TODD: But -- so, you want, like, 40 to what, 75?

DR. NASIR: Around that range, yes. Now, of course, the question really is, Todd, is why are we worried about these numbers? Why you and I, and our colleagues, and our peers, and our communities are having conversation around LDL’s and bad -- high bad cholesterol and trying to achieve good cholesterol is because we’re trying to avoid having a heart attack and stroke. Now, as I said, what we have learned, especially over the last five years, that historically, we used to focus on the cholesterol numbers a lot and there was a reason. One, it’s one of the most important risk factors. You have treatment that you can do something about it, and it give us a good guesstimation of what you’re actually happening inside. Now, in 2023, over the last ten years, now we have known, we have simple methods and tests that can tell us whether the effect of these good, bad, fat cholesterol combination, has that resulted in any damage? And if yes, how much? So, let me give you an example. About 50% of individuals who have their LDL in the worst range and may have a low HDL and even may have high triglycerides and they would walk into my clinic. How many do you think that if we did a CT scan would have no plaque?

TODD: Some significant percentage.

DR. NASIR: Yeah. Almost 50% of them would have no disease. But these are the ones that we wanna treat them more intensely. On the other hand, about 40% of individuals who have no plaque, none of these disorders who may have a normal HDL, they may have an HDL of 50, an HDL of 95, and a triglycerides less than 100, they may have underlying plaque build-up. Now, if you follow these individuals, actually the ones who have the disease and normal cholesterols are gonna have more heart attacks and strokes than those who have the worst cholesterols but no disease. So, in essence, that’s kind of the big message that in absence of your prior heart attack or stroke, truly the numbers can be less meaningful if you look at in isolation unless and until you do some testing like a heart scan, to look for the coronary calcium, or a neck ultrasound to see if you have a plaque buildup or not. Because otherwise, we’ll be making these decisions in a vacuum, and we may not identify the right patient who may need the right treatment at the right time.

TODD: So, why is there so much focus on cholesterol numbers instead of these tests that can tell you --

DR. NASIR: So, again, historically, as you know, for various reasons. Number one, is access. Cholesterol testing and these are blood works you can easily get them. Secondly, historically, the guidelines have been more reluctant to recommend newer test unless and until there are random trials showing that utilizing that test will help reduce outcomes. And thirdly, historically, most of the preventive cardiologists have been lipidologists and we didn’t have data. However, over the last five to ten years, mostly from our groups and our colleagues in the country, clearly have shown that the value of the Coronary Artery Calcium testing, especially in identifying those who need treatment is pretty high. And actually, in 2019 the newer guidelines brought that in and updated that recommendation. So, if you look at Houston Methodist, the practice if -- that’s really one of the most growing spaces, we’re almost about, I think, 15-20,000 patients each year get Coronary Artery Calcium testing. That has doubled or tripled over the last three years, happening all across the country. Unfortunately, Medicare has yet not responded because it still consider these tests as part -- Not part in parcel of the regular care. We are still working with CMS to it reimbursed. However, at places like Houston Methodist and most of the others, you can pay around $100-150 out of pocket to get that test.

TODD: That’s the best way to get it rather than going through your insurance?

DR. NASIR: Yes, right now. We are hopeful in the next few years, it should be covered by insurance. But the question then will become, how much would be the out-of-pocket cost again? And hence, most of the places have brought it to the point that majority of individuals can afford for such an important decision, whether you need to be on a Lipid-lowering therapy for the next five to ten years of your life or not.

TODD: And insurance doesn’t cover it based on, like, whether your doctor’s ordering it up versus you probably wanna do this on your own preemitively?

DR. NASIR: No, it doesn’t. So, right now, it doesn’t. Actually, we -- in Texas, they have a bill where most of the insurances should be paying $200 out of pocket. So, if there is somebody who is willing to take that case to the insurances, there’s always an opportunity. But in all honestly and in our conversation, most of the patients are willing to pay that $100-150 out of pocket. Because in essence, even if it’s covered by insurance most of the time that maybe the deductible or the out-of-pocket cost.

