this program is presented by university of california television like what you learn visit our website or follow us on Facebook and Twitter to keep up with the latest UC TV programs tonight we’re going to talk about cholesterol this is a challenging subject I just came from an hour spending on this discussing this topic with colleagues physician colleagues and there’s a lot of uncertainty and areas of controversy and to complicate things there’s a lot of brand-new guidelines that really change the way many of us practice medicine in this regard now many of you may be managed by physicians or nurse practitioners or other clinicians who do this a little bit differently and again I’m not here to practice medicine although I do practice medicine but today I want to mostly talk to you about how I read the medical literature and how we’re thinking about this as a medical community a medical community primarily of generalists and primary care physicians who are balancing the needs of individual patients with the needs of society at large and I’ll highlight those aspects as I go through this let me say at the outset that I have no relevant conflicts of interest no conflicts of interest at all related to this subject also most of you whose email we have should have received an email this afternoon with a link to this website so these slides are now posted and dr. Julian slides from last week are now posted and we’ll continue to do that either just before the lecture preferably or just after the lecture throughout the course of course these are easily too easy to print if you prefer to have a hard copy but I think in the name of conservation that we’re going to try to do this electronically of this year since there’s so many of us okay so just a few words about the impact of treating high blood cholesterol in the United States over the last thirty years between 1980 and 2000 the death rate fell by about half from heart disease and stroke in the last 10 the next 10 years from 2000 to 2010 it continued to fall down by about a third now when we try to figure out why this rate has gone down what we can model and analyze is that approximately half of it comes from the fact that we manage acute myocardial infarction what we call acute coronary syndrome as well as acute stroke very differently and much better than we did 10 20 30 years ago so a lot of the lives are saved because of treatment in the community the early use of highly potent medications and stents and procedures both for heart disease and stroke the other half though comes from the treatment of risk factors and this includes all the traditional risk factors most of which we’ll talk about at some point during this course but certainly in addition to cholesterol high blood pressure cigarette smoking diabetes treatment and so on exercise weight and so on when we analyzed that half that has improved because of risk factors half of that or 1/4 of the entire amount comes from the treatment of high blood cholesterol now one would like to say that this is because we changed our diet or that we started to exercise more but that’s not the case and we’ll talk about that later in the course as we talk about the role nutrition and exercise play in the prevention of these illnesses but the the primary reason why the death rate has gone down for heart disease and

stroke in the United States and last several decades has been the use of medications to treat high blood cholesterol and this primarily refers to the class of drugs we call statins so let me begin with that premise and so I know there’s a lot of controversy about statins but I’m going to spend a lot of time talking about sentence I do not own any stock in statin companies I would rather treat all patients without medication when I don’t have to use medications but statins do work and they are more powerful than dietary therapy and they have led to this very beneficial effect now we’re going to spend the rest of the night talking about decisions we make with individual patients this though refers to entire populations of patients and so you can see if we can decrease the rate of stroke and heart disease by this much over the course of this many years we prevent a lot of events and save a lot of lives so from a social aspect of social justice aspect of population health aspect of cost-effectiveness aspect this this strategy to treat high blood cholesterol to prevent heart disease and stroke is working it’s cost-effective and we’re saving lives now what the decision that you as an individual patient or anyone as an individual patient makes may be different but this is what happens if when we move through recommendations as a population now the way studies have been done to determine that cholesterol-lowering medications work are the classic randomized controlled Percy Bo trials that is we take a large number of patients usually thousands of patients we give half of them a statin medication in a way they don’t know that they’re taking it the other half takes a sugar pill they don’t know which one they’re getting we follow them for five years and we see how they do in terms of heart disease strokes life expectancy and the like and there have been now several almost almost several dozen studies of this design this is a slide with some of the first early six of them but the last dozen and a half have been virtually identical and that is to say that in each study the patients who are given the cholesterol-lowering medication in this case statins versus the sugar pill had between a 25% and in this case 38 percent reduction in events that is recurrent heart attacks and recurrent strokes the so you can the take-home message here is that statins reduce events by a quarter or third now whenever anyone in medicine tells you or anyone in the news tells you that something whether it’s a medication or some other intervention lowers something by a quarter or a third or any number your very first question back should be a quarter or a third of what this is the central principle of all preventive medicine now for example if your risk of having heart disease and stroke over the course of the next ten years or so is very very low to begin with for any of the reasons that I’ll explain as we go through this then if we lower that number by a quarter or a third we haven’t done very much but the harms of any medications stay the same the cost of the medications stay the same but the benefit is really small so what we’re looking for are those individuals whose risk of having a heart disease or stroke is very high and then when we lower that by a quarter or a third we’re really doing something so much of what we’re going to focus on the rest of this talk is trying to figure out for whom and how should we figure it out is cholesterol lowering medicine worth it that the benefit is worth the harms that we know exist and we can set that up in terms of a balance beam we know that cholesterol lowers the risk by quarter a third but there are side effects some people get muscle aches some people just don’t like to take them there’s expense and so the question is always it lowers it by a quarter or a third but what is your native risk what is your risk of having that event but before we worth the medication so that we know what we’re lowering by 1/3 1/4 or 1/3

