Heart Disease Prevention: What You Need to Know

all right thank you so much for having me thank you David and it's wonderful to be here to see such a good turnout for the preventive session it really does warm our hearts I'm going to talk about genetics and my goal here is that not to intimidate you in any way it's to make things simple and tell some stories and and see if any of it resonates with you I I do I work with the charity and as a volunteer I'm the chief medical adviser for a charity for FH that's my disclosure and obviously the reason that we're here is that cardiovascular disease heart disease is the leading cause of death around the world and it has been for for many many years number one in 1990 number one in 2013 there have been some changes if you look over here measles is it we used to be a very very common cause of death and now it's moved down in the rankings and that's gained a lot of notoriety lately obviously cardiovascular disease is this green is this light green here this this light green and as we all get older this is age heart disease becomes a bigger risk factor and so by the time we're sort of Social Security age it's it's the bleeding bleeding cause of death and so what I wanted to talk to you today is how new technologies and new knowledge that we are learning from the genetic revolution may impact this going forward and I'm going to tell you a few short vignettes short stories not go into great depth about the science about several ways that that genetics is helping one is discovery how how we discover the genes that are leading to heart disease how we how that translates into a better understanding of heart disease for researchers and physicians how that can lead to smarter and cheaper drug discovery there's some very good examples of that how it can improve risk prediction taking an individual person and trying to figure out whether they're gonna have a heart disease and maybe even in personalized therapy changing what drugs are recommended for you based on your genetic background and finally improving public health and this is something that many of you probably haven't thought about that I've been thinking a lot about now the the next this is all we need to know about genetics for this talk genetics is not rocket science it's not even brain surgery it's it this is this is what we have here this is the each of these books this represents the genome 3 billion base pairs that's a lot of base pairs remember this is just the alphabet this is the book of life ace T's GS and C's strung together in chromosomes so that we have 46 chromosomes the DNA 3 billion base pairs is aligned on these 46 chromosomes and part of these chromosomes are genes not all of the chrome not all of the DNA our genes about we have about 20,000 genes and that's only about 1% of the total sequence now the rest of the DNA is doing important things but it's beyond this lecture to talk a lot about that what I'm mostly going to be talking about is is the genes that we know and and this is really something that's we we're in the beginning of the genetic revolution I mean it was only in the year around 2000 when we first mapped the human genome this was a you guys funded this through your taxpayer dollars it cost 300 million dollars back in the in the 90s to sequence the first human genome and not only do we have a map but we know now a lot about what makes us all the same similar to one another and what makes us all different and I know that you all are not going to do it who recognizes this guy anybody come on people raise their hands please okay all right this is this is Shalom sis's and and I'm you're not going to remember everything I say but I do want you to try to put a few things in your in your mind Palace and so try to remember one or two things and I think you'll you'll get a lot out of this talk so understanding genetics and there's really two flavors of genetic conditions and they're and they're both very important and it all depends on how big the needle is in the haystack that you're looking at so some needles some genetic diseases are some some conditions are really caused by a single gene defects with very large effects in this case the the genetic background really overwhelms the environmental impact it plays somewhat bigger role than in the environment but most and this this is I'll give you some examples of this kind of genetic condition but most of heart disease is not caused by one single gene with a really large effect it's caused by small changes and so you're hunting for the needle in this haystack small changes in many many genes working together to lead to an increased risk and so I'm going to give you some examples of both of these and how they are different in this end and the same and so the one that's most close to me is it's called familial hypercholesterolemia now I know that how many of you knew about Benedict Cumberbatch how many of you know what familial hypercholesterolemia is raise your hand so very very few more people know about Benedict than they know about FH but at the end of this talk more people are going to know about FH than Benedict so this is a disease where the genetic effect is very very large and where one misspelling I told you about the the the language of life the DNA language of life one misspelling in those 3 billion base pairs can turn a clean coronary artery no disease into a very diseased coronary artery and for FH didn't use of genetics the time is now you know the time is now we should be doing a lot about this now many of you how many of you heard of cystic fibrosis okay everybody the very Marfan syndrome how many of you heard of that okay good hypertrophic cardiomyopathy the killer of young athletes how many of you heard of that many many of you but but very very few have heard of FH and that's a real shame because FH is way more common than any of these other conditions it causes a 20-fold lifetime increased risk of heart disease if you're a man and you have FH and you're not treated there's a 50% chance you'll have a heart attack by each 50/50 and if you're a woman there's a 30% chance by age 60 it caused hundreds of million dollars to our health care system every year and yet we don't we don't know about it and we estimate that in the United States there are about a million people with FH less than 1% know they have it and that means it's important because if they don't know they have it then their kids don't know that they're at risk etc and that's the bad news the good news is that if we didn't know about everybody that have FH and we treated them appropriately then we could their risk of heart disease approached that of the general population so just with very simple treatments medications to lower cholesterol we can make an FH patients risk disappear and that's shown here so people that have FH with drug treatment their morbidity and mortality is that of the general population if you don't have FA if you if you have FH and you're not on treatment then the chances that you die early are very very strong now in the United States we haven't done a good job of doing this but in the Netherlands in other countries we're trying to change this they take a different approach and they use genetics in a very sophisticated way they say if they find one patient with FH they send a nurse to all their relatives they take a DNA sample from the first patient and if they find the genetic mutation that causes that FH they screen all of their relatives for that mutation and in that way they started with 5,000 patients and they identified 60,000 family members that did not know they had FH before and they costs it was very cost saving very cost-effectively saved lots and lots of lives so this is an indication for where genetics can be used right now to improve our ability to diagnose a deadly condition and get people on the right therapy so that's a that the time is now for the use of genetics in FH now put-put FH in your mind palace I want everybody here to leave the room knowing what FH is genetic form of high cholesterol now like I said most of us don't have FH you know it affects about one in 250 probably people most of us have a predisposition to heart disease caused by small mutations working in concert together with our environment to lead to heart disease and it's only in the last five or ten years