Cholesterol continues to be challenging to manage in the pediatric population. When should pediatricians institute cholesterol-lowering medications? Dr. Damon Dixon reviews tools that can aid in this decision.
Phoenix Children's Grand Rounds - April 18, 2023. CME credit provided only for participation during live sessions.
Ch uh cardiologist here. He's been on staff for eight years now and he uh does uh a lot of satellite clinics. Uh He goes to Yuma Kingman Flagstaff as well as the Valley I Clinic. Uh He did his medical school training in the University of North Dakota School of Medicine, uh followed by pediatric residency at the Medical University of South Carolina. Uh Prior to his fellowship, he served as a general pediatrician for six years in the Indian Health Services in both Nevada and Arizona. And he's a previous member of the A PC uh Committee of Native American Health. He then went on to do a cardiology fellowship at the University of Minnesota uh where he has a special interest in preventative cardiology that includes obesity, hypertension dyslipidemia and insulin resistance. He's a member of the NL A which is the National Lipid Association as well as a member of the NL A committee on pediatric dyslipidemia. He publish articles on pediatric lipid screening implementation and imaging techniques and pediatric disc aia. He serves on the medical board for emerging uh lipid uh lipid biotech company in the development of new cholesterol medicines. He's a member of the PC H obesity Interest Group and member of the PC H Developing Bariatric Program. And he enjoys playing soccer and a member of the PE CH cardiology soccer team and enjoys hip hop dancing on Monday nights. So, the title of his talk today is Risk Risk Stratification for subclinical pediatric Risk. Lim. Welcome Doctor Dixon. Thank you for the introductions and yes, you did hear that right? Hip hop dances Monday nights. Uh Do you uh like to hip hop dance? Get a hold of me and I'll show you um some fun times. There we go. Ok, perfect. All right, great. All right. So this, so we'll talk about cholesterol today. And so um a lot of people ask me, well, why should we talk about cholesterol in the pediatric world? Well, um it, it continues to be a problem especially for our uh general pediatricians in the outpatient world. And I feel that they don't have a quite great uh get a grasp on on what the values mean. And when should they initiate a cholesterol lowering medications? So now we have a lot of um additional tools that from a primary pediatric standpoint that they can use to help the general pediatrician to make that decision whether or not a child should be placed on a cholesterol lowering medication. So we worry about cholesterol because cholesterol is an integral part of cardiovascular health and cardiovascular health is the leading cause of death in the United States and, and, and across other countries. Um, and so we should talk about those and have a better understanding in managing in Children with, uh, pediatric lipid abnormalities. Six. Let's see. Just to, oh, let's see. Go. Oh, yeah, sorry. Just checking. Uh, so there's my disclosures and, uh, we won't be talking about any of those medications that we use, but just to let everybody, uh know, I wish we could have gave this talk like uh two weeks ago, but it was natural triglyceride day if you didn't know that. Uh So enjoy the uh carbohydrates and the high glycaemic foods that we're eating today. And uh it's the one day that your triglycerides can be, be high and, and, and we celebrate it. So, um I always like to bring this up too. So, uh a lot of us have seen the pictures of uh Mona Lisa and uh um Leonardo Da Vinci, um was known for his detailed work and uh he has left us some clues in the Mona Lisa that has to do with dyslipidemia. And for how many times we've seen this picture, we've never really noticed it before, but I've never been to the loop. So, from what I've been been told is that this is what the scene sort of looks like. So it's very hard to see the details of the, of the, of the picture. But uh at the end of the talk, I'll reveal those uh lipid clues that are in this picture uh that we're all not aware of. So we want to talk about uh pediatric dyslipidemia and we wanna talk about the subclinical state and have a better understanding what that means in pediatrics. We wanna talk about some of the uh blood biomarkers that we have available to us um that are simple to use to help our general pediatricians to decide whether or not a child should be referred to subspecialists for cholesterol management or whether or not they should be placed on a cholesterol lowering medication. And the overall big theme is I want general pediatricians to really understand um these two broad categories of Children. We want to be able to recognize kids who have genetic dyslipidemia and kids who have atherogenic dyslipidemia. And these are the two broad populations that would require cholesterol lowering medications. So, in 2011, the, the NHL B I, which is the National Heart Lung and Blood Institute released uh the cardiovascular integrated Health guidelines and it's a guideline. Uh Actually, here's right here. I forgot I brought it. So I don't know if everybody has seen this, but this is sort of the Bible for uh lipid management in kids and it was released in 2011. And um in that those guidelines, they made one of the most controversial statements in the pediatric world. And that statement and recommendation was that all kids between nine and 11 should be universally screened with a, with a lipid panel. And this is regardless of family history, risk conditions and risk factors. And this caused a lot of controversy uh in the general pediatric world because they were afraid that we're gonna be putting every kid on a cholesterol lowering medication. They recommend