 Good morning everyone. It's great to be here every year talking about stuff related to cholesterol and risk. Obviously it's always good to catch up with a lot of old friends here as well. I trained here this is I think going on to 11th year since I graduated from THI. So a proud THI graduate always glad to be here and catch up with old friends and talk about a few things. So what what I have been given as as the as a topic for discussion today is to talk a little bit about personalizing risk assessment for patients when we see them in our office and I'll talk a little bit about how we do that. This is based on the 2018 cholesterol guidelines as some of you would know these guidelines came out in November of 2018 like any other guideline effort. This was a major major effort so I'd like to just thank all the members who are listed here our two chairs who've been really the grandpas of cholesterol management doing it for 34 years and part of all the guidelines. So I have no relevant disclosures related to this slide just a few comments on what this guideline entailed before we get into risk assessment. This guideline writing committee basically included members from about 11 organizations that you will see here listed at the top. So a lot of organizations including both physicians nurse practitioners and our physician assistant colleagues it is it is in chunk format so it's much easier to read but despite that it has 121 pages but it is divided up into sections now any of you who has not seen this I would highly recommend you go and look at it because it's much easier to read it's not one of those long guidelines you're only allowed about 100 to 200 recommendation supportive text for each recommendation so you read a recommendation and the guideline writer has to make sure that you know in those hundred 200 words they explain you the rationale for that guideline so it's called a modular chunk format of the guideline that's happened now for the last year or so so they're easier to read you'll see that there are 29 class 1 recommendations 26 class 2a which means something that can be done 2b which is something that may be done about 14 and class 3 something that should not be done and then there are two value based recommendations based on cost and benefit. So what I want to achieve in the next 25 to 30 minutes is discuss the rationale for recommendations for the treatment of three primary prevention groups again remember this guideline talks about four major groups one group is patients that you and I take care of a lot which is patients with established cardiovascular disease those who already had a heart attack or a stroke those who had a peripheral arterial disease that's symptomatic that's not the group we're talking about they have declared themselves we don't calculate risk in those that's a secondary prevention population I'm happy to talk about it because I was intricately involved in that section of the guideline but that's not what we're going to talk about today we're going to talk about prevention of first cardiovascular event and when we talk about that there are three patient populations that you really need to know about one is patients with high LDL cholesterol and what I mean by that is LDL cholesterol levels 190 the second group is patients with diabetes who have not had an event yet and then if you don't fall into any of these two categories then we talk about pure primary prevention patients a patient who's 55 years old who comes to your office who just has hypertension or maybe has nothing and wants to talk to you about their cardiovascular risk so those are the three primary prevention populations that I'll talk about and again this is the mantra that we use how and why we estimate risk first we estimate the risk again as I'm not using the word calculating because it's not that precise then when we estimate the risk how do you personalize that risk to your patient because you know these calculations and risk equations are great but how do you personalize to the patient that you're seeing in your office and then the last is how do we reclassify it because nothing is perfect in the world so how do we make it as much precise and I think this is where these guidelines are are an enhancement over the last set of guidelines from 2013 I think the 2013 did very well in terms of estimation of risk and these guidelines talk more about personalization and reclassification and that's what I would like to tell you okay so this is really the slide that summarizes everything that you need to know about primary prevention as far as cholesterol is concerned now I'll go through this slide and each of the you know big boxes you have there so try to remember as much as you can I don't expect that you will remember everything this is all available publicly so you can pretty much download and just put this wherever you're practicing but I'm going to give you some rationale for each of the recommendations things that are in green our class one recommendations something that should be done as I said to a are those that you you can do and again to be would be something that may be done so let's start out with the first group that's the group of LDL cholesterol greater than or equal to 190 remember the mean levels of LDL cholesterol in US population right now at about 120 milligrams per deciliter with very very small standard deviations when you go about 160 of LDL cholesterol you're already in the top 20 30% of the population above 190 you're in the top 5% of the population whether you have familial hypercholesterolemia or not and I wanted to show you this because we all miss this you know a lot of times you get these patients with first MI and the LDL cholesterol is 195 in the chart people write high LDL cholesterol but it never occurs to them that a lot of those patients may actually have familial hypercholesterolemia or a genetic cause of the elevated LDL cholesterol I put this slide up which is difficult to follow but I'll summarize it for you what they've done is they've taken patients with LDL cholesterol of 190 to 220 and they have compared them to those whose LDL cholesterol levels are less than 130 which is the average for our US population whether they have FH or not look at what is your risk of having a heart heart disease related event five times