all right and that’s what’s called the difference between the relative risk of a medication working and the absolute risk in other words the headline always says new drug lowers such and so by 10% but if it’s something that doesn’t occur very often than 10% of something that’s a low number doesn’t matter very much and so you always have to combine the percent decrease of the treatment and the beginning risk or the native risk in whom that treatment is being used and that’s true if we’re talking about cancer screening blood pressure treatment cholesterol treatment and many of the other interventions we’ll talk about in this course just a few words about women’s health as it relates to high blood cholesterol early in the studies related to a cholesterol lowering the subjects for all men and then for many a series of studies they were mostly men and that is still the case when you put together all the individuals who have participated in the studies there are still more men than women and so in in many respects the data is more secure the evidence is stronger in men than in women for what I’m going to describe having said that though our current thinking that’s based on lots and lots of evidence is that the recommendations for the prevention of heart disease and stroke are the same for men as they are for women in most cases there are some subtle exceptions however the biggest difference is the magnitude of the app the actual absolute potential benefit because I’ll show you later on a woman of say 63 years may have a risk that’s relatively modest with the same risk factors and cholesterol levels we’re the same person changing only their gender may have a 2 or 3 fold increased risk so it works the same in both people it lowers the risk by a quarter or a third but the quarter or a third of what is different at the same age between men and women now as women catch up usually within a decade or so the numbers are the same but there’s usually about a decade difference in the absolute risk so therefore the absolute benefit at any given age statistically is a greater absolute benefit in men than women and we’ll go through some examples a few definitions this is a language that if you don’t work with it every day is a little bit confusing LDL cholesterol stands for low-density lipoprotein cholesterol and it’s a fraction of cholesterol that’s carried in the blood and it’s the fraction that we think is the most a thorough genic or the one that is most associated with heart disease and stroke and I like to tell the students that the way to remember this is L for lousy high density lipoprotein is the good cholesterol we know that in individuals with a high HDL level their risk of heart disease is lower and it’s true at any level of LDL so people with equal LDL levels even if they’re both high if one also has a high HDL cholesterol their combined risk is lower because the HDL is protective now come back to this point but we’ve us because of that observation and because in the test tube and in animals we understand how HDL is part of the recycling if you will of cholesterol in the blood we’ve always assumed that if we could figure out a way to raise the HDL cholesterol fraction that people would do better and they’d have less heart attacks and strokes and unfortunately that’s a very long story but the punchline is we haven’t figured that out yet so there was really no evidence that medications that raise the HDL cholesterol by itself as the primary intervention confer any protection triglycerides are a complicated topic if if one likes Clint Eastwood one could call this the good the bad and the ugly triglycerides might be the ugly but I tell the students for the most part to put their thumb over the total cholesterol and ignore it and their thumb over the triglycerides and ignore it and focus mostly on the LDL and HDL cholesterol now you’ll see in some of the equations we use we do put in the total cholesterol as one of the factors but the problem is that the total cholesterol is the arithmetic sum of the LDL cholesterol the HDL cholesterol and

the triglycerides so you can have a very high total cholesterol and have it be very high because you have a ton of really good HDL you can have a very high total cholesterol because you have a lot of triglycerides which I’ll come back to in a moment but aren’t that bad in most individuals or you could have a really high total cholesterol because the LDL is bad that would be bad so the total cholesterol doesn’t give you very much information in an individual patient in populations of patients it can be used to differentiate people at relatively lower risk and relatively higher risk but in an individual patient it doesn’t differentiate sufficiently to tell whether the cholesterol issue is mostly good mostly bad or mostly neutral if you will when I say triglycerides are neutral it’s a little bit controversial if we look at all the other risk factors and then either at a high triglyceride or a normal triglyceride the people with with the high triglyceride probably have a little bit of extra risk but the number is relatively small and most and the reason for that is that most people who have high blood triglycerides have it not as a primary genetic disorder but as a result of something else that’s gone amok and those other things that have gone amok can be captured elsewhere in the equations for example the most common causes of high triglyceride is on elevated blood sugar so people with pre-diabetes and certainly diabetes that’s not well controlled will have a high triglyceride alcohol use can raise your triglycerides estrogen you see there is a contraceptive or hormone therapy can raise your triglycerides and then there are some other diseases like low thyroid what’s called nephrotic syndrome a type of kidney disease that can do so as well and then there are also genetic disorders which cause high triglycerides but if triglyceride was a really bad actor for heart disease and stroke then then one would expect that the individuals that have super high triglycerides because of genetic disorders and I mean really high if normal is less than 150 there are people with 10,000 and you would expect those people to be dropping dead like flies and they don’t and so we don’t think that triglyceride per se in and of itself is a major factor in whether we’re going to treat someone’s cholesterol or not we focused primarily on the LDL and HDL and our thought process but like I said we do put in the total cholesterol in our equations to predict risk and as I’m showing here total cholesterol does include does reflect a high triglyceride now there’s also other conditions if your height if your triglyceride is very high we do recommend treating that to prevent inflammation of the pancreas where we go pancreatitis separate disease separate medicines separate conversation not to be confused with treatment of lipids to prevent heart disease and stroke and then you’ll see on some of the slides HS CRP that stands for highly sensitive c-reactive protein that’s a measure of inflammation as you probably have heard over the years one of the hypotheses related to heart disease and stroke has been that it’s an inflammatory condition this is a controversial area there are believers and non-believers and we’ll talk about the highly sensitive CRP towards the end of the talk we don’t use it very much as an initial approach but that could change with new science it does predict it does increase your risk by some amount but our current guidelines do not recommend doing it routinely but rather saving it for a tiebreaker when we need a little bit more information in a close call I’ll also include some organizations and actually one disease and some organizations on some of the slides so CH d stands for coronary heart disease it also is known as coronary artery disease or CA D and that refers to heart attacks and in this when we talk about heart disease outcomes or cardiovascular disease outcomes related to CH D or CA d we’re talking about non-fatal Mis that is heart attacks from which you do not die or fatal M eyes that is heart attacks from which you do die and those are the hard endpoints if you will for

coronary heart disease you can also have softer endpoints in some of these studies like angina means chest pain usually with exercise or how often people have had a stent placed or an operation done and those are other events that sometimes get measured in some of these studies but well for the most part in some of the conversations we’re going to have tonight about estimating risks we’re going to talk mostly about hard CHD endpoints and by that I mean non-fatal Mis and fatal M eyes now if you add stroke to that conversation both non-fatal and fatal stroke then we call that more reflection of cardiovascular disease rather than coronary heart disease and that’s why you’ll see CVD instead of CHD and the a S stands for atherosclerosis cardiovascular disease so when you see that term which is also one we’ll use a lot that refers to the combination of both heart disease and stroke now this is particularly important a because stroke is disabling and a dreaded disease when it’s severe and also because particularly in women especially at a certain age the risk of getting a stroke is not that far away from the risk of having a heart attack whereas in men heart attacks are more common than strokes so now that we start combining strokes into our thought process it gives us more events more things to happen and I’ll come back to this but it sort of enriches the numerator if you will that is if we’re trying to estimate the risk of an event happening by having stroke in the equation it increases the events it increases the risk and that’s relevant to women and I’ll show you some examples of that the US Preventive Services Task Force I think Kathy defined last week that stands for the I’m sorry that the abbreviation is the USPSTF they’re the body of part of the branch of government related called arc that develops preventive services guidelines and is made up of volunteer physicians and experts and these days when the US Preventive Services Task Force recommends an intervention it means Medicare pays for it and a Medicare pays for something it means most private payers pay for it so that the USPSTF recommendations are extremely important and then we’ll also talk about some recommendations in fact the main recommendations tonight that we’re going to talk about were published about a year ago now by the American College of Cardiology and the American Heart Association to professional organizations predominantly of cardiologists but also include lipid ologists and preventive medicine experts so those are some definitions and abbreviations that you’ll see throughout the night now I’m not going to spend a lot of time tonight talking about lifestyle recommendations I’m going to save that for later in the course we will definitely talk about heart healthy diets and exercise and desirable body weights we won’t say too much about tobacco except to say that the single most important thing one can do to prevent any disease practically but certainly heart disease and stroke is to avoid tobacco but the new recommendations do again emphasize not with new information or a change in recommendations particularly but do recommend the importance of lifestyle recommendations for the prevention of heart disease and stroke so we continue to advocate for these and just because I’m talking about the medications tonight rather than this does not isn’t intended to create a greater emphasis on one than the other we will save that though for a whole lecture on itself later in the course it is worth noting some of you may have heard the headline last that just this week that the Dietary Guidelines experts are now recommending in their draft recommendations the elimination of dietary cholesterol as a bad food as part of the American diet most of you are old enough to remember they work in the certainly the 60s and 70s of that the main one of the mainstays of a cholesterol-lowering diet was the to decrease dietary cholesterol and people used to get this confused all the time dietary cholesterol is what’s in turn eggs say what you eat and blood cholesterol is what you measure in the blood they’re different same chemical but they’re in different places they have different significance and it was