that uh fasting or nonfasting uh lipid panel. And overall, the goal had had two things. One, we wanted to identify Children who are at risk for premature and accelerated atherosclerosis development and to identify those individuals who may have genetic dyslipidemia. So two years after the release of the, of the guidelines, I was interested in the pediatric providers and what their knowledge and understanding of the new guidelines um were. And overall what we found is that we found that most pediatric providers were very uncomfortable in managing pediatric dyslipidemia and they still continued to be very uncomfortable. Um Some of the barriers were that they had a poor knowledge of pediatric loop of the lipid guidelines. They didn't know that the new guidelines were released. Um They were afraid of missing a genetic type to sleep in the pediatric world. Um There was some confusion between what the, the normal and abnormal values um uh were recommended in the guidelines and um and uh they were very uncomfortable in initiating or starting a cholesterol lowering medication ie a statin. So what we know for sure, um is that atherosclerosis begins in childhood? Ok. And uh we first became aware of this in the, in the late sixties and early seventies, um, from young soldiers who died in the Korean War and the Vietnam War. And when they came back and they died, they had all these autopsy studies. And, uh in those autopsy studies, they sh they, they found that a lot of these young soldiers already had signs of atherosclerosis in their vessels. And so that substrate, that foundation for atherosclerosis development in kids is the fatty street. Ok. So we can see that by autopsy studies, we have confirmed that with histological um testing. Um we have done staining techniques to, to see that um within the vessel in pediatrics. We also have non-invasive imaging techniques like the TED IMT that can show intimal thick name and the and the fatty streak inside the vessels itself. Um So we have multiple studies that, that shows this and so uh this is an important aspect in the seventies and the eighties. Um it was initially reported that the fatty Streep developed between 12 and 16 years of age since the onset of of obesity. Though um a lot of reports have now suggested that the fatty strip now begins between the ages of four and eight and that's very concerning. So, what is the subclinical atherosclerosis state in kids? So, uh that usually um uh describes two scenarios. The first scenario is endothelial stress or endothelial damage, which is the substrate for the development of, of the fatty, of the fatty streak within the vessel itself. And so most of the kids that we scream between nine and 11 years of age, um are asymptomatic. And um and this is um uh fueled by um the risk factors in childhood. And so what we wanna do as general pediatricians, so we want to prevent the addition and the progression of the fatty straight to the adult type. Um A S CBD, which is the A sclerotic cardiovascular disease and which is in adulthood, they are, they, they are symptomatic. So we have certain uh prevention strategies and as primary pediatric providers, we, we should be practicing two prevention strategies. The one is primordial prevention where we want to prevent the development of the risk factors um in Children. And then later on, then we want to practice primary prevention, which is controlling those risk factors and preventing those risk factors to develop into actual clinical disease as they get older and they develop the clinical disease, they would kind of switch our, our prevention strategies into more of a secondary prevention where they actually have the disease, but we're looking to reduce the complications of the disease state itself. So let's look at an example. So this is the common uh scenario that we see in the, in the pediatric outpatient world where we have an overweight obese child or we have a history of family, history of the family, having high cholesterol. So what we see normally on the traditional lipid panel is that the cholesterol may be high and we tend to see this general pattern where the triglycerides are high and the HDL is low and normally the LDL is pretty low, what we don't actually really appreciate, but it's just like the Mona Lisa pitcher. There are clues in the traditional Olympic panel that we don't necessarily see unless you're looking at it. So that's what I'm hoping to show everybody today. And what we're looking for are these atherogenic particles? OK. And what that means is that they have smaller dense um lipo protein uh uh particle size. They have signs of um uh inflammation, they have signs of insulin resistance and we can use all these little biomarkers that I have listed there that can be used from just the traditional lipid panel that we get every day. So the P day study, which is the pathological determinants of atherosclerosis in, in youth showed that by autopsy study that the more risk factors that a child has, the more likely that they will develop um changes within the endothelium. And so those traditional risk factors included family history, um adiposity, uh the glucose level hypertension, uh cholesterol, um smoking back in the day because these initially came out in the, in the uh seventies and eighties. But now probably in our, in our day and time, it's, it's vaping um in their activity level. Um now with our newer knowledge, they have also coined a new term which are called enhancing the risk factors. So, these are additional risk factors on top of the traditional risk factors that we think about and that includes non hdlaob lipo protein little A um high sensitivity CRP which is a surrogate marker for inflammation and endothelial dysfunction, which we can measure by noninvasive uh imaging techniques, um insulin resistance and as we also