Chapters Transcript Pediatric Dyslipidemia Dr. Sumski discusses pediatric dyslipidemia. Good morning everyone and thank you for joining Early Bird Round today. We'll go ahead and um turn our attention to our speaker today, which is Doctor um Christopher Stumsky who specialized in pediatric cardiology. All right. Thanks everybody for coming. I hope everyone is staying OK. Uh, first off, I'll start with my voice. As long as I could, but it finally caught up with me in the past couple of days and so I've got a little bit of a frog in my throat, but we'll, we'll make it through, hopefully, fingers crossed. So, um, I'm gonna talk today about pediatric dyslipidemias. Um, I don't have any conflicts of interest or disclosures to report. Um, some objectives for the talk, we're gonna talk a little bit about physiology and path of physiology. We're gonna review some of the most common causes of dyslipidemia in pediatric patients and the current screening guidelines, and then talk a little bit about interpreting a lipid panel and some interventions for dyslipidemia and some uh techniques for lifestyle counseling, that's a big part of this. Getting started, we'll talk first a little bit about some lipid physiology, which you guys probably know is pretty complicated. Um, so there's a lot of things that happen if, uh, you know, gut absorption in the liver. And fortunately for all of us here today, we're not gonna talk about the vast majority of that because it is. Not super applicable to most of our lives. Um, and so we're not gonna cover all of this nitty gritty little detail, but I've tried to boil it down to the, the basics that will help us kind of understand some of the treatments and some of the, the screening guidelines. So starting kind of at the basics, um, cholesterol is a molecule that I described to to kids and families as a Lego, you use it to make stuff. We use it to make your cell membranes, you may use it to make steroids and hormones and bile and different things that your body needs. And triglycerides, which we also talk about frequently when we're talking about lipids, those are a dietary fats. So you get that more directly from your diet and um we use that to burn for energy, store for energy later on. It certainly gets much more complicated than that, but um that's kind of the, the basic way that I described it to families and kind of start from. These molecules are nonpolar, um, and so they're not soluble in water. And as we all know, our blood is mostly water, and so they, uh, need to be packaged so that they can be transported in our blood. And this is what our cholesterol particles are. And so they are packaged together with different proteins called apolipoproteins and the different types of lipoproteins depend on what type of apolipoprotein, uh, they're paired with and. You can tell that this terminology is a little bit mind-bending and that's why we're not gonna talk about it more than we absolutely have to. So, I actually think this chart is reasonably helpful. You can see there's different types of apolipoproteins. That's the protein that your cholesterol is packaged with, and that yields different types of lipoproteins. There's other differences, mainly how much cholesterol is packed into that or how much triglycerides are packed into that. But your apolipoprotein really determines a lot of what the physiologic um uh uh. Functions of those molecules are. And so we talk about AOB and ApoA. You'll see that your AOB is here in your chylomicrons, your very low density lipoproteins, and your low density lipoproteins. So those are your non-HDL cholesterol. So if we talk about your non-HDL, you're taking your total and you're subtracting out your HDL. This is essentially what you're getting and you're kind of accounting for all of your AOB containing molecules. And that is helpful because those are all of your bad cholesterols. So your HTLs, your good cholesterol or your happy cholesterol, so you're all gonna roll your eyes, but you're gonna remember it now. And that one is not paired with AOB, it's paired with AOA. The rest of them are AOB. Best, um, physiologically. Well, these molecules, they can diffuse across your subendothelial space, and the AOB molecules get stuck back there. So they get into the entema into the subendothelial space of your arteries, and they get stuck and they start interacting with inflammatory cells. They get consumed by macrophages, they turn into foam cells, and over time they build up to these atherosclerotic lesions which can then calcify and rupture. So ApoB diffuses across the subendothelium, gets stuck. AOA or HDL doesn't get stuck and it actually scavenges some of that cholesterol and recycles it to the liver where it can be processed and used or um and uh actually makes those atherosclerotic lesions smaller. So that's why the APA and your HDL we term your good cholesterol, and then your LDL is the biggest component of those AOB molecules, but your non-HDL, your LDL, those are kind of the bad cholesterols. Physiology that comes up clinically. So if you have really high triglycerides, um, one area that those triglycerides are living is within your VLDL molecules and uh particles and they can interact with your LDL and HDL and they can actually swap out triglycerides for cholesterol esters, and what this functionally does is it makes your LDL particles smaller. And that can falsely lower your LDL reading if you're just getting a milligrams per deciliter, which is the vast majority of the labs report out. So you get a falsely reassuring low LDL, but those are smaller particles that are more atherogenic because they can diffuse across that subendothelium a little bit easier. And then it also does the same thing to HDL, but HDL is already smaller, right? So you can see in my beautiful drawing that I made here that this HDL is a little bit smaller. And they can get small enough that they get filtered by your kidneys and excreted. So high triglyceride levels can drive a falsely reassuring LDL number, and it can make your HDL lower. And so that's one of the clinical pictures that we see is elevated triglycerides, a normal appearing LDL, but really it's high concentration of pretty atherogenic particles and then a low HDL. So now that we've talked about all of that and we can move on for physiology, does this matter to kids? Um, there's actually a lot of evidence going back several decades now that, yeah, this does matter in kids. So, um, there's several seminal heart studies, Lousa study, the PDay study, um, some autopsy studies in, uh, victims of the Korean World War II and, and Vietnam War that showed that fatty streaks and raised regions are occurring early in life. Um, they start to increase in number in the age of 15. 