[Music plays to signal a brief interjection in the interview]

ZACH: You might think all the attention given to cholesterol in recent decades has been sufficient to raise awareness. But a 2023 survey commissioned by the American Heart Association found the people most at risk lack basic knowledge about the issue. The survey, conducted by the Harris poll, included responses from 3,000 US adults. More than 500 of them reported having at some point experienced a stroke or heart attack, or both. Among the survey findings are 70% of heart attack and stroke survivors were unaware that LDL cholesterol is commonly referred to as bad cholesterol. 47% of that population was unaware of their LDL cholesterol number. And only 49% recognize the need to prioritize lowering their cholesterol. The Heart Association recommends adults 20 or older should have their cholesterol check every four to six years. After age 40, doctors use an equation based on cholesterol numbers and other factors to calculate the patient’s ten-year risk of having a heart attack or stroke.

[Music plays to signal resumption of interview]

TODD: To me the big question is, what we know about causes high cholesterol? I’m old enough that I was sort of indoctrinated in the -- in the idea that it was high cholesterol foods. That it was steak and butter and eggs. And if you ate a diet rich in those things, you were gonna have high cholesterol. That is not the thinking anymore?

DR. NASIR: It’s definitely much more complex than the simplistic views we had in the past where we had strict dietary and regulations or I would say had advice against it. Now what we are learning is that, that many people who are hyper responders. So, you know, Todd, we can -- you and I both can have three eggs and a steak together and how we will respond will be differently, and how much LDL that we will have will be much more significant. Now, it also depends upon what’s our overall diet, it is more fiber rich, vegetable, fruits, are we having more lean proteins. A lot of this combinations also affect. So definitely, the role of the diet being solely driving the bad cholesterol, I think so, we are moving away from them. It’s more around how much bad cholesterol is produced by the liver and how much it’s --  Of course, these are the things that do influence, of course, things like trans fats, saturated fat. Yes. On the other hand, if you’re focusing more on the polysaturated fats like olive oils, and salmons, and fish oils, that may actually improve your LDL. Now, as far as diet is concerned it’s going to mostly affect the triglycerides which is the fat and HDL. And you’ll be surprised rather than the fat, it’s the sugars, and the refined carbs, and the processed carbs which are more responsible for elevated triglycerides and low HDL. So, the message is, if you are able to refine your diet you can definitely have a 10 to 15% lowering of your bad cholesterol, but the significant lowering of your triglycerides which is the fat cholesterol and improve the good cholesterol. If you lose weight, now there is data that about 5% reduction in the bad cholesterol can happen. But the major benefit, about 50% reduction in the fat cholesterol and improvement in HDL, same with the exercise. So, in essence, Todd, if you wanna enjoy a steak you can but the advice is do it in moderation.

TODD: And how about like butter and cheese?

DR. NASIR: Same. You know, in all honesty, so one of the key things is as a preventive cardiologist, I have a lot of conversations on diet, and I’ve spoken to various groups. And you can see depending upon which side of the bed you wake up or which religion you believe in, folks have very strong opinions on the diets be it, in our old days it was Atkins, and then we have Mediterranean, and South Beach. And now we have many other variations, Paleo diet. We have the plant-based diet, vegan diet. And everyone’s sure how effective their diet is. But, you know, Todd, if you critically review them, you will see that they have -- most of them are similar than differences. There are three major things that are extremely similar. Number one, almost in all diets or lifestyles, no sugar or fructose. That’s kind of like be it a plant-based diet, or the Mediterranean, or South Beach. Focus on cutting back as much as possible on processed and refined carbs, and thirdly, small plates. So, now if you have cut out sugar and fructose and you’ve taken out processed carbs and your diet is in moderation, it doesn’t matter if you supplemented with salmon, red meat, lamb, a lot of vegetables, lentils, legumes, I think so, that’s kind of what it is. So, as long as we can get this basic concept to our communities and our friends out there, I think so, we’ll find that lifestyle changes -- adapting healthy lifestyle changes is not that difficult especially if you wanna maintain good cholesterol levels.

TODD: So, I’ve also heard of new measure lipoprotein A. What is that?