have have discovered that we know that our environment is and social aspects also affect uh those risk factors. So, social determinants of health and adverse childhood events and it, and it's great to see that I've seen some of the general pediatric notes that we do now screen for that and, and, and that's a good thing. So here's a paper just showing that um that the aces or the adverse childhood uh events does play a part in the development and the risk factors for developing cardiovascular risk in Children. And uh we know just like additional other risk factors. The more ace components that you have, the more likely that a child may be at risk for developing obesity, insulin resistant hypertension and dyslipidemia. So, what is cholesterol? So, um it's important to always remember to especially in the pediatric world that cholesterol is a precursor and it's an important biological uh substrate for, for all these uh other um uh pathways, cell membrane uh uh components. Um it's a precursor to steroid hormone precursors and why this is important to remember because um in my view, I don't think there's terribly an urgency um to aggressively lower cholesterol levels in kids before puberty. And because cholesterol is an important still biological molecule that the kid needs during development. So let's look at the pathways in and cholesterol itself to get a better understanding. So when we talk about cholesterol, we talk about the lipo protein itself and the lipo protein is composed of 22 components. Uh the triglycerides and the cholesterol ester. Out of those two, the ones that the one that we really, really care about that causes atherosclerosis is, is the cholesterol ester. OK? They're hydro, they're hydrophobic. So they need to be encased by a hydrophilic membrane to be processed throughout the body. And uh attached to each lipo protein itself is a, is a little zip code which is called the APY protein and it has two components. It has an ALE A and an ALE B attached to each one of them. OK. What's important to realize that ale A is the zip code for good cholesterol, IEHDL cholesterol. APL B is a marker for all the bad cholesterol which we call atherosclerotic lipo proteins. OK? So we want to remember Ale B. OK? Um So there are two pathways and um they all the roads and uh at the mothership in the liver. So just like today, we're having our snacks, we, we utilize the endogenous pathway we eat, we absorb it through our gut and then uh the fat gets uh packaged into kylo microns. It goes through our lymphatic systems for our heart and then into our vessels. Once it gets into our vessels, it's um basically the fat is cleaves off by an enzyme called lipo protein lipase and lipo protein light pace basically cleaves off all the triglycerides because the Kyla Myron is a big molecule that has a lot of uh fat and triglycerides and, and not that much cholesterol ester. So it's just kind of shaving the fat off um through the system and eventually it gets kind of smaller and it's, it's forms into um a cholesterol ester. So once it shaves off all the, the fatty acids and the triglycerides, we use that for energy. If we're not very active and we don't use it for energy, then we store that fat if the system becomes overwhelmed for because we're eating too many high glycaemic foods. And we find carbohydrates, then that cluster those free fatty acids, triglycerides have to go someplace and usually they're stored either on the liver um in our gut um in our butt muscle. Ok. Um So once those get to the liver, then we uh utilize the endogenous pathway and the molecule that's released there is the VLDL, which is sort of the cousin of the KICS. It contains a lot of triglycerides and not that much cholesterol ester. Same thing as it goes through the system. It, it's, it's cleaved by the lack of protein, light pace and eventually makes itself to the LDL or the low density cholesterol, which has more cholesterol ester than it does have triglycerides. Ok. And then it's reabsorbed back to the liver via the uh LDL receptor. And that's important to remember there because uh this is the mechanism for genetic type dyslipidemia. If we have a mutation in our LDL receptors, we will have higher levels of LDL. OK. So that's the mechanism behind that. So it's also important to uh understand when we order a lipid panel, we, we should understand how that result is uh uh resulted on a piece of paper that we see all the time. And this is one of the confusing part, confusing parts for the primary provider. Um So the lipid panel that we traditionally get that's composed of the total cholesterol, the HDL, the triglycerides and the LDL is based on density and side. OK. And as I talked about before, the more, so when we talk about the lipo protein uh particle itself, it's composed of triglycerides and cholesterol esters, the more triglycerides you have the fatter, the molecule is gonna be. So that's why you have ploys and VLDL. That's why they're so fat because they have a lot of triglycerides. But as they get shaped through the system with the lipo protein, light pace, what we're left with is the LDL particle that contains more cholesterol ester. OK. So if we look at the little cartoon diagram, we can see the, the yellow, that's all the, that's all the uh triglycerides and see how fat those molecules are. Um And what we really care about is the sort of the pink shaded part. And there's a little clue right there underneath where it says bad cholesterol, you see that term non HDL. This is a good s another good surrogate marker that we can use from the traditional lipid panel to uh recognize all the potential aro um genetic uh lipo protein particles that would put a child at risk for developing atherosclerosis. Um So now we need a little bit of background uh information and this is where it gets a little confusing, I