Atherosclerosis starts in childhood – and so should screening. In this primary care guide, pediatric endocrinologist Sonali Belapurkar, MD, reveals which patients need evaluation (spoiler: it’s all of them); talks about assessing genetic and environmental factors; clarifies which tests to run first (and second); and describes behavioral modifications that have a real impact on lipid levels. Also: Learn when to consider prescription meds and how to monitor kids on statins.
Thank you again. Thank you all for coming and joining us today. You know I just wanted to review are kind of going over what is the definition of this lipid e. Mia atherosclerosis and briefly wreck recognize the genetic causes of um Hipaa bulimia. Hipaa dracula's redeem mia and then discuss screening and you know not so much management but dietary modification and management of lipoprotein disorders. Um So as we all know, CVD is the leading cause of death and morbidity worldwide and in United States and most of the burden of CVD you see in adulthood. Um however research over the past 40 years has indicated that the process of atherosclerosis begins early in life and it has also become clear that an important genetic component of the disease um plays a big role and then other environmental factors like physical activities and dietary choices also contribute to the disease process. So just you know briefly um Disl epidemiology, how do we define this lipid E me A and our Children? Um And so it's a it's a genetic and multifactorial disorder of lipoprotein When total cholesterol is above 200 or LDL above 130 we get worried because it's about the 95th%ile for age and sex of the child. Um And then in terms of triglyceride levels more than 100 in our kids between 0 to 9 years of age and more than 1 30 of triglycerides above 10 years. HDL below 40. We all know that the non HDL which represents all the anthropogenic lipoproteins in our blood if that is above 1 45 we get worried because that's about 95th percentile for age and six. And you know, we need to closely monitor that just briefly going over the atherosclerotic process. Again, studies have shown that the process starts in childhood. But what the first step in the acute, you know, is the accumulation of lipoprotein particles in the intimate. So what happens is when there's increased LDL or lipoproteins and the serum macrophages imbibe these lipoprotein particles and form these form particles which are rich in um lipoproteins LDL and the early earliest pathologic finding in atherosclerosis is known to be fatty streaks which is just accumulation of these lipid filled macrophages, macrophages within the entire mouth and artery. And the progression of atherosclerosis is characterized by continued accumulation of these lipid film, macrophages and proliferation of smooth muscle cells here and ultimately leading to formation of fibrous plaque and that and you know, narrowing of our artery and ultimately resulting in um cardiovascular incidents. Myocardial infarction stroke. So I just briefly, I wanted to go over that and again, studies over the past 40 years have shown that atherosclerosis begins in childhood. It was first identified in our korean and Viet number war casualties. Um So you know, during autopsy findings, they started um noticing these fibers black and streaks, fatty streaks in our young adults 21 to 23 years or even younger um individuals. And then the two main studies that actually um demonstrated that atherosclerosis begins in childhood is the PD study and the Bogalusa heart study. So in terms of the google was a heart study, this was a comprehensive school based epidemiologic study in a biracial community. And what these investigators did is they followed a cohort of kids in a school based um uh you know community. And then as a as a part of their routine examination they obtained their cardiovascular risk factors including lipids, B. M. My blood pressure, tobacco use and lipid had both total cholesterol, LDL HDL tricolors rights. They measured that. And subsequently as a population became older some people died of accidental causes. And they found that there was a strong core relationship was seen between the presence and the intensity of these risk factors and the extent of atherosclerosis. Um And so from these studies it became clear that the process starts early. The risk factor for the development of atherosclerosis um are identified in childhood and there's a strong relationship between the presence and intensity of risk factors and the extent of atherosclerosis that we see in our kids. So as a result, you know pediatricians we started thinking that the early identification and treatment of these risk factors could delay the atherosclerotic process. So what are the cardiovascular risk factors that um we should be looking at. And so you know, we all know I mean the most common modifiable cardiovascular risk factors that we see is obesity elevated B. M. I. Insulin resistant lifestyle factors such as smoking, lack of