 Medicine for the Layman, a lecture series presented by the Clinical Center of the National Institutes of Health. The subject of this lecture is cholesterol, diet, and heart disease. The speaker is Dr. H. Brian Brewer, who is Chief of the Molecular Disease Branch National Heart, Lung, and Blood Institute. Dr. Brewer. This evening we're going to be discussing cholesterol, and as Dr. Liss had mentioned, it's a hot topic, and we'll try to review tonight what we know about cholesterol and what you've undoubtedly been reading, what is good cholesterol and what is bad cholesterol. And what we know now about the process of hardening of the arteries or atherosclerosis and what we know now are risk factors for the development of hardening of the arteries and heart disease. Now it's very clear that everyone, I think, has heard about cholesterol, and there is clearly a lot of information about cholesterol, but I'd like just briefly in the beginning to show you what cholesterol and the other major lipid triglyceride are and some of the foods that contain them so that you can become aware of what these particular lipids are. This is cholesterol. Cholesterol is a complex heterocyclic compound, as you can see here, which is present in a variety of different foods that we eat and is present in the body in several different organs, and in both the cell membrane of the organ, and this structure, cholesterol, is also involved in many of the other different compounds of the body such as the steroids from the adrenal gland and the sex hormones. So this is a heterocyclic compound that is made both by the body and taken in a variety of different foods that we eat. Now cholesterol, which is present principally in many of the food products and also in several of the different types of meats that we eat, and normally the cholesterol in the average American's diet, which we'll come back to later on, varies somewhere between 600 and 800 milligrams per day, and if you are going to eat what people would now consider a better level of cholesterol, it's about 300 milligrams a day. Well, you can see from this list of the amount of milligrams of cholesterol that are actually in the different food stuffs. If you have two eggs in the morning, you've already exceeded what the usual amount of cholesterol that is recommended now that you would take. If you have two eggs in the morning and go out to Gino's at lunch, then you're in, if you start counting up the amount of milligrams of cholesterol that you take in, you can see that it'll mount up very quickly in the variety of the other food stuffs as you can see here. Give you an idea of what amount of cholesterol that we're talking about that really can be in the diet and particularly in a diet when one is not looking or not thinking about the amount of cholesterol that's actually in the diet. There's another major lipid that we eat every day which really hasn't received the publicity of cholesterol and that's the triglyceride molecule and triglycerides. In reality, this is the kind of fat that you see when you're eating your steak and cutting off the fat and this is the lipid that is in your fat cells and stored in the body and this is called triglyceride. Triglyceride is a molecule which has a backbone of glycerol which is shown here and then fatty acids which are attached to the triglycerides at these points. Again, there's been a lot of discussions over the last one or two years and really dating back as long as 10 to 15 years ago about the type of fatty acids that we're eating that is polyunsaturated versus saturated fatty acids and these are the fatty acids that are attached onto, for example, these triglyceride molecules. Again, if you consider how much fat that we take in the form of triglyceride most Americans are taking anywhere from 60, let's say 80 grams of fat per day in their diet and if you would reduce your fat intake to what again appears to be the more ideal level that is about 30 to 40 grams per day you can again see about how much fat that you would get from individual portions of the foods that are listed here including hamburgers and frankfurters and so forth. So if you go to McDonald's and get two eggs in the morning and you go to Geno's at lunch and then Roy Rogers on the way home you can see that the amount of lipid that you can take in in a given day can be really quite high and as you I think all know that the amount of fat intake and cholesterol that the average American takes in is really enormous compared to other countries and we'll come back to it, some countries are higher and it appears to correlate with the degree of cardiovascular disease that these different populations have. Now the two major lipids that we've talked about, cholesterol and triglyceride are taken in the body and have to be transported around in the plasma. Now neither one of these two lipids that is either the cholesterol or the triglycerides are soluble in the plasma or serum or in the blood and so they have to be transported around in what we've shown here as a boat. So they have to have a vehicle to transport our friends now, cholesterol and triglyceride around in the plasma to transport them to the various sites where they're going to be utilized. The boat here has a protein which is another component and this boat which is made up of these four components is called a lipoprotein. So the cholesterol and triglyceride are not free in the plasma but are transported around in the form of boats which carry them and these boats are called lipoproteins and the protein moiety here is shown to be the captain and it's directing the lipoprotein to go to the various different tissues so that the cholesterol and triglyceride can be transported around to the different sites which they'll be utilized. Now if you would take a sample of blood from an individual and then look at the blood under a powerful