think for the general pediatrician because I think we reflect a lot of our pediatric management of lipids based on what we hear about in the adult world. And as we have always been told, Children are not smaller adults. Ok. So in the adult world, they um uh have some differences. Um And so let's look at those differences. So, in the adult world, when you, when we typically talk about adult, we, we are talking about at least a 40 year old individual and they usually already have the developed risk factors. That's, that's a part of a part of them and they're usually nonmodifiable. Whereas in pediatrics, they have emerging developing risk factors and those are modified. Ok. When we talk about their risk for developing atherosclerosis in life, it's based on a 10 year risk score for the adults in pediatrics. We talk about a lifetime risk which is generally 30 years. Ok. Um, the adults have a, uh, a, a risk calculator. Um, and here's a little picture of it. Um, you can download it and put your information in there and it will tell you your risk of developing atherosclerosis in your life and the 10 year risk as an adult in pediatrics, we don't have a calculator. Ok. In the adult world, their primary job is to prevent a cardiovascular event um or death. And they do this by primary secondary prevention strategies in pediatrics. Our real main goal is to prevent the establishment and additional risk factors and we do this through primordial and and primary prevention as I talked about before and overall, our goal is to prevent premature and accelerated development of the fatty acid to develop atherosclerosis diseases later in life. So here are some of the level of evidence and um recommendations um for pediatrics, but there are some um highlighted things that I wanted to talk about. So still the cornerstone for obesity, um central hypertension and dyslipidemia is uh lifestyle counseling and lifestyle therapy. And it has a one, a green recommendation. If we look at the second one, the two a which is the yellow one here. This is an another key clinical thing to remember that any child or adolescent, 10 years and older who has an LDL persistently greater than 1 90 tends to be associated with familial hyperglycemia, which is the genetic type dyslipidemia. So remember 1 90 if you have an LDL, greater than 1 90 more than likely they have a genetic type dyslipidemia pretty easy. And then lastly, we look at number seven here, which has a two B recommendation that they put for universal screening. Again, as I talked about before, the, the controversial recommendations were that all Children between nine and 11, regardless of family history, risk factors and risk conditions should be screened um with uh uh a lipid panel. So here is um the 2018 last adult li guidelines for the adults in terms of primary prevention. And there are some things on here that we can take away and extrapolate in the pediatric room. And as we talked about before just recently that in all adults and in all Children too, if you have an LGL, that's greater than 1 90 they recommend high intensity statin which in our world, in the pediatric world is a genetic type to slim. Ok. If you have diabetes, you should be placed on a statin. Same holds true in the pediatric world. The highest risk factors for in the, in the general pediatric world are Children who have insulin resistance, type one and type two diabetes. Um, we go to the next line, I have some things that are highlighted. They have some of those markers that I've kind of alluded about. If they have additional enhancing factors such as elevated A ob high sensitivity CRP and lipoprotein little A, they should consider be, be being put on a statin medication. We look down to the next one. If there are signs of inflammation, um, should be considered, um, starting on a, a cholesterol lower medication. And then the last two ones just really shows those risk calculators, um percentiles uh for an adult. Uh and and uh what type of uh stat medication they should be put on? Um And then, and then lastly, there is one little tiny um uh segment in the adult lithic guidelines that has something about kids. And it says any uh Children and adolescents um ages 0 to 19 with a clinical diagnosis of familiar hyperchloremia can be safely placed on a statin starting at the age of 10. So that's very important to know. So again, an LDL greater than 1 90 more likely has a genetic type, familiar hyperchloremia and that's important for the general pediatrician to know. Um So it says, yeah, so it can be safely started at 10 years of age. The only exception to that is would be someone who has homozygous faul hyper cholemia. Um Most kids that we see have heterozygous cluster, um fami highly, which just means they got the the mutation defect from one parent if you're unlucky. Both parents have the, the mutation and the child received both mutations and their homozygous and um, their LDL cholesterol are, are usually in the thousands and they need to be on multiple medications. So, in 2007, the American Heart Association looked at um, additional risk factors or risk conditions that are more specific to the pediatric world. And, uh, so let's take a look at some of those and they develop a treatment guideline for each one of those. But in terms of the high risk for the general pediatrician world, as I mentioned before, the highest risk factors are people who have, who are kids who have diabetes, type one and type two. Ok. So should be considered, definitely be putting on a cholesterol depending on what their levels are. Um, uh if we go to the, the moderate, um severe obesity falls in that category. Um and then, um, and then the at risk or that or the insulin resistance. So those are the most common populations that we see in the general pediatric world in terms of um cardiology for my cardiology. Um