that we really have started to understand some of these risks and it's really been caused by technological revolutions that allow us to survey the entire genome at a cost that's reasonable and so this all started you know even though the genetic revolution has really started in the last ten years the discovery of the genetic basis of common disease really can be traced back to the 1830s when Charles Darwin went on his famous voyage with the Beagle and released to think about evolution now this genetic revolution ten years ago if you'd ask me how many genes do you know that contribute to garden-variety heart disease and I would have said zero and now that that landscape has totally changed and I'm going to show you a different plot and this plot the most important thing to know is these are all the chromosomes and each of these dots represents a locus a gene that's contributing to heart disease so ten years ago none of this was known now there's at least fifty or sixty genes that we know contribute to heart disease yeah we are learning and this is this is the money that you guys put into the genome project now some of these findings were completely unexpected the top finding we had no idea that this gene was was going to contribute to heart disease other of these genes LDL receptor that makes a lot of sense but so we're finding things that we thought we might find but we're also finding things that were completely novel I mean who would have ever guessed before this all started that the blood group whether you have a blood be blood or o blood does slightly change your risk of heart disease because blood groups are broken down a little bit differently liver can change your cholesterol levels so the genetic revolution is leading to new discoveries and some of these are translating into new genes and I'll talk about that next one of these genes this gene over here pcsk9 is really the poster child for genetic medicine changing the way we think about developing pharmaceuticals and that's uh that's epitomized by by new drugs and and the pcsk9 story is very interesting about simultaneously people in France were discovered that had an overactive pcsk9 it's the enzyme in the blood if you have overactive pcsk9 you have extremely elevated levels of cholesterol you have FH and you die an early heart disease simultaneously people in Texas were found to have under active pcsk9 and then people that had under active pcsk9 they have very low cholesterol levels from birth and they never get heart disease so the risk of heart disease is almost nil and people that had a naturally occurring in activating mutation in this gene and what did the pharmaceutical companies do they said while this is amazing I found a gene that causes if I if I inactivate it causes almost no heart disease and the way it does that is it lowers cholesterol and so there's many pharmaceutical companies that are now developing drugs that will soon come on the market that lower cholesterol by activating by inactivating this pcsk9 so this is a poster child for how the genetic revolution is changing the way we develop drugs and directly leading to therapies that will treat many many people in the room now we know more than ever but we're still at the tip of the iceberg remember that when some some people say you know the genetic revolution is not translated into enough yet and I say we've only been at this for ten years you know give us some time because it's it's already translating into things that are important now what what else is the genetic revolution doing well it's helping us to avoid costly mistakes and this is important we have finite resources and I'll give you the poster child explanation for that so many of you have heard of HDL cholesterol who's heard of HDL cholesterol the good cholesterol okay we all know that many large scale studies have shown that having a high HDL is associated with a lower risk of heart disease but being associated with the lower risk of heart disease is that because HDL causes a lower risk of heart disease or just that the fact that having a high HDL is also associated with people that exercise more eat a better diet you know etc etc is it is it really the HDL that we should be targeting should we be trying to raise HDL levels with drugs or should we be trying to tell people to exercise more to lose weight to eat a better diet and that is something that we never knew the answer to until recently until you know genetics and genomics have helped us with that and I'm going to tell you a little bit about why this is so important so again association does not equal causation and I'll give you two examples for why this is a Bugaboo for medicine so turns out that that reading a newspaper is associated with a very high risk of heart disease and why is that is that because you're reading a newspaper was causing your heart disease you see some stressful news no it's because the people that tend to read newspapers are their sitters but they're also older so nowadays people don't read newspapers you know your grandkids and your kids we read you know blogs on off the off the internet they'd a reason newspapers so the only people that are reading newspapers tend to be older and those people have a risk of a heart attack so Association does not equal causation if I if I tell people not to read newspapers it's not going to decrease the risk of heart attack now the other example is is ice-cream so it turns out that ice cream consumption is associated with risk of shark attacks now does that mean I should tell people not to eat ice cream no because why is that it's because people eat ice cream in the summer months people swim in the summer months and so these things are associated but they're not caused cause causing things so by telling people not to eat ice cream I'm not going to reduce the risk of heart attacks now it turns out that HDL is associated with heart disease but is it causal and it turns out that we can now use genetic information to figure that out we can use genes if HDL is this is causal for low risk of heart disease than genes that raise HDL should also be associated with the lower risk of heart disease and it turns out that's not the case so the the HDL association with heart disease is not causal it's it's just telling us that people that have high HDL are the people that are exercising that are eating a good diet etc etcetera so so basically what would that tell us drug companies is that you know treating giving people drugs that specifically raise HDL is probably not gonna work what we'd rather should be doing is telling people to exercise and eat a better diet and that's been the case not only for HDL but for many other biomarkers so causal biomarkers LDL cholesterol the bad cholesterol is definitely causal for heart disease flavored protein little a some of you've heard about that that's definitely causal for heart disease blood pressure is definitely causal for heart disease etc and if Pfizer or these other companies had known about these type of studies 20 years ago they might not have invested 800 million billions of dollars in creation of drugs to raise HDL levels so the genetic revolution is changing the way that pharmaceutical companies spend their money okay what about pharmacogenetics so pharmacogenetics is the idea that i can take your genetic background and I can look at your genetic background and I can make intelligent treatment decisions about what medicines to put you on now how does it work now now this is the idea of personalized medicine and now now Norman Rockwell didn't conceptualize personalized medicine as being able to change you're here your treatments based on your genes he said of personalized medicine as a doctor that goes to your house and listens to you and takes care of you but nowadays personalized medicine means something a little different so how does it work now well your doctor says well your cholesterol seems to be a bit high and the patient says well what do you think I should do well you should take this medicine and then it kind of patient comes back later and says well you know I got these muscle aches oh well you know that's too bad let's try this other medication well I owe this a little bit better well let's try this other medication so it's this it's this idea that it's this iterative process that that can take a long time