microscope or by electron microscopy what you would see is a collection of particles and these are our boats. These are a variety of different sized particles which are lipoproteins which range from molecules that are almost a thousand angstroms to ones that are very small. And we have a polydispersed collection of the plasma lipoproteins that are circulating around with the major lipids cholesterol and triglyceride being transported to different sites in the body. Now with this different polydispersed collection of lipoproteins we can begin to separate this group of lipoproteins and one method to do that is to separate them by their size and as you can see they're really quite heterogeneous in size and so if we separate them by their size and hydrated density we see that there are basically four different types of lipoproteins that we have in the plasma. There are groups of particles which are the largest particles that you saw which are termed chylomicrons. The next largest group of particles are called very low density lipoproteins or VLDL. The next group of particles are low density lipoproteins or LDL and the smallest group of particles are called high density lipoproteins or HDL. Now if, as I'm sure that several of you have done over the years, someone measures your plasma triglycerides or measures your cholesterol, what they're measuring is the cholesterol moiety which is shown here in yellow on all of these different particles and the triglyceride again is measured on this particle and this particle when you measure the triglyceride level in the plasma so you're measuring all of the particles and the two lipids, the cholesterol and triglyceride that are in the four different boats that are going around in plasma. Now in general approximately 75% of the cholesterol in the plasma is attached to the low density lipoproteins. Approximately 15% is attached to the high density lipoproteins and the other 10 to 12% are attached to the chylomicrons and very low density lipoproteins. Now we'll come back to this in a moment and this is important because I'm sure some of you have been reading in Time Magazine or Reader's Digest about the different types of lipoproteins that are there and good cholesterol and bad cholesterol and it relates to the cholesterol that's on these different groups of lipoprotein particles. The chylomicrons and the very low density lipoproteins contain essentially all of the triglyceride in the plasma so that all of the triglyceride is carried in these two types of particles and the cholesterol on all four but approximately 75% of it on the low density lipoproteins or LDL. Now what are the function of these four types of lipoproteins and basically how do these lipoproteins fit together in a scheme of transporting cholesterol and triglyceride around in the plasma and what are the disease states associated with these different types of lipoproteins? Now as we mentioned that if we start from the plasma that the food that you've eaten contains cholesterol and triglyceride and it goes into the intestine and is present in the intestine in the form of cholesterol and triglyceride it is absorbed through the intestinal wall, the apoproteins are added as part of the boat and the phospholipids and basically we have the production of a lipoprotein particle that is carrying the cholesterol and triglyceride from the diet. And this is shown schematically here is from the intestine now we have particularly the triglyceride and the cholesterol which are transported into the plasma on the chylomicron. Now the chylomicron's major function is to transport the dietary cholesterol and triglyceride to other sites where it can be utilized both for energy sources and as a supply for cholesterol for other cells. So this is one of the first of the particles that we'll now discuss and that's the chylomicron so that after you've eaten the meal about three to four hours later you get a large increase in the amount of chylomicrons in your plasma and actually if you would draw a plasma sample at that time you can see that it's cloudy and it's cloudy because of these very large particles that are transporting the dietary cholesterol and triglyceride into the body. The body can also make cholesterol and triglyceride it gets a certain present from outside of the body and a certain present from the inside of the body and one of the major sites of synthesis in the body for cholesterol and triglyceride is the liver shown schematically here and so that the liver also makes particles which are very similar as we've seen to the chylomicron and the very low density lipoproteins both of these containing a large amount of triglyceride and some cholesterol. So the function of the very low density lipoproteins is the transport of endogenous cholesterol and triglyceride as the chylomicrons are transporting exogenous or the food stuff cholesterol and triglyceride that we've eaten. Now these two groups of particles contain a large amount of triglyceride as we've seen and a certain amount of cholesterol and these boats circulate around in plasma and at the point if you now look at what happens as you go around in the plasma basically we have an enzyme which is called lipoprotein lipase and this enzyme is able to metabolize the triglyceride and to cleave off the fatty acids from the triglyceride and basically we have a metabolism of the lipoproteins where these particles were large particles containing a lot of triglycerides where they undergo metabolism where they lose their triglyceride and you have a formation of what is called IDL or the intermediate density lipoprotein finally to the low density lipoprotein or LDL. Now the fatty acids that are metabolized off of the triglycerides by the enzyme lipase can be utilized for energy or they can also be re-synthesized in fat cells to be stored as energy in the form of fat in the