guys, um Kawasaki with aneurysms, um someone who has had a cor repair, um, anything with the coronary should be considered to be placed on the cholesterol lowering medications in terms of primary dyslipidemia, uh defects. Um familiar hyper cholemia if you have heterozygous, a homozygous, uh um FH and also you can see moderate risk too. You can see the little lip, the LP a little A and that's again, one of those markers that we can measure in the pediatric world. So, what are some of the tools that we have for the general pediatrician to use? Um We have um blood markers and we have uh non-invasive techniques. We also have other um uh cardiovascular imaging techniques that can uh measure endothelial dysfunction. OK. I like to think of the blood markers um in five broad categories. Um So we have the traditional markers that concludes the lipid panel and hemoglobin A one C, we can measure particle size in the two things that we can use non HC and A B um in terms of lifetime risk. So 30 year risk in pediatrics, the two that correlate very well are persistent non HDL levels and lip protein, little egg. Uh in terms of insulin resistance, we can measure insulin and a new and emerging uh ratio that's been out in the pediatric in the, in the lipid world is the triglycerides to HDL ratio. Um And then in terms of inflammatory markers, we have high, high sensitivity CRP and oxidized LDL. So we can use these in the outpatient pediatric world to give us a better feel of who's at risk and who should be placed on a lipid lowering medication. So this is just a table from the guidelines that shows normal and abnormal values. Uh what's important here where I see a lot of confusion from the outpatient pediatric world is when we order a a traditional lipid panel, the levels that are reported as the reference range on lab core and Sonora quest is the acceptable range values. So oftentimes when I get a referral, the lipids are all lit up, they're, they're, they're bolded or they're red, but they're not actually abnormal, abnormal is greater than the 95th percentile. And uh and they're in the high category. So, so for example, let's say that you order a, a lipid panel, the pediatrician orders Olympic panel and the total cholesterol was 1 75 on that piece of paper. It's gonna be red and bolded and they're like, oh my gosh, this kid has a lipid disorder, but in general, we don't really worry about it until it's at least about 200. So what, that's one of the downfalls that I see a lot, a lot of referrals that come uh to me, um when we talk about those additional lipid markers that we can use, we do have normal values for the pediatric world. We have as I talked about before non HDL and we'll talk about what NON HDL means. But uh the non HDL level should be less than 1 45 in the pediatric world. We have a OB which is the zip code for all agentic particles and it should be less than 1 10. We also have normal values for the lipo protein. Little A which is um the highest independent risk factors for developing athero SSIs in the pediatric world. And we have no more values for those. So when we talk about the traditional lipid uh panel itself, we have the total cholesterol, we have triglycerides, uh LDL and um uh HDL. What we have to remember is that the traditional lipid panel is really just a surrogate marker for all these other things. So when we talk about triglycerides itself, it's really just a big molecule. That's a surrogate marker for all the KICS, the Kyron remnants VLDL and ID L. And again, these all have an attached ALE B marker on them, which is, which is the marker of aro genetic particles. The LDL is really a surrogate marker for all the cholesterol ester. And it's the cholesterol ester that we really worry about. It is also a marker for small density LDL particles in oxidized particles and in an apart lipo protein, little egg and again, attached to those is an apple B zip code HCL is the good, is the good cholesterol. And uh it's a reflection of all the small particle hel particles and it has an AP A uh code to it. And that's the good cholesterol. Well, that's the one we want to be high. And then uh we can also traditionally measure the lipo protein little. So the most recent big cardiovascular uh trial that was done in the adult world just recently was looking at the diabetes population and the effect of uh lowering triglycerides using a fibrate. But what they came to the conclusion of is that we can stop worrying about triglycerides because triglycerides do not affect the overall cardiovascular outcome for, for cardiovascular events and death itself. So they said, if our goal is to prevent cardiovascular events, we need to focus on cholesterol particles. And so we have ways to measure cholesterol particles because those are the particles that can clog, that can clog the heart. And um it tends to be a more useful strategy. So we can do that in pediatrics too. So size matters, you can have a whole bunch of individuals with the same cholesterol level. So in in a little cartoon diagram, everybody can have a cholesterol of 100 and 25. But there are certain people who are at more risk than others and this has to go due to the fact of um particle size itself. So as I mentioned before, when we talk about the traditional lipid panel, the traditional lipid panel is really based on density and size. So if you have the bigger type cholesterol pattern, you're not at risk as much. Versus the the lady that's on the far right, that says high risk she has smaller particle size. So the thought process behind that is is that these little tiny particles are able to squeeze their little lipo protein butts between the endothelium and cause a chain reaction to cause inflammation and, and start the cascade reaction for atherosclerosis and the fatty acid and the fatty street development in pediatrics. So, we