34, um, high lipid levels correlate with childhood, uh, with high lipid levels in adulthood, and higher LDL in teens is independently associated with increased carotid entema thickness, which is an ultrasound measurement that would correlates to atherosclerotic, uh, cardiovascular disease. So elevated cholesterol in childhood does start to cause disease. It's just an indolent and slow and silent disease until it's not anymore, and the high cholesterol numbers in childhood does correlate to higher cholesterol numbers in adulthood. And overall cardiovascular disease remains a major cause of morbidity, morbidity and mortality in the US and um early identification and intervention can help prevent that burden of atherosclerotic cardiovascular disease. So, now, moving on to some of the more common causes of dyslipidemia, I think of it as kind of two buckets. You've got your, uh, some genes, but mainly environmental lifestyle causes bucket, and then you've got your more genetic causes bucket, and those can certainly overlap. They're not mutually exclusive, but those are kind of two of the big um themes that we see in patients when they come to us and the the clinic. Some of the environmental causes, having a high dietary fat intake, poor fruit and vegetable intake, or uh fiber intake, and then a sedentary lifestyle. So there's no surprises there. And then some of the genetic things that we worry about the most common of which is. Uh, familial hypercholesterolemia, but you can also have polygenic causes also a very common thing, and then, uh, familial hyperchylomicronnemia, um, which is really elevated triglycerides, and that's more rare, but we do occasionally see that. So when we're screening family, I really can't emphasize or screening kids, I can't emphasize enough that what we're doing is we're screening to catch familial hypercholesterol inmia. So we know that, that we can counsel kids on lifestyle. We can identify those, um, unhealthy habits early on. We don't need a cholesterol panel to know the kids that we want to counsel on being more active and eating better and those sorts of things. You don't need to get a cholesterol panel for that. But what you We do need to get a cholesterol panel for is to screen for familiar hypercholesterolemia. So the um incidence of that is, is pretty high. It's about 1 in 250, 1 in 300, um, so it's a very common genetic disorder and we have interventions that can. Um, that, that work and are safe to, to help treat those. So the, the main reason that we're screening is not to catch people that have, you know, lifestyle changes that we need to make. We can counsel them on that without having that lipid panel, but we really need the lipid panel to help identify these kids that have the, the fairly common familial hypercholesterolemia. Speaking a little bit about FH, so it's a pretty common, like I said, monogenetic cause of elevated cholesterol, and it results from deficient or defective LDL receptors. So the way that I explained this to families, you got uh cholesterol floating around in your blood. Your body needs to use that to make stuff, right? But it needs to bring it into the cell to be able to use that, so your cholesterol receptor grabs onto it, brings it into the cell. Now your cell can use it to make steroids or lipid bilayer or, you know, bile, whatever that cell needs to make. And you've got one copy of that from mom, one copy of that from dad. And heterozygous FH, uh, which is the common one, that is, uh, one bad receptor. And so you might have half your receptors from one parent that are chugging along, working at the expected level, and then one pair of one copy, so about half of your receptors that are functioning at 10% or 15% of the expected capacity. If you got homozygous FH that is too bad copies of that gene, and so you've got significantly more elevated cholesterol in those patients, that is more rare. So, depending on the study that you believe anywhere from about 1 in 200 to 1 in 300 for your prevalence, and it results in an elevated LDL at a pretty young age and leads to a more rapid progression of that atherosclerotic cardiovascular disease. You should be suspecting this when you get a patient with an LDL that's above about 160 and um they have a first degree relative that has a similarly elevated LDL, a history of premature cardiovascular disease, or positive genetic testing for FH. If they've got an LDL that's greater than about 190, they don't necessarily need to have that family history, that's FH. Homozygous FH, like I said, is much more rare, about 1 in a million, although there's some studies that say maybe it's a little bit more common than that 1 in 500,000, something like that. But you get much higher levels of, uh, LDL cholesterol. So you get levels in the greater than 500. I've got two patients that I follow that have this. One of them presented with an LDL of about 800, the other one was about 450. So you get different varying levels of severity with this. It requires much earlier and more aggressive treatment, and we do recommend genetic testing cause that can help us determine what the best treatment strategies are gonna be. A lot of times these patients present with other findings, so they don't necessarily present with cardiovascular disease. Xanthomas are pretty common, so these are actually cholesterol deposits, and they can deposit on the extensor surfaces. You see them over the knuckles, over the elbows, over the Achilles tendon. Um, you can also see them in the palms of the hands. You can get an arcus, which I don't have a great picture of in this slide, but that's cholesterol deposits around the iris of the eye. So those are, are different ways that it presents. One of my patients with FH actually presented because they thought that she had warts on her knees, and they tried treatment and tried treatment and treatment and finally sent her to erm. Derm biopsied them and then found cholesterol crystals, and she's the one that had