peripheral cells. This enzyme lipoprotein lipase is attached to on the wall of the blood vessels so that this metabolism where you have triglycerides being cleaved off of these particles gradually makes a particle smaller and smaller and you have basically transported the triglycerides around to the body and utilized them as an energy source and also as a storage for energy in the rest of the body. Now the cholesterol is still in the same boat. It hasn't jumped out like the triglyceride has and as it goes down this cascade from VLDL to IDL the LDL cholesterol is now in the low density lipoproteins or LDL and as you saw in one of the earlier slides the major lipid in the low density lipoproteins in terms of cholesterol and triglyceride is the cholesterol. Now the cholesterol which is in the form of LDL then is gradually taken up in the peripheral cells such as the blood vessel wall, the smooth muscle cell, the fibroblast, the muscle cells and a variety of other cells in the body and what the low density lipoprotein does is supply the cholesterol for the cells so that they do not have to make their own cholesterol. So we've gone down the cascade where we have had a cycle from the liver transporting the cholesterol through this system to the peripheral cell and the peripheral cell uses the cholesterol for making membranes, other functions that it has and doesn't have to make its own endogenous cholesterol in the peripheral cell so it acts as a storage during the process here that is being transported and then LDL is metabolized as shown here. Now you can see in this pattern of cascade from VLDL to LDL that basically it's going in one direction that is we're putting cholesterol in for example a cell in the wall of a blood vessel so that we have now through a variety of different experiments and a variety of different labs around the country identified that the cholesterol is being added to the peripheral cell by the low density lipoproteins. As you can see we've got one half of a cycle here and it is now as a result of a large number of studies become clear that at least one role for the high density lipoproteins may be to transport the cholesterol from the cell back to the liver so that you have a pool of cholesterol that's in the cell and we have the high density lipoproteins which then transport the cholesterol back to the liver because the liver is the only organ that we know of thus far that can really get rid of the cholesterol. So what we have now as a cycle where we have the cholesterol being taken to the peripheral cell and one of the functions now postulated for HDL is to take the cholesterol back from the peripheral cell to the liver where you can get rid of the cholesterol and with this system now I think it will become clear of what individuals have now been talking about in terms of good cholesterol and bad cholesterol. Good cholesterol is a cholesterol that is attached to the high density lipoproteins that's basically coming in this portion of the cycle taking the cholesterol out of the cell back to the liver where it can then be taken out of the body. The cholesterol that's bad cholesterol is a cholesterol associated with the low density lipoproteins which is putting cholesterol basically into the cell and this is the cholesterol that was writing on the black horse and the article and the reader's digest and this is the cholesterol that's writing on the white horse in terms of HDL. As a result of this you can see that there's a great deal of interest in what things tend to elevate the low density lipoproteins and therefore the cholesterol and the low density lipoprotein particles and the things that will tend to elevate HDL cholesterol because they tend to be a negative risk factor and we'll come back to in a moment that the low density lipoproteins are the cholesterol that is associated when you have a high cholesterol and you have an increased incidence of cardiovascular disease this is a positive risk factor whereas elevations of HDL cholesterol have now been shown to be a negative risk factor and we'll return to this in a moment. Now that we've briefly reviewed the lipoproteins and the lipoprotein particles that are transporting the cholesterol and triglyceride the question is what happens when this system does not work appropriately and we have basically cardiovascular disease or there are several names for it atherosclerosis, arteriosclerosis, or hardening of the arteries. These are processes which are well known I think to everyone and are associated as a major cause of cardiovascular disease in the American population and that and cancer represent one of the major causes of death in this country as well as around the world. Now what really is going on with atherosclerosis and what really is the process? If this is a normal artery that's shown here on the left basically this is a nice division or bifurcation of the artery and there's no impedance to blood flow as the blood goes along the artery and an artery that has atherosclerosis or hardening of the arteries basically you have a narrowing of the artery as shown here in which there is a gradual narrowing of the artery where there is a decreased amount of blood flow that can go through a given artery and the cells in this artery are filled with cholesterol and if we now take and look at a side of what would be happening in the artery we see that this is a normal artery here and an artery with atherosclerosis or hardening of the arteries it gradually gets filled with cholesterol laden cells some cells die and the reason that it's called hardening of the arteries is to actually get calcium deposits in the cholesterol rich area on the vessel so that it actually becomes calcified very much like bone and that's where the term hardening of the arteries came from or calcium in the arteries you have a breakdown of this vessel so that a lot