have two markers that we can assess in the pediatric world. Um to, to, to analyze for small particle size in pediatrics. Uh The first one as we talked about here a little bit was the NON HDL and the NON HDL is a very useful marker and it's nice because we can use it from our traditional lipid panel. Non HDL is a surrogate reflection of all the atherogenic um sub particles um in the body. And all you have to do is take your total cholesterol minus your, your HDL and you will get your non HDL level in general should be less than 100 and 45. And you can see by the cartoon diagram, it's a reflection of all the atherogenic sub particles. And also um you can also notice that each atherogenic particle there's an attached zip code of the apple B. We can also measure APL B and a lot of studies have shown that A PB might be a lot, a lot more superior than LDL cholesterol and non HDL itself. And we can measure that. And as I talked about before, we have normal levels for APL B and pediatrics. OK. So in terms of like small particle size, we have non HDL that we can get from our traditional lipid panel through our calculation or we can measure it directly with ALE ALE B levels. Um The European Society just recently came out with this nice little diagram which basically shows all the primary secondary LDL cholesterol trials that were performed in, in adults. And um what we know for sure is that LDL levels correlate with cardiovascular events. But what they later found out was the people who were at risk for a cardiovascular event for those who had small particle LDL size and who had oxidized LDL particles. So the oxidized LDL particles is the mechanism of how we get these small um LDL particle size. And again, once they're small, they're able to squeeze yourself through the endothelium and cause that chain reaction for the development of atherosclerosis. Now, in terms of lifetime risk for pediatrics, we have two markers. So in the adult world, they talk about a 10 year risk. In the pediatric world, we talk about a 30 year risk and those two markers are non HDL and lipoprotein little A OK. So by the Little graph, you can see if a child has persistent elevated, non HDL, which is a simple calculation that she can do on your traditional lipid panel, more unlikely they're gonna, they, they will have a lifetime risk of, of cardio of a cardiovascular event uh in the future. And this can track into adulthood in terms of like protein, little egg. Um They mentioned here in the article that um uh that the uh a child with a high lipoprotein Little A and high LDL cholesterol had a four times greater risk of developing atherosclerosis. So, those are the two markers that we can that we can utilize for lifetime risk in a pediatric patient. So, what is like a Protein Little A um it is the strongest independent genetic risk factor for cardiovascular disease that we have. You're either born with it or you're not. Ok. Um uh There are some uh recommendations on how we should screen for it, but generally most of the time, the way that I see it um is um either there's non family history and um someone measures it and no one knows what to do with it. Um Or um a child has a um some sort of arterial clot and the hematologists order it. And the question for me usually is like, should they be replaced on an aspirin? Um The clots in, in the cholesterol LP A level are two different mechanisms. But why lipoprotein little A is deadly? Um uh is because it has this trifecta, uh it's pro inflammatory, it's um it's uh uh prothrombogenic that it can form clots and it's also pro agentic. Um So um the lipo protein uh little A is really the bad cousin of the LDL uh particle itself in terms of kids that we see with um uh overweight and obesity. Another useful marker that we can use is the triglyceride to HDL uh ratio, which is a good surrogate marker of insulin resistance. And again, this is a very useful one because we can use this on the traditional lipid panel. Just take your triglycerides and you divide by HDL and uh uh it correlates well, for those kids who are insulin resistant. So, insulin resistance um is the underlying uh issue in most of the overweight obese kids that we see and uh and it affects all of us. Um Usually our insulin levels are not able to drop. So if your insulin levels are always high, you're always in this fat storage mode. Ok? And you're not able to use to utilize the, the glucose that you use. And we see this a lot. Um and a lot of us um we're like try to lose weight, I'm trying to eat healthy, but there's so much hidden glucose in the foods that we eat that our insulin levels are always high and because it, it always kind of high, they're never able to go down normal. We, we're constantly in this fat storing mode. And so then we have to store uh the fat and the fat um overwhelms the system and you have these kids with high triglycerides. And so for example, a lot of us will think we're eating healthy like we'll, we'll eat a, a yogurt. And if you ever look at the back of a yogurt, um the reason why it tastes good is because there's there's a high glucose alone on there in the back of it. It's usually anywhere from 20 to 30 g of sugar in the back. So, even though you think you're eating healthy with, with yogurts all the time, you're still getting a lot of hidden glucose. That's really your insulin level. And so what do we, a lot of us do on top of it, we put a granola, we put the granola brand mix on top of it and that's even worse. I mean, those have like anywhere from 50 to 90 g of sugar on top of it. A Snicker Bar has only like 20 g of sugar. So you can see, even when we think that we're eating healthy, you're, you're constantly getting a whole bunch of hidden sugar that's raising your insulin level itself. And so that's what happens to a lot of these families. Even when they're trying