and you know it turns out that we might we're not at the point yet where we're using this routinely we might get there in the near future and now who knows who these guys are yes Watson and Crick and you know there's a DNA molecule you remember the DNA molecule was only discovered and I mean really conceptualized and really figure out how it worked in the 50s so it's not that long ago and you can actually see this model in London they still have this model it's unbelievable to see it so how is this gonna help us you know for preventing heart disease well it turns out that statins I mean there's a lot of people that are taking statins and many millions of people in the country they're the most prescribed drugs besides narcotics in the world so amongst the top ten medications that are prescribed in the world lipitor is so Corvis at and simvastatin receivest at and all these are amongst that really the most prescribed drugs in the world but and they're really good but who knows what the major side effect from taking a statin is the major the major adverse side effect is is-is-is muscle aches but the major side effect from statins is actually living along longer life so for people that need them so but 40% of patients with an indication of her statin are not treated and many of those are because they don't want it people don't want to take them because they cause these adverse side effects like muscle aches about ten or fifteen percent of patients have muscle aches now it turns out that there are genetic variants that have been identified that predispose you to muscle aches and they all involve how you or your body handles the statin how it recycles it how it breaks it down and some people with mutations and some of these genes are more likely to develop muscle aches and others and they're particularly more likely to develop with certain statins there's about eight different statins and some of them are more likely to cause muscle aches and people that have these these conditions so if you happen to know your genetic background for this gene then there are recommendations now for what stat you should take now we're not at the point where this is being widely implemented because we don't know the genetic background of most individuals and we still need to do trials to show that it saves money and saves lives to do this kind of stuff but this is the way it might work in the future now what about risk prediction what if I knew your genetic background you came to me and I said how well can I predict your risk of having a heart attack or stroke or something like that currently we based those recommendations many of you came around to the table and we gave you your your wrist estimate based on a statistical model and that was based on work that was done in many studies over the years epidemiologic studies the most widely known is Framingham so who knows what Framingham Framingham was okay so Framingham is a very interesting very important study again paid by taxpayer dollars started in the 50s and 60s and they went to this this town in Massachusetts called Framingham and they basically recruited everybody to be a participant in this trial and they measured everything they could measure the cholesterol the blood pressure the heart disease remember this is what before we knew that cholesterol and blood pressure were risk factors for heart disease and then they followed those people for many many years and they figured out what risk factors led to heart disease and this is how we know this is why we measure cholesterol this is why I'm your blood pressure this is why we measure whether you have diabetes or not and so we can build these statistical models based on on our knowledge of Framingham we can say if we took a hundred people just like you that had your blood pressure your cholesterol etc what is your risk of heart disease now that's not that's not that's telling you about your risk factors but it's not telling you about your genetics I would turn that on its head and say if I happen to know your genetics how well could I predict your risk and it turns out that I can predict your risk just as well as Framingham but I can't predict it any better currently and so are you a glass half-full person saying man I'm we're just at the tip of the genetic revolution and I can do just as well with fifteen risk markers fifteen genetic look low side than I could do with Framingham or are you a glass half empty person and say well Framingham is pretty cheap you know all I need to know is my blood pressure cholesterol and so right now genetics risk score predicts risk just as well as traditional risk factors but not better so again we're not quite at the point where we're using this routinely but in the next ten years maybe we will be okay so those are a few vignettes I'll just have a couple more what about this can we improve health by giving people information about their genetic risk and I love this slide says motivation some people need more than others and here's this shark chasing this canoe right so so we know dr. Marin will talk about this it's almost it's very very difficult to change behavior I mean you guys have all been to your doctor they say you know lose weight exercise take your medicines stuff like this and how many of you truly if you if you really ask your sahami you take those recommendations not not very many and that I there is this idea that maybe people treat genetic information differently maybe they will pay more attention to genetic information they would pay to other information and that's the idea of genetic exclusivity so currently there none of the governing bodies recommend doing genetic testing for heart disease again because there's never been a trial that says if I give people genetic information it makes them more motivated to lose weight and exercise and improve their diet etc and and we are at Stanford asking the question is that really the case or not and so we're in the middle of a trial where we're giving people information about their inherited risk of heart disease and we're seeing whether it alters their behavior and we don't know I think it's gonna be hard to show that people will react differently but we'll see now I don't want to give you guys the impression that genes are at you know we're all products of our genes and in our environment and you know this is what this is the kind of thing that's happening in the world the obesity epidemic you know and so and David will talk a lot more about this this soon but it is true and that that that people that have a higher risk for for obesity for instance have should even even more so probably avoid sugar sweetened beverages so this is a paper that came out in the New England Journal of Medicine and it took people that had a risk a genetic risk a genetic load that predisposed them to higher weight and it divided the group people into four groups those are the highest genetic risk and those are the lowest genetic risk highest genetic risk lowest genetic risk and they asked you know how much soda they were drinking basically and it turned out that the people that had the highest genetic risk that drank soda gained more weight now this is not a massive amount of weight it's a few pounds and so for each individual this is not a huge effect but if you took the whole population of the United States that would be millions and millions and millions of pounds that were gained by people that were now do I need genes to tell me that I shouldn't drink a lot of soda no but at just telling us that and can I blame the obesity epidemic on genes no our genes are the same in the United States now in general as they were in the 1800s that does not explain why the United States is getting more and more overweight but it is it is a contributing factor so so in general we should take our genes and we know that they're they're playing an important role but lifestyle is is playing even more important role you can alter your genetic none of these genes are really destiny but you can alter your future based on on your diet and lifestyle and and David is going to talk a lot more about this but the foundation of good health remains exercise so this is what I favorite slides here's a some people going to the gym taking the escalator to the gym obviously that's a bad idea we should be exercising more we should be eating