of the lipoproteins which are in the plasma come through here you have an increase in the number of cells particularly the smooth muscle cells that line the wall of the blood vessel and you have a lot of scar tissue that can form so the effect of atherosclerosis is to gradually narrow the artery and to impede the blood flow now I'm going to show you a series of slides which will put the process of atherosclerosis in basically what happens in a period of probably in normal man over a period of about 20 years and this is a normal artery and this is a coronary artery one of the arteries that supplies the heart with its blood supply and it's important to note that atherosclerosis does not have one single cause but has a variety of different causes and several different disease processes end up with atherosclerosis and the other important point is that atherosclerosis takes a long time it's a process that goes on for years and I think is probably several of you have read when they looked at autopsies of Korean war veterans which had been killed in action and they found that approximately of those American soldiers approximately 30% of them had a 15% narrowing of their coronary arteries and their average age was 22 so this is a process that takes years to develop and gradually will accumulate in the narrowing of the artery and so as this artery gradually now begins to fill up with the process of atherosclerosis you begin to get calcium deposits, scar tissue in here and the artery gradually begins narrowed this process continues over the years and the artery begins again more and more compromised in its ability to carry blood flow through the artery to the point that you see that it is a completely occluded so that you basically have very little blood flow only this tiny rim is carrying now blood through this coronary artery so the process of atherosclerosis you've had a gradual narrowing of the arteries and this process which takes several years gives you symptoms in the areas where the artery has been narrowed so if we look at four major sites where the arteries may get narrowed of which undoubtedly several of you have heard of individuals that have had the various problems you can have narrowing of the arteries connected with the heart you can have narrowing by the process of atherosclerosis of arteries leading to the brain and also narrowing of the artery in the leg and if we now look at the heart basically the heart has a series of blood vessels which supply its blood supply to the heart just like any other muscle has and the heart really is just a typical muscle that requires a blood supply and is dependent upon that blood supply even though it itself is pumping the blood around the body so these are the two major coronary arteries that are shown here that are supplying the blood to the heart as you've seen if we would then narrow a artery and obstruct the blood flow in the heart we would gradually get an area which has been deprived of its oxygen supply and you would get an area which did not have enough oxygen and you would basically have what is called a heart attack if that isn't a complete occlusion as we saw in the final set of four composites then you can have an area where the muscle has actually died and a heart attack or a coronary thrombosis are basically an obstruction of the blood supply to the heart through the process of atherosclerosis if we now would take and put dye in one of the coronary arteries you can actually see a narrowing in a coronary artery by the process of atherosclerosis or what's called a plaque and you can see this is now the coronary artery which is coming down here which is filled with the contrast material and basically the heart is sitting here and you can see by this arrow the point where the artery has been narrowed by an occlusion or a partial occlusion by the process of atherosclerosis so if a blood vessel to the heart has been narrowed basically the symptoms you get as you well know are pains in the heart called angina and when that artery becomes significantly compromised you have a heart attack or a coronary thrombosis now if the vessel that is principally narrowed is one in the leg this process can occur very gradually and you get the symptoms when an individual is walking where they get pain in their leg and if they stop for two or three minutes the pain will go away and you get what's called intermittent claudication that is again the problem is due to the fact that you can't get enough blood supply through the leg and as the muscle needs more oxygen as you're walking it will require more oxygen you can't deliver it and you'll get pain which is basically the muscle is telling you that you don't have enough oxygen going to it now this process is a very slow one as we've talked about and what happens the reason that this leg doesn't die is that you gradually have an increase in what are called collateral vessels because this process occurs very slowly and you get vessels which will transport the blood around the blockage if you have this blockage acutely such as if you would throw a blood clot into your leg you don't have the time for the collateral to develop and that's why basically the limb then is in great peril because you've not had the long process where the collateral circulation will occur and therefore with an acute obstruction of an artery it has to really be removed or you'll lose your leg if you look now again with an x-ray and look at the vessel this is the bone this is the leg here is basically the vessel which is going down here and continuing on here and you'll see that the contrast material basically doesn't really get there to there except by very fine collaterals which are getting the blood supply further on down the leg so that if the process of atherosclerosis affects the limb principally you get symptoms of pain in the legs particularly