an LDL of about 700, so. Um, keeping a, a high degree of suspicion when you see some of these lesions, um, is, is helpful. Genetic testing can be performed. Um, like I said, we don't always do it in patients that have heterozygous FH because it's not gonna ultimately change our treatment strategy for those people, we're gonna start with statins and then adietamide and things like that, but For homozygous FH it can. So if you've got two bad copies and your receptors are working at like 0, then treatment modalities that try to raise the number of receptors that you have just aren't gonna work. And so genetic testing can be helpful in that homozygous FH population. If it's pursued, it should be done with genetic counseling, talking to family about the implications of genetic testing. I think it's always important no matter what screening you're doing. And then it's really important when you find a uh a patient to screen family members. So, um, I think a key thing to remember is when you identify a pediatric patient with FH you're identifying a whole family, not just one patient, and so do we we call it reverse cascade testing, so those first degree family members should get tested if a kid. It has a heterozygous FH then one of their parents has it, um, and you should do screening there and then kind of branch out from there to identify the family members because again, this is a pretty common disease that can lead to pretty severe outcomes, but that we have really good treatments for. And so it should be something that we're trying to identify. Yeah, um, or if you identify a family member with this FH, um, if the family members that you're screening like the first-degree family members, if you screen them and they're negative, do you need to keep re-screening them at like intervals like every couple of years or a one-time thing? Listen a little bit to what genetics tells us, um, because often what you're looking for is, are there any genes that we didn't know about beforehand that we have now discovered to be helpful, and I think it depends a little bit what on that panel says. If you get some variants of unknown significance or something like that, it probably makes a little bit more sense to screen. And it also depends a little bit on that patient. If it's someone with heterozygous FH that's responding well to a statin, I probably feel a little bit less strongly about getting that testing, especially if it's expensive. It depends on insurance. If I've got somebody with really elevated LDL or that isn't responding to treatment, then it can be a little bit more helpful. I might bark up that treat again in the future. I think a helpful way of, um, conceptualizing this is this very busy, uh, picture, but I, I do think it's helpful. And it kind of correlates to the concept of like pack years for smoking. And so I found that actually my patients and families don't understand the term or know the term pack years anymore, which I think is probably a good thing, right? So, um, I like that, but the idea is that you have a lifetime burden of cholesterol that your arteries have seen. And so if you have really high cholesterol, that builds up your lifetime exposure to cholesterol builds up quicker, right? So if you're smoking 2 packs a day for 6 months, that's a pack a year. If you smoke a pack a day for a year, that's a pack a year, right? If you've got homozygous FH, your lifetime exposure to cholesterol has a much higher slope than somebody that doesn't have any FH, right? And the idea is that there's this kind of theoretical threshold where cardiovascular disease is much more likely to happen, we're much more likely to see the strokes and heart attacks, right? And there are things that can move where that threshold is. So being female, not smoking, not having high high blood pressure, those can all raise that threshold, smoking, having high blood pressure, having diabetes, having. Um, other things beating, uh, you know, uh, uh, Kawasaki's disease with aneurysms. Anything that's beating up on your arteries lowers that threshold. And so what I'm talking about with families when we're talking about starting medicines is they're trying to intervene on that slope, right? I'm trying to make cholesterol lower so that we don't truck along. So that we cross that threshold at about 35 years old with the heterozygous FH but we started a statin early on so that we're pushing that out more towards 53, which is kind of what we see in a lot of our population and obviously these numbers are estimates and kind of just there for the sake of, of understanding. But the earlier we can start that and the better reduction we can get in that LDL, the further out I can push that so that you're not having that heart attack or stroke at 35, but we're pushing out to 50, 60, 70, die of something else at 110 years old before they ever have that heart attack or stroke. That's the goal. Many patients, not all of them, but many patients with FH will require uh treatment with LDL lowering medications. Sometimes that's in childhood, sometimes it's not. Um, but we do have several options, statins and azeamide or the, the bread and butter, this bile acid sequestrans are a little bit less tolerated with stomach upset. And we don't use those quite as often and PCSK9 inhibitors are newer medicines that we're starting to use. Those are approved in children specifically with FH, um, uh, but not in, you know, our lifestyle patients. So, uh, getting that diagnosis is helpful if you're thinking what you need to be treating with those. Elevated triglycerides are a little bit different, so that's usually more of a lifestyle component. So there are genetic causes of hyper triglyceridemia, but those are a little bit more rare and so usually the pattern that we see with elevated triglycerides is a strong lifestyle component, um, that can often be driven by medications, diet, high-end simple carbohydrates and refined sugars. Alcohol can do it. And then this is the one that's very sensitive to fasting versus non-fastening. So screening labs, totally reasonable to do non-fasting, but if you come back with high triglycerides, that's the one where I'm gonna go, you know, we need to repeat a fasting level. Um, and that makes sense because this is what's more absorbed directly from your diet. So if you have a milkshake right before your blood