Cholesterol: The Good, The Bad, and Lipoprotein (a)

good morning everybody I'm Dr Dennis Goodman Welcome to our heart health lecture series presented by the center for prevention of cardiovascular disease next slide I am a clinical professor in the department of medicine and director of integrated medicine and the founder of our lecture series I'm very proud of this lecture series and it's very much part of our prevention team and our preven program uh we have a very loyal audience which is growing rapidly and I'll tell you about some of the lectures we've had and we're very excited to have a wonderful speaker tonight next slide so this whole series is based on the idea that I have and everybody has that prevention is so much better than trying to cure something uh 80% of heart attacks and strokes are preventable and many other chronic conditions and and the ways that we focus on prevention are nutrition uh and that includes supplementation at times supplements exercise and flexibility sleep the importance of sleep Stress Management and socialization and connection which is so important uh for being healthy and preventing heart disease and and cardiovascular disease and many other chronic illnesses next slide so we've had a hardal lecture series based on many of these topics uh many of you are regulars we've been doing this since 2015 we've held over 60 lectures on topics related to heart health and conditions that increase cardiovascular risk and you can see many of those topics we've done cholesterol in the past but we like to update uh things every few years and we very lucky to be able to get an update tonight next slide so we have a video library and most of the lectures have been recorded and you're able to go and hear them if you miss it or if you want to hear one again uh and we've had over 35 on demand videos and we've had about 80 to 90,000 hits uh on our videos so we're very very excited about that and we'll tell you how to get to those videos in a minute so registrations opening soon uh and the next topic is going to be an update on aspirin and blood finers by Dr Jeffrey Burger who is head of our prevention program and that's on Tuesday March 12th very shortly we'll be opening up for registration and I'll give you the website address to register and that will be an outstanding program so if you want to register for that and any of our programs the website address is nyulangone.org heart health lectures next slide so if you keep in touch with us I just gave you the website you can also email us at Health at nyulangone.org we're also on Instagram and Twitter at NYU CBD prevent this is just to tell you that if you have a question uh during the talk you can put it in the Q&A and I'll be filling the questions and I'll ask as many as possible we've already had several questions that have been WR sent to us and we're going to tackle those as well next slide this month heart February uh and it's heart month and we have to remember that it's so important to think about cardiovascular disease uh both in men and in women um but we do everything we can to educate the public about how important it is to know about your heart health and to do everything you can to stay healthy next slide so tonight we have an unbelievable outstanding speaker who's going to talk about colle lesterol I call it The Good The Bad and lipoprotein a which is a very hot topic and Dr anber Dr andberg is going to speak about it our speaker tonight is an our NYU our very own langone expert Dr James underberg he's got very many titles he's a clinical lipidologist he's a clinical assistant professor of medicine at NYU school of medicine and the NYU Center for prevention of cardiovascular disease he's undergraduate and graduate degrees of from Yale University and his medical degree is from the University of Pennsylvania his internship and residency was at NYU and BW hospitals in New York City Dr anderberg is the director of the BW Hospital lipid Clinic he holds joint appointments in the division of General Internal Medicine OCR and endocrinology at NYU Dr underberg is Master of the national lipid Association he's the past president of the national lipid Association he's the past president of the American Board of clinical lipidology and current president of the foundation of the national lipid Association he serves on the editorial board of the journal of clinical lipidology and is a section editor of current atherosclerosis report Dr anderberg clinical interests focus on the clinical management of patients with lipids and lipoprotein disorders and cardiovascular dis disease prevention he maintains an active clinical research program in these areas and has authored numerous articles and book chapters in the field of clinical lipidology he sees patients that B View and uh in a private practice setting Dr anber it's a pleasure to have you uh I consider you a friend and and a world expert in this area we all turn to you uh with problems and difficult cases I don't think you see any simple cases any more simple uh problems they're all complicated and you're very much a world expert on familial hypolipidemia and how to manage lipid problems and how to deal with LP a so welcome to our lecture series and thank you so much for joining us I'll hand it over to you well thank you very much Dr Goodman it's it's great to be able to talk to everyone today I appreciate the kind introduction I always remind everyone the definition of an expert is someone who's more than 50 miles from home and shows slides um so I'm unfortunately still here but I do have slides so I guess that counts a a little bit um this is is me and my home which is NYU and bellw I did my training at Bellevue and and still um have very fond memories of my time there which is why I spend one morning a week running our lipid Clinic there at BW um you can also find me on Twitter at lipid doc um my tweets are limited to cholesterol and heart disease prevention but I'm I'm always amazed at how many people are interested in this area so so um certainly feel free to follow us both at NYU CBD prevent and at lipid doc these are my disclosures um I do some Consulting in the development of new pharmac pharmacologic agents in the field of lipidology and a lot of medical education to other Physicians um I wanted to start with this um interesting um kind of piece it it appeared online in 2017 from a a famous cardiologist who did a lot of online blogging named Milton Packer it was right after a clinical trial had been published that didn't show benefit that was considered robust enough to allow a new drug to come to Market and he wrote that lipid research died last week he goes on to say I've never been interested in lipids but some of my good friends are totally devoted to lipid research that would include me at least on the lipid research side billions of dollars have been spent to make every everyone's lipid profile look good but I fear that we may now have reached the point of diminishing returns my friends who are experts in lipids should not feel terribly sad and my response to that at the time was actually I don't find that interesting at all um and I'm going to show you throughout the course of this talk