DR. NASIR: It’s the new kid on the block. So, lipoprotein A in essence is the same LDL but it has an additional layer of protein around it which is APO-A. So, as you know, cholesterol cannot transport in the vessels in the blood by itself. It has to have a protein covering. Most of the traditional LDLs like the LD -- the bad cholesterol that we talk about has a covering called APO-B. And hence, some of our colleagues and folks in the community would really like to check APO-B. But this has an additional covering called APO-A. So, that’s why it’s not measured by the traditional, you have to do a separate test. And now, why it’s important? It’s important because this is what I would call the more inflamed and stickier cholesterol. So, it has a higher risk of sticking with the arteries and causing the plaque build-up. That’s number one. And hence, clearly has a slightly increased risk of causing a heart attack than those individuals who don’t have a high limit. That’s number one. Number two, it is more genetically determined. That’s number two. So, if you have it, it’s clearly a predisposition that you have some familial components. The other thing is you can’t get it tested by the normal testing, so you have to have a special test ordered for the lipoprotein A. They’re still trying to standardize it. The major thing is, what do you do about it? With the LDL we have therapies like statins and many of the other emerging, but you cannot lower lipoprotein A. Alright. Now, there are two investigational therapies which are working upstream in trying to block the production of lipoprotein A, are being studied in phase three studies. We’ll see if they pan out. As you know, we have our disappointments in the past with trying to increase the HDL. So, it’s hard to know whether lowering lipoprotein A is going to be effective. Now, so the question is, what do we do now? Who should get checked? In essence, if you have a very strong family history of heart disease, or you had a heart attack at an early age, and especially if you do not have any major risk factors like you’re non-diabetic, your cholesterol numbers are fine, you were never a smoker but still had a heart attack and stroke. These are the three or four categories that you should always try to check the lipoprotein A in. Now, Todd, you can ask, “Okay, I -- we saw the lipoprotein A. It’s elevated. At least it gives us an idea why they’re at risk. What do you do?” You maximize their preventive measures. For example, these are the ones that I will focus more intensely in lowering their bad cholesterol. If you had a heart attack, rather than trying to get your numbers traditionally, your doctor will say, “Get your bad cholesterol numbers below 70.” We’ll try to push them 40 or lower. So, that’s what we would do. We’ll try to be more aggressive with aspirin, their blood pressure control,  and lifestyle. But I would say, Todd, let’s keep tuned on this issue. We’re anticipating in the next 12 months to have the first insights whether addressing the lipoprotein A will make a difference. And if that’s the case I think so, it will be critically important for our very high-risk individuals. About 20% of those individuals have an elevated lipoprotein A and we still have residual risks. So, the residual risk concept is that even after lowering your bad cholesterol, there is some of the risk that we are unable to mitigate. Because even if you take the cholesterol down all the way to 70 and 40, about 10% of individuals still have heart attacks. And a lot of this can be covered by lowering the lipoprotein A and other items here.

[Music plays to signal a brief interjection in the interview]

ZACH: Dr. Nasir mentioned the ongoing research into medication to treat lipoprotein A. The genetically based sticky cholesterol that increases the risk of blockages and blood clots in the arteries. Earlier this year the results of the first research were unveiled. In a randomised double-blind study, researchers in Australia reported that an experimental oral medication developed to target LPA lowered its levels by more than half during an early phase clinical trial. The study involved 114 participants who received either a placebo or the medication Muvalaplin, the first oral drug ever developed to target LPA. Doses given for 14 days range from 100 to 800 milligrams. Within just 24 hours after the dose, researchers reported blood plasma levels of LPA dropped. The amount of reduction depending on the dose, but it reached 65% for some patients over the course of the trial. Muvalaplin works by disrupting LPA’s ability to form in the first place. Important because the vessel clogging cholesterol is so hard to reduce once it’s already become established. Attempts to reduce levels through existing cholesterol treatment and changes in diet and exercise have met with little success. Muvalaplin is currently undergoing a much larger study which will test its effectiveness with much greater statistical power.

[Music plays to signal the resumption of interview]

TODD: So, with Lipoprotein A, you mentioned a lot of it’s family history. How much would choles -- high cholesterol generally is genetic? And if it is genetic, can you do much about it?