fruits and vegetables we should not be smoking etc now I'm gonna get a little bit futuristic even more futuristic and look into the future for the last couple minutes the last couple slides and say what is the future hold and and I told you that the first human genome sequence cost 300 million dollars and it took five years to do and so I want to I'm going to show you an example of how cheap genotyping and genetic information is now relative to how you that used to be and so I'm just going to show you this example of a Ferrari Spyder so this is the cost of a Ferrari Spyder and imagine the cost of the first human genome sequence was 300 million dollars and that's equivalent to three hundred ninety-eight thousand dollars you can go down the street El Camino rial and plop down your three hundred and eighty eight thousand dollars and drive away with your Ferrari Spyder now if the price of a Ferrari Spyder had dropped as precipitously as the price of genetic sequencing how much would it cost how much would a Ferrari cost nowadays hundred dollars anybody else two hundred ten dollars okay it turns out that the cost of sequencing has dropped so precipitously that the new price if the cost of the Ferrari had come down that quickly would be 40 cents so the cost of genetic sequencing is is unbelievably you know we can now sequence a whole genome from an individual in about a week for less than a few thousand dollars less than five thousand dollars certainly maybe ten thousand dollars when you add in the cost of interpretation that he goes up but you know 300 million to ten thousand that's a big drop and so what if everybody's genome was available in their medical record and some of my colleagues and I had to various you know I played a small role in this paper when when my name is like down here out of like 50 I'm like down here this was led by one of our you and Ashley and he was approached by one of our colleagues at Stanford who actually is an inventor he invented his own technology to sequence and he sequenced his own genome and then he said well I'm not a doctor what do I do with this so he went to my friend Ewan and he said well what do I do with this and so they you and got together this whole team you could imagine it's it's this is a lot of people spending hundreds and hundreds of hours looking at this single genome and and they found out that here he is and he had a family history of heart disease and it turns out that he was a higher risk for heart disease and he was at low risk of having problems with cholesterol-lowering medications he didn't have a very high risk of having problems he had a high cholesterol and so the recommendation was actually to change his therapy based on his genetic background and so we made him that recommendation based on this and five years later we asked do you think he's taking his cholesterol-lowering medication no so so I mean this is a you know we're still we're still you have to prove that this information can be useful but nevertheless the genetic revolution is getting cheap enough that this could be envisioned I mean a CT scan an echocardiogram all these things cost now a sort of equivalent to what a genome sequence cost and so with great power comes great responsibility so here's the three billion pieces and here's the scientist saying I think I found a corner piece so how do you look how do you look at three billion six billion data points three billion base pairs is six billion data points and so we've also asked the question well what do you do if you take a bunch of healthy people and you look at their genomes how many variants do you do you need to look at and how long does it take and it turns out that if you take individuals that are basically healthy and you sequenced their entire genome you find a hundred variants that you say well you know really I need to look at those cuz those look kind of worrisome but it's not that easy to do that it takes a a person on average about 60 minutes to look at each of these variants so 60 times 100 I mean that's a lot of minutes and then we have to look at those variants and in the end it turned out that one to three of those variants would lead to a new diagnostic test so it's not all strawberry and cream strawberries and cream you know you have to think that there's going to be downstream of costs associated with genome sequencing now despite that we discovered that there were two to six personal disease risk findings that were discovered and one person had a very deleterious mutation in a breast cancer gene Allah Angelina Jolie and that led to this woman being screened much more rigorously with imaging and and things than she was before so that brings me back remember your mind Palace who was in your mind palace well it was Sean Combs and so we now refer to you and as the Sherlock Holmes of the genomes at Stanford and so the and the last few slides are that that this technology is now not being routinely used for the people sort of in this room but we are using it routinely for people that are medical mysteries these are people that have had a condition they don't know what it is they've been to 50 doctors they've had every test that they can and they and they still don't have an answer and in those kind of situations the use of these sequencing is leading to new diagnoses every every day and and we're even occasionally I'm using it in in pediatric intensive care you know there's a case recently where a baby was born this baby had a malignant arrhythmia the sequencing was sent off they found the genetic variant that was causing this and they changed the therapy that the baby had based on this information so the genetic revolution is here it's altering our ability to do all kinds of things and and we still have we still have a ways to go so thank you so much my name is David Marin I'm director of preventive cardiology at Stanford and I'm going to talk about diet cholesterol and heart disease my disclosures are on this slide I have some funding from the NIH and I consult for a company called beyond meat so I'm going to review with you some evidence that links diet and heart disease and review with you what the current guidelines are from the government from the US Department of Agriculture and if time permits make a few comments about making lifestyle change so where where do we get this idea that diet is connected to heart disease and it comes from different lines of research we know from some animal experiments we know from feeding people and studying the effects and some what are called cohort studies like the Framingham project that Josh mentioned and we know from clinical trials so first some animal studies this over a century ago some Russian scientists fed some rabbits high fat high cholesterol diets and then did autopsies on the men and this picture is a color photograph it's actually not from the 1909 publication which had a drawing of the aorta but these are from more recent studies that are very similar a typical rabbit chow diet and these are aortas showing a lot of atherosclerosis atherosclerosis is that process where cholesterol and inflammatory cells are formed deposits inside arteries and basically cause obstructions that lead to heart attacks and strokes depending of course on which arteries are are getting clogged up these scientists over 100 years ago found that okay if they just feed cholesterol alone and take away the fat that that also caused a thorough score in rabbits now we don't do the same kind of experiments in people for some ethical reasons but people have been fed high-fat high cholesterol diets and we have studied the effect on their blood cholesterol hundreds of experiments have been done and they show that when you feed saturated fat to people their cholesterol goes up and specifically their LDL cholesterol goes up low-density lipoprotein cholesterol when you feed cholesterol to people the cholesterol in the blood also goes up but not nearly so much is when you feed saturated fat now to make sure everybody's on the same page I have made some slides to help remind everyone what foods have saturated fat in them and sat they're called saturated because they don't have any double bonds and we get saturated fat in meat in dairy products meaning butter and whole fat dairy products whole fat milk products cream cheese and in tropical oils like