today that that we've really reached a very exciting time in the management of lipids disorders and I actually feel sad for some of my colleagues in other fields because I do have a lot of amazing options that I can offer my patients to help them manage their cholesterol and it's exploding at a rapid rate and I wish some of the other fields that we care for were experiencing the same explosion in new technology so here's my outline I'm going to try and get through this relatively quickly um so we have time for Q&A but I always like to start out with a little bit about history and and I have an interest in art history so I try to combine the two some fun facts worth knowing about cholesterol the role of cholesterol and causing heart disease in case anyone ever challenges you on that you'll have some great information to have a conversation a little bit about cholesterol lowering medicines we could spend hours discussing this and I do when I educate other Physicians but but just to give you a framework of how to think about it and then I want to spend some time talking about I think an under recognized risk factor for heart disease called lipoprotein a and I think everyone should know about this and then a bit about the future I love this from the Chicago World's Fair in 1933 A Century of progress and I think that's what I feel we've come to now and so I start with with um the Mona Lisa painting and I hope that that this doesn't spoil your ability to view some of these in the future but but we know that Leonardo painted did this pasting um over a period of 3 years um from 1503 to 1506 and the name of the woman who sat for the painting is listed there um she was born in Florence in 1479 married at an early age to a um older gentleman a maresi um and it at at age 24 actually sat for the painting and unfortunately she died several years later at a young age age 37 for caus is unknown but we do know what she didn't die from she didn't have a lingering illness which was often from infectious disease at the time um she died suddenly in the middle of the night went to bed healthy and woke up the next morning and had passed away well didn't wake up the next morning and had passed away she wasn't killed in a in a traumatic event she wasn't knocked over in a Dunkey cart accident or or fell from the top of a tower um it was sudden death in the middle of the night and and so so so what do we know about her well if you focus in on the painting itself there are a couple of very interesting findings on this painting there's an area in the inner part of the nasal fold of her left eye that is a a prominent finding um and you can see it a little closer here it almost looks like yellow discolorations in a patient who has inherited high cholesterol very similar to what we see in the painting of the Mona Lisa and if we go in and look at her hands there are some Curious nodular densities on the surface of her hands and fingers that also resemble nodular densities that we see in patients who have extremely high or inherited high cholesterol familial hyper cholesterolemia and in fact um the Mona Lisa May indeed represent a woman who died sudden death in the setting of inherited high cholesterol something called familial hyper cholesterolemia um here's a a portrait of an older woman um painted by France halls in 1633 and again if we look at our hands we find these nodular densities that may represent arthritis but also may represent some of the findings that we see in patients with very high cholesterol and finding if we go back much earlier in times I don't know any of you have seen this great statue the the charer of Deli it exists um not only um overseas but a a copy of it sits um on the steps of the Museum of the Philadelphia Museum of Art and if you look down at the heels um in the Achilles tendon of this statue there are these protuberant findings that resemble something called Achilles xanthoma that we also see in patients with inherited high cholesterol and we tend to think of cholesterol as a a abnormality that exists because of our lifestyle in the 20th and 21 for a century but we can find evidence of early accumulation of high cholesterol and early atherosclerosis going back to some of the studies that have been done on mummies that have been found from early Egyptian times so cholesterol remains important today the American Heart Association lists what it considers life's essential eights eight things that you really need to focus on to help prevent heart disease um and lipids I have pointed out on the bottom here in the purple um arrow and over here on the right also control cholesterol high levels of bad cholesterol I hate using that term bad cholesterol there's no bad or good cholesterol there's just cholesterol some of it maybe hangs out with the wrong type of folk but in general cholesterol is cholesterol and and we describe it as HDL or LDL based on how it's trafficked in the body and I'll explain that in a little bit but maintaining optimal levels of cholest cholesterol is a very important component of a heart healthy lifestyle and I never like to discuss cholesterol without looking at it within the context of these other risk factors weight blood sugar blood pressure healthy sleep smoking or not smoking ideally activity and healthy eating and all of these interact to create a millu that promotes heart healthy lifestyle so some fun facts about cholesterol um adapost fat tissues stores the majority of what we call triglycerides in the body and about 25% of cholesterol 50% in in those who are obese and these fat cells produce limited cholesterol and rely on certain types of of products to deliver cholesterol to the body and we've heard about different types of cholesterol containing particles LDL people often think of as the good cholesterol I mean the bad cholesterol HDL is the good cholesterol but the primary mechanism or or or role of LDL and HDL is actually to deliver cholesterol to organs in the body that don't make enough on their own and most of that delivery is actually HDL cholesterol not Lal cholesterol endocrine glands um cholesterol is required to make certain endstage products such as estrogen cortisol progesterone testosterone all comes from estrogen and and most of these make enough on their own but if they require extra cholesterol again it's delivered by HDL the organs with the greatest concentrations of cholesterol of the adapost tissue brain liver muscle intestine skin and while the liver is the main regulatory organ for cholesterol um it may contribute only about 10% of cholesterol synthesis the rest of these other parts of our body make cholesterol on their own so what else do we know well the brain makes all of its own cholesterol it's an independent Corporation it's kind of neat to think about that the brain is such an important organ we wouldn't want it to be short of fuel and cholesterol represents fuel in many cases for a lot of important organ functions and so the brain makes all of its own cholesterol in fact LDL cholesterol doesn't even get into the brain from the bloodstream it doesn't cross what we call the bloodb brain barrier depending on the health of a mother at Birth LDL cholesterol can be very