DR. NASIR: So -- and again, we think that LDL has a strong genetic predisposition. Now, of course, when we talk -- when you and I are thinking genetics we are in general thinking about extreme forms. One of the most common one is what we call familial Hypercholesterolemia. So, if your -- multiple family members have very high cholesterol of they had early heart attacks in their 40s and the 50s, the most common cause is familial Hypercholesterolemia. Where there is a genetic defect that leads to impaired cholesterol receptors. Now, the downside of that is now you’re born with LDLs of 190, 200, 250 or more. And over a period of 20, 30, 40 years you’re exposed to a significant elevated LDL, and hence, increases the risk of heart attack and stroke. Not in your 50s and 60s but even in your 30s and 40s. So, what do you do about it? The first thing is as a society I advised that most of us should at least in their 20s or early 30s start getting their cholesterol checked. Now once you find that, of course, then you need to intensify the treatment. You can do genetic testing to make sure that you’re not vulnerable, and if you are it can also lead to what -- a concept we call it cascade screening. That means make sure your family members are also checked because there is a 25% chance that they may have it. Thirdly, they may be candidates for what we call the more intense therapies beyond statins which all of us know, and that’s been out there for the last 20 years for newer novel therapies like the PCSK9 inhibitors. That’s in the market for the last, almost ten years, to get your LDL as low as possible. Now, how often do we see this? This is almost I would say, one in 200 individuals in our society which is not meagre if you look at that. There is a significant proportion of those. Now, apart from that, these are the ones who are gonna have very high LDLs. Now, majority of us who have elevated LDLs may not be due to a strong single gene defect, but multiple smaller genes impacted, that we call the polygenetic effect. And now they’re being -- test being developed that can help us understand that. But long story short. Everyone should have their cholesterol testing in their 20s and 30s. That’s a great perimeter for you to follow and keeping a healthy cholesterol is a lifelong commitment that we need to have. And if you have high cholesterol then make sure that you’re seen by a cardiologist or a preventive cardiologist who could get to the bottom of it and help create a more personalized treatment plan for you.

TODD: Is high cholesterol not uncommon in people in their 20’s?

DR. NASIR: In general, I would say one in 200 will have very high, about -- if you look at the NHIS data which is the National representative population, we see almost more than one in three individuals even at a young age having suboptimal LDLs. Now, the question really is, what do we do about it? Should we start them on medications? My philosophy is that at an early age I think the focus still needs to be as much as possible on the lifestyle. Dietary modifications, healthy diet, exercise, weight loss, quit smoking. All of these things can get your bad cholesterol at least 10 to 15 to 20% down and I think -- so that should suffice. However, if you have a lot of risk factors, diabetes, metabolic syndrome, and the obesity pandemic is growing and so is with that -- prediabetes. Then maybe at age 35 or above you should start thinking about screening your arteries if you have any effect. And if you do, definitely that’s the time to start very intense treatment.

TODD: So, the coronary artery calcium scan we talked about...

DR. NASIR: Yes.

TODD: Is that something that, say by your 60’s it’s probably not a bad idea for most people to do just have to have a baseline?

DR. NASIR: I would say that even earlier. In general, the -- from my standpoint is you should start getting it by age 45 or if you’re ill.

TODD: Even without have the conversation.

DR. NASIR: Even without the conversation. So, it’s just one time test. It cost about a $100 to $150. It takes about two to three minutes to get it done. You don’t need any contrast. It does come with radiation and the radiation is equivalent to what you get with the mammogram which almost all women have after a certain age every year, or, Todd, if you wanna fly from New York to LA and be back it’s the same radiation. But it’s the most accurate indicator of your heart health and whether you should commit to therapies beyond lifestyle intervention or not. Younger than 45 I would recommend if you -- if you have strong family history, if you have a combination of risk factors, like, diabetes, hypertension, high cholesterol, and obesity. In fact, we have shown that even in young individuals, if you do this targeted screening, you may identify one in three who gets screened who have the earliest plaque buildup that you would never think of. And that’s the time once you detect it you make those significant changes and nip this process in the bud.

TODD: So, cholesterol science sounds to me from our conversation here it’s like it’s still really evolving and seems pretty complicated.

DR. NASIR: Look, I would say cholesterol still remains the top risk factors for development of heart disease but not the only one. The reason why we focus a lot on cholesterol because we also have options to treat it. And clearly, in individuals who are vulnerable to developing heart disease or already have heart disease, the number one, number two, and number three treatment that’s gonna lower your risk is getting your bad cholesterol under control. So, that’s well established. Now, extrapolating that to the general population becomes a little complex because majority of those individuals don’t have heart disease. And if you don’t have heart disease or plaque buildup then the cholesterol numbers may not have the same significance. That means we may not have the need to put too many people on treatments or intensify on treatments, but rather focus on lifestyle management. But it will also allow us to identify a small group of individuals who are harboring the disease where we can intensify the cholesterol management and hence reduce them getting to a point where they had a heart attack or stroke.