coconut oil and palm oil so red meat cheese whole fat dairy and then we have polyunsaturated fats poly for multiple double bonds and so sunflower oil safflower oil corn oil soybean oil liquid vegetable oil at room temperature linoleic acid is the most common polyunsaturated fat that we eat and then there are monounsaturated fats and these are common in nuts in olive oil in canola oil Cotto's so that's where we get our monounsaturated fats you've heard of hydrogenated oils they can be completely or partially hydrogenated this is by forcing hydrogen atoms onto vegetable fats and they create trans fatty acids which you can it turns out it's really good for shelf-life of foods so it keeps them few kind of fresh and they stay on the shelf for a long time you can find them in popcorn and in Donuts and all kinds of pastries french fries and fortunately they have been there are rules now against trans fatty acids in certain industries so they're disappearing from our our foods but they're bad so when you eat trans fatty acids that those raise your LDL cholesterol and then of course there's cholesterol in the diet not to be confused with cholesterol measured in the bloodstream and foods that are high in cholesterol or egg yolks and you get a lot of cholesterol in shellfish so that's just a quick reminder of those foods that have saturated polyunsaturated monounsaturated fat and cholesterol now how much cholesterol is in and it just is an average avocado none educated group you're absolutely right and the point is that plant foods don't have cholesterol you get cholesterol only in animal products animal cells have cholesterol in their membranes plant cell walls no cholesterol so for those of you may not see a whole egg may have 550 milligrams of cholesterol and egg white zero cholesterol cream cheese for a 100 gram portion 120 milligrams and and so on so this is a summary slide of hundreds of experiments showing that when you replace saturated fat with polyunsaturated fat you lower cholesterol and if you replace saturated fat with monounsaturated fat you lower the cholesterol but not quite as much and when you eat less cholesterol you lower the cholesterol level in the blood a little bit and so there's really no debate saturated fat raises your cholesterol and if you substitute polyunsaturated fat or monounsaturated fat he went with you know in foods that would take the place of high saturated fat foods you lower your cholesterol now based on the average age in the room I'm guessing that you know who this man is in the wheelchair that is Ike Dwight D Eisenhower the year was 1955 the event Ike Eisenhower had a heart attack he was six 64 years old he was put on a highly publicized low-fat diet there were twice a day press conferences for weeks and our nation became focused on diet and heart disease in that year there was a guy named Ancel keys those of you who have heard of the K ration he was the K that developed that food ration for u.s. soldiers he made the observation he did he did a lot of those food experiments showing that if you replace saturated fat with polyunsaturated fat you lower cholesterol he noticed in Europe after the war that rates of heart disease were going down because food rich foods were not so available as they were in the United States and American businessmen were having high rates of heart disease and he proposed that there's a connection between what we eat and and getting heart attacks and he made this proposal at a World Health Organization meeting in 1955 and got a lot of criticism and that helped motivate him to perform something called the seven countries study which I'll mention in a moment the guidelines from the US dietary guidelines from those days suggested that we should eat a food from the basic seven food groups and those food groups were green and yellow vegetables oranges and tomatoes potatoes and other kinds of vegetables and then there was a food group for dairy for meat and for breads and then butter and and margarine 's had their own food group those are those were the basic seven and at that time in around 1955 we ate almost half of our calories in the form of fat so 44 percent of our calories came from fat 17 percent of our calories from saturated fat that was our peak the guidelines changed around the time that Ancel Keys made his proposal about the diet heart connection and the food groups were consolidated into four groups we got the milk group the meat group the fruits and vegetables and the breads and then in 1961 Ancel Keys published the seven countries study and the seven countries study was a a it's observation of almost 13,000 men who were apparently well when the study started from sixteen places within seven countries and he found basically that there was a good correlation between how much saturated fat on the x-axis was being eaten in a given country and how high their cholesterol was so this is a pretty strong correlation or Association and he also showed that there was a pretty strong correlation between the I'm sorry let's see on this slide was the correlation between saturated fat and the cholesterol level and on this slide it shows the correlation between the cholesterol level and the chance of dying from a heart attack and it was a pretty strong connection and so if a causes B or a is associated with B and B is associated with C then a is associated with C meaning diet leads to high cholesterol high cholesterol is associated with dying from a heart attack ergo eat a diet high in saturated fat you have a high risk of having a cardiac death and so this really caught on and the American Heart Association in that same year published its first set its first scientific statement on diet and heart disease and that really has permeated our lives and that is you know if you think cholesterol eating cholesterol is bad or eating saturated fat is bad it comes from the these guidelines that were published in 1961 and there's been a lot of debate ever since a lot of studies I'm gonna show you a couple 1970 here's a study looking at what is the impact of feeding a high-fat high cholesterol diet on the coronary arteries of monkeys and is it possible to reverse bad effects a lot of people ask us is it possible to have regression can I remove deposits inside the arteries once they've been established so there were actually 40 monkeys in this study 10 were a control group that got regular monkey Chow 30 were fed a high-fat high cholesterol diet for a year and a half and then 10 were sacrificed they looked at their coronary arteries 20 others continued on a very low-fat low-cholesterol diet or on a high polyunsaturated fat low cholesterol diet and and here's what was found in the the monkeys that were sacrificed after 17 months they had very narrowed clogged up arteries this is where the blood flows in the middle of the artery yeah these are arteries ready for bypass the monkeys had some heart attacks they had really bad arteries on the bottom two sides you see what the arteries looked like for monkeys who are on the so called regression diets you'll notice that the diameter the artery is actually much larger and the passageway is much bigger so there was presumably regression presumably these arteries look like these but then they have the the months and months of the cholesterol-lowering diet so pretty strong evidence that diet causes heart disease in non-human primates and that you can actually improve it with a better diet Time magazine you may remember the cover in 1984 this actually was after the the first successful cholesterol lowering drug study in people who had high cholesterol they were given drugs that we don't use that much anymore today they're called bile acid binding resins but the connection that the public made and the time magazine made was don't eat eggs and bacon because it raises your cholesterol and it'll cause heart attacks so that year the Dietary Guidelines changed and they said don't eat so much fat don't eat so much cholesterol particularly avoid saturated fat and eat a lot more carbohydrate and the American public got the message so we we ate in those years a lot less fat and and we really dropped our total fat consumption our saturated fat consumption and we increased our carbohydrate content and what happened is really remarkable story look at the the colored states this the the the pale blue