low between 20 and 65 milligrams per deciliter I always remind people of that because one of the things people often ask me about is hey Dr underberg is my cholesterol too low should I worry and at the time we're born when all of the important things in our body are developing including our neurologic system and brain cells our cholesterol is as low as it's ever going to be and so again low cholesterol probably not much of a concern I'll speak to that in a little bit more than half of the cholesterol in your bloodstream is not inside cholesterol containing particles such as LDL and HDL it's actually on the surface of red blood cells so when you're cholesterol levels are low you still have plenty of cholesterol no need to worry about this at all so people often talk about use a phrase the LDL hypothesis hypothesis that LDL causes atherosclerosis cardiovascular disease heart disease we in the cholesterol field do not use the term LDL hypothesis because it's not a hypothesis it's been proven that LDL is causal in atherosclerosis and that's based on animal experiments where you can raise cholesterol in animals and show that they develop atherosclerosis and you can lower cholesterol in animals and show that the cholesterol the the atherosclerosis melts away goes away there's a lot of great what we call observational or epidemiologic study data showing that if you look at populations of patients and you measure their cholesterol their risk of heart disease stroke heart attack vascular disease Etc tracks with levels of cholesterol as cholesterol levels go up for a group of patients over a period of time their risk for cardiovascular disease and atherosclerosis goes up and as their levels go down that risk diminishes uh more recently we've got a lot of great what we call randomized clinical trials these are where we do interventions to lower cholesterol we wouldn't do interventions to raise cholesterol but these cholesterol lowering trials have gone back since the early days of my training um and I'm not going to tell you when that was but um we've learned over a long period of time that if you lower cholesterol safely you can reduce the risk of heart attack or stroke now you probably have to lower cholesterol ol a certain amount probably have to lower it about 30% to really see benefit so a 5 10% reduction in cholesterol probably isn't enough to see that benefit um but we do know that if you lower cholesterol safely through a variety of different cholesterol lowering mechanisms you can reduce the risk of heart attack and stroke and then finally I think the most compelling is genetic analysis we look at at patients who have um genetic mutations that either raise or lower cholesterol over the course of their lifespan and it turns out that if you have a gene that increases your cholesterol over time you're at greater risk for heart attack and stroke and the opposite if you have a gene that lowers cholesterol you seem to be protected heart attack and stroke and atherosclerosis so so LDL is causal and and I'm going to try not to show you too many charts and graphs like this I know it's a lay audience but I think this is very very important this shows different types of clinical data and in the red these are the randomized clinical trials we give people drugs they're the shortest they're three to five years and the curve is the least steep the medium curve in the middle in blue is the observational studies where we follow people between 10 to 30 years to see what the effect of having higher low cholesterol is on heart disease risk and the curve that is the steepest showing the greatest effect is the genetic data meaning that the longer you are exposed to over the entire course of your lifespan if you have mutation it begins from the day you're born so the longer you are exposed to a risk factor such as high cholesterol or a longer that it is removed if you have low cholesterol for a longer period of time you benefit the greatest but why is this important because it speaks to the important of early intervention if if we know that patients who have low cholesterol from birth do the best Common Sense would tell us then that impacting cholesterol earlier on in life makes a lot more sense than later on in life it's kind of like you buy a new car and the front end is out of alignment you can wait until you've been driving it for five years and need a whole front engine replacement but if you go to the the auto shop and have them balance your tires you never have to have a problem and so I think it's very important to think about this data in the context of why we want to intervene sooner and understand risk as soon as possible so how is cholesterol trafficked in the body I'm going to give you some information when I'm done you're going to know more about cholesterol than most Physicians do so cholesterol does not float in the blood like logs in a river it can't and the reason it can is because cholesterol and triglycerides are fats they're oils and the blood is essentially water and we know that oil and water don't mix so cholesterol is trafficked throughout the body inside water-loving vehicles or particles these particles have names that you already know LDL vldl HDL think of them as vehicles on a road you have different kinds of vehicles you have cars you have trucks you have Vans the passengers inside the vehicles are the cholesterol and the triglycerides and they're being trafficked inside these water loving vehicles and they're called lipoproteins and this is what A lipoprotein looks like the lipoprotein has cholesterol and triglycerides in the center and then it's surrounded by a coating of um water loving um um water loving molecules that protect the cholesterol and the triglycerides from the water that they're actually being trafficked in and it's these lipoprotein particles that bang into the artery wall and force their way in so if we want to understand what's going on with cholesterol and risk for heart disease we don't really want to know how many passengers there are we want to know how many vehicles there are and that's why L looking at ways of measuring these vehicles becomes a far more sophisticated way of understanding someone's cardiovascular risk when it comes to cholesterol and so rather than just measuring things like cholesterol LDL HDL we often measure things like AP B apob is a measure of the number of particles and it's a far more accurate way of thinking about how someone's colesterol is interacting with their artery wall so where does cholesterol come from well about 20% comes from the food you eat why is that important well many people want to lower their cholesterol by reducing the amount of cholesterol in your diet well if only 20% of the cholesterol in your body is coming from diet and you reduce your cholesterol intake by half by 50% you've only lowered the amount of cholesterol in your body by maybe 5 to 10% as best and guess what if you reduce your cholesterol intake the body is smart it just starts to absorb more of what you're giving it and so typically dietary manipulations of cholesterol don't change cholesterol that much now I I put a word of caution on this there are some people who happen to abser