TODD: Is there a link -- any link between stress and high cholesterol?

DR. NASIR: Not much that we have seen. In some smaller studies there could be an indirect link with stress, indiscreet eating, poor lifestyle, poor sleep leading to prediabetes, insulin resistance leading to low HDL and a high triglycerides. I think this are more indirect effect of poor lifestyle leading to metabolic syndrome, leading to high fat contents of the triglycerides and low HDL. But really, truly, we don’t think that there is a direct connection between and stress and the cholesterol numbers.

TODD: And is total cholesterol meaningful? I’m never quite sure of that.

DR. NASIR: I’ll be honest, I have ha -- I hardly pay attention to the total cholesterol. The most important key for me is your LDL. Especially, as I said, if you are a patient who already have a known heart disease, a stroke, or blockages in your leg arteries. The second one is the triglycerides. And the least one that we pay attention right now is HDL. But of course, the combination is, these are being used mostly for advising lifestyle interventions than anything else. So, the idea of the total cholesterol being a parameter that we use to focus it’s -- we’re shifting away from a more emphasis on the LDL which is the bad cholesterol.

TODD: Smoking and alcohol have much of a role?

DR. NASIR: Smoking is bad in the sense, let me tell you. It injures your arteries. So, think about it. Your arteries are -- have more injury and now you have a lot of fuel floating around. It just increases the risk of that high LDL getting accumulated under your arteries and with the high inflammation causing the oxidization of creating the plaque. So, that’s number one. And smoking also, once you have plaque it just increases the risk of the plaque rupture and also increases the risk of clot formation. So, if you have high cholesterol, or familial Hypercholesterolemia, or if you have heart disease, one of the most important interventions on top of taking the cholesterol pill is quitting smoking. So, that’s definitely one. Alcohol can definitely impact the triglycerides. So, if you are one of those individuals whose triglycerides are historically high -- and by the way, triglycerides can not only increase the risk for heart disease, but if they’re very high, can also cause a life-threatening condition, pancreatitis. Where your pancreas became inflamed and can lead to catastrophic conditions. So, for individuals that we see who have very high triglycerides cutting back on alcohol or alcohol cessation is definitely one of the top recommendations.

TODD: Are there warning signs of high cholesterol? I mean short of chest pains when disease has set in, you know, but is there anything before that?

DR. NASIR: I wish. No warning signs really in the end. Unless an until you were born with the genetic defects. We do see individuals who may have -- who may come in and have cholesterol deposits beyond the arteries. For example, an eye examination can show a rim of cholesterol deposits or some under the skin. In very few individuals we see deposits in their tendons. But I can tell you that over the last 20 years I’ve seen only three of those. So, unfortunately, no signs. But fortunately, it’s very e -- it’s an easy available test that most of us have an access to. And as long as you’ll have access to healthcare, you’re seeing your primary care, most of the primary care physicians I’m hoping are getting those tests for adults age 30, 35 and above. But my suggestion is, even at a young age there’s no reason not to get it once. And if there are still in that range -- abnormal range that you can then follow them up.

TODD: When you prescribe statins for people, does it -- is it typically for life then? Or can they improve and go off them?

DR. NASIR: That’s always one of the discussions we have with our patients. You know, my thinking is that unlike infections or antibiotics where you can have it and use it for a month or a few weeks, it addressed the condition. This is mostly genetics. Of course, you can improve your LDL with lifestyle, but the numbers may drop from, if you had an LDL of 130 with lifestyle may bring to down to a hundred then. Now, the issue is if you had a patient who had a prior heart attack, we want to get you down all the way to 70 or lower, or maybe even 55. That’s very unlikely to happen with lifestyle alone. Statins still remain the best choice because not only they lower the bad cholesterol, they have additional benefits like improving your inflammation and direct impact on stabilizing the plaque. So, they still remain the first choice. Now, unfortunately, about 7% to 8% of individuals may be unable to tolerate them because of symptoms which is the most common muscle aches or joint aches. Thankfully, in 2023 we have additional options. A couple of other oral pills like bempedoic acid and ezetimibe, and of course the new injections which are widely available. The Repatha, the PCSK9 inhibitors commonly known as Repatha or Praluent. So definitely my advice to the patients and the listeners are if you’re one of those patients who have a heart disease, stroke, my recommendation would be consider these therapies for life. The question is, is not the can you, the question is should you be off? Because if you’re off these medication the cholesterol level is gonna go back up again. It’s gonna put you again at risk of progression of disease, making those plaques more unstable and the risk for having another heart attack or stroke. And also, if you’re one of those individuals who have high amount of underlying disease in absence of heart attacks. For example, a high coronary artery calcium score. My advice would be the same that, persist with it. It’s a great once a day pill. I would say consider it like a vitamin that lowers your bad cholesterol, improves your inflammations, keep your heart arteries healthy, and reduce the risk of a heart attack.