is less than 10% or obese the darker blue 10 to 14 percent and the colors will change over the decades I'm going to show you now this is what percent of our country following a higher carbohydrate diet became obese and it is remarkable how obese our nation has become this is not a genetic evolution it is all environmental even in our healthy state of California this is 20 to 24 percent obese in the year 2010 so we got the message to cut down on fat increased carbohydrate we ate a lot of simple carbohydrate meaning refined and sweetened foods bad Atlantic magazine you may remember this covered Thomas Moore in 1989 there's been a lot of controversy if the guidelines that we are given are right and there are people who have made a lot of money selling alternative ideas this quote says diet has hardly any effect on your cholesterol level not true drugs that can lower it often have serious or fatal side effects no I mean rare rare serious not fatal side effects there is no evidence at all that cool lowering your cholesterol will lengthen your life at the time true for people without any history of heart disease no longer true with the advent of statins and studies that have shown long-term follow-up so Time magazine also changed its cover this is after a study from Harvard showing that one egg a day will not increase your risk of heart disease if you don't have diabetes that that was true for people with diabetes higher egg intake is actually was associated with an increased risk of heart attack and stroke and here's Time magazine again last year changing its story eat butter it's not really a faithful interpretation of the evidence but the evidence is confusing enough that and there enough people here in the room suggesting we need to try to understand better what is the truth what what is the evidence so yeah this is a summary slide for you replace saturated fat or replacing saturated fat with polyunsaturated fat is good replacing it with monounsaturated fat is good and replacing it with sweets is bad I mean I'm trying to I'm trying to really make it clear this is this is a picture of the Mediterranean diet and this is one of the dietary patterns that clearly is associated with better health there's also another diet pattern that's similar it's called - Dietary Approaches to stop hypertension they encourage nuts like the Mediterranean diet low-fat dairy products these kinds of diets lower blood pressure they lower cholesterol and most importantly they lower the risk of heart attack and stroke pretty med was the name of a study in Spain using the Mediterranean diet in healthy people and they showed it it's a little the rate of heart attack and stroke in healthy people meaning no history of heart attack and stroke the rate is is really small and you needle thousands and thousands of people to prove a benefit but that's exactly what was done in the Preti Med study this is a blow-up showing the control diet versus a diet that's enriched with extra-virgin olive oil or with nuts the Mediterranean diet beat the usual diet it helped prevent heart attack and stroke in a great study that was done in France in Lyon men who had a history of heart attacks were randomly assigned to the American Heart Association diet or Mediterranean diet and they found that there was no difference in the cholesterol levels between the in people who were taking the heart association diet versus the Mediterranean diet no difference in the cholesterol levels but there was a big difference in the risk of having another heart attack or a stroke or dying and so this is you want to you want to be honest on the top here and this is everybody is alive at the beginning of the study and and the lower you go the greater the event of having in this case cardiac death or a non-fatal heart attack this is the American Heart Association diet and this is the Mediterranean diet so there's pretty good evidence that the Mediterranean diet is a healthy way to go this is a summary slide showing again heart attack event rates you you want them to go down and this is when you replace saturated fat with polyunsaturated fat the rate of heart attack goes down so the Dietary Guidelines say eat a diet that has lots of fruits and vegetables whole grains seafood legumes nuts and low and nonfat dairy products you've probably heard all this we have dietary guidelines that were just released last week there's a comment period before they become official for I think we have three months to make comments yeah I've scanned it it's 570 pages really dense science it's really well written and this is basically what they say along with don't eat 3 s's reduce your intake of saturated fat sugar and sodium I could think of some kind of slogan to keep it simple but these things you know they're gonna be people who have covers on an Atlantic magazine or time but these things are very consistent and they have been over decades now so what do you think the top sources of saturated fat in our diet butter beef baked goods fast foods okay so you guys are right this is a little hard to see but I'm going to read the top five regular cheese pizza grain-based desserts also known as probably cake and cookies dairy desserts ice cream and chicken and chicken mixed dishes also known as probably chicken tenders and fried chicken kind of thing in a fast-food restaurant yeah and it goes on with sausage Franks burgers etc the very brand-new guidelines from the USDA have something that is sort of surprising to many of you and that is that cholesterol is no longer restricted from the the guidelines say that literally available evidence shows no appreciable relationship between consumption of dietary cholesterol and serum cholesterol cholesterol is not a nutrient of concern for overconsumption I would say that's what the evidence shows and so you know cholesterol is connected to saturated fat but it can also be disconnected for example when you eat seafood crustaceans shrimp and lobster you're getting very little fat when you eat those it's mostly cholesterol and it really doesn't have much effect on your serum your your blood cholesterol it's harder to separate cholesterol from saturated fat in meat for red meat for example so that's something new that you may have read about in the news and that's what the evidence supports you know I want to leave plenty of time for Question and Answer so I'm gonna stop here and say that and ask Josh to come up and we will be happy to take questions from this from up here the podium I am please please remind people to write out their questions and to fill out evaluation cards so let's have a free-for-all and we have mics on the chairs thank you very much okay so while we're waiting for questions to make it up to somebody want to stand and yes what about goat cheese thanks a lot yeah so I I don't know a lot about goat cheese the I'm not gonna I'm not gonna turn to Josh even though I unless you you would like to feel that question okay goats are I have a good friend I didn't put it on my disclosure slide I have a good friend who has a goat farm and I'm gonna have to ask him about that I'm sorry cuz I don't know if there's any particular benefit from goats as compared with with cow milk cheese so I would I would go with moderation as a general rule but I don't I don't have a a good answer Josh have you got a question there what about wine okay so there's a lot of attention about red wine in particular which has something called resveratrol which may have some beneficial effects on the artery wall that here's the thing about alcohol if you drink moderately you're at a lower risk of dying from heart disease than if you don't drink at all that's study after study shows that drinking is healthy for your heart if you don't overdo it are there any special attributes from red wine as opposed to any other form of alcohol beer hard spirits not in large studies it just if you drink one drink a day for a woman not to exceed two drinks per day for a man it they're good outcomes what about coffee good news for coffee drinkers the new guidelines actually say coffee is good for you and specifically it's good for your heart so don't worry about doing you know if you're avoiding coffee because you think it's bad for your heart don't worry about it the evidence is just the opposite now if you drink a lot of coffee and you get a lot of