higher risk even if you don't have FH if you have FH that risk goes up to 17 what that's telling you is that if you have FH then you had a lifelong elevation of LDL cholesterol to the risk is definitely high compared to someone who does not have FH but despite that the risk is extremely high when was the last time you saw an odds ratio of 17 for an event or for that matter five generally we're dealing with odds ratios of 1.502 so remember be very careful when you see these high LDL cholesterol levels don't just write high LDL think of FH because FH is an autosomal dominant disorder the whole family needs to be screened it's a genetic disorder 50% chance of a person giving it to their kids so just remember that do not do any risk calculation in a patient who has LDL cholesterol levels above 190 that's the biggest mistake you can do go ahead and treat them because their lifetime risk is very high this is the other thing that I would like to mention this is again a more recent study that came out that that tells you that when you look at patients above LDL cholesterol the 190 again you don't have to have FH if you look at their event rates in men look what you what happens here if you are 40 to 49 and your LDL cholesterol levels are above 190 your event rate is comparable to someone who may be 60 to 69 years old but has LDL cholesterol levels less than 130 so what you're doing is that CHD is accelerated by 10 to 20 years by having high L levels of LDL cholesterol if you look at men women it's accelerated almost 20 to 30 years in terms of the risk of events so it's not trivial don't forget about this group and then we know this is data from forest study that when you give statins to these patients statins work so the question is what should we do well this is what we know if you have homozygous FH they get their first event you know in the second decade of life if you have heterozygous FH which is what you and I see and frequently miss in their 40s early 40s mid 50s having an event these are the patients but if you give them statin therapy early on you can pretty much bend the curve and bring it closer to an average person so start early start aggressively so that was our first group the second group that we have in the guideline is the group of patients with diabetes and I put this slide from the CTT meta-analysis there's one for blood pressure there's one for cholesterol obviously these are the most I would say close to the truth kind of analysis because these are patient level meta analysis of multiple RCTs and what you will see here is that per millimole about 39 milligrams per deciliter reduction in LDL cholesterol you get about 21% reduction in major vascular events whether you look at diabetics or non-diabetics it's the same but that's not the point the point is this if the relative risk reduction is the same despite that if you look at the absolute event rates diabetics have much higher event rates compared to non-diabetics so if you take the same relative risk but your absolute risk is high you're going to gain more benefit if your 10 year event rate is 10% and I say I'm gonna lower it by 10% that's 1% absolute risk reduction but if your baseline risk is 20% and I say that I'm going to lower it by 10% now I'm lowering your absolute event rate by 2% so remembering diabetics for the same relative risk reduction we're getting more absolute reduction in events and that is why we treat diabetics so aggressively even when they don't have established cardiovascular disease the other thing that this guideline talks about is risk enhancers for patients with diabetes and they all make intuitive sense you and I take care of patients and we all know that these things matter long duration of diabetes having albumin urea having nephropathy retinopathy if you have subclinical PAD by having ABI if you've measured it you don't have to but if you have those are the things that make diabetic patients even higher risk what the guidelines are saying is that you should use modern intensity statin therapy in all patients with diabetes but if they have these risk enhancers then think about using high intensity statin therapy because they are the highest of the high risk okay so we've talked about two groups up till now LDL cholesterol above 190 without history of cardiovascular disease patients with diabetes so those were the two primary prevention groups and then we get into the big bucket of primary prevention which is patients who don't have any of this and they just walk to your office it's a man or a woman in their 40s or 50s says well what can I do to reduce my risk of having a cardiovascular event and there the most important thing is to assess risk if we don't know what is this person's 10-year risk of having a heart attack or stroke or dying from one we will never know what to do and I'll give you some examples here why it is so important not to use intuition but actually calculate 10-year risk we talked some of this you know in the in the blood pressure talk as well but this is what we know if you have a patient that you lower LDL cholesterol let's say by two millimoles right if you have that patient's risk five-year risk of major vascular events of less than 5% you're going to prevent 10 events but as your risk goes up look how many events you will prevent 10 versus 120 it's an order of magnitude higher the same holds true for blood pressure as well if you lower systolic blood pressure by you know 12 millimeters of mercury in a patient whose major vascular event risk is less than 5% you're going to prevent 14 events versus much higher much much higher if your five-year risk is much higher so everything depends on the absolute risk not relative risk and that is why it is important for patients to know what is my 10-year risk of having a cardiovascular event if they know that they will understand the number and we know that half of the patients that you and I prescribed cholesterol lowering medications or anti-hypertensives especially in primary prevention are not taking it your or my assessment whether my patients are taking it is a you know point us I mean 50% chance that you and I are wrong so again if they know their numbers it's better that they will actually do it so it's a class one recommendation to be doing a 10-year risk assessment in patients there's