draw, you're gonna have more triglycerides in your blood. High triglycerides can lead to pancreatitis. That risk does go up as your triglyceride level goes up, but it hits an inflection point around 1000. So, certainly have a higher risk if you've got somebody with 4 or 500 than somebody with 100, but that, that big inflection point is around 1000. That's when you really start worrying about, oh my gosh, is this kid gonna get pancreatitis? And so we um try to get those down a little bit more expediently when we've got levels approaching that high. Talking a little bit about the screening. Once again, I can't emphasize enough we screen these kids to catch FH um because it is treatable and the treatments work and are, are really well tolerated. Over the history of the past few decades, we've progressed from pretty limited screening based really on family history to more universal screenings, um, and then doing it earlier on in patients that have that concerning family history. So what we found in the initial guidelines were do the screening when you've got that family history, right? Because if you have FH in the family, then you probably have the family history. So we can just screen when there's a family history, but what we found with studies is that that was missing up to 30% of people that would have qualified for statin medication. And so it really wasn't catching enough of these kids. And so we've now progressed to more universal screenings. Like I said before, non-fasting panels are very reasonable for an initial screening, especially if it's an otherwise healthy kid that doesn't have a concerning family history. So the 2011 NHLBI guidelines were the first ones to really um emphasize universal screening, and so they recommended screening at 9 to 11 years old and then again at 17 to 21 years old. The idea was to catch kids before puberty and then again after puberty because we know that there are lipid changes with the course of puberty tend to go up kind of earlier on in puberty and then come down a little bit and then at 17 to 21 years old, reach a little bit of an age. and then we have a slow creep up over the rest of your life. And so the idea was to catch them a little bit before that and catch them again afterwards. And then we recommend targeted screening of high-risk patients that concerning family history down to about 2 years old. Anything before 2 years old is not predictive. And so that, that LDL at that point is I would anticipate to be really low and it's just not gonna tell me anything about what their LDL is gonna be like in 2 years or 3 years or 5 years. Also, we'd be hard pressed to, to treat a patient that young and so it's a little bit less imperative um to treat, you know, test somebody because you're probably not gonna be instituting treatment. It can be helpful to keep an eye on things and know and talk and counsel with family, but um 2 years old is about where we start thinking about testing. In 2018, the AHA and ACC came out with uh primary prevention guidelines for children and adolescents, and they recommended that it was reasonable to measure a lipid panel between 9 and 11 and then again 17 to 21. And then in kids with a family history of early CBD, uh, it's reasonable to measure a lipid panel as early as 2. So really pretty much in agreement with the NHLBI guidelines, um, maybe not quite as, as strong, but essentially saying the same things. So what do we do for these patients? Well, first, let's talk about what you're gonna get that lipid panel and what kind of I do and I think that. So the first thing we get several different labs when we get a lipid panel, first thing you get is your total cholesterol. And what I do with that is ignore it. It's not very helpful to me. It doesn't break down LDL versus non-H uh non-HDL, you know, it does, it's not very helpful. With the HDL, I mostly ignore it. I do think that there are some clinical implications of having a low HDL and if they get very low, then that can be uh something that you would consider with your treatment. But the fact of the matter is that there's not a ton of things that we do specifically to try to boost your HDL. It's a tougher one to get to move in the clinical setting. And so I think that I pay attention to it, especially when it gets kind of at the extremes of its of the levels, but it's not the one that's really driving my clinical decision making. The ones that I'm really using to drive my clinical decision making are primarily the LDL and the triglycerides. And so LDL, I'm looking for, you know, familial hypercholesterolemia if it's really high in the, you know, 140, 150, 160, 170 range, I start thinking about maybe is this FH and then higher than that, I'm thinking, yeah, this is probably FH and then triglycerides give. And a little bit of an idea about lifestyle. Like I said before, certainly there are genetic causes of hyper uh triglyceridemia. Those are a little bit more rare and so we do sometimes see genetic implications of that. But a lot of times it's giving me a little bit of an idea of what the lifestyle is like. So we kind of plug a lot of these, uh, these lipid profiles into three kind of buckets. And so this is, I adapted this from uh a lecture that Amy Peterson gave to the Family Heart Foundation. She's a lippidologist up in um Madison, but the, the first kind of bucket that we see when we're looking at interpreting a lipid panel is kind of the predominant lifestyle one. And so that with that you'll see cholesterol numbers that are mild elevated, um, but mostly normal. HDL that's maybe a little bit down or maybe even significantly down. And the LDL that's probably normal, maybe a little bit elevated, but then higher triglycerides. Um, if it's lifestyle, it's usually less than 500. If you're getting over 500, then I'm questioning whether either A, that was not a fasting panel, or B, is there a genetic cause. Um, and again, you would be falsely reassured about that LDL because while the measurement is probably normal or only mildly elevated, those are the smaller, more dense particles that are, are particularly estrogenic. You can get a mixed picture, so somebody that has a genetic hyperlipidemia, but also has some, uh, lifestyle, uh, factors as well that you might see mild uh to significant elevations in your cholesterol. Your HDL is probably normal, maybe a little bit