on exercise and it's again due to the same process the similar process in the cerebral vessels this is a vessel leading to the brain you can have a gradual obstruction of the vessels and these are the carotid vessels leading to the brain and the symptoms that you get from that are a stroke these may be the large vessels here in the neck or the smaller vessels up in the brain again if you look at an x-ray and you can see at this point right here that there's a significant obstruction right here where this vessel should be going right out here again you have a significant narrowing of the vessel at this point in the arteries which are leading to the brain so the process of atherosclerosis is a generalized one there may be more symptoms related to the heart in one individual or symptoms related to the leg or to the brain in another individual but basically the process is the same and the symptoms really relate to the artery and what it's supplying the symptoms the individual will mention well this has really taken us now through a large number of different studies over the years which have really delineated the process of atherosclerosis and the symptoms that you get and obviously it's become a very important question over the years is can we pick out as individuals or in groups of individuals types of things which will increase the risk of developing cardiovascular disease in the form of atherosclerosis that is are there risk factors for the development of atherosclerosis so that you have those particular risk factors your chances of developing cardiovascular disease are greater than individuals who don't have the risk factors and there's really two parts to this question one is can we identify the risk factors and second is if we change those risk factors can we clearly change the chances of a given individual of having let's say a heart attack if we change the risk factors now a lot of different studies over the years have now clearly delineated that if you take a group of individuals and look at individuals that have premature cardiovascular disease and premature is individuals who have heart attacks before the ages of let's say 64, 65 many individuals will have heart attacks in their 40s and I'm sure that you're all aware of the executive type who didn't has been getting along without any problems and has a heart attack at age 45 and basically a number of studies and a number of different centers across the country have identified now three risk factors which are clearly associated with the development of cardiovascular disease at an earlier age than people normally get cardiovascular disease that is a disease in many ways of old age that everyone gets it after a period of time but the question is how soon do you get it the three risk factors that have now been identified are shown here one is the cholesterol level in the plasma and it's important in actually all three of these risk factors to note on the vertical axis is the incidence of cardiovascular disease per 100,000 population and it is a graded risk factor that there's no such thing as having one level where you're okay and when you step over a magic line that you have a high cholesterol and therefore have a greater risk but this is a gradual increase in risk as your cholesterol goes higher and higher the same is true of the second major risk factor and that's blood pressure again your blood pressure is not normal or abnormal the incidence of cardiovascular disease gradually increases as a function of how high your blood pressure becomes again smoking I think there's been a lot of publicity particularly in relationship to cigarette smoking and lung disease but smoking is a very potent risk factor also for the development of cardiovascular disease and just as it is in terms of the risk of developing lung tumors with the amount that you smoke also that's true for the development of cardiovascular disease as a function of smoking so we basically have three major risk factors now which can clearly be identified that individuals that have these have a higher incidence of cardiovascular disease than those who do not have them and that they're graded risk factors now as we've reviewed for years it was thought that the cholesterol level was basically a cholesterol factor which was always a negative one and if the highest cholesterol that you get the higher cholesterol the more and more of a risk that you have for the plasma cholesterol and this is particularly true as we now have reviewed for the LDL cholesterol so that if you have a higher and higher level of LDL cholesterol you'll have a greater chance of developing cardiovascular disease on the other side of the coin is the HDL cholesterol the higher the HDL cholesterol in epidemiological studies have suggested that HDL cholesterol in this sense is a negative risk factor and the higher your HDL is the less cardiovascular disease that you have and you really have now the extremes of LDL and HDL individuals who have disease called familial hypercholesterolemia and have very high levels of cholesterol and cholesterol levels that range between 800 and 1000 will have heart attacks when they're 10, 12 or 14 years of age individuals who have high levels of HDL cholesterol which are called now long livers have a syndrome which appears to be a longevity syndrome where they're octogenarians and they have high levels of HDL cholesterol and they appear to be protected from cardiovascular disease at least as appears to be associated with this risk factor so it becomes apparent now that before an individual who has a cholesterol level before he decides what he should do with that it's now important to know whether the cholesterol level is attached to the LDL lipoproteins or the HDL lipoprotein as you might have anticipated that there is an enormous amount of work going on at the NIH and several other laboratories