always thought that the eating of high dietary cholesterol was a big factor in the development of high blood cholesterol but it turns out that’s not true if you’re on a low-fat diet and it’s also highly variable based on genetics so for many and most individuals it’s not a major factor so you’ll see that language moving out of the Dietary Guidelines finally in this next draft we’ve been recommending the ingestion of eggs for some time they’re extremely healthy food especially if you’re trying to restrict calories or maximize your protein intake and as well as many vitamins and minerals and finally eggs are sort of back in business although they’ve been doing fine for the last several decades but alright so when I was a medical student and a junior faculty in the early 1980s the laboratory here only measured the total blood cholesterol the total cholesterol and a normal value was less than 300 so we pretty much ignored cholesterol and we had an outstanding department of lipid medicine here we still do where many of the basic science aspects of lipid disorders were discovered and continue to make scientific advances in lipid metabolism and so with those who had a cholesterol over 3300 that usually meant that they had a genetic disorder they went to lipid clinic they got placed on some of the early medicines that were available then but most of us in general medicine or primary care were not doing much to manage high blood cholesterol in part diet was hard drugs were not that effective and so and our normal was very high and then in 1988 came the first government-sponsored recommendations for the management of high blood cholesterol and ever since then the recommendations have been revised every several year every five to eight years or so most recently was I think 2004 until 2013 and part of that was I think it took a while to get consensus there’s a lot of controversy in this area that the approach that people who work with lipid molecules is different people who the approach that of people who work with populations of patients for people like me sort of in between interested in both it’s our job to sort of sort out these different tensions and controversies to make recommendations to individual patients but in 2013 the guidelines were published in a way that will that will change medical practice and this has been slowly evolving it’s not based on new science so much as based on a more rigorous analysis of existing science that is to say the the experts who wrote these guidelines pretty much restricted themselves to looking at those big sophisticated randomised trials that I described at the beginning 10,000 patients half cholesterol-lowering Medicine half K trigger pill what happens and so it’s a little bit less of an analysis of what happens in a test-tube what happens at the molecular level what happens with animals what should happen in people based upon that what happens in populations if we just follow them with that intervention all that knowledge exists and is sort of around these recommendations but the recommendations really rely on the highest quality of evidence which a randomized clinical trials or RCTs so the recommendations take a very complex area and simplify it a little bit by identifying really just five new factors and they’re suggested here number one it’s more precise and defining based upon the randomised trials which patients are likely to benefit from taking statins secondly it takes all the existing statins and divides them into three categories high intensity moderate intensity and low intensity and basically says forget the low intensity that most of the randomized trials have been done with moderate and high intensity and that’s what we should stick with and I’ll define that the biggest change or one of the biggest changes and the probably the biggest change from a

patient point of view is that there’s no LDL treatment targets in addition there is no longer an LDL treatment goal so depending on which conversation you had when with your physician he or she probably said to you your LDL is a hundred and thirteen and therefore I don’t think it’s worth it to put you on a cholesterol-lowering medicine or they might have said your cholesterol is 165 I think we need to start a cholesterol-lowering medicine it was based on the the actual measured LDL level and we used to joke about this and try to create a memory tool for the students and make it into a song which was 100 130 130 160 160 190 because that represented three risk groups and a starting point and the treatment goal point and we had some controversy whether the treatment goal should be less than 100 or less than 70 usually we said less than 100 but if we can get to less than 70 that was better but we really focus on the goal and now we’re not going to do any of that we’re not going to treat based upon what your cholesterol level is except in one exception and we’re not going to follow what that level is except in one exception and I’ll go through all this in addition in the old way of doing this if the statins didn’t get us to a goal then we would add a second drug now that makes sense that’s what we do for high blood pressure that’s what we do for diabetes that’s what we do for all sorts of things we start with one drug we measure we had a second drug and we’ll talk about that next week with high blood pressure it’s standard practice but as I’ll show you or at least describe the the evidence for non statin therapies that is the medications in other classes do not provide do not work that well do not provide acceptable risk reduction what do I mean by that that’s the resins and that’s niacin that’s the fabric acid derivatives and that’s a Zetas me bore zetia and I list those again for you later they all work a little bit by themselves but when added to a statin they either do not contribute very much or actually do harm and again we’ll go over that and the final thing that’s new and this is very confusing and controversial and unresolved is that everyone for whom we are considering the treatment of high blood cholesterol should have their 10-year risk of cardiovascular disease estimated now this is new in a couple of respects for about the last decade or so we’ve recommended that almost all patients have their risk of heart disease CHD estimated as part of our treatment algorithm but now we’re going to do it a for everyone and B we’re going to include stroke as well as heart disease so that’s now why you’re seeing the V the CVD instead of CHD and as I implied because now you have more events in the numerator you’re going to have higher rates or or higher risk estimates so we’re measuring an additional set of illnesses to estimate your risk we’re still using the 10-year approximation and we’ll go over that in some detail so those are the five points and I’ll go through each of those in some detail but just again to summarize only a limited number of patients to benefit I’ll use the high intensity and moderate intensity statins pretty much exclusively we’re going to come up with a different set of reasons to treat rather than the LDL target and we’re not going to follow the LDL very often we’re not going to use we’re going to use less of the other drugs and we’re going to use an equation to estimate risk and everyone all right so this is one of the studies that was on that first slide it’s one of the earlier generation of studies but I like it because it taught us some important stuff back quite a ways ago that was recognized by many of us but never really made it into the guidelines until this current iteration if you look at the Green Dot in this slide so the way this works is again same thing about 5,000 patients half of them get statin in this case sympathetic and the other half get a sugar pill we see what