low, and then you're gonna see big elevations in your LDL and your triglycerides. So this mixed epidemia panel, um, is gonna be a little bit of both. It's becoming more and more common, um. You gotta think about genetic FH and lifestyle dyslipidemias. Those are not mutually exclusive, and as we see raises in childhood obesity, sensory lifestyles, was certainly becoming more common, and with the heterozygous FH being common, we see this overlap more and more. Is that familial hypercholesterolemia and uh those are gonna have significantly elevated total cholesterol and LDL. Your HDL is probably normal and your triglycerides are probably normal. The general buckets that I can plug into, if you've got an LDL of about 160 to about 300, those are your varying degrees of heterozygous FH. If you got an LDL over 500, you're probably thinking about homozygous FH, and if you're in that 300 to 500 range, it could be either. And so I would say particularly if you're looking at over 300, that's somebody that you should probably be thinking about getting genetic testing in. So now that we've kind of gotten this lipid panel and interpreted it and looked at it, what are we gonna do with it? So the first line is always gonna be lifestyle interventions. Um, that's gonna be the bread and butter of what we do in in lipid clinic. We're always gonna talk about trying to optimize your dietary, um, habits and optimize your lifestyle habits and being active. Those are gonna be the big things that we do for just about everybody, right? So if I've got a genetic cause. It might not be the cause of their high cholesterol, but it's still a tool in our toolkit to try to optimize that as much as we can. And if we think that there's a, uh, a strong lifestyle component to the causes of their dyslipidemia, this is definitely what we're gonna be doing before we think about any pharmacological interventions. So what are some of the things that we think about? I've got somebody with a high LDL. I try to get them to really focus on the, the high fiber, um, lots of fruits and veggies in their diet, and shifting to more, um, unsaturated fats. So high in those poly and mono unsaturated fats and some low unsaturated fats and completely devoid of trans fats. Trans fats is one of the few things that I tell families they should just cut out entirely and I think that that that's also. Happening, we see less and less of that kind of in general in, in a lot of the products from the grocery store, uh, but it's still out there. Your saturated fats are gonna be the ones that are more solid at room temperature. And so the big, uh, players there, your butter, coconut oil, um, the animal products, palm oil, those are gonna be the ones that have more of a saturated components of the brown bar there is saturated fats. And then your poly and monounsaturated fats are the ones that are gonna be more likely to be liquid at room temperature, and so your canola oil, your um sunflower oil, your olive oil, those are gonna be lower in your saturated fats are gonna have more mono and polyunsaturated fats. So, emphasizing those things can be helpful, um. Other interventions for high LDL, avoiding those trans fats, so that has a pretty good magnitude of effects. So the 1 + is less than 5%, 2 pluses is a 5 to 10% effect on your LDL. So we've got good evidence for that, reducing those, uh, saturated fats, increasing the dietary fiber as much as you can, and then increasing the physical activity a little bit less of an impact on your LDL that's still an important thing. When we're talking hydroglycerides, it's a similar story, but not exactly the same. So increasing physical activity, even independent of any weight loss can help bring down triglycerides. And so I always try to stress that with families reducing the amount of dietary carbohydrates. So the things that really drive high triglycerides are a lot of your things that have added sugars added to um yours with the sugar-sweetened beverages, those simple carbohydrates so trying to to reduce the intake of that. And then reducing your intake like your dietary sugars like I said, um, alcohol intake I didn't highlight here, but like you can tell has quite uh uh impact on your triglycerides and being conscious of the fact a lot of times we're taking care of teenagers, college age students, and that can certainly have a big impact and so making sure that you're not neglecting the counsel about that in the appropriate patient populations. Physical activity, so the NHLBI guidelines recommend an hour of moderate to vigorous physical activity every day of the week for everybody that's older than 5. The AHA guidelines say at least 5 hours a week of moderate to vigorous exercise. Nobody ever really defines moderate to vigorous exercise. To me, that's enough that your heart rate's up. You feel out of breath, you're tired, and you're sweaty enough that you should probably take a shower at the end of it. So. Um, Rocky here is certainly getting moderate to vigorous exercise and I don't know that we necessarily expect our patients to be doing quite all that. Um, and an important side note here, when I was searching for this picture, I found out that somebody mapped out the training montage from Rocky II, and it's a 31 mile long run that is just this bonkers course throughout Philadelphia. If you take away one thing other than screen for FH, it's Rocky is ridiculous. How do we get families to do this, right? So the hardest part about this lifestyle, um, interventions is a lot of times we're telling families what they already know. It's just trying to help frame it in a way that emphasizes the importance of it and gets them to actually start to take action. So the first thing that I really try to counsel families with is that these changes are hard, but they're possible. So if you think or believe that this is going to be impossible, you're never gonna do it. And if you think that it's gonna be easy, you're probably gonna get really discouraged really early on and give up. So understanding that the changes, the lifestyle changes are hard, but they're possible, I think it's a really good and important place to start from. I would build from the stuff that they like, right? There's no magical vegetable, there's no magical fruit, there's nothing if you've, you've got somebody that just hates Brussels sprouts, don't eat brussels