to eat healthy, they're getting all these hidden uh sugars in their foods, that's raising their insulin levels. All right. So now let's switch our mode of thinking and we briefly talked about um uh the genetics of lim. Um So the most common uh mutation that we can that we see in the pediatric world and that we, that a primary pediatrician should be able to recognize is uh elevated high LDL cholesterol, which is consistent with familiar hyper cholester M or FH OK. So the most common type is due to the mutation of the receptor within the liver itself. And so the LDL particle is not able to be pulled in by the liver to be further metabolized. And it comes in two forms. It's either uh heterozygous or homozygous homo and heterozygous is the most common form and it's all over the place. I see a lot of kids that have heterozygous, similar hyperglycemia. Um which means that 111 of the family members, either mom or dad has a disease. So this is where family history is important. If mom, grandma, the uncles have all on a cholesterol medication or have some sort of cardiovascular, then more in likely they have familiar hyper cholemia and a lot of the times, um, we do a lot of what we call cascade screening. We see the, we see the child, we make the diagnosis familiar hyper cholemia and then we tell them to check the other Children and they all have it too. Ok. Um, so the general pattern that we see that the general pediatrician needs to recognize is that the LDL is high and the non HDL is high, the triglycerides are normal. Ok. So in general, if you have an LDL, that's at least 1 90 as we talked about before, more than likely they have the genetic type from hyperglycemia. Ok. And they will need lifetime cholesterol lowering medications. IE A statin and these kids are the ones that need to be referred to a sub specialist when we look at the use of statins in Children and, and more specifically in Children who have familiar hyper cholemia. The statins are very effective and they weren't in terms of the general pediatrician. I think they're very hesitant to use stats because they're not familiar with it and they worry about safety reasons. Uh, there have been a lot of studies to demonstrate that statins are very safe in Children and we know this because we have to use it in kids who have familiar hyperglycemia. Um that's the the basic treatment to treat their disease process. So here in this article, they show the 20 year follow up in kids uh who had mila hyper cholester again, the effect of statins. And you can see compared to their siblings who did not have FH that statins lowered their LDL the total LDL cholesterol compared to their uh their, their siblings who were not affected. So stats were affected there, they also looked at the freedom of a cardiovascular event and death um compared to the parents who were later diagnosed and then later placed on a on a statin medication later in life. But because of our screening techniques, we were able to recognize those Children who have FH and place them on a statin and their uh uh events were were lower compared to their parents. So in summary, we should all remember from a, from a general pediatrician standpoint that universal lipid screening should be performed between nine and 11 years of age, regardless of family history, regardless of the risk conditions, regardless of the risk factors. Ok. We uh uh uh a no, uh a fasting lipid panel is the preferred method. But if we don't, we can use uh a nonfasting uh li panel. Overall, our, our goal is to identify those Children who are at risk for premature and accelerating atherosclerosis. Those Children who have the aro gen genetic uh dyslipidemia patterns are pro inflammatory. They have insulin resistance and they have a lot of small density lipo proteins. In terms of lifetime risk, we have three components. We can measure non HDLAOB and lipo protein little A out of those three, I would say lipo protein little A is the best uh marker that we have. And then lastly as we talked about before genetic dyslipidemia, that pattern usually is a child with high LDL and high non HDL levels. And these Children will require lifetime cholesterol lowering medications. And then lastly, let's look at Mona Lisa. So uh Leonardo Da Vinci was known for his detailed work. And if we look at Mona Lisa's hand on the top or the extension part, there's a little bump there and uh some um examining some uh people have examined her, her death, which is not really known but also her family history. But this may be the first uh painting of someone who had uh dyslipidemia. So that could be a xanthoma over her uh her hand and then also she may have a little xanthoma, the corner of her, her eye there. So I thought that was pretty interesting despite us how many times we see this, uh picture all the time, but that's the end of the talk. And uh thank you for uh joining us today. Any questions? Yes, thanks. Um, gene testing, we can. But usually the phenotype that we get from the is pretty probable if they consistently have an LDL greater than 1 90 us. But usually most of the time, most of the time we say they're, they're in the two hundreds to three hundreds in general a child or, or any adults, their LDL cholesterol shouldn't be that high. Um, but the only time we really do the genetic testing is if they're resistance to the certain types of statins, so we can find out what statin is better for them. But now we also have all these other emerging new, uh, cholesterol lower medications that we can use. But, but no, in general, we don't necessarily need to do the genetic testing itself unless Stanley requests it. Yep. Yes. Yeah. Oh, yeah. So I'm sorry. So, so again, so the, the family history that's kind of borderline. Yeah. Yes. Correct. Yeah. So usually, yeah, those, those family histories are kind of benign and they may have