happens after five years or so anything to the left of the solid line means that there’s been a reduction in risk with statins and you can see the green diamond is for all the patients all the subjects and it shows a 24% reduction with fairly narrow confidence intervals suggesting that like I said cholesterol lowering with statin drugs lowers your risk of events by a quarter now what was interesting about this particular study is that when we broke down it was big enough to break down into groups and the patients who had a cholesterol over 130 at the beginning of the study did great they lowered their risk by a quarter no surprise there that’s our treatment focus but then we saw that patients who cholesterol was less than 130 but over a hundred also did better and sure enough was about the same number about 1/4 but most interesting of all was that the people whose cholesterol was less than 100 who were started were treated with a statin medication for follow for five years also had a quarter reduction in events so this is the kind of evidence that suggests that it doesn’t matter what your cholesterol is what matters is are you on a statin and as your risk high enough to merit being on a statin so that big number rather than that number so this and many other studies like this helped emphasize that point that statins and and statins work no matter what your starting cholesterol level is it brings it down now as I said that the guidelines say that there are only four groups of patients who benefit from statins that sounds simple but these are big groups so there are a lot a lot of people who qualify for sentence millions of people and I’ll show you some of the us the data in a minute and but in these four groups are some of the ongoing controversies now we have believed for some time and the studies are quite strong and they’re strong in both men and women that individuals who already have evidence of cardiovascular disease that is a prior stroke or these an ischemic stroke and heart disease benefit from being on a statin there are other medicines they also benefit from aspirins beta blockers ACE inhibitors and so on depending on the circumstance but they also benefit from being on cholesterol or medicine with a statin and so that’s that’s been a consensus for quite some time since the earliest days of these reports this is the group we are most confident in if you take a statin you have a much lower chance by a quarter or a third of having an event a recurrent event and because you’ve already had an event your risk of another event is really high so therefore that’s the group in whom lowering a quarter or third really matters so that one’s straightforward no controversy there the second group of those with genetic disorders so if you’re a bad cholesterol LDL cholesterol is really really high then you have you almost certainly have a genetic disorder a family history and those are people for whom the evidence suggests should be on statin medications exactly starting at what age is controversial but generally people think that at least at a certain age people should be on statin lowering occasions although this guideline does not tell us what that age should be so there are some pediatricians who will treat there are some internist who will treat young adults interestingly the US Preventive Services Task Force makes recommendations about screening and in order to recommend screening they have to have evidence of benefit and they recommend screening for high blood cholesterol and Men starting at age 35 if there are no other risk factors that is know obesity diabetes smoking high blood pressure and so on in women they say forty five now if there are other risk factors they say screen earlier and the Heart Association says forget that let’s screen everyone at least at 21 but it is worth noting that from age 21 to 35 there is a controversy and certainly in pee and children a controversy as to whether these genetic disorders need to be treated early in life or can start middle middle of life or a little bit earlier that is to say the the the conceptual issue here is is 40 years of

taking a statin better than 10 right that’s that’s really a question we don’t have an answer to now when most of you were growing up you may remember hearing about Korean War veterans who at age 18 or 22 on the battlefield in Korea who died were found to have fatty streaks and their blood vessels and that that kind of thinking gave rise to the idea that atherosclerosis was this disease whereby your vessels were a pipe and when you were a kid and young adult bad dietary practices would give you some fat deposition and every time you had butter or cheese or ice cream you lay down a little bit more and then eventually you had that final stake it clotted off you had your heart attack and you died and that was the that was the image of atherosclerosis that we not only grew up with but that I learned in medical school I mean that was the concept was a pipe theory of atherosclerosis and so with the pipe theory of atherosclerosis it made sense that earlier the better right if you could prevent that plaque from forming the better and in fact there’s still a lot of cardiology based upon pipe theory right we put instance to keep pipes open and there are a lot of cardiologists who will do that at relatively modest amounts of blockage but we don’t know however what we necessary well we now think though is that at least a good chunk of heart disease if not a big chunk of it is actually due to other factors that the plaque itself is fragile and unstable and it breaks off and then sometimes as new plaque it’s more unstable and older plaque that’s more stable and it has to do with the plaque and in tears in the plaque and the lining of the blood vessel and what platelets are doing and other clotting factors and so it’s a much more complicated process and that’s why other medicines are involved in the conversation like aspirin and plavix type drugs and so on so the the unknown question is still is 40 years better than 10 years and so the ideal if you could predict the future based upon what we currently know what the day you would want to start taking your statin is ten years before you were going to have your first heart attack or stroke right because everything we know about cholesterol-lowering is based on ten years studies so the problem is we can’t predict that accurately yet so we estimate it with various equations and we’re going to spend some time talking about those equations in a few minutes the third group of patients with diabetes this is also not new we know that patients with diabetes predominantly die of heart disease and strokes and there are good studies that suggests that lowering cholesterol in these people prevents those heart disease and strokes the studies suggest that we don’t have to treat really young people with diabetes necessarily unless they have compelled family histories of premature heart disease but certainly the majority of diabetics in that by this I mean type 2 diabetics between age 40 and 75 should be treated with a cholesterol-lowering medication is statin now you’ll note both here and in the next bullet that the age limit stops at 75 so what’s that about well the main thing it’s about is that there are no clinical trials in this disease that have included people over 75 or at least not many and high blood pressure it’s a different story you can almost never be too old to treat high blood pressure and I’ll show you that next week but with cholesterol if you if this for a room of 50 five-year-olds and I measured your LDL I could put you in different parts of the room pretty accurately predict your risk of having a heart attack based upon that one number but as you get o in to your eighth decade that’s no longer true that is to say high blood cholesterol does not predict heart attacks and strokes and people over 75 so what I do is I if a patient makes it to 75 without evidence of heart disease or stroke and they’re taking a statin medication and they would like to discontinue that medication I offer that as a 75th birthday present now I must say most of my patients don’t accept that present because most people have been on the drug for a while it’s not that expensive if they had a lot of side effects they already stopped so if they’re still taking it there’s no side effects they’re doing fine with it and most people will say well I’m doing fine why rock the boat but the truth is that the evidence to say that this benefit conferred at that age and that