absorb more cholesterol than others and for those patients dietary manipulation of cholesterol matters more and in fact one group that it really matters a lot in are patients with inherited high cholesterol because they tend to absorb a lot of cholesterol so they respond well to diets that are restricted in cholesterol and saturated fat but most of the cholesterol is made by organs in the body including the liver and So 20% of your cholesterol comes from food you eat 80% is made in the body including in the liver and so when when we measure cholesterol it's a mix of both one of the things that comes up often is how safe is very low cholesterol we've got all these great ways of lowering cholesterol now so I always want to make sure when someone asks me about it I first talk about the benefits so what are the benefits well it seems to reduce the amount of plaque that people have in their in their arteries um it reduces the risk of cardiovascular death heart attack stroke need for procedures to fix blockages called coronary revascularization and reduces the risk of of something called unstable Ana which is which is new onset of chest pain or or reduce blood flow to the heart statins and low LDL cholesterol in general um do have some side effects um there may be an association with worsening blood sugar I don't think this is clinically relevant it's trivial and I tell people about it because I think they need to know about it but I do not think it's a reason to not take cholesterol lowering medicines some people ask about bleeding and whether there's bleeding risk especially in the brain with low cholesterol and again the data seems to not really support this however in the setting of aute stroke that was related to bleeding I probably would wait until someone was stabilized before I gave them cholesterol lowering medications um low cholesterol does not cause cataracts and there's no data to support any association with cancer risk any liver toxicity any causes of dementia issues around um low testosterone levels um or blood in the urine so I make it clear low cholesterol is pretty safe now high cholesterol can be caused by lifestyle and be contributed by diet but genetics plays a big role and I always say that cholesterol can be a family affair I remember that TV show from growing up so I put it here for you but there's a condition called familial hypercholesterolemia I spend a lot of my time seeing patients with this Condition it's more common than people think um and it's often mistakenly referred to as a rare disorder and it's not um patients with familial hypercholesterolemia have high cholesterol from birth um they have a family history of high cholesterol or early heart disease uh typically heart attacks or Strokes in men before the age of 55 and women before the age of 65 and typically their LDL ch olol untreated is greater than 190 milligrams per deciliter in adults and 160 milligrams per deciliter in children and we call it FH I've lifted two resources here not just for FH but for cholesterol issues and lipoprotein a which I'm going to talk about in a little bit um one of them is called the family heart foundation and you can find them atam heart.org and the other is the foundation of the national lipid Association full disclosure Ure I'm the current president of this foundation and you can find us at learn your lipids. that's learn your lipids. both of these are not for-profit organizations that promote awareness um information advocacy and screening around all types of of lipid or cholesterol disorders not just familial hyper cholesterol emia but familial hyper cholesterol emia as I mentioned is not uncommon it's seen in approximately one in 250 people worldwide but in the Tri State metropolitan area New York New Jersey um um Connecticut it's probably closer to 1 in 110 and the reason for that is there are certain groups of patients that are at greater risk of having familial hyper cholesterol emia and we tend to see those patients living in this area um patients with familial hyper cholesterolemia have a greater than 20 times risk of heart disease over the course of their lifetime these patients tend to be underdiagnosed noed more than 80% don't know they have high cholesterol and we actually published a study many years ago our our fellow at our heart disease prevention center published some data um showing that that only about 1% of patients who have this condition are actually told by their practitioners that they have it so if you have familial hyper cholesterolemia certainly ask your provider about cholesterol lowering medications take medicines and it's also important to screen first-degree family members I can't emphasize this enough when I see a patient who has this condition I always talk to them about their siblings their parents and their kids they all need to be screened for high cholesterol I showed you that artwork early on and patients who have familial hyper cholesterolemia can have findings around the eye we call this zanol Asma or they can have something called a cornal Arcus at an early age which is a white ring between the Scara and the iris they can have these nodular densities in the Achilles or on the extensor surfaces of the hands um these are called xanthoma and so there are physical findings now we have many medications that are now available to us to lower cholesterol and I mentioned that in my introduction How Lucky I Am to be able to access all of these options statins Remain the Cornerstone and many of you may be on statins they have names like atorvastatin ruist Statin simvastatin um they used to be called cresto Lipitor zokor Etc they're all generic now which is great they're less expensive easier to obtain um and they lower cholesterol about 30 to 50% and they've been shown to reduce the risk of heart attack and stroke in addition we have another drug often forgotten but also around for a while called a zamite used to be called Zeta lowers cholesterol around 15 to 20% Works through a different mechanism that statins it works on blocking the absorption of cholester ol in the intestine but it does not have any stomach related side effects statins work by blocking the production of cholesterol and they almost trick your body into removing cholesterol from the bloodstream into the liver Zia is not as potent or Edomite not as potent as statins it lowers cholesterol 15 to 20% and there is data showing just like statins that reduces the risk of heart attack and strokes um we have newer agents that are injectable called pcsk9 inhib these are more potent even than statins between 50 and 60% they're injectable given every 2 to 4 weeks and the newest agent in cerin I listed on the bottom can be given only twice a year by by injection there is data with both of the um pcsk9 Inhibitors that we call monoclonal antibodies their branded names are ratha and praluent evolab and aliim um and we have data that they reduce the risk of of heart attack and stroke when added to statins um in ceran which is a different technology to lower pcsk9 levels um I said lowers cholesterol more but we don't have data yet that it reduces heart attack and stroke risk there is a clinical trial ongoing and I suspect