around the country to try to figure out how we can raise HDL in individuals women have a higher level of HDL than men do and they are protected against cardiovascular disease into the menopause and they also have higher levels of HDL cholesterol than men do so that the HDL cholesterol has been the point of interest now of a variety of laboratories because as drugs can now begin to control LDL and HDL cholesterol we must distinguish between the two since one appears now to be a positive risk factor whereas the other appears to be a negative risk factor now the three major risk factors that we've delineated is an elevated serum cholesterol particularly now LDL cholesterol elevated blood pressure and cigarette smoking if you're an average 45 or 50 year old man and smokes one pack of cigarettes a day has elevated blood pressure is defined as having a systolic and diastolic above 140 over 90 and has a cholesterol level that's greater than 250 you have a nine times greater chance of developing a heart attack than someone who doesn't have those three risk factors if you have a upper limit of normal of blood pressure an upper limit of normal of cholesterol and smoke a pack of cigarettes a day or more you have a five times risk of developing cardiovascular disease so that the major question that obviously has been addressed by a large number of people is can we change these risk factors and therefore change an individual's chance of developing cardiovascular disease now the elevated serum cholesterol has attracted a great deal of attention I think as you're all aware and has become a very hot topic both now that we've learned there's quote good and bad cholesterol and also what is the effect of cholesterol as this important individual shows here eating his ice cream cone the question is will lowering of cholesterol in an individual at a point in time affect the possibility of his development of cardiovascular disease we now have drugs and diets that will clearly lower cholesterol but will it do a given individual any good and that's a question that is still a major one and a question that still has a great deal of controversy surrounding it I think as we've reviewed now you'll see that since this is a long term process number one and two that there may be multiple causes for the development atherosclerosis you change one risk factor will you significantly change it and when you decide to change it depending upon how much of the artery has reached a point which it cannot change are major questions which make the question of will lowering cholesterol make any difference a very difficult one to answer now the evidence that is available is really incomplete but in two general areas one is studies related to the human and other are experimental studies it's very clear from the epidemiology point of view that certain groups around the world have a great deal more cardiovascular disease than other groups for example people in Finland who have one of the highest intakes of saturated fats and cholesterol have a very high level of cardiovascular disease as compared to Japanese individuals who only have about 10% the level of cardiovascular disease in terms of myocardial infarctions as the Finnish individuals and their cholesterol levels are 140 verses roughly about 280 for the two populations so as you go around the world you can see different areas which have different dietary intakes which clearly have different incidences of cardiovascular disease and a particularly interesting study was done where they took Japanese individuals and looked at them as they basically became more westernized living in Hawaii and then on the west coast their diets changed their cholesterol and fat intake increased and their incidence of cardiovascular disease became more and more like the individuals in the United States that their level of cardiovascular disease clearly increases as at least their dietary changes occurred the second level of investigation of changing cholesterol levels and saying basically will it change the incidence of cardiovascular disease are now a few studies which have been done on individuals with the familial hypercholesterolemia as I mentioned those are the ones that have cholesterol as high as 800 to 1000 they have had their cholesterol lowered and studies done in England and in Colorado would suggest by using coronary arteriography that with the lowering of cholesterol and using the criterion of changes in the degree of narrowing of coronary arteries as studied by coronary angiography that the vessels become less narrowed after a prolonged period of time in which the cholesterol level is low the third series of studies are really related to animal studies and animal studies in which they have taken in this case monkeys given them a very high cholesterol and fat diet in this case for 17 months and this is a picture which now I think you're familiar with and this is a coronary artery that is significantly narrowed with the process of atherosclerosis they took in a group of these animals and put them on a low cholesterol diet and for the next 40 months and then looked at their arteries and the coronary artery at that time period was significantly more open to the transport of blood through it if they took an artery and looked at it in terms of one of the leg arteries again it was very severely occluded after the high cholesterol diet and after putting them on the lower cholesterol diet again the level of opening appeared to be significantly greater but I think this is still a major area of controversy whether diet will in fact change the incident of a given individual if he changes his diet and I think right now the NIH is supporting several studies both in the intramural program and around the country to basically answer this question but it's going to take years before we can really come up with a definitive