sprouts. Eat something else. Build from the stuff that you like. Don't try to like run into this brick wall of getting them to, to eat stuff that they hate. So. So if they like green beans, eat a ton of green beans. Try different recipes, try different ways of cooking them, try something that's similar, or maybe they can do snap peas, maybe they can do asparagus, build out from their areas of strength. Don't overemphasize the things that they that that are are barriers. And then set realistic goals, right? So sometimes I get kids that have genetic FHs or I get kids that have lifestyle, uh, dyslipidemias. They love their fruits and veggies, but they just love the pizza rolls more, right? And so you get a lot of, you know, patients that really don't like their fruits and veggies. I have different goals for them, or I try to get them to come up with different goals that I have the kids that go, yeah, I love asparagus, I love broccoli. I just also, um, you know, having really unhealthy snacks after school. And so you might have somebody where a goal is, I'm gonna have 4 to 5 servings of fruits and vegetables every day. You might have somebody that has a goal of, I'm gonna try one bite of a vegetable every day. And I think that you really have to tailor that to your specification. Same thing with exercise. I hate running, there's nothing magical about running. Don't run, play volleyball, play baseball, play basketball, play tackle football, just please wear a helmet, you know, whatever it is that they like the most, whatever it is that they hate the least, try to get them to do something, right? That recommendation is not for moderate to vigorous exercise in running, it is. Anything that they can do, anything that gets their heart rate up. Um, again, this is something that's gonna be really specific to your patient population. Uh, you can't assume that that kids have a safe place to go run and play basketball outdoors. Like they might not have that depending on where they live, depending on what their neighborhood is like. So find. Ways to work with them. Um, you know, there's a great exercise things that they can do on YouTube. Pull up videos of yoga and Pilates and do that before they go to bed. Walking around the house, dancing is a big one. I get lots of kids that love to get their exercise with dancing. That's great. Whatever it is, they can get their heart rate up. And then also starting slow. If you've got somebody that's not doing anything for physical activity. Give me 5 minutes a day, right? It's a whole lot harder to go from 0 to 5 minutes than it is to go from 5 minutes to 10 minutes. So let's make that kind of activation energy as low as we can. Give me 5 minutes a day for a month, and then it's not gonna be as big of a deal to go from 5 minutes to 10 minutes because you're already doing it. But if you can make that, that initial ask. A little bit more palatable and a little bit more reasonable to them, then you might get that by it. One of the nice things about treating patients, uh, that are pediatrics with this, is very rarely are we running into that, you know, red alarm, oh my God, cholesterol emergency. We've got time to make slow and steady changes in these kids, and it's much more likely to stick if you're able to do that. And then something that I think is important to make the default option success. If you have no willpower with ice cream, and you can tell that ice cream is one of my many, you know, uh uh faults. Then don't keep it in the house. That's not saying you don't get it. I want you to still have those sometimes food. Sometimes foods are still, sometimes they're not never. But maybe go out as a family and get Ted Drews or Andy's or whatever it is that you particularly love, but don't have it in the house, because if you have it in the house, you're going to sit there and go, no, I shouldn't do it. And then 10 minutes later you're gonna go, no, no, no, I shouldn't. You're going to do that 20 times a night until finally you cave and then you're sitting in front of ghost hunting TV shows with Doctor Somsky eating a pint of uh Haagen-Dazs, right? So don't expect yourself to have this magical willpower that you don't have now. Set yourself up for success. And then I think one of the biggest things that honestly one of the hardest things that these are the changes that need to happen in the whole family. So one of the few things that we found that correlates with long-term success in like making lifestyle changes is if the whole family does it. And so, if everybody else is getting ice cream sandwich for dessert, and Little Billy's getting a celery stick cause his triglycerides are 300, that ain't gonna work, right? You're gonna breed resentment, they're gonna get angry, they're gonna go sneak that ice cream sandwich and nobody's looking. This can be really hard. And this can be really hard when you have lots of adults in the house, or when you have teenagers that are able to drive and able to get whatever they want, and then they come home and they go, I'm not the one with the cholesterol problem. That's Li little Billy's issue. It's really hard to navigate. I found that grandparents are the worst with this. Grandpa's been eating 1 pound of bacon every morning and smoking a cigarette every day for the past 50 years, and his heart's just fine, thank you very much. It's hard, and as much as you can, trying to, to communicate, get everybody on the same page, I try to get those grandparents into clinic sometimes and talk to them as well. I don't have any magical solution to that, but we do run into it a fair amount of times. But as much as you can get everybody on the same page, these are changes that are only good for everybody, they're healthy for everybody, and the only way it's gonna work is if you're not singling somebody out and making them feel bad. And then finally, they have to do it, right? Most of the kids that are coming to me are old enough that they've got some autonomy here and so they have to be willing to do it. And I try to get as much buy in as I can. This is where your motivational interviewing can be really helpful. Don't come up with ideas and give it to them because then they're gonna start thinking of all the ways that they can shoot it down. Make them come up with ideas, make them think of ways that it might work. That way they're trying