population is relatively little that’s not true if you have a heart attack or stroke so Neph top bullet we treat throughout the life cycle until you get to the point you’re at the very end of life now the final bullet is the most controversial and this is what we call primary prevention you don’t have evidence of athletics karateka but a vascular disease or diabetes you’re in that middle range of age your cholesterol is not super super low it’s what we used to goal at goal or above and we calculate your risk and your risk is above some arbitrary number now one of the things that makes medicine this this type of preventive medicine that we’re going to talk about particularly this week and next week and in my final presentation is that when we look at things like cholesterol or blood pressure or weight these are all continuous biologic variables that is to say the risk of having an elevated body mass index or an elevated LDL cholesterol or an elevated blood pressure is curvilinear increases starting at relatively low levels and just increases steadily and then gets steep at the at the highest levels there’s some areas of controversy about that maybe we’ll talk about that in the context of obesity but in general these are biologic continuous variables so anytime we draw a line and say the magic numbers of BMI of 30 or a blood pressure of 140 or 150 or an LDL of 100 or 130 it’s arbitrary right and so that’s why when experts get together and and come up with guidelines and recommendations there people have different opinions because they’re arbitrary and you can draw the line in all sorts of people places and so what we’re trying to do is always balance benefit and harm and including both the risks of the harms being the risks of medication and the expense and the benefits of being that which we’ve discussed so these are the four groups of patients the first one is easy if you got the disease we’re going to treat you with a variety of medications including statin if you have a genetic disorder and a striking family history then we definitely want to give you the benefit of treatment if you have diabetes we think treatment prevents stroke and heart disease and then if you haven’t had anything yet but your risk adds up to a number that’s above some threshold that we’ll discuss then we also recommend cholesterol-lowering medication now the threshold for ten years used to be 10% these new guidelines they said 7.5% why I wasn’t in the room some people say people at conflicts of interests related to their research and and work with industry but those were disclosed and I think attempted to be resolved but nonetheless I think it’s an arbitrary decision to pick any one number in this conversation I think if you if you polled physicians and the number was 20% you would get a high concordance of agreement that 20% is too high and the reason we think 20% is too high is because that’s about the risk of having a recurrent MI or stroke if you’ve already had one that’s that top bullet so if we get to that high then we think you’re high enough so there I think there’s be pretty good consensus whether that number then should be 15 10 or 7.5 that’s where we don’t know the correct answer and we’re we’re sort of guessing but it’s it has to do with and it also has to do with the this tension this dialectic if you will between what’s good for an individual patient and well it’s good for the population as a whole because the more people we treat even though it may not benefit anyone of us if the whole society has less heart attacks and strokes and we collectively benefit so that’s where the tension is in this conversation now as I mentioned not only has the number gone down from 10% to 7.5% but now we’re also including strokes so it’s more likely for you to be over 7.5% or over 10% right because now there are more things that we’re counting to get you there so those are the controversies so these new guidelines lead to more people being on cholesterol-lowering medicine rather than less the good news is next week I’ll tell you about some new guidelines for high blood pressure which actually suggests less people being on medication for high blood pressure now as I mentioned part of the guidelines are to divide the statins into high intensity moderate intensity and low intensity and I’ll define that in just a moment but for most conditions we want patients to benefit from the

highest intensity of the drug if they can tolerate it and we know if anyone has ever been hospitalized with a heart attack or stroke every patient the United States virtually will get eighty milligrams of a torva statin or an equivalent statin as part of the treatment of their acute stroke and acute heart attack and because there are studies that show that your short-term outcomes are better so in primary care if you’ve never been on a statin and you come back to my office you’re on a tee so I don’t have much to say about what dose to start because it was already indicated when you were in the hospital but for some of these other patients we do start in the office and there’s a debate whether to start low and slow go slow and build up or pick some number and start and we’ll come back to that but you’ll see with individuals who have the disease who have clinical ast VD we use a high intensity statin you can lower the dose in people who are older to prevent side effects people with the genetic disorders we use a high intensity statin so not much variety here people with diabetes we use a high intensity statin if the risk is over 75 7.5% of having an event in ten years which includes almost all diabetics so that so most of them will get a high intensity statin and for primary prevention they sort of hedge their bets and says we’re not sure so you can use either but don’t use the low intensity so you can see as you go through this list most people should be on what all people should be on a mod of these people should be on a moderate or high intensity statin and most of the conditions merit a high intensity stem well here they are and again this is a very evidence base meaning these are the drugs that we use in the clinical trials now these are the generic names and in the high-intensity it’s defined by a lowers your LDL on average by 50% so if your LDL cholesterol is 160 if you take these doses shown on the top bullet your cholesterol will go down to 80 on average and conversely if you use the lower dose or the moderate intensity or the other drugs it lowers LDL a bit less by a third to half on this list all of them are now generic with the exception of receive a statin which is a trade name Chris store so that’s still on patent but the others are available generically and depending on the dose in this category are relatively equivalent now you’ll note that we are not recommending that people take ten milligrams or twenty milligrams of lovastatin or 20 milligrams of pravastatin or five or ten milligrams of simba set and those are off the list because those don’t give you the benefit of this intense cholesterol-lowering the side effects do increase with dose mostly the side effects of muscle aches sort of symmetrical proximal is close to your inner your core muscle aches many of the other side effects are rare and we don’t worry as much about liver disease as we used to we don’t recommend checking liver enzymes anymore for ongoing therapy it’s mostly muscle aches that people complain about and that can be 10 15 20 percent of patients on high-dose now this is more for doctors than for patients but if you’re a doctor and you like to use medicines that are generic and patients would fit in that category too and and the the page from the patient point of view you only need one drug in one dose but from the doctors point of view the point I’m trying to make is that a torva statin is particularly convenient here because it covers both categories so it’s the only generic drug in both categories now that doesn’t mean that if you’re on a moderate intensity statin that atorvastatin is better than the other ones listed there they’re equivalent so I’m not suggesting that you switch by any means but if a doctor wants to master one drug and they’re armamentarium in their toolbox then atorvastatin is an easy one because you can either start high or start low and you get pretty quickly to either moderate or high intensity when patients come out of the hospital as I described on a tee we can either keep them on a tee or if they’re having side effects we can lower them to 40 and still call it high-intensity sentence so that’s something that’s a possibility conversely you can start people in the office with ten and raise them to 20 or 40 depending on which category they fall in or there are some doctors that say I’m just going to put everyone on 40 and