TODD: The medications that you mentioned as alternatives of statins, are those just for people who can’t tolerate them well or in any way are those considered next generation drugs that might be better than statins?

DR. NASIR: I would say those are more to supplement than complement. Because the recommendation is stick with the statin as much as you can with the highest dose. Now, I can put you on a statin and I can get your bad cholesterol for example into the numbers 80s or 90s. But now we know from studies that even if you lower it further you can reduce the risk by another 30%. So, if the statin alone doesn’t do it, then we start thinking of adding these additional medications, or these are also as an alternate if you are unable to tolerate statins. So, the message still remains the same. Statins are still the best medication out there. If you have underlying heart disease you should try to get on the highest dose that you can tolerate, which by the way, most of the individuals can, and then supplement with additional compounds as needed.

TODD: I hear some doctors, I think there are almost kind of a wonder drug that more people should be on than wh -- very moderate levels of high cholesterols, taking statins in low doses. What are your thoughts on that?

DR. NASIR: You know, and they’re different schools of thoughts and of course, I understand their viewpoint is -- but I truly believe this is an issue of patient autonomy. Right? So, as long as everything’s done in a shared decision-making process. Look, if there are patients who are willing to do anything and everything and they don’t mind taking a statin, my view is very agnostic. I don’t -- I think that the statin if you wanna take it even if you don’t have the major risk factors. For example, if you don’t have a coronary artery calcium score, your risk of having a heart attack is very low. This is very unlikely going to reduce the risk of having a heart attacks. Actually, some studies have suggested that it may not. But if you’re willing to lower your LDL and improve your inflammation. As long as you’re on board there’s no issues. But, you know, most of us in the society and I can tell you my biggest challenge is convincing patients who actually even need it, to commit to a therapy with a pill a day. So, I think – that there is definitely this dichotomy where some of the experts are trying to put too many people on statins. And I respect and understand their view because it’s cheap, it’s effective, and very few people have side effects. The crown reality is our communities and our patients don’t want to be on pills if they don’t have to, however good it is. And that’s why I think again the coronary artery calcium testing is such a great tie breaker. Because if you’re uncertain or you’re unsure what your risk of heart attack is and whether you should commit to a great therapy like statin for lifelong, that test can give you that answer. Because if you don’t have the disease, you may not have to take it. And if you have the disease, then that’s a great incentive for you to start the preventive measures much earlier.

TODD: Okay, very good. So, any final message you wanna leave the listeners with about what they should know about cholesterol, how they should approach it, how to main acceptable levels?

DR. NASIR: Absolutely, I think so. Again, the message is don’t underestimate cholesterol. Always, it’s one of the most important risk factors for not only development but progression of the disease, causing heart attack and strokes. So, the first thing is know your numbers. Of course, traditionally, you’re gonna get the LDL, HDL, and triglycerides. And that’s fine, I think, so they can suffice. Make sure that your physicians, your primary care can explain to you more in detail. Now, my other recommendation if you have a very strong family history of heart disease or you already had a heart attack at an early age and especially if it happened in absence of major risk factors, make sure you get your lipoprotein A checked. Now, lifestyle is key here, and then again diet. My advice is any cholesterol in moderation is fine. Try to avoid saturated trans fats. Cut back on the carbs, refined carbs. Sugars that affect your HDLs and the triglycerides. Make sure it’s a balanced diet with more fiber. Fruits, vegetables, lean meat, smaller plates, main a healthy body weight. That’s critical because that’s not only going to help maintain a good level of LDL but also the fat cholesterol and can improve your good cholesterol. Thirty minutes of moderate exercise is key. Smoking is really bad in all honesty, so try to avoid that especially if you have heart disease or a lot of plaque buildup. Now, this should be done by everyone. Now, if you’re at a point where either your primary care of your physician is recommending you to start or start considering statins or cholesterol lowering, my advise is think about getting a coronary artery calcium test because that will give you much better indication whether you need it or not. Now, if you are one of those who already had a heart attack and stroke then make sure that you get your LDL, the bad cholesterol less than 70. Try to be on the highest dose of statin, use additional cholesterol lowering to help you get there if needed. And if you have your triglycerides more than 150 then we also have guideline recommended therapy which is called eicosapentaenoic acid. It’s a special type of a fish oil which is a more purified EPA rather than the genetic fish oils that can help you with that. So, to sum it up cholesterol critically important for cardiovascular health, trying to maintain optimal cholesterol levels is a lifelong commitment that should not wait till you have a heart attack or stroke. Start early. Know your numbers. Healthy lifestyle. And if you are one of those with the early disease, then start with the medication so that we can block the cycle of getting to a heart attack or stroke.