answer and it will be very difficult as you can see because of the multifactorial cause of atherosclerosis and the narrowing and also the long period of time that disease takes to develop the second risk factor is elevated blood pressure and what can a given individual do to change his blood pressure if indeed he does have elevated blood pressure well elevated blood pressure is somewhat easier in that the individual who has high blood pressure the drugs are very effective for lowering blood pressure and again the dietary changes can be significant the average American takes in approximately 12 grams of salt a day it clearly should be reduced in terms of blood pressure as far as we know now to approximately about 5 grams and if you have high blood pressure it should be lowered to approximately 2 grams a day so again dietary changes can affect the level of blood pressure and we have very good drugs now for affecting a return of the blood pressure an individual to a normal level now studies have been shown clearly now to indicate that changing the blood pressure of an individual from a high level to a normal level can clearly affect the incidence of strokes that is still being accumulated for the development of myocardial infarction or heart attacks but it clearly does change the stroke the third is smoking and as I mentioned smoking is not only a risk factor for the development of lung disease but it clearly is a factor in relationship to development of cardiovascular disease an individual who is 45 and as the studies have been done would suggest that you are at having basically twice the risk if you only have this one risk factor and smoke a pack of cigarettes a day that you about have twice the risk of developing a heart attack than if you are a non-smoker so again one thing that's relatively easy to prescribe to individuals but as you well know is very difficult to do is to stop smoking so that those three major risk factors we can clearly take a positive approach as an individual to change them and the clearly the data is as yet not clear whether or not we will totally change the development of a given individual his chances of cardiovascular disease the other factor is the gradual increase in weight that Americans have and basically from the age of about 20 to 25 to age 50 we put on one extra pound per year and by the time we are approximately 50 we have 25 extra pounds of weight so as this individual shows he is eating his ice cream cone and has high cholesterol and indeed it does not have ideal body weight and clearly the average American needs to watch the calories and also not only to change what he is eating from all the information we have but also develop an exercise program so that you will have a return to the ideal body weight and get rid of the 25 pounds that you picked up from 25 to 50 and instead of watching the world go by you clearly should get in the point where you are jogging like the other people are on the highways and develop an exercise program not only to change your weight to the ideal body weight but you also get an increase in your HDL cholesterol and it lowers the triglycerides and it helps maintain ideal body weight so you have to basically develop a program where the ideal body weight of the individual is established and maintained individuals who are obese clearly have more work for the heart it is harder to control blood glucose your lipids are higher and with a program of appropriate caloric restriction and changing the diet to a cholesterol diet as we saw on the first slide of approximately 300 milligrams per day and having the fat content be approximately a third of the calories and developing an exercise program you can lower the lipids you clearly will make it easier to control blood glucose problems which become more and more a problem as an individual gets lower triglycerides and you will raise the HDL level when this was done in a series of physicians at Stanford and they looked at the levels of HDL cholesterol since it is now a negative risk factor for the development of cardiovascular disease and compared them to individuals who are not exercising the runners had a significant in all age groups higher level of HDL cholesterol on the average it was 64 as compared to 43 for the control individuals which were not exercising so it's become clear now over the last few years that we can identify three major risk factors and it is become clear that we have drugs to lower cholesterol we have drugs to lower blood pressure and we can clearly now suggest that changing from being a smoking individual to a non-smoking individual can clearly at this point in time be very suggestive that we will have a major reduction in the incidence of cardiovascular disease as we begin to accumulate more and more data related to these risk factors but I think as individuals one can see that the evidence is strong in support particularly at an early age if these three risk factors are identified and corrected that there may be much less cardiovascular disease in the future thank you there is a normal test taken that identifies the cholesterol level and triglyceride level now is there a normal blood test that will identify the HDLs and LDLs? yes basically it's just a somewhat more sophisticated study which is now being done in a lot of laboratories where they take the blood sample and they will get the total cholesterol and they will also now do the cholesterol on LDL and HDL I recall reading a while back a suggestion as far as exercise a nice long walk 45 to 75 minutes uninterrupted and the reason they suggested that is some people do have heart attacks while jogging plus some people have damage to the legs you know tendons and stuff jogging I was wondering if you could comment on that other form of exercise no I think that that's it's clearly a very effective method I think the thing that