see what happens so big systems who are looking for simple approaches will often say well let’s just pick 42 or Bessette and 40 if it’s people get side effects we can go down if not we’re done and so that’s there are a lot of simple approaches here but certainly if you’re on the appropriate dose of love a 7% and simvastatin and receive a set and that’s totally fine we don’t think that any one of these is better than the other they’re just more potent at lowering LDL cholesterol so the the bitterness if you will the advantage is based on the intensity of lipid lowering not something specific to a tour with statin versus receive a statin for example let me digress a little bit and now talk about this issue of a risk calculation because remember this whole premise is based on the fact if your risk is high it’s time to move your risk is low we have time to wait as you get older your risk is going to get higher so waiting now doesn’t mean you’re you know you’re you’re off the hook because age is the single most important predictor of risk now in the old days and by that I mean the last decade we have risk for patients with lipid disorders in almost all cases certainly we have taught that in our own practices and the recommendation is more or less followed that but it’s worth noting that the old Framingham risk calculator which is the standard one so if until last fall or the two December’s ago if you had your risk calculation done you probably went to the ATP 3 the cholesterol website National cholesterol education program website or some handheld smartphone website app and calculated your risk but you probably didn’t know the answer to some of these questions shown on this slide for example the calculator include hard outcomes that is a my non-fatal MI and fatal mi non-fatal and mine stroke or did include things like angina or stents or things like that was it measuring CHD or did it include CVD that is stroke did it include diabetes some did some didn’t peripheral vascular disease which is a predictor of bad outcomes raised in ethnicity almost none of them did family history and or CRP only one of the risk Al’s does did it ask for an exact number or a range of numbers did you do it on a by paper counting up points or on a computer or a phone app so these were all variables that existed even before the new risk calculator came out and I tell this story because the new risk calculator is imperfect and the point here is that the old risk calculator was already imperfect so now we’re doing we’re trying to decide the best of two imperfect tools but it’s not like we went from a perfect tool to a mediocre tool that that’s sort of the point of this paragraph now the most important thing that’s absent and a lot of this is what does the patient want to do and so as you’ll see as we go through these numbers the advantage of taking these drugs for end of patient is relatively modest and I’ll illustrate this towards the end with some shared decision-making tools so patients absolutely must make a decision for themselves whether the risk is worth it the benefit is worth it for you because for some cases it’s a slam dunk and if you say doc well what do you think well if you have had a heart attack I’m going to say you should take the medicine but if it’s if you if you say my risk is you know ten point five what do you think I say well let’s talk about it and we’ll try to find that middle ground because the issues are not so clear so this is what we call shared decision-making so this is where you find the new calculator this is what came out in December 13 so on this particular website is the Heart Association website and but it’s pretty easy to Google risk calculator but if you want the new one get it from the Heart Association because again some of the commercial ones that are available and some of the others have some of those assumptions that I showed a couple of slides ago and you may not know exactly what you’re getting with this one what you’re getting is measurement of these factors and they’re the things that we for the most part think are important so age gender race at least white and african-american it does not deal with ethnicity total cholesterol

which again incorporates a little bit of both your LDL and your triglycerides if you remember the equation the HDL cholesterol your blood pressure whether you’re on medications for blood pressure whether you have diabetes and whether you use tobacco and the outcome as I said is the 10-year risk of CVD or sarita cardiovascular disease which includes fatal and non-fatal MI and strokes so when they came up with this list they said this is the state of the art right this is the best we can do and we developed this they said from five cohort studies cohort studies are like the Framingham Heart Study or a study where you define a group at the beginning in the case of Framingham was people who lived in premier Massachusetts measure a bunch of things follow forward for a bunch of years and see who develops what kind of event and what of the original measurements predict those events that’s called a cohort study or an observational study and so they looked at the five studies and said alright these are the things that we think predict the best and so we’re going to come up with this new tool and we think of it because it’s going to include things like race include stroke include diabetes and so on we think it’s going to be a little bit more accurate than the old one the problem is then they tested it in three other studies and since then you know going forward what we go prospectively that is studies that were not used to develop the model and since then there have been I think four or seven others I think for others so seven total in which the new calculator has been tested and it turns out the new calculator overestimates risk in most populations most groups of patients not necessarily for an individual patient but for groups of patients like middle-aged women or older men or whatever and you can define it and I’ve taken out the slides that show you which calculator is better for which groups of patients because it’s just it’s still preliminary data but the point of this slide is from three studies the light bar suggests what the predicted rate would would be this entire gray bar and the dark grey represents what it was actually observed and you can see that depending on what the risk calculator was it overestimated the risk in each of these studies by a fairly high percent somewhere almost about double in most of these examples and some of the recent studies one was just another one which is published this week continue to show that so most people think although not everyone most people think that the new calculator as it’s currently written over estimates risk and that maybe some other method of estimating risk would be better now in the old days what we used to do is count risk factors you get six risk factor if you had two or more we put in the highest risk category and then the VA less than zero one was the low-risk category this is all better than that so we have made progress but we haven’t nailed it yet now if you use the new calculator so the ACCA h.a stands for the new calculator and the ATP three stands for the old calculator based upon framing the Framingham Heart Study what you can see is most of the increase that is these bars represent the number of people who would be on medications that most of the increase represents individuals age sixty to seventy-five who don’t have the disease that is to say this brown bar that brown group here are those who are in this base up on the risk equation or primary as opposed to diabetes genetics or coroner or having the disease you can see that this added increase here or individuals aged 60 to 75 who have not yet had the disease and in fact for a man with almost perfect risk factors at about 63 65 or so you bump above the 7.5% just based on Asian gender so that’s really weird right so now you have someone who’s 65 or 70 72 who for the last five or ten years I’ve been telling your LDL is you know 102 you don’t need to be on a statin because you’re your cholesterol is not that high and you’re fine and now just based on their risk the recommendation would change so so the question is is that the right thing to do or not and the answer