it will um there's no reason to think it won't the safety data seems to be similar and again you only have to inject it twice a year um very recently we had new data from a brand new agent it's been around for about two years now called bidic acid bidic acid reduces cholesterol between 17 and 25% um and it's been shown then combined with other cholesterol lowering agents but in patients who can't take Statin Statin and tolerance to reduce the risk of heart attack and stroke this is relatively new information it's a great trial done in people who couldn't take Statin and for the first time a clinical trial more women than men so very exciting to see this data and so you can can see we have a lot of different things available to us and here's some fun facts about statins statins reduce the risk of heart attack stroke and death from heart attack and stroke the benefit is greatest in those with the greatest risk for cardiovascular disease and that's always important when we think about using these agents greatest benefit is in those with the greatest risk but people will often say well I'm young and healthy age is a risk factor so if I'm young I don't have high risk but that's not always true because if you're young and have very high cholesterol and you multiply the exposure of that cholesterol over the course of your lifetime it automatically makes you high risk okay so it's important to remember not just as what is my cholesterol today but for how long have I exp have I have I been exposed to high cholesterol so what else can we say about statins they don't cause liver disease they don't cause dementia they prevent vascular disease from progressing throughout the body including the brain and vascular dementia is the most common cause of age- related memory loss statins do not cause diabetes they slightly increase blood sugar statins do cause muscle aches we call that myalgia about 9% is a good number to hang your hat on the risk is greatest based on age increasing age female sex and people who are on other drugs sometimes there can be drug interactions that Mak statins more potent so to speak and again the earlier you treat the better so in the last part of this talk I want to talk about lipoprotein A lipoprotein a is an underrecognized risk factor for heart disease there's been a lot more awareness about lipoprotein a recently and I think part of that is because it's a very exciting time we've got several new drugs in development that specifically Target lipoprotein a so what is lipoprotein A lipoprotein a is essentially LDL cholesterol with an extra little piece attached to it the way I explain it to my patients is think of it as LDL cholesterol with velcro attached to it so so LPA lipoprotein a which is LDL that is stickier is more likely to get into your artery wall and stay and do damage to the underlying vasculature and so when we measure lipoprotein a we're really measuring LDL with this extra little protein attached to it called apoa and the entire entity is called lipoprotein a and this is what lipoprotein a looks like over here on the right the spherical structure is LDL and wrapped around LDL is a very important protein called apob that gives it its identification and then attached to the apob Via a little Bond here called the disulfide bond it's this repeating unit of of of what we call Pringles that forms the apoa molecule that gives the entire structure its name lipoprotein a and why do we call these repeating units cring because they look like a Danish Pastry called aingle and so so why does this increase the risk of heart attack and stroke well I like to think of lipoprotein a as a fishing tler and a net if the fishing troller is LDL think of the net as the apoa part of lipoprotein a and the fishing troller goes through the ocean over the course of the day and it's running its n underneath the boat and at the end of the day the contents of the net is dumped on the deck of the fishing troler and there may be fish in the fishing trer but there's also a whole collection of flum and flum and Jetsam that needs to be discarded and that flum and Jetsam it's being collected over the course of the day is exactly what lipoprotein a is collecting as it moves through the bloodstream it's collecting things called oxidized phospholipids and these oxidized phospholipids are are highly toxic to the artery wall and also to the surface of of heart valv such as the aortic valve and patients with evated lipoprotein a have an increased risk of aortic stenosis along with an increased risk of heart attack and stroke the prevalence of this is very high 20% of the population has elevated lipoprotein a so that would be 73 million in the United States alone and you can see it's distributed throughout the world lipoprot a goes up based on race sex and risk for heart attack and stroke um black patients tend to have higher lipoprotein a than white patients um South Asians Chinese have the lowest women have higher lipoprotein a levs than men and you're more likely to have atherosclerotic cardiovascular disease if your lipoprotein a level is elevated and data from observational studies and data from genetic studies shows this this what we call linear relationship between levels of lipoprotein a and risk for atherosclerosis and it seems to be a continuous relationship although there are certain cut points that we typically think of if you measure it in nanomoles per liter the matric number is 75 is elevated if you measure it in milligrams per deciliter 30 is elevated It's always important to ask for this I think everyone should have it checked when they're an adult at least once the US recommendations are to check it if you have risk factors for heart attack or stroke family history if you have heart disease or high cholesterol in Europe they suggest every adult measured at least once I think here in the US we're getting to a point where everyone will get a check once we're not there yet but the recommendations are actually being updated right now I mentioned that elevated lipopro a can also lead to valvular disorders in the heart specifically something called aortic stenosis so if you have aortic osis you should get your lipoprotein a level checked and if your lipoprotein a level is elevated you should certainly be screened for aortic stenosis so what can we do now why do we want to know about this well there are no drugs that are specifically approved either to lower lipoprotein a or to reduce the risk associated with elevated lipoprotein a but I think it's important to assess it at least once per lifetime especially in high-risk patients why well because it's a risk factor it's just as important as knowing whether or not there's a family history of early heart disease it's just as important to know whether or not you're a smoker or whether or not you exercise or you eat a hard healthy diet so it helps contextualize your risk going forward for heart disease if it's elevated it also means that family members should be screened first-degree family members I always say north south east and west so parents children and siblings we also know that if you're like lipoprotein a level is elevated lowering the LDL seems to minimize the risk from