TODD: Alright. Very good. I appreciate you taking time to educate us all more about this.

DR. NASIR: It was fun talking to you, Todd. Thank you so much.

[Sound effect signals end of interview]

ZACH: Well, Todd, I learned a lot about cholesterol. And to your point earlier I do think I should probably go out and get mine checked ‘cause I’m way overdue.

TODD: Good.

KATIE: It’s a simple blood test too. So, I mean, you know, they’ll just -- they’ll take some blood at your annual checkup and then a week later you’ll get some numbers.

ZACH: Mhmm.

KATIE: So, pretty easy.

ZACH: You get this big piece of paper or an email or whatever it’s got all these numbers. It’s like a cell phone bill. It’s like, “What are -- what is this? What is a state tax? What does that,” -- So, I mean, these number you should take time to know much you’re paying for your cell phone. You should also take time to know, you know, what are these health statistics. What is the point in going to get a physical if you’re not gonna take those numbers and learn about yourself and then do something with them. Right?

KATIE: Yeah. I was actually, Todd, as you -- you know, when I was listening. I was kinda, like, pulled up my My Chart numbers. Because remember what you and I talked about, after my last physical my LDL was like a little high or, you know, they say it’s quote and quote “High.” But it’s in that kind of, like, almost elevated range where he was like, “Yeah, you know, that’s where you’re starting to worry, but it’s not high yet.” So, you know, that was to clarify where we ended up the last time we chatted about that. Todd and I talk about out health numbers all the time.

ZACH: Kim, you and I should start talking about our health numbers. What are your health numbers?

KIM: I don’t know off the top of my head, but I have had a physical. I think listening to the episode what I was struck by was that I didn’t know about the equation that after you hit 40 there’s the equation about your likelihood to have a stroke or heart attack in the next ten years. I recently had milestone birthday so now that is another cool new fact I’ve learned about my age.

ZACH: Kim just turned 21 everybody.

[Laughter]

KIM: Again. So, yeah. Fun.

ZACH: Although his analogy of like dump trucks. I was like, “Wow.”

KATIE: I liked the analogies.

ZACH: That’s a good visual. Like, “Oh, okay.” So, I thought that was very unique. I had not heard that term before.

KATIE: Yeah. And the gas LDL being the gas. You know, ‘cause I’ve also heard we’re not really technically supposed to call LDL quote unquote “bad” cholesterol anymore. But I think calling it gas is a very like clear indicator of, “It’s not great.”

KIM: Yeah.

TODD: So, you know, I’ve always paid close attention to my cholesterol numbers unlike you, and kind of tracked them over the years, and they’ve always been solid, could be better. But I focused a lot on dietary cholesterol, of course, ‘cause that was what was emphasized. Now I know that the more important thing is saturated fats, and processed foods, and exercise. I’m pretty good at that -- all that already. So, I don’t think I have any issues. But next up for me is to get that calcium artery scan that he talked about.

ZACH: Yeah, which is apparently a pretty easy to do procedure.

TODD: Yes.

ZACH: Nothing to be intimidated about.

TODD: Yes. You don’t have to do that yet. Kim, it’s coming up for you as you said. That seemed kind of early to me but it’s definitely in my age range now that I should probably get that.

ZACH: Alright. Well, that’s gonna do it for this episode of On Health with Houston Methodist. We drop new episodes every Tuesday morning, so be sure to share, like, and subscribe wherever you get your podcasts. And until then, stay tuned, stay healthy.