no harm calculating a number doesn't harm anyone on the other hand it has shown that if we do that it actually improves initiation intensification of blood pressure and cholesterol lowering medications as well as 10-year risk at follow-up goes down because people are taking their medications they probably are making some lifestyle changes as well which are extremely extremely important so this concept of risk assessment is not only limited to cholesterol guidelines I think Dr. Taylor will talk about it but because of sprint now we know and and by other trials and from CTT meta-analysis of blood pressure even in blood pressure as I showed you the benefit you get from a therapy is dependent on your absolute risk so even blood pressure guidelines are now are recommending using pool cohort risk equation for risk calculation to actually identify what your treatment goal is for blood pressure lowering so now here is where we are we talked about these two groups you said if you don't fall into these two groups then you do a 10-year risk calculation if you're between the age 40 to 75 and then you get a number all of this is publicly available using pool cohort risk equation what you do is you get a 10-year less than 5 percent 5 percent to 7.5 percent which we're calling borderline 7.5 to 10 percent 20 percent which is intermediate and more than 20 percent which is high risk now what do you do in a hundred thousand health care providers and nurses doctors physician assistants and if you do a pool cohort risk equation I am pretty sure it will overestimate risk because it's not picking up a lot of risk that is there because of you know lower risk that's there because of high SES or a patient that's very engaged on the other hand if you did the same thing it took a lot of HIV patients pool cohort risk equation will underestimate the risk the reason being that they have a lot of other things that lead to cardiovascular disease HIV itself could do it psoriasis could do it at the same time we know that low SES or socioeconomic status itself is associated with poor cardiovascular outcomes so you have to know when you do this that just this number is not enough and that is why clinician patient discussion and further calibration of risk is extremely important we should not stop at calculation of 10-year risk but go beyond that and that is where these kind of like go so that's one concept the other aspect of this is I put down the three major primary prevention studies here I don't think you should even try to read this I just want you to focus on this part if you calculated a 10-year ACVD risk in the placebo arm of those studies you will see that patients who were even 5 to 7.5 percent 10-year risk derived benefit we know that even if you have 2 percent or 3 percent risk 10-year risk you will derive benefit from statin therapy the question is how many patients will you need to treat to actually get a meaningful benefit right but 7.5 percent is a very good threshold whereby patients seem to start deriving benefit and I'll say even 5 percent you have a clinical trial-based evidence F caps tax caps or and mega where you could actually start therapies much much much sooner so now this is where we are you have seen a patient you calculate the 10-year risk if the risk is less than 5 percent they are at very low risk of having a cardiovascular event just do lifestyle modification which is extremely important and reassess the risk in 5 years don't stop risk assessment is a continuum it should not happen once and then never if the risk was less than 5 percent well talk to the patient then go ahead and do lifestyle modification if the risk is more than 20% or 10 years to have a heart attack or stroke or dying from one well they're very high risk go ahead and do lifestyle and drug therapy which we know is statin therapy here preferably a high intensity statin therapy they have much higher risk of event right so these two I think it's fairly simple what we need to do what do you do with this borderline and intermediate rules that is where I think a lot of calibration needs to happen and this is where we say that you have assessed the risk now you need to personalize the risk does the patient have a few things in their history whereby they might be at higher risk of cardiovascular event which will prompt you to discuss with the patient that maybe taking therapy now is better for you and what would those things be and this is where these guidelines are in enhancement we're talking about a concept of risk enhancers this is how you refine risk at an individual patient level when you do a 10-year risk and you can do it you can Google it now whole court equation or ACCH risk calculator you will see that family history is not a variable if you saw my patient that's 52 years old comes to your office and says my dad had his first time I at the age of 54 that 10-year risk is 8% should you start them on therapy or not well it's a risk enhancers it should prompt you that maybe I should and continue with the lifestyle what happens if you actually have a patient with metabolic syndrome well it should prompt you to maybe start therapy early what do you do when you have primary hypercholesterolemia when you haven't crossed the 190 threshold but you between 160 to 190 we know that at 20 years follow-up they have a higher risk of CHD and mortality from CHD so maybe treat them early patients with chronic kidney disease we know their high risk how about chronic inflammatory diseases psoriasis HIV lupus for the first time we're talking about women history of premature menopause or history of pregnancy associated conditions preeclampsia pregnancy induced diabetes for the first time we are saying that when you're assessing risk of a woman to have a heart attack or stroke ask about their menstrual history ask about their gestational history and that is the reason because we know those women have higher risk of events if you see somebody age of at the age of 55 their 10-year risk is 8% but they had pregnancy induced hypertension guess what you should do probably start therapy early on and then some of the other biomarkers if you want to use and I wanted to just bring your attention to that this is the first time that the guidelines are actually picking that up and then there are some ethnicity associated