the elevated lipoprotein a there's also some newer data that lowd dose aspirin especially in higher risk patients May benefit patients who have elevated lipoprotein a I'm not by any means suggesting that everyone with lipoprotein a elevations be on lowd dose aspirin I'm just letting you know that there's some data out there suggesting that in some patients the use of aspirin may be beneficial there may be other W other ways to better find out who those people are but what's really exciting is that we've got a host of agents in the future um that are in development right now um that seem to do a great job at targeting lipoprotein a um we've got some drugs that we call anti-sense oan nucleotides they they seem to to break down the the coding RNA that that creates the lipoprotein a the apoa protein um there are drugs that interfere with the messenger RNA um and I've listed two here for you that are in development um this is very exciting right now and we're doing some of these trials at NYU my colleague Howard wein TR and our heart disease prevention center leads this effort um and it's great because we can refer patients to our Center who have these issues and get them um enrolled in trials that offer some of the newest agents um there are agents right now that do reduce lipoprotein a the C ck9 Inhibitors that I mentioned earlier for LDL lowering lower lipoprotein a about 25 to 30% the issue here is that when you look at genetic data it seems that you need to lower lipoprotein a about 80% to make a difference now the drugs that are in development that specifically Target lipoprotein a do lower lipoprotein a anywhere between 80 to 95% pcsk9 Inhibitors only lower lipoprotein a 25 to 30% so while it works whether or not it's actually doing anything beneficial I think Still Remains to be seen nasin is another drug that lowers lipoprotein a but we don't use it to lower lipoprotein a because it's got a lot of other side effects and um hasn't really been shown when combined with other cholesterol lowering me medications to reduce the risk of heart attack and stroke um people often ask me about estrogen estrogen will lower lipoprotein a but I would never put a woman on estrogen to lower lipoprotein a um and statins actually can raise lipoprotein a a little bit but that doesn't seem to have a negative effect and so do not be alarmed if you're on a Statin and your lipoprotein a goes up so if we think of the evolution of lipid lowering therapies from statins to aomi to the monoclonal antibodies against pcsk9 Inhibitors and now the um bi anually um injection of encan we''ve come a long way we've got newer drugs in development that Target lipoprotein a and I've listed some of them um we've got some folks working on vaccinations but I think the real excitement in the future going forward is actually something called Gene editing or crisper cast 9 and I'm sure you've heard about this in the news there is one company up in in Boston called Verve Therapeutics that's working on a one-time intervention to turn off the gene either or pcsk9 or something else called an ptl3 and if you do this you lower cholesterol at any time once you make the intervention it's a single intervention the only potential negative here is that it's not reversible so once you make the intervention it can't be undone um but there are clinical trials going on right now in humans with Gene editing with crisper cast 9 to see if we can not only lower LDL cholesterol permanently whether or not this has a beneficial effect on future risk of heart attack and stroke and and I Envision a time one day maybe where in those who have cholesterol levels above a certain number you might be eligible for this intervention when you're young and never have to worry about medications or potentially future risk of heart attack and stroke going forward so take home points here Statin and aetam are really first and second line options for lowering cholesterol they oral they're generic and I think they're they're relatively safe although there always are side effects that you have to be aware of it's important to get your cholesterol checked understand it in the context of other risk factors for heart disease because remember it's your risk that determines benefit from cholesterol lowering check lipoprotein a I think if if if you're going to get your cholesterol checked in my mind that qualifies you at least once to have your lipoprotein a checked it's inherited if it's high you got it from your mother your father or both and if it's high you need to screen any kids or siblings as well new lipid lowering Therapeutics are alive and well pcsk9 Inhibitors now include two different moralities monoclonal antibodies and what we call small Inhibitors of RNA pruin and ratha are the monoclonal antibodies and encin is the small inhibitor of RNA bidic acid called nexletol offers another approved oral lipid lowering option ESP in patients who are stat and intolerant and there are outcome trials going on with in glycerin and finally new Therapeutics and development targeting lipoprotein a are in progress and Gene manipulation is closer than you think so finally I always like to finish in the words of Ferris bu life moves pretty fast you don't stop and look around once in a while you could miss it so I thank you very much um this is bellev hospital where I trained um I have a collection of old postcards from bellw and I have very fond memories of my time there and enjoy my time there now it's a wonderful institution um and we're lucky we have it here in New York as well as NYU and our heart disease prevention center so I'll end on time with 15 minutes left for Q&A not bad Dr Goodman and I'll send it back to you you know what that was outstanding you're an absolute Pro you did an absolutely amazing job and I you simplified the topic so well and gave so much amazing information I've got several questions uh we put some of them up on the screen because it just makes it easier um and you can try to answer them sort of short in briefly so we can get to as many as possible but we're going to start off with what is the optimal range for cholesterol sure and again you have to contextualize Optimal levels also within the particular patient and risk for heart disease so in someone who is otherwise healthy I would say an LDL cholesterol less than 100 in my mind would be optimal in someone who had heart disease I would want the LDL to now be less than 55 and so those are just two quick numbers to hang your hats on thank you very and that is one of the reasons that we are so aggressive uh in bringing the LDL down in people who have heart disease or they've had a stroke because we know the data is so clear that if as the lower the cherol the LDL cholesterol the better um and luckily as you've mentioned we've got really amazing medications that can really lower the LDL very significantly next question why do I get yellow spots under my eyes and my cholesterol is low oh that's a great question so I showed you that patients with very high inherited cholesterol familial hyper cholesterolemia can get deposition of not cholesterol but kind of reactive what we call reactive giant cells in the inner nasal folds around their