Cardiologist Clifton Watt, MD, presents an update on lipoproteins, including how genetic factors can impact test results and whether pre-measurement fasting actually matters. He discusses two commonly used risk calculators, with caveats on interpreting results, and gives prevention algorithms for patients based on age group and cardiovascular risk. Bonus: Learn a simple equation for 1% risk reduction that you can use to motivate patients with high LDL levels.
Uh As I was asked, I'll tell a little bit about myself. Um As Doctor Chang said, I'm a cardiologist here in the Bay Area. Um at U CS F, I am a non-invasive cardiologist uh with special interest in imaging, cardiac imaging, as well as structural heart disease and participate in the structural heart program um at U CS F. Um So, you know, talking about lipids, you know, I'm a general cardiologist as well. Uh uh and, and talking to this audience here. Uh You know, maybe I feel uh you know, I may be preaching to the choir um about lipids. Uh But I'm happy to uh give a review uh likely to, to, to the audience here and I'll, and I'll jump right in. So we'll talk about lipids and management of lipids at, at the current time and I'll try to provide salient points here because as I said, this is gonna be a review for, for, for all of us because we see this all the time. So basics and not to go over too many, too many uh you know, uh basics because we all know it. But cholesterol, cholesterol uh in, in in our body is transported by multiple different carrier lipo protein molecules. And some of the most famous ones we know about are L D L uh um L D L and, and as, as well as L D L is V L D L, very low density lipo protein and low low density lipo proteins. And why we care about these are, is, is that we know that they promote um the the disease process of aosis. Um And that's been very clearly proven. Um um non H D L um is the combination of these two agentic uh types of molecules. L D L and V L D L. Um V D L V L D L also carries uh trigly rides. Um And uh again, this, this combination of, of molecules we know as, as a disease promoting. Um we also know about a lipo protein B E and this is, this is something that is