factors for example South Asians we know get MI at a very very you know early age and it's very aggressive disease so that's also there in these risk enhancers so you calculate the risk bring the risk enhancers into the equation so this is how you would do it you do a 10-year risk okay there's a decision point decision for no drug therapy or even if you meet 7.5% and you have brought risk enhancers into the equation and if the patient is comfortable you're comfortable go ahead and start decision I mean you made a decision start therapy you don't have to do anything else but after that if there is any uncertainty on your part or the part of the patient then use a calcium score for further risk stratification such a three-step process as I said assess risk personalize risk make a decision whether you want to treat or not still uncertainty reclassify using an imaging study so don't do a calcium score on everyone and we know now that calcium score is very powerful and if the calcium score is zero well maybe you can withhold therapy for at least five to ten years and reassess if your calcium score is high above a hundred or above 75th percentile treat we know those patients have very high risk of events and then if it is between 1299 or less than 75th percentile generally most would say that go ahead and treat especially if you're above the age of 55 okay but this is a gray area so that's how we do it the whole risk assessment and personalization and this is what the calcium data is again if we say that 7.5% is a treatment threshold where we seem to think that you derive a lot of benefit from statin therapy this is what happened in Mesa study what they did was they did calcium scores and followed these patients this is at the follow-up of ten years if your calcium score was zero even when you had ten year risk that was above 7.5% look it provided you a good test which could be used as a decision support that the tenure event rates were below 7.5% if your calcium score was zero so you could potentially withhold therapy with some caveats don't do it on everyone only when it's uncertain okay and we can talk it talk about it as a question and that is why calcium score is there in the guidelines but remember if you're above 20% risk even if your calcium score is zero your tenure risk is still 11% the observed risk so you should treat so don't do calcium score in patients who are very high risk what I'm trying to tell you on the other hand if your calcium score was you know 1200 which is that mid category you can see it's all over the place right it's indeterminate some of them are above 7.5% some of them are just reaching 7.5% some of them are not so what I would suggest to you is use your clinical judgment always air on the side of treating patients early because we know that even at 5% risk they will derive a benefit and when it's above 100 we know that everybody almost everybody derives a benefit okay and again you're not going to do it in this category but you're going to do it in 7.5 to 20% and maybe some who are between 5 to 7.5% tenure risk so this is how we are I mean low risk right low risk lifestyle modification if you are high risk lifestyle modification and medication therapy if you're in this borderline risk do a discussion look at risk enhancers you're still uncertain the patient does not want to take statin therapy for their entire life do a calcium score and then decide where you fall so again estimate personalize reclassify those are the three steps so again we talked about this group the patients with diabetes as well as high LDL cholesterol we talked about this group if you don't fall into any of those two categories you do a 10-year cardiovascular risk assessment if the patient is low risk just lifestyle modification if you're high risk go ahead and do lifestyle modification but also treat don't do anything further if you're not in those categories and you're in this borderline to intermediate risk do some risk discussion look at risk enhancers if you have those enhancers treat even before enhancers if you have 7.5% you and patient are comfortable go ahead and treat you are going to be right only when there is uncertainty look at risk enhancers if there is further uncertainty on your part or the part of the patient then go ahead and do a calcium score these are the risk enhancers that we talked about but then if you're still uncertain go ahead and do a calcium score to give you an answer use it as a decision support not as a screening test is what I would tell you don't do it on everyone that's intermediate risk now I haven't talked about this group but this group is extremely important as well these guidelines actually talked about from the age of 0 up to the 39 years of age again these are the groups where you want to pick up FH kids who have family history of cardiovascular disease or a parent with FH and again 20 to 39 years you're going to estimate lifetime risk we don't do a 10-year risk because these equations we only do in patients 40 to 75 years of age but I just want you to remember that that part is also there so again take home messages emphasize a heart healthy lifestyle in everyone whether it's less than 5% more than 20% that's the key that's number one but then treat patients with LDL cholesterol above 190 and those with diabetes early and aggressively if you don't fall into those two categories then assess or estimate ACVD risk when you're 20 to 39 years it's a lifetime risk it's not a 10-year risk 40 to 75 years old it's 10-year ACVD risk if you're 40 to 75 year old you have diabetes use a moderate intensity statin therapy high intensity if you have some of those risk enhancers in diabetes if you don't have diabetes your 10-year risk you've done and your intermediate risk well you can start therapy right away based on multiple randomized control trials if you still want to then do the risk discussion bring risk enhancers into the equation if there's still uncertainty you can use a calcium score to be used as a decision support not as a screening test so again there was a lot of information I gave you I expect that if you can just remember that flow diagram we had which is directly from the guideline I think it will help you a lot and again if there are any questions later on then I'll take those as well thanks for your time