eye and it's called xanthelasma and it's a yellow waxy appearance but it's not cholesterol but it turns out that the most common cause of this is no cause at all and it doesn't come from high cholesterol and unfortunately these behave often like keloids and sometimes when people try to have them removed surgically they can actually come back with a vengeance so I always caution patients who are referred to me with these findings that if it's not because of high cholester ol which is usually the case be very careful about what you do to try to remove them cholesterol lowering medicines won't have an effect um they can be removed surgically but it has to be done by someone who really understands what they're doing right is it possible to have a normal cholesterol and still have blockages or still have a heart attack and the answer is of course um you can have normal cholesterol but you could have high lipoprotein a that's one of the first things that you and I always check for Dr Goodman is when someone comes to me and their cholesterol is normal and they've had an event I want to make sure we check their lipoprotein a but there are lots of other things that can cause vascular disease that don't relate to cholesterol um and so it's just part of the puzzle I showed you that life simple eight cholesterol is just one of eight in that question there I remember a patient I had who was very strong fit 39y old male he was on the basketball court he had a heart attack he came in I had to put a stent in and he did well but his lipids look great uh and I it was to this point to this question I checked his LPA and it was very high so it's just to your question to your point that the LPA alone can be a significant factor and that's why it's so important to check it how can a heart scan that's a Cy calcium scan show a high score while other tests aren't showing blockages um I'll just weigh in quickly and say we do use I don't know about you Dr anber but I know I use a lot of calcium scoring and you also do it it's just a noninvasive way of looking to see if there's plaque in the arteries and we call H it's it's called hard plaque because it's calcium and there can be a high score the calcium score could be over 400 and you may not have a significant blockage you have artherosclerosis but you don't have a blockage that's % or more and so what we often do with patients who have a high score is to do some kind of stress testing to see whether or not there is es schia related to a blockage turns out that when a score is over 400 there's about a 25 to 30% risk of having a blockage and many a patient uh who's actually been asymptomatic has had you know calcium scans and L up having stance and byass surgery especially in the old days before we had trials that show you can be more conservative with treatment so I I'd like you to add to that and just tell us how often you use the calcium score well you know the calcium score is a great tool originally it was recommended as an additional risk assessment tool that we could use to help determine whether or not we felt the patient needed to be on cholesterol lowering medication almost like a tiebreaker if you weren't sure I would tell you that our thinking I think you would agree with me has evolved and I have patients that are on cholesterol lowering medication and now I sometimes use a calcium score to help me determine if I'm doing a good enough job do I need to be even more aggressive when we didn't have a lot of tools there wasn't a lot we can do but now because we have the ability to make cholesterol low I don't want to miss an opportunity in someone who needs to have low cholesterol and so it's just another way of unearthing risk and getting kind of to the to the core of what's going on so to speak I had a question from Laura which this is applicable to I think who's let's say she's 60 years old um and she has a high LDL cholesterol over about 165 but with a high HDL as well no other risk factors and um let's for just say that she has a family history of heart disease um and she wants to know should she her LDL be treated and I think this is a perfect example of a situation where the calcium score can be very helpful it can be and I would also remind people that that that high HDL cholesterol which is often mistakenly I think referred to as the good cholesterol does not it does not protect you against elevated levels of LDL cholesterol and in fact when HDL levels become very high the HDL becomes dysfunctional it doesn't work right and it can actually be what we call proatherogenic or promote atherosclerosis and heart disease and Fin finally there is a syndrome that's been identified in patients with very high HDL that seems to be associated with high lipoprotein a levels so when I see a patient with high HDL I want to immediately know what their lipoprotein a is HDL is made primarily in the intestine and when someone has high HDL it's also a clue that they might be a high absorber of cholesterol and this often happens after the menopause in women they start to absorb more cholesterol in HD levels can go up and it's not a protective event because we know the risk of heart disease shoots past men after menopause so HDL can tell you a lot about what's going on in summer to your point you know many years ago as you know fisa had a dry C to craid which was a CP inhibitor and the HDL cholesterol was going up 70 or 80% and it turned out the study showed that people on this drug were doing worse and what we figured out is that maybe it's partly because of slot increasing blood pressure but it also turned out that we think the HDL was dysfunctional so to your point how do we know if someone's got a high HDL whether or not they have a dysfunctional HDL because in some patients it is protective isn't it yes and some in some I think it represents things that are protective right HDL goes up with certain diets that are heart healthy HDL goes up with exercise HDL goes up if you stop smoking but we don't yet have an assay that measures hdl's ability to do good things so to speak so I think it's important to look at some of the other surrogates such as a coronary calcium scan as you mentioned okay and also I think an LPA would be very important there too because if the LPA is elevated we would certainly treat that lady Laura what test can I get to diagnose familial hypolipidemia so it it starts with the LDL cholesterol typically untreated we use the number greater than than 190 which is the 95th percentile but we've now got the ability to do genetic testing specifically targeting the most common genes that mutations have been found in that are associated with the condition familial hypercholesteremia and I tell my patients that genetic testing is kind of like cell phones they were once very expensive it didn't do much now theyve become relatively inexpensive and in fact free in many cases and do everything and that's the case with genetic testing the cost of this has come down significantly and it is a part of the diagnosis of familial hypercholesterolemia but there are some people who have familial hyper cholesterol nemia but we don't identify a mutation and it doesn't mean that you still don't have to treat