is we don’t know yet but that’s why if you’ve gotten any curveballs lately we’re clinician told you after telling you you look your lipids are not a problem now all of a sudden they’re saying well we should be on a statin anyway this is where it comes from so what I’m doing right now when I have the time with patience or would I ask patients to do on their own is look up both calculators and use that to frame the discussion and I’ll show you a website that has both both calculators on in just a moment so and we don’t know and I’ll show you some examples in two cases we don’t know yet exactly how they’re going to act in different patients in general though the overestimation is greater in women than in men and I’ll show you some examples of that now there’s a website that the Mayo Clinic has put together called the Staten choice decision aid and you can google that phrase and find this quite easy but here’s the the link or the the website if you want but just google Mayo Clinic Staten choice decision aid and I’ll show you a screenshot of it in a few slides but this has both the old Framingham risk calculator and the new ACC Heart Association calculator and so you can put in both the numbers in both and see how you do and again you may have to come up with exactly the same number or you may find that there’s a range that difference may matter or may not and I’ll show you some examples as we go through this this website also has some very interesting tools to help you make the decisions and I’ll show you an example of that towards the end okay so let me give you some examples of how this plays out in real life so this first case is a 63 old woman who’s had a heart attack so she’s got the disease she’s in that first group there’s a consensus should be on a statin so even though her LDL cholesterol is not that high we used to say under 130 was pretty normal we would still recommend that she go on a statin and that’s because her risk of having another mi is pretty high probably about 20% a year 20% Prytania is a 2% a year and she falls into this category she’s an individual who has the disease and so the recommendation again just repeating the recommendation is to treat with a high intensity stat and/or if she’s older which is not a moderate intensity sentence oh she would have gotten eighty milligrams Vittoria statin or the equivalent in the hospital when she had a mi if it was recent and she could either continue on eighty if she’s doing okay or back down to 40 but not much lower so – or versed in 40 is the only drug on this list of choices that is in the high-intensity group that’s the point of this question she needs high intensity that’s the only one in the group that is high intensity number six would have been the right answer a year and a half ago so or two or three years ago whatever whatever would get her down less than 70 but now we don’t care about what she is as long as she’s reduced by 50% from her starting point this is a sixty three old woman who also has had a prior mi heart attack and she’s already on atorvastatin 80 her LDL cholesterol is 95 her HDL was not bad like a little higher and a woman triglycerides a little high but not too bad and but usually we would say I’ve said a year and a half ago you know 95 is okay but we’d really prefer less than 70 there’s a little bit of added advantage in preventing events when you compare a 95 getting less than 95 or getting less than 70 in the old system so we might have said well let’s some of the choices are we could either keep her on our current therapy we could switch it to receive a statin or in the old days and both of those turned out to be the right answers in the old days we might have said well let’s say at another drug and the choices we might have had or fina fibrate fish oil works to lower triglycerides in particular niacin and was always a very favorite choice especially around here Beck a half decade or so because it lower triglyceride a raised HDL a lowered LDL is a great second drug we thought and also zetas my boards it via is on the list the problem is that even though we think these second drugs should work should add more value when each one has been studied the studies have been negative so very good science where you take

people on a statin or high-risk treat them with statin plus one of these other drugs particularly niacin or FINA fibrate and they do not do better and in fact in one of the niacin studies they did worse that more strokes and heart attacks and the study was stopped before it was finished so we no longer recommend adding a second drug to a statin so just to summarize a lot of complicated studies in one slide and a half just what do we know about lipid lowering drugs at this point we’ve said enough about statins already they work based on randomized trial data there’s no evidence of support adding niacin or fibrin ester derivatives on top of statins if patients completely cannot take sentence and they have to really prove it or don’t want to for whatever reason although we would try to work through that and try to suit depending on the indication both statins and fibrin gaster derivatives can have some benefit but it’s much less potent than statins so niacin and fabric acid derivatives and is that at me traditionally most of the studies have shown that it’s very little clinical impact to complicate things though in November of this year a new study was presented at the Heart Association meetings called the improve-it study and this has not yet been published has been discussed as an abstract so we don’t know yet we need to see the study in its full glory but it’s a large study these are patients who had coronary heart disease and they were randomized to simvastatin versus simvastatin plus ezetimibe this is marketed this combination marketers vytorin usually these studies last for about five years and we call it a day five years this was a negative study but they kept going and it’s seven years they were able to find a small difference with the combination therapy but it was a very small difference it was 34.7% events versus 32.7 so it’s two percent absolute difference and it’s about a six percent benefit remember the statins are a quarter or third so we think when we see this study and its glory it won’t influence practice but we’ll have to see I think certainly the drug company is going to try to get the FDA to approve this for a new indication based upon this theta it’ll prob a well get approved but my personal opinion is that this data is the whole story that it probably shouldn’t be used with the added expense and the modest benefit if any so we’re still stuck with sentence for the most part so this patient falls into this category again she’s had an mi and so what we would recommend for her is either leave her alone on her tour versed and even though she’s not less than 70 which was our goal not that long ago we would now leave her alone and say continuing your medication and don’t worry about it you could also switch to receive a statin but again it’s off pat it’s on patent and formulary hassles and and there may be additional expense but it may but you could try it if you wanted to because it may unpredictably have a more potent effect that is you can’t predict remember I say 50% but there’s a range is the Gaussian distribution around the 50% so sometimes you get lucky and one drug is more effective than another but my own practice would be say you’re doing great let’s leave it as it is but the take-home point here is that we no longer add niacin or fibrin acid derivatives or other medicines all right the last case is a woman with primary prevention there’s a 63 old woman no other risk factors shouldn’t smoke no blood for sure no diabetes blood pressure’s normal her LDL cholesterol is 155 and you say well it’s it’s getting up there her HDL is a little protective 55 average and women is about just under 45 triglycerides are high normal and so if you look at this from the end of the bed you might say well she might merit therapy she’s in her 60s LDL is pretty high I don’t know what should we do and the answer is let’s figure out what her risk is because we can’t guess and if we guess it’s just a guess so we’re going to calculate but we have to now calculate with the uncertainty of not knowing which calculator and and what we’re going to do exactly with the

number when we get it so again here are some choices for her so when you do the Framingham calculator the old calculator her risk of an event in 10 years is 2% that is its 0.2 percent per year so that’s one of these that’s one of these small numbers that if we lower that by a quarter we go from 2% to 1.5% right or 0.15 percent per year so it’s it’s quite low and when you do the inverse of that absolute difference you can figure out what’s called the number needed to treat you’d have to treat a lot of patients they’ll just like her to prevent one heart attack so that’s where that whole thinking is that she that’s just not worth it interestingly if you put in the new calculator she’s one of these people where the risk is more than double on the new calculator and again part of that is because stroke is now included and women at this age I have a higher risk of stroke but this is an example where the to the fact that the two calculators are imperfect doesn’t matter because the number is small in both counts you with me so even though she’s of age and has a relatively high LDL the answer is no so she does merit a lipid lowering medication now what’s interesting is if we do the same case but make it a man everything else is the same all the numbers are the same his risk is 10% on the old calculator and set at 2% and 10.8% on the new calculator again men get a lot more heart attacks and strokes so therefore the numbers are a little more similar we don’t know if this is an overestimation of his risk I’m reassured that it’s showing up on both calculators and but in the old calculate in the old system 10% was our threshold now we’re saying 7.5% but these are these are close to calls right and so we don’t know this is what I would call a clinical toss-up and when there’s a clinical toss-up it’s what the patient wants is what carries the day so if they say doc what would you do you know I’d have to figure out some way to say well patient what would you do and I’ll try to understand a little bit what they’re how much of a risk taker they are how risk-averse they are whether they’re more concern about benefit or side effects and so on and work that through now if one had all the time in the world and if you’re at home trying to figure this out for yourself you do you know though in the office your doctor may not you should go to this Mayo website or something like it and try to play with these numbers so here’s what it looks like with some happy faces and sad faces so if the risk and in this example I put in these numbers for one of the calculators so first of all up here this is that male thing that I told you about so and it’s a three step process so current risks gives you the two calculators and you can put in both numbers it also gives you a third calculator just to confuse you to do the third calculator you need another blood test which is the CRP and so most of us don’t recommend using the CRP routinely but it is available it’s not that expensive and it may be a good time a cur if the CRP is high risk of another 20 or 30% if it’s really low it lowers it by another 20 or 30% it doesn’t take you from 10 to 25% it takes you from my ten to thirteen or ten to seven so again it may or may not make the difference and you have to decide that before you do the blood test so you actually have three calculators to play with in the study that just came out this week compared all three calculators and for different populations each of them was slightly better in different different settings in this particular study the third calculator the so called Reynolds calculator performed well here’s this person who has I put in the numbers so 10 10.8% same numbers rounded off to 11 on the new couch on the new calculator and this is without without a cholesterol-lowering medicine and you can see that although 11 people will have a heart attack in 10 years and one-tenth will have a heart attack in 1 year the vast majority of people even though the numbers are bad and the risk is high will have a good outcome smiley faces so it’s very important to understand and that as an individual patient the odds are still in your favor even if your risk is moderately high if this were to even 20% even if you had another heart attack it’s still remember