this and that there's really no, uh, strong indication. So, unless they're between nine and 11 years of age, there's not necessarily urgency to, to screen them yet unless they fall in that in that broad category. So the kids like, you know, four or five and they, they, and they don't have. So I would say the next event would be obesity related type on top of that. So that's an additional risk factor. So they do, then you may want to screen a lipid panel. Um you know, a lot of the times too, it just kind of depends on, at least in that I've seen in the, in the outpatient clinical world, I've seen pediatrician get that, that exact same scenario and they, they just, they just measure it and um uh they get a traditional lipid panel and they get, you know, the hemoglobin A one C they check the thyroid and, and in general, most of the time, it's, it's pretty normal. Um So again, so once it kind of makes, makes it to me, I get a little more detailed family history if they. Um uh so I should say what you can use from a general pediatrician standpoint when you get the traditional lithic panel is a used on HDL. That, that's the good marker. So if you're non, so if the rates are high and the HDL is low, you can cal calculate the non HDL. So your total cholesterol among your HDL should be less than 100 and 45. If it's 1 61 70 that kind of raises your eyebrows a little bit. So they may have something underlying that just hasn't been revealed yet. So you may have to do a little bit more advanced testing either with the April. April B, the Liro protein little A or repeat it. But because I have seen sometimes too, once we repeat it sometimes, um it, it, it's a little bit more in the normal I range. And I should say too, the biggest mistake that I see in most outpatient pediatric uh referrals to me is uh a lipid panel that was not performed fasting. It's very common because I think what, what happens is they order it and uh they, they get the results and like I said, the, it's all lit up. It's, it's red, it's bold. It and they're like, oh, go see endocrine, go see cardiology and they don't necessarily look at the values itself. And then again, I think it gets a little bit more confusing because the reference ranges that they use in the lab are really just the accepted ranges which is less than the 75th percentile abnormal is above the 95th percentile. But again, it's just bold. It, it's red and they're like, I don't know what to do with this. I'm, you have to go to cardiology. So, yeah, somebody who does a lot of screening trying to get some. Yeah. Yes. Uh how, so again, I would use non HDL the non AC L So if it's abnormal, your non HCL is normal, then more likely it's probably normal. Just like, then you, so you, yeah. So depending on the, the value itself, you know, um, I would say anywhere from three months to six months, a lot of the times and again, I would always ask too, the, the most important question I usually ask most families is, was it done fasting too? That's, that's really important to always ask. In fact, I saw two kids yesterday, they came from uh Kingman and the other one came from Lake Hau and um it their, their, their uh lipid panel were not, was not done fasting. And, and I said it's hard to make any interpretation of what this really means. Unless it was fasting. You have really good questions. The chat. Oh Let me, let me ask really quick. OK. Yeah. Yeah. A in general. The right. Yeah. But then again, you can use the NON HDL as a surrogate marker for any underlying issues. Correct. Correct. Yeah. So again, when we see kids who are overweight and obese and they have high triglycerides and low HDL. I use non HDL as that marker of, of whether or not they should be placed on the cholesterol lower medication itself. OK. So the NON HDL is 1 65 1 75. That means that they probably have um small particle size like proteins. Yes. This question if kids are on a second generation antipsychotic and have elevated triglycerides. Should I think about treating or like you were saying, not being too concerned since, uh, 2030 years ago. Yeah. So the only true indication to treat triglycerides is really pancreatitis itself. But most people feel uncomfortable, you know, when the 2 to 3 hundreds, but in general, there are less than 300 you could probably just watch the other population that we do see is, are the kids who are on Accutane, triglycerides will go high. Um But in general, it's reversible. It's the same thing with the antipsychotics. It's reversible. Now, uh again, using non HDL would help because it, again, if they just get a traditional lipid panel itself, there may be other underlying things they just assume is from the medication itself. But in general, their triglycerides are high, their NON HDL should be pretty low itself but the NON HDL is high on top of the high triglyceride, there might be something else brewing that they just don't know. And then here's a request from the uh outside pediatrician. Can we have a nice condensed table for a general pediatrician for screening blood test with the important markers with the latest recommendation? Yes. Ok. Do you have one or we'll have to make one? Ok. Yes. Yes. But yeah. So again, I don't know if was here before, but has everybody seen this? So this is the lipid Bible itself which is uh uh released in 2011. But it's got a lot of good information but this is what we use to make those assessments. Um, I've heard in the background that they're going to be updating the pediatric Olympic guidelines, which will probably include some of the stuff that I talked about because now we have a whole bunch of more emergent studies to confirm those suspicions and, uh, and correlate with the adult studies itself. Um, but, but great, it's at 8 30 I know everybody's got responsibilities and, um, they're free to leave if they want to. Mhm.