caffeine and you have palpitations or it makes you jittery then just use common sense and avoid alright one of the questions is is the size of the LDL particles an important test and this is a good question so when we talk about LDL cholesterol we're talking about the concentration of the LDL cholesterol in the blood there are many ways of assessing how much cholesterol is in the blood one is how many particles there are one is what is the cholesterol concentration etc and it turns out that at a very broad level they give the exact same information so have if you have information about one of those tests you have everything that you need to make an informed decision and for historical reasons going we have much much more information about cholesterol concentrations and so that is for the test that's favourite with all the large epidemiologic studies were done with cholesterol concentration so in general that's the measure that's that's favored if we were all starting from scratch and we had to do it all over again an LDL particle number chuckle size was the same cost and we had the same evidence then that might be different but in general the additional information that you get from LDL particle number particle sizes it's not useful what about coconut milk yeah you know the story with coconuts is kind of interesting it has made the list of tropical oils coconut oil that is rich and saturated fat and and worrisome but it looks like coconut oil raises HDL not LDL and coconut milk mmm may not be so bad for you after all so you know the more we learn the more these rules from the past get obliterated and so the latest on coconuts it not so bad all right how about this three-part question vegetarian versus Ornish versus paleo diet do you want to take that you're so good at the diet question I'm handling them all the year all right well whoever asked if you don't mind whoever asked about the paleo could you give a quick description of what you are thinking when you say paleo no grains okay so a vegetarian diet can take many shapes you you you've heard of lacto-ovo vegetarian or vegan I mean those are not sentient synonyms vegan is pure vegetarian no animal products at all so no eggs no dairy then there's lacto-vegetarian would be dairy plus vegetarian and lacto-ovo would have the egg a vegetarian diet can be extremely healthy if it includes a lot of whole grains fruits vegetables it may be ideal although it's it doesn't have fish and fish twice a week is associated with a reduced risk of dying from heart disease you can eat a vegetarian diet and be very unhealthy it can be just you know you can just eat muffins and white bread and macaroni and cheese and have a really unhealthy diet so it depends on how you define if you're eating Whole Foods and they're plant-based that's that's really probably one of the best diets that you could eat Paleo diet you know the average life expectancy in the Paleolithic era was you know maybe 25 to 35 years and people didn't get old enough to get heart disease so I would say beware of eating a really high meat diet when we have so much evidence that it's bad for you and not a whole lot of evidence that it's it's good for you the last thing I'll say about this is that when you compare an Atkins diet with let's say a Mediterranean diet for weight loss they're they're the same in terms of the ability to lose weight it boils down to how many calories you eat this has been done I had some slides on it that I didn't show this morning so beware of the long term metabolic effects of eating a very high fat or high-protein diet there there's no long-term evidence that this is a healthy way to go all right I'm going to feel these to let you off the hook for a second what about sugar cane sodas in moderation so the sugar Wars there's lots of press about is high fructose corn syrup or pure cane sugar or whatever is any of these preferred and and honestly the the evidence is that simple carbohydrates like sugar high fructose corn syrup are handled by the body in essentially the same way and there's really no good evidence no strong epidemiologic evidence that that the type of sugar that you're eating actually matters so it's more the amount of consumption of simple carbohydrates can you talk about blood types and heart disease that's probably my fault so it turns out that if you're born with a certain blood type a versus B versus O that there are very very very tiny genetic effects on your risk of heart disease mostly because the body recycles blood cells that are a versus B versus O slightly differently and so the cholesterol levels and those individuals are slightly different but there is no evidence that's for instance changing your diet based on your blood group will have any impact on your risk of heart disease every every the recommendations for everybody remain the same no matter what type of blood group you have see calcium supplements what about calcium supplements that's one thing what about pumpkin pie in moderation so yeah again these things come these things come we're not up here to try to dissuade you from occasionally eating a piece of pumpkin pie but remember that that every choice that you make has very small implications going forward so you know pumpkin pie if you put in lots of simple carbohydrates like simple sugars and lots of butter then it's gonna be slit slightly raise your cholesterol level but that might be outweighed by the good time that you have on Thanksgiving I love pumpkin pie in case anybody wants to I don't see it but here's a question what about fish oil supplements I have a lot of patients who take omega-3 fatty acid supplements because they just out of curiosity how many of you actually yeah Wow a lot of you ok why because you don't eat fish because it thins the blood okay so here's here's what fish oil does in high doses it lowers blood triglycerides that's for sure and III have a fair number of testimonials that it helps with arthritis should people who don't eat fish take fish oil supplements I don't think we know the answer to that I will say that there have been several studies in the last few years looking at fish oil supplements versus placebo and heart disease events meaning heart attacks no benefit really disappointing but no benefit so you know it's clearly helpful for people who have high triglycerides meaning like triglyceride level over 500 taking fish oil supplements in a high enough dose will lower triglycerides what kind of dose you need a high dose I mean at least 2,000 milligrams a day of EPA and/or DHA that will lower triglycerides you take a single supplement usually has maybe 350 milligrams of EPA and DHA in it so that segues into there's so several questions about triglycerides one of the dangers of triglycerides and how do we control them so triglycerides are are definitely we know causal for heart disease now so very elevated triglycerides the normal level for triglycerides is less than 150 milligrams per deciliter there are many reasons that triglycerides can become elevated some people have primary genetic forms of very high triglycerides and and those type of people fish oil or other supplements are usually needed but most often high triglycerides are an indication of an insulin resistance or sort of pre-diabetic State and in those in those individuals the most important things that you can do to lower triglycerides are things like exercise more you know 45 minutes a day five or six days a week lose moderate amounts of weight even five to ten pounds can have dramatic effects on triglyceride levels decreasing simple sugar intake decreasing alcohol intake all those things can lower triglycerides and it is going to be important medications to lower triglycerides have been a little bit disappointing and they're really usually reserved when triglyceride levels are very elevated as a primary form of therapy so it's not until triglycerides are over 500 that we would usually consider medications to primarily for triglyceride lowering so it's mostly diet and lifestyle what do you really think of statins okay so this is always a question you know I don't get any money from statin companies all statins are generic now essentially all statins except receive a statin or crest or a generic so the drug companies are really not making a lot of money on statins statins are based on naturally