I would also like to emphasize that tomorrow don't everybody start running out and jogging that you clearly should also be well aware of your own medical problems and before you start an exercise program you clearly should check with your physician to see the degree of exercise that you should start the type of exercise may be not nearly as important as the way in which that you do exercise to basically get cardiac conditioning and in fact you can jump rope and it will give you a ten minutes of jumping rope is the same thing as jogging for 30 minutes so that if you develop a exercise program which involves walking it may be just as effective as jogging jogging is not a cure all you can do in many different ways would you please comment on drugs to lower cholesterol when they would be used how effective and what side effects certainly I think that there to be used only after dietary manipulations that is a sense that if you have a high level of cholesterol and have ascertained that that cholesterol is indeed LDL particularly if you're a female and a jogger you may have extremely high levels of HDL and you may have an elevated cholesterol level which is due to HDL in that sense I would tell you to keep on doing what you're doing and not do anything if you indeed have elevated cholesterol levels in the form of LDL then I think that the dietary treatment is the initial dietary treatment should be the first line of therapy for that given individual depending upon the amount of cholesterol and triglyceride that you take in that may be enough to normalize your cholesterol to the American quote normal levels if it doesn't on a period of let's say for example two months on a cholesterol diet where you're at ideal body weight with low cholesterol and in fact do have still an elevation of cholesterol then I think that the type of drugs that can be used are really there are three major drugs that are currently employed for lowering cholesterol you have to also distinguish whether the individual has triglycerides as well so that if you have a triglyceride elevation as well as cholesterol then you have a different series of drugs than if you only have cholesterol but in a word the side effects of these drugs are really particularly with the drug atrimid which is useful for cholesterol and triglyceride elevations rather minor and it's a well tolerated drug colostyramine is the second drug which has a difficulty in adherence for individuals taking it because it's a little bit like sand but there are very little side effects from it the third drug is nicotinic acid which initially has some side effects such as fleshing but again no major side effects so in general the three major drugs that are currently employed by physicians in this country have I think in general rather small side effects Doctor you mentioned things which lower the cholesterol cholesterol but I don't recall what you said about increasing the HDL in food not necessarily drugs and other than exercise are there dietary ways of increasing your HDL well there are not a great deal of effective ways to increase HDL that we currently know the if individuals have a very high level of triglycerides and if you go on a very high carbohydrate diet you can lower your cholesterol and if you change from a very high carbohydrate diet back to a normal diet you will increase your HDL but basically as yet we've not identified any dietary manipulations other than the changes that occur with high carbohydrate diets that affect HDL levels estrogens will increase HDL levels and treatment of hyper triglyceridemia with nicotinic acid for example will increase HDL in the exercise is there any information if genetics plays a role in controlling the blood levels of the various lipoproteins and two does race or groups of individuals groups of people seem to have particularly high levels of HDL the answer to your first question is certainly yes that of the types of high cholesterol levels that is particularly high LDL cholesterol the genetics is probably a major factor individuals who have what is called familial hyper cholesterolemia are not a small segment of our population in studies that have been done in several centers around the country people have one defective gene for a high level of cholesterol or a heterozygous for that and they are between one and four hundred and one out of five hundred live births per year so that there is a large number of individuals who will have genetically determined hyper lipidemia that's only one form of genetically determined hyper lipidemia and even a more common one is called combined hyperlipidemia which again the two incidents of that is not as yet known but clearly the genes play a major role just as the genes for high levels of HDL if you can pick your parents for a high level of HDL you obviously can make a very astute selection there are clearly groups of people who have high levels of HDL in the Georgian area of the Soviet Union there are people who quote have high levels of HDL or their long livers basically and they can have what is now maybe more important than just the HDL and LDL level but it may be the ratio between the LDL and HDL level so that there are clearly tribes which also do a lot of running which may help the HDL in the area of Jamaica which have high levels of HDL and again they have what appear to be a longevity syndrome the Eskimos who eat all that blubber and continue to thrive without much of a problem also have high levels of HDL for whatever reason there seems to be greater emphasis placed on cholesterol than on the triglyceride factor what is can you comment on the relative significance or importance of these two I think that overall it's very clear that as a risk factor that the high levels of cholesterol and particularly LDL cholesterol are clearly a much more potent risk factor than the triglycerides are