to think about what could work as opposed to what's gonna be wrong with the plan that this, you know, boring cardiologist is coming up with. Um, I try to get them to set those goals, right? I give them some frameworks. I try to work through smart goals with them. So something that's specific, something that's measurable, something that's achievable. Um, but I try to get them to do it, right? I'd always tell them that I try to get them to make a goal around including good for your foods, a goal around limiting sometimes foods to just sometimes, and a goal around physical activity. But I want them to make those goals because if they've got a little bit of skin in the game, they got a little bit of buy-in, they're more likely to do it. So a lot of times we are able to, to make a good headway with lifestyle changes. Sometimes we're not, uh, and that might be because of a particularly tricky lifestyle or a genetic cause or a combination of both. And so we, I wouldn't say often but sometimes get into a situation where we need to be considering medications. So at what point do we start to consider medications? Now, if the LDL is above 190, they probably need to be started on something because that's FH. If the LDL is greater than 160 and you've got a family history, they probably need to be started on something that's FH or if they've got one or more high risk factors or two or more moderate risk factors. This is from the 2019 deferentti paper that was the AHA and ACC guidelines, and it blocks out some of those high risk and moderate risk risk factors, uh, that, that patients can have. The way that I think about this is stuff that beats up on your arteries. So if you've got type 2 or type 1 diabetes, those are high risk factors. If you've got end-stage renal disease, if you've got Kawasaki's disease with persistent uh aneurysms. If you've had a transplant and a stem cell transplant, those are all high risk factors. Moderate risk factors, things like hypertension that's bad enough to need treatment, severe obesity, um, elevated LP little A, which is kind of a subset of LDL that's very genetically driven. Chronic disease. Stenosis or a childhood cancer survivor that had chest radiation therapy. Those are all things that fall into that moderate risk category. And so if you've got two or more of those moderate risk factors in an LDL greater than 160, you should be thinking about treating with the medication. And then finally, if you're in that 130 to 160 range and you've got two high risk factors or a high risk and to moderate risk or clinical evidence of cardiovascular disease, um, then you should be thinking about treating with statin. And again, all of these I would do after 3 to 6 months of lifestyle changes. I always try to give them a little bit of that time again, there's not very often. That we run into, oh my God, cholesterol emergencies. And I think that giving them a little bit of that leeway is helpful for that long-term relationship with that family. Patients don't want to start medicines for the most part. You get some families where, yeah, dad's first heart attack was at 30, Grandpa's first heart attack was at 25, everybody's on a statin. We knew this was coming, just give me the statin. We get that every once in a while, but most The time, patients and families want to avoid medicines, pediatricians want to avoid medicines. I want to avoid medicines. And so it is a rare circumstance that I start somebody on a medicine the first time I see him. I think even if my suspicion is that they're gonna need it, I try to give them that 3 to 6 months, make sure that everybody's on the same page, make sure that everybody's kind of in agreement. I think that the long-term adherence is a lot better with that. I'm so sorry to interrupt, but somehow your camera got turned off for the virtual audience. I think I have that face. Can you still see the slides, OK? Yes. OK. OK. on the laptop, but while we're doing that I can keep talking because the slides are definitely more important than looking at me, um, so. I'd say that with pharmacologic interventions, medications are primarily utilized in patients with familiar hypercholesterol. The vast majority of patients that qualify for statin are kids that have FH. People with predominantly lifestyle causes are usually the ones that are higher than 160 after working on lifestyle changes, so still pretty significantly elevated cholesterols. How do these medicines work and what do we use? So the first line treatment is statin medication. Uh, we sometimes consider adding aceamide before getting to a higher dose of statin and not seeing as much change in that LDL as we would like. And then PCSK9 inhibitors are available for patients with FH. They're approved for pediatric patients, specifically that have a heterozygous homozygous FH. How these medicines work. So a statin interrupts the synthesis of cholesterol and actually causes upregulation of your cholesterol receptors. And so if I've got somebody with heterozygous FH, I give them a statin. What I'm really doing is I'm tricking their body into making more receptors. That means that they're making more of the ones that work and they're making more of the ones that don't work, but they're able to get more cholesterol out of their blood. Aetamide is a cholesterol absorption blocker and so you get a block of that absorption from the gut. And then PCSK9 inhibitors are another way of trying to get more cholesterol receptors. So PCSK9 is a molecule that degrades and recycles your cholesterol receptors. And so if I inhibit that molecule, your receptors last longer. So you have more more cholesterol receptors to get that cholesterol out of the blood. Most of the treatments that we have for high cholesterol work by trying to upregulate LDL receptors, and that's where we run into trouble with the homozygous patients that have no mutations where they just, their cholesterol receptors work so poorly or not at all. Medicines don't work as well for that, and that's why it's helpful to try to get genetic testing on those patients that can help guide our therapy earlier on, so it's more effective ways. It's really not tons of options, so ANTL um inhibitors can, can help that works outside of your LDL receptor, but those are new and coming down the pike and and still being investigated in pediatrics. So when talking about