exercise, poor dietary choices. Um psycho social stresses have been implicated because it causes inflammatory reaction, oxidative stress, depression, sleep are all the modifiable risk factors. And so so those are the modifiable risk factors. But how about our non modifiable risk factors, genetics plays a big role. Family history. Um diabetes mellitus, type one diabetes, we are seeing that it has become um it's becoming more prevalent and especially in our kids with type one diabetes militants duration is one of the non modifiable risk factors which puts them at high risk racial and ethnic disparities play a big role. And again non modifiable risk factors. And the one thing that I wanted to kind of briefly mention is cholesterol concentration varies in childhood. So um serum lipid level increases during early childhood soon after birth. The first two years it gradually increases and reaches levels similar to those seen in young adults, about two years of age. And then based on an Haines data, we saw that the peak total cholesterol level is attained between 9 to 11 years of age And during puberty. Actually the values decrease. Um and um you know, there was a decline in all the cholesterol levels and then again it reaches a final level that's seen in young adults by 17-21 years of age. And this this data. This information. This knowledge is important because this you know this the guidelines uses our recommendation based on this data that we received from enhanced So Nationals all heart lung blood institute expert panel integrated guidelines which was published in 2011, provided the most comprehensive and up to date approach to pediatric academia In these guidelines, they recommended universal screening and all kids and younger adolescent is recommended. Sorry, I'm just At around before puberty, around 9-11 years of age. And um and then after puberty around 17-21 years of age. And you the universal screening helps identify kids with genetic Disl epidemiology or lifestyle related disease. Epidemiology with the increase in obesity epidemic insulin resistance. We are um screening more and you know, finding more kids are identifying them with lifestyle related to epidemiology, they did recommend that they did recommend target targeted screening or selective screening based on family history of premature cardiovascular diseases. Or if they had any other risk factors like obesity, kidney disease and stage renal disease. Um Kawasaki is with persistent aneurysm and in all those kids you know, they are considered high risk and you Screen them early, starting at age two. So again going, you know as part of screening we do have to evaluate for secondary causes of dis lipid e mia rule out hypothyroidism, liver disease necrotic syndrome. And then um the one thing why universal approach, they you know there were some studies that they that showed that relying only on selective screening or targeted screening approach based on family history had, you know, we would potentially miss 30 to 60% of Children with substantial elevation of cholesterol and that's why the recommendation was for universal screening. What age to screen. So again, um if there's a family history where one or both biological parents have a history of high cholesterol are on lipid lowering medication or if they have a family history of premature cardiovascular disease where men had had an event of premature CVD event less than 55 years of age or women less than 65 or you know, they also recommend kids who are adopted. Their family history is unknown to get, you know, to have a selective screening. Um And in terms of LDL C level, we know that it's calculated value and using the freedom ball formula, traditional formula. And now there's a there's a martin Hopkins, that's what we use. But I'll tell you um what's the difference between the two? So LDL, the way it's calculated is total cholesterol minus HDL minus stragglers right over five. And because drag Liz stride levels can vary between a fasting and non fasting state. You know, we do want to fasting a lipid profile to accurately calculate LDL level. And traditionally for years we used this floatable formula which had, you know, try to illustrate over five. But then, you know, recent studies have shown that this five can vary based on you know, the number of Trackless. Right? So the new um calculation that we used has this novel factor. So Trackless right over novel factor which varies according to the level of their non HDL atherosclerotic lipoprotein and their triglyceride levels. Um So that with the with the implementation of this novel factor it has shown higher accuracy as strike illustrate levels trend higher and non HDL cholesterol tend lower. You know, that goes higher. LDL trends lower. But with this new novel factor the LDL levels are accurate. We do recommend direct measurement of LDL C. and triglyceride levels are above 400. So um just going over universal screening, it's recommended between 9 to 11 years of age, pre puberty and now