if your risk is 20% of having an event it means 80% is not so your odds are 4 to 1 in favor so now if you take the drug is meant these blue ones so I see three blue ones so you’ve lowered it from 11 to 8 and that’s that quarter or a third reduction and this is with a moderate satin on the high-dose statin it might be four out of eight and you can see that when you look at it this way it doesn’t look so good right because your eyes are still pretty good right that you’re in this other category so it really depends whether you’re how you feel about your odds and whether you want to take take a drug which probably won’t have any side effects and the bed majority of patients that lowers your risk somewhat but it’s not a cure-all and your odds weren’t that bad to begin with so this is what’s called a shared decision-making tool and I think it really helps people understand what we’re dealing with here so please feel free to play with this website it’s free all the yellow ones are possible good possibilities for this patient for one reason or another and I won’t go through them again now I’ve tried to make it simple of course nothing is ever as simple as it seems there are various reasons why doctors would take exception to these guidelines in an individual patient and they’re shown here certainly if the family history is striking I think all of us would pay attention to that interestingly most of the scales don’t take it much account of family history because of the way the data was collected and some of these other tests I won’t go into in great detail but we do not recommend using CRP routinely or coronary calcium score routinely but when available they both add some additional information so just to summarize this part of the talk and I’m almost at the end the the new guidelines have a lot of good parts to them they continue to focus on healthy lifestyle they focus on statins and off away from other agents that have been shown not to be effective they teach us to focus on people based on their risk and they they tell us to treat patients that should be greater than 190 sorry about that or who have diabetes and cardiovascular disease now not having an LDL target is controversial but it makes sense and again this idea that 25 percent of what is the central question here and so you don’t need the LDL target so much what you need to know is the risk the problem is we still don’t know how best to calculate the risk and our current state of the art is to use these various calculators and then pick a treatment threshold but which calculator we use and what treatment threshold we use is where the controversies lay now let me end with one other curveball now I’m not going to go into great detail is a new paragraph there’s a totally different issue most of you have heard back over the last decade of certain anti-inflammatory medications or non-steroidal anti-inflammatory medicines like ibuprofen and Aleve and so forth that there are some medicines in this class like Vioxx that have been taken off the market because they caused increased risks of heart disease well it turns out that Vioxx was certainly one of the worst culprits but there are several lines of evidence to suggest that all of these drugs when taken in high doses for long periods of time let me say that again high doses long periods of time so this is not three weeks because you shoulder hurts or every third day cause your back hurts but high doses long periods of time increases the risk of heart disease and stroke and increases the death associated with that and highly statistically significant about 40 to 50 percent and there may be a difference between some of them some of the studies show that the Naprosyn type drugs and the ibuprofen type drugs Moute the ones that are over-the-counter may be safer than the ones that are on prescription but there’s evidence the other direction also pretty much they all sort of probably increase risk to some extent now the take home message here is that risks are competing so that if you take some of these patients that we’ve been discussing say you have a patient whose risk is 10% in ten years and you put her on a statin and you take that statin religiously and you lower your risk by 30% your risk is now 7% if you then also take a medicine that increases your risk by 50% now you’re

back up to 10% so the risks are additive and subtractive to each other and so just remember that as you’re doing all this hard work to take to lower your risk that you don’t do something that increases your risk and that would certainly be true with various lifestyle choices and so forth the lowering a statin will look taking us that’ll lower your risk smoking will increase your risk and you’ve competed doesn’t mean it doesn’t help because there would be the risk would be even higher if you’re on NSAIDs and didn’t take the statin but you’ve counteracted the – so pay attention to these kind of issues so this is not proven yet but this is concerning and so that’s why many of your physicians even though the anti-inflammatory drugs can be quite useful they have side effects to the stomach and kidneys as well but this is one of the reasons why people have become a little bit more conservative with those medicines all right so let me wrap up and we’ll take questions for the remainder statins are effective and cost effective in groups of patients we don’t know what age to screen at but if you believe in screening at age 21 what you’re thinking you should do is find the people with the genetic disorders otherwise you can probably wait if there’s not a striking family history you can probably wait to 35 and men and 45 and women as we talked about you want to use statins and people have vascular disease have a hiked LDL and diabetes and those without the disease whose risk is over a certain number that numbers probably should be seven and a half percent to fifteen percent we don’t know exactly where the right cut point is and we don’t still know exactly which risk assessment to use but you can use two or three of them see where you land use the right intensity sentence that is mostly the high and moderate intensities it’s important to monitor adherence we want to make sure not only that you’re taking the pill which we can usually do by just talking but also to make sure that the pill is working so we will check follow-up blood tests to make sure you’re getting that 30 to 50 percent reduction but we won’t check it every six months or every year the way we used to you know once we know you’re in a stable regimen the drug is working we may start backing off on checking it as often the drugs don’t work very well in patients on dialysis who are bad heart failure the evidence is accumulating that the other drugs don’t add much value unless the patient truly can’t take statins and avoid other risk factors other factors that raise risk as much as statins and the first time my list for this is anti-inflammatory drugs with that I’ll stop and thank you very much for your attention you you