the condition one of our audience made the point that a lot of doctors don't check LPA and maybe the incidence is even higher than what you mentioned and I think that's a good point yeah we get the the numbers the incident numbers from from large databases and so it's it's independent of whether someone's screened or not um but um still um I think that that at least here in the United States the the information I hear often from patients when we find out that their LPA is elevated and I tell them to get their family members greened is they'll say oh my brother's doctor didn't want to check it because they told him there's nothing to do about it and my answer is well there's nothing to do about a family member who died from a heart attack but you'd sure want to know about it and so again I think information is a good thing even if we don't have a drug yet approved to treat it right and as you said we the future is looking Rosy in terms of finding drugs that will be able to lower it significantly do statins prevent heart attacks you've answered that beautifully absolutely in people who have high cholesterol is cholesterol really the problem and I think I'm going to change that too is cholesterol the only problem because we know that LDL cholesterol clearly is a major factor and that's why statins work but what about other things that we should be focusing on and clearly we've got this is where it's so important to think about Lifestyle Changes um the exercise the eating healthy Stress Management sleeping well and and and and as I said socialization and connectivity what's the best way to reduce LPA I think you've discussed that we we it's not possible to reduce LPA uh without taking some form of medication one one of our audience said to me that they were on a Statin and aide and the LPA went up by seven points I don't think that's clinically significant um what do you feel is a you know is there any evidence that the LPA can go up with medication and would you worry if it went up slightly so the answer is yes it does we know that Statin slightly increase LPA um and that doesn't seem to impact the benefit on cardiovascular risk reduction um and it would be a would not be a reason for me to stop someone Staten um because LPA creates a patient in a higher risk category and we know the higher the risk the greater the benefit from the Statin given the same amount of cholesterol lowering one of the things that LPA does though it creates the blunted effect for cholesterol lowering so if you don't respond to a Statin the way your provider thinks you should then make sure you get your lipoprotein a checked because if the lipoprotein a is high it could account for a blunted effect on LDL lowering I do want to point out one thing before we're done which is that we haven't mentioned that for patients with elevated lipoprotein a who have heart disease and continue to have events or problems there is one accepted treatment it's it's rather invasive it's called apheresis where we literally remove the lipoprotein a from the bloodstream much like dialysis and then give the blood back without the lipoprotein a and so there is something that we can do right now today if needed in the worst cases you covered the the next two questions let's go to the next one what are the negative side effects of staking statins you did mention you can get muscle aches somebody want to know why do you get muscle aches um and why do we get you know sometimes joint pains and muscle aches and I know that Coq I know that you know the lowering of CoQ10 has been tarted as one of the things that can do that and the studies haven't really borne out that it can make a difference but I do want to say in my own practice I have the people on CQ 10 at times and it has made a difference I don't know if you ever use it or whether you're a purist and uh you you start tell us how you would handle muscle aches just briefly yeah I I generally try to find a drug that doesn't cause a problem um sometimes if people have tried multiple statins um they consider it but it's it's not an inexpensive supplement um and the data surrounding its use isn't that robust so I don't I don't promote it um you know we used to think that low vitamin D might in increase the risk of Statin related myalgias newer data doesn't seem to support that either unless perhaps it's extremely low below 15 um thyroid disease intercurrent thyroid disease can increase the risk of of Statin related muscle complaints and so there are some things we can do um and sometimes just changing to a different Stat or alternative dosing seems to help but we try everything we can to get people to take these medicines since they work so well I just wanted to quickly just mention that I had some questions about eggs it's a one of those controversial areas I wanted to just refer people to an article that's that was written in a in a journal called nutrients and you can look it up on Google eggs healthy or risky by meline May and she makes a she does a great job of talking about eggs and the fact is that eggs are very healthy they've got a lot of choline folate vitamin D iodine and high quality protein and most of the time the eggs are not a major problem and you can have between two and four eggs a week as long as your your cholesterol is not going up because of the eggs and that is something that's very easy to check I also wanted to say Doc Dr underberg that I as you know I'm I'm integrative and I have had some patients who don't tolerate Statin very well um and I've managed in patients who don't who don't have significant heart disease at that time to use a drug called bergamont which is from the lemon of a citrus uh lemon that's grown in Italy and I've seen reductions of you know 30 to 40% in the cholesterol so there are some Alternatives but it's very important that you do it in conjunction with your physician if you have significant underlying plaque or you have had heart attacks or Strokes or already cardiovascular events I believe it's absolutely essential to be on a stattin or other one of the other medications Dr andberg that was outstanding I wanted to just uh if you could just put the number up uh Anya uh for patients that would like to come and see somebody uh on our team NYU langone center for the prevention of Cardiology disease you can make an appointment at 212263 4300 we have a a team of excellent preven of cardiologists and you will get all the information you need about prevention of cardiovascular disease our website to register as I said is NY nyulangone.org heart health lectures and if you've got any questions or you've got any suggestions please email us at health nyulangone.org I got a few comments to say how much the audience has enjoyed your presentation today Jamie so thank you so much it was really outstanding I really appreciate it and thank you Ana as usual so long thanks so much everyone that was great Jamie thank you all right

Channel: NYU Langone Health

Views: 3,114

Keywords: NYU Langone, Center for the Prevention of Cardiovascular Disease, heart health, Cholesterol, cholestrol, cholesteral, NYU Langone Health

Id: C0D4tDpXfkw

Length: 63min 2sec (3782 seconds)

Published: Mon Feb 12 2024