with the kids going through puberty early, you know 8.5 is okay in girls boys to sooner nine or 10. Um But start with non fasting knowledge dl and if that's above 1 45 then perform a fasting lipid level. They say if fasting lipid LDL if it's above 1 90 it's indicative of FH um non HDL more than 1 90 suspected of HN ALg over that with you in a minute. What um if it means familial hypercholesterolemia, I have a kid a case and that will just use this to kind of discuss a little bit more about the diagnosis, the genetic diagnosis that I was talking about. So, you know, and otherwise healthy, eight year old girl comes to your clinic and you do a um regular well child check and as part of her lipid levels she's now found to have an isolated hypercholesterolemia in screening test because of a family history of premature cardiovascular disease. She's otherwise healthy. Not on any medication. Her B. M. I. Had blood pressure other than normal limits. So are risk factors for other you know we're looking at other risk factors. Her mom was treated with atorvastatin for high cholesterol hypothesis, bulimia since the age of 20 years of age And maternal grandfather has a history of CVD at 44 and required a coronary artery bypass graft at 55. So clearly she has a family history um of um uh huh premature cardiovascular disease. And then on her non fasting lipid profile shows total cholesterol of 302. Trackless right 62 LDL of 2 50. HDL 40 and lipoprotein. Eight. We'll talk a little bit later. Was five was perfectly normal. And you know, you did labs to rule out secondary causes of dis lipid E. Mia. So the thyroid function test was normal liver function, normal albumin. To rule out a frantic syndrome normal hemoglobin A one C. Was normal. So what do you think? What's the differential? So in terms of you know like diagnostic consideration we do want to rule out familial hypercholesterolemia and I'll go over that it's one of the most common metabolic disorders. So hetero zegas familial hypercholesterolemia is in the differential again, secondary causes of hypothyroidism. Necrotic syndrome, diabetes needs to be ruled out. Medic vacation steroids O. C. P. S. I. So retin nine are factors that play a role in influencing your cholesterol levels. So you know, and this girl didn't have any of those secondary causes that could have contributed. So going over FH hetero cycles, FH I'll talk about that. So genetic causes of hetero cycles, F. H. It's a group of inherited genetic defects which results in significantly elevated levels of LDL And it's autism all dominant has autism, a dominant or co dominant transmission with about 90% or higher penetrates so high. Um you know, it's transmitted to the to the next generation LDL levels are elevated usually about 190. And the risk of premature cardiovascular diseases elevated um to 20 times and untreated patients with FH um So just looking at the prevalence of FH It's one of the most common continental metabolic disorder. And here it shows its in relationship to all the other um you know, like sickle cell, multiple sclerosis, Huntington's neurofibromatosis. The prevalence is much higher. It's one in 200 to 500 individuals in North America and europe. And in certain populations like French Canadian where there is founder effect. It's it's even higher um with the prevalence is 100. Um And again, Children with Metro six FH they're clinically silent but they have levels of total cholesterol and LDL 2 to 3 times higher than an unaffected individual, Homocide is much rare. It's the biologic mutation is associated with Hios Ikea's the cholesterol levels exceed 500-800 beginning in infancy. And um these kids, the homosexuals, kids actually they have clinical um the president for tendons and Thomas before the age of eight um and 10. And then coronary events. We do see kids having Heart attack and other events beginning in the first two decades of life and lifespan is shortened if untreated. So just going over the San Thomas, tendons and Thomas can be present before the age of 10. And um you know, you can see in at least tended it's much more common and then the finger extensive tendency is also common. So during um the physical exam, especially, you know, during when we see our kids with the page, we do um report and look for the exam, thomas on physical exam. So in terms of the diagnosis, the diagnosis of FH is clinical and otherwise these kids are and it's silent. I mean they have really no other um significant concerns or history. It's just that the family history is really important in identifying these kids and if on screening, if LDL is more than 1 90 it's indicative of genetically defined F. H. And kids with LDL level of more than 160. But there's a family history of premature cardiovascular disease, then there's a high probability that the child has a feature. Yeah. So based on the lipid phenotype and the family history. The eight year old that we presented has, you know has um diagnosis which is consistent with Metro six FH um going