statins with families, what do I tell them? I tell them they do a really good job of bringing down that bad cholesterol. They do an OK job of raising your good cholesterol, and they do an OK job of bringing down your triglycerides. Most common reported side effects are myalgia, uh, elevations in your liver enzymes. They can cause birth defects if you're to become pregnant while you are gone. I have had less than 5 patients that have myalgia. I really don't see that very often in the pediatric population. And the 2 or 3 that I think of off the top of my head were college athletes. They were very worried about my conscience. So there's a lot of debate, especially in the adult literature, as to whether or not the myalgia is a nocebo effect or if it's an actual effect of the statins. I see, you know, pretty rarely in in pediatric patients do we see that and so I don't wait too much into that discussion. Honestly, this comes up when I've got a family where dad or mom or grandpa was on a particular statin that caused muscle aches and pains, and so I just start the kiddo on a different one if I can. The uh birth defects in women, so these used to be pregnancy category X. They are no longer category X. Um, initially when they were first approved, they had birth defects in animal studies, and those were at super therapeutic doses of statins, and again, animals, not humans. When we've done studies after um approval of the medicines, we've not really been able to recreate that risk in human beings at physiologic dosing, and so they have taken away that pregnancy category Xs and made it more of a conversation. It's a similar thing to what's happened with the blood thinners in the past. Warfarin used to be an absolute no no. Now it's a conversation, why do you need to be on warfarin? Maybe we can keep you on a super low dose. Maybe it's better for your overall risk profile to be on a low dose of warfarin. Than it is to be off of it altogether and have a big clot risk. Same thing with statins. The vast majority of our patients are gonna be better off without the statin. So I tell families most of the time that the adult world is gonna tell them come off the medicine a couple of months before you decide that you want to. Or try to have a family and just go on afterwards, uh, or go back on afterwards. We do see some elevations in LDL during pregnancy as a physiological response to being pregnant, um, but usually the overall risk profile is much lower to just come off the statin during pregnancy. And I tell this to every single girl that I put on a statin. I don't really care how old they are, mostly because I don't want anybody to be surprised. If I'm putting somebody that's 567 years old on a statin, there's at least a decent chance that they're gonna be on a statin in their 20s or 30s when they're thinking about starting a family, but I don't want anybody to be surprised by that. So I go over it with the family every single time. People that require females that could become pregnant, um, to be on birth control in order to be on a statin. I don't do that. Most of the people that I know don't do that, but there are some, uh, uh, lipid specialists out there that do that. I think that that's relatively rare, but it's out there sometimes. And then finally, I do talk about one of the best studies to um advocate for using statins in that heterozygous FH population. came out about 5 or 6 years ago now in the New England Journal of Medicine. And it looked at about 20 years of patients with heterozygous FH on statins that were started in early adolescence, and it followed them and it took that it looked at how many of them had heart attacks and strokes and then compared that to unaffected siblings, right? So this is an autosomal dominant inheritance pattern. So if you've got a family where one parent has heterozygous. had about a 50/50 shot with each of those kids. And so compared the kids with FH on a statin to their unaffected siblings and found that there was no difference in heart attacks and strokes between the two and that their stroke rate was significantly reduced when you compared them to their parents, that started on statins in their adolescence because it really wasn't an option at that point. So there's pretty good evidence that statins work not only to bring down your cholesterol to actually impact your clinical. Finally, when to refer. So the things that I would say is if you've got abnormal, if you've got an LDL greater than 130 on somebody that's being treated, you should probably be talking to a lipid specialist. If you got a greater than 150 LDL regardless of whether or not they're on treatment, you should probably be talking to a lipid specialist. Your triglycerides are, are higher than about 200. I think it's reasonable to be talking to a specialist. Otherwise, if you've got a concerning family history, so if you've got a first degree relative that had an MI at an early age, I think that it's reasonable to have that family talking to aid specialist or if you've got multiple family members or first degree relatives with significantly elevated cholesterol. I would tell you to be careful with getting that family history. Don't just ask about heart attacks and strokes because statins have been around long enough now and they're effective. Enough that grandma or grandpa might have been started on a statin at 50 and they never had that heart attack or stroke. And if you just ask about heart attacks and strokes, not about statin use or all that cholesterol, you might be missing a significantly, significant family history. So it makes the family history gathering a little bit trickier, but I think it's overall a good thing cause it's fewer family members that are having those heart attacks and strokes. And then I would emphasize anytime that you're uncomfortable with it, anytime that you're not sure about it, you're not comfortable, you know, managing it, send them over to me. I'm always happy to chat with you guys. I'm always happy to see a patient. I'm always happy to weigh in and offer, offer my thoughts or, you know, any lipid specialist. Um, if, if you're the primary provider is uncomfortable, then, then you should be calling somebody. So I've got lots of references which probably look at. Created by Presenters Christopher A. Sumski, DO Cardiology, Pediatric Cardiology View full profile