occurring mold products that were discovered in Japan many years ago they unquestionably caused muscle aches and a small percentage of people like 10% to 15% of people but they also unquestionably lower LDL and lower heart disease risk they're a godsend for people that have genetic forms of heart disease like FH and in the very very large unbiased trials have clearly decreased risk now the decreased risk from statins is also core is also a relate related to how high the risk was to begin with so the higher the risk is to begin with the better the benefit of statins so if you've already had a heart attack or you already have diabetes or you already have cholesterol that's through the roof then then statins are extremely beneficial if you're low cholesterol low risk then they're probably a less benefit the the one of the things that I talked about earlier was was was is LDL really causal for heart disease you know I think some of you probably seen you know certain celebrity doctors hosting programs on TV where they say you know LDL this is not causal for heart disease and I think that's clearly false and and statins are probably the most effective way of decreasing that risk what about juice well fruits and vegetables should be part of every healthy diet is it possible to overdo it probably I don't know if part of that question had to do with oh can you replace wine with grape juice that's a good question you know with grape juice you can have the same antiplatelet effects platelets platelets are the things that make your blood stick and aspirin is an anti platelet one of the things that you get from wine from grape skin is an anti platelet effect you can get the same thing from grape juice but obviously you don't get quite the same thing with because there's no alcohol I don't know if that was really what the what the question was about they're not the same but they're similar yes okay okay an issue for people who do not drink alcohol and for children who might want to have the benefit that alcohol can can okay so I was it I don't think the evidence is that is there to say that you can replace that yeah juice it just isn't the same I mean our graves but there there's a little overlap when it comes to grapes and wine there's a little overlap but but it's not much and the one I know about is the effect on platelets that's beneficial all right I'm gonna handle two more question about statins and then I'm gonna throw it to David for oat brain and flaxseed so what about coq10 for printed preventing side effects from statins and and and this is something people often do and it's one of those things where we don't have good evidence one way or the other the large trials of supplementing people with kohutek to prevent side effects from stands have not shown benefit does that mean that they don't have benefit in an individual patient no but there's no large-scale evidence to support them one way or the other do what are the other side effects from statins do statins cause dementia do they cause diabetes and and and the recent evidence does support that statins cause a slightly increased risk of diabetes that risk is greatly outweighed by the benefits of in people that really need to take them by a decreased risk of heart disease but they do have a slight increased risk of diabetes especially in those that were near diabetic to begin with do statins cause dementia these studies have are much more conclusive in that in large-scale trials there's no evidence that they caused increased risk of dementia some people say that in an individual basis they impair their memory but that that again and very large-scale trials has not been borne out if anything they reduce the risk of cerebral vascular disease and stroke and stroke is a major cause of dementia so again the balance of the evidence supports that they decrease the risk of dementia through decreasing stroke and that they have a slightly increased risk of diabetes and stay tuned because the NIH is funding a study looking at the effect of statins on cognitive function given the change in the ranking of shellfish and cholesterol with the new guidelines is the following a great good or poor meal in the Mediterranean diet spectrum and I think that says hardened wheat or its wheat pasta durum wheat durum wheat Josh's from North Carolina durum wheat pasta shrimp and olive oil you know I think that that's a good Mediterranean meal if you have to watch your carbohydrate intake because of diabetes then you should moderate the amount of carbohydrate or the dose of insulin but whole grain pasta shrimp and olive oil great is oat bran or flax seed helpful to lower cholesterol oat bran yes how much a little depending on how much you eat but oat bran is a water soluble fiber will lower LDL cholesterol a little we're talking about if you eat a cup a day it'll lower your LDL cholesterol maybe by five percent so a statin at a good dose will lower it in the 30 to 50 percent range it does flaxseed lower cholesterol not to my knowledge flaxseed will is is a precursor to some long-chain fatty acids called omega-3 fatty acids and so you can get omega-3 fatty acids from eating a lot of flaxseed but not so much cholesterol-lowering all right I think we'll have time for two more questions we won't have time for everything okay people if they cannot take a statin because they have muscle aches are there alternatives like zetia or ezetimibe it turns out there are and the original cholesterol-lowering medications were bile acid binding residents and those are still available and they lower cholesterol about ten or fifteen percent again statins lower cholesterol thirty to fifty percent as that am a Bizen other-- drug it's also known as zetia it also lowers cholesterol by ten or fifteen percent and there was a very important recent trial of about fifteen thousand people that they followed for about ten years that was published a few months ago and it showed that not only does it lower cholesterol levels but it also reduces the risk of heart attacks and strokes and so in people that can't take statins it is an alternative but it's not quite as effective what about calcification of blood vessels so the thing about a Carosa switch is this process by which the blood vessels become full of cholesterol and inflammatory molecules it proceeds in the same progression in every individual we known from autopsy studies from army people that have died in the Army in in their 20s and 30s and 40s we know from autopsy studies of trauma victims that we all have heart the start of atherosclerosis is starting in all of us in our 20s and 30s and in some people that progress is much more rapidly than others we don't exactly understand all the ways the end-stage the LAT in the last stage of atherosclerosis development the plaques actually become calcified so if we find that there are calcified plaques in an individual it means those plaques have been around for long enough that they've become calcified and it also tells us that there are probably other plaques in there that are around that are not been classified so it's a marker a burden of disease certainly if we know about calcified plaques we want to treat patients aggressively for that I would mention that there is a way to find out if you have calcium in your coronary arteries it's not covered by insurance generally it's called a coronary artery calcium scan it's a CT scan you can get it at all the healthcare facilities in the area and it will tell you if you have calcium in your coronary arteries or not if you do have calcium you have some amount of atherosclerosis and that might make the difference between deciding to go on a statin or not go on a statin or to take aspirin or not take aspirin I think that our time is up we do have a few more questions but I don't think we'll be able to offer at all well we'll stay around for a little bit thank you all very much for coming you you

Channel: Stanford Health Care

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Keywords: Stanford, Stanford Hospital, Bay Area Healthcare, Medicine, Medical Science, cardiology, heart disease, heart disease prevention, tips for heart health, diet, cholesterol, heatlhy heart, cardiovascualr disease, familial hypercholesterolemia, genetics and heart health

Id: e3H3SV7F2I4

Length: 83min 34sec (5014 seconds)

Published: Mon May 18 2015