over, I mean this is a diet that we recommend for all our kids. But this is the cardiovascular health integrated lifestyle diet to one which is for the general population. That we encourage them to limit sweetened beverages. Total fat has to be 25 to 30% of daily K cal intake, saturated fat here is 8 to 10% of the daily calorie intake and avoiding trans fat. Um, cholesterol should be less than 300. We do ask them to you know, eat a high fiber diet and eat breakfast everyday family mill meals and limit fast food. The difference between this and the child to do that, which is for families or kids with high cholesterol is the saturated fat intake. We asked them to limited to less than 7% rather than the 8-10%, which you know, most of our kids take or we is recommended. Um So we do ask them to limit red meat, your shellfish, saturated fat from palm and coconut oil and butter. And um you know, the total cholesterol intake should be also less than 200 mg. It's we do encourage adding high diet. Um or you know, dietary fiber and I'll just go over that in a minute. So, you know, the one thing that studies studies have shown that just with dietary changes, we can achieve up to 7 to 15% reduction. So in terms of red meat, there are some families that are eating five um times a week just by limiting it to two times a week and then adding fish two times or chicken two times the other times we have seen significant drop in their LDL levels at least, you know, 7 to 10% reduction, avoiding high food, high in saturated fat. Again, we talked about the butter and cheese and eating lean meats, low fat dairy and then um exchanging saturated fats with polyunsaturated fat, corn, soybean and mono and saturated fat like peanut oil, olive oil helps. The other thing and that's included in our child to diet is the recommendation of adding water soluble fiber, psyllium can be added. And usually you know when we recommend our kids 4 to 5 servings of fruits and veggies a day that um that kind of, you know, kids do get around 4 to 6 g of fiber a day, but you know, not every family or every child is able to sustain that kind of intake. And so we do ask, especially with our kids with high LDL level to add six g of added water label fiber for kids between 2 to 2, 12 years of age and 12 g for more than 12 years of age. So we do say in case you know, for your breakfast, if you're adding yogurt you can add um some fiber and then add some almonds, creek yogurt and Grc. So uh and going over plants Tunnel so are healthy diet typically contains about 200 to 400 g of sterile and sternal a day. But what are these? I mean, you know, so these plant derived kennel and sterile. They are their structure is very similar to cholesterol. Their fighter cholesterol and they inhibit absorption of cholesterol um in the distance. So these are again, you know, fitter sterile and um they're presenting all our legumes, seeds, nuts, vegetables and plants paid plant based diet. Um But even our healthy diet we get about 200 to 400 mg a day. And the recommendation is up to two g a day. So you know, um some food, There are some supplements and some foods are fortified to contain up to two g of servings per day. And you know, talking to our nutritionist or you know, doing research. We can kind of guide them to do that. But just overall eating, you know, adding um beans and nuts and legumes and daily intake helps increases the amount of plant as Tunnel and sterile that we can consume. And then statins. I didn't go into too much detail into statins because I felt like I just had to cover a little bit more about other genetic conditions. So I'll just briefly go over a 16 year old girl with long standing history of obesity are typical Type two diabetes comes and you do a hemoglobin a one c it's 10%. This kid has a high tricolor stripe but I wanted to kind of briefly review the genetic mutations leading to our hyper trickles. Redeem. Yeah. So her total cholesterol was 5 45 triglyceride level 5000 HDL 26. And all the other analysts like based liver function were normal for age. So just going over briefly lipid overview. You know, I wanted to you know, the kylo microns. So kyla microns are large triglyceride rich lipoproteins which are produced in our intro sites from dietary fat. And they are when our levels of trackless rights are above 1000 kyla microns are major component of you know, the hydroxyl straight level. So the LDL and Kyle omicron both carry trickles, right? But when levels are above 1000 kyla microns predominate and dietary fat is packaged in the intestines to form kyla microns. And the, you know, the tissue capillaries have this lipoprotein like bees which kind of hide relies is triglycerides and kyla microns and releases free fatty assets for use as energy Callum MacRae anemia syndrome. The reason is you know, you'll start noticing that we we say, oh, multifactorial color micro anemia syndrome, which is the most common hyper cause of high significantly elevated him. Patrick list with anemia. The mono genic form, which is autism recessive because of loss of function mutation and lipoprotein. Um Light based the you know the enzyme that hydra lies is triglyceride or omicron from the diet. So that is um it affects that there's a loss of function and that results in hyper colored micro nemea in terms of um multifactorial kalachakra anemia. It's apologetic disorder. So you have these small accumulation of several genetic factors but environmental triggers play a big role and so poor dietary choices. Obesity are metabolic syndrome. Pcos hypothyroidism uncontrolled. Type one. Type two kids we see that they have um multifactorial Kalachakra anemia. So there is a component worsened by our environmental triggers. So in terms of you know kind of the only reason we worry about these kids the complication is acute pancreatitis. And we have a lot of kids coming um you know because of presenting to our er because of acute pancreatitis because F. C. As the familial um micro anemia syndrome is a rare but the multifactorial kylo kylo micro anemia syndrome is much common and I just wanted to kind of you know like the features that we see in both familial and multifactorial as eruptive exam thomas detainees and thomas. Some of them do have this like e mc retinal is this is more common in our kids with FCS that you know an exam and retinal exam we do like femia retina list. Um And this is just you know Kyle omicron accumulation on the top and be refrigerated sorry in terms of um again, you know like in terms of diet because you know first and with obesity and Disl epidemiology to we do see most of our kids will have hydroxyl is right but there travelers red levels are usually um below 400 unless they have these cluster of genetic mutation and which kind of worsens our hyper trikus Rudy mia. So but in case if you see a kid with a triglyceride level of 1 42 or 200 we do ask them to make dietary modification and at that level diet plays a big role. So again asking them to have a void should guarantee we do have them limit the saturated fat to less than 7%. 10% is from mono unsaturated fat replacing you know saturated to mono. Unsaturated is the key because they're still growing kids they need their um less than seven percent of the diet has to be fat. Um But less than you know, limited restricted to less than 200 mg per day of cholesterol, avoid trans fat as much as possible and increase their dietary intake to increase omega three fatty acids um increase their fish intake. So I do have briefly yeah this and then the three main fatty acids. Omega three fatty acids are alpha linolenic acid, E. P. A. And D. H. A. E. L. A. Alpha linolenic acid is actually planned. It's found mainly plant oils, flax, seed oil, canola oil um soybean oil and the D. H. A. N. E. P. A. They're found in fish and other seafood and fish has to be cold water fatty fish such as salmon, mackerel, tuna. Um And you know we all also have to make sure that mercury is high in certain fish. So to avoid that sources of fish, um nuts and seeds, flax seeds, chia seeds, walnuts have high levels of omega three plant oils such as like I said um L. A. Is rich and flax seed oil, soybean oil and um canola oil going over the prescription fatty um omega three fatty acids. Lowassa. So one g of Lowassa and especially you know in kids who struggle right level is above 400. We do Saturn on prescription Lowassa. one g of Lowassa contains 4 65 mg of E. P. A. And 3 75 of D. H. A. And it's the E. P. And D. H. A. Which are the active Fatiha said proven to lower a very high track list right? The one thing to remember is um you know it's four capsules. So a day like 22 g doses so for a day they cannot open crush or chew these big pills Over the we have to be very careful about over the counter Omega three fatty assets because remember the requirement is hi E. P. A. D. A. J. So four g per day. And if you look at these supplements, they have about 1 80 mg of E. P. A. And 1 20 mg of D. H. A. Per capsule. So you need about 11 capsules for equivalent prescription of four g a day. And that can become tricky. Um You know one because of the fishy taste, Dyspepsia, diarrhea all travel JIA you know families and patients don't like taking it and um you know we have to also monitor their liver function. Test. It can cause some pro writers and rash. What are the common Side effects we do? You know fibroids are indicated if triglycerides are over 400. The reason is there are times you know families are disappointed when the blood sugar when the trigger is right is about to 50 it's high. But we don't start them on medication. Diet. Diet. Diet is the first line of treatment for hyper trickle academia. And vibrates is an acting to lipid lowering diet and not the first line mode of therapy. And it's not approved in pediatric population. Um Fibroids can reduce Regulus rights by 30 to 50% most of the time we start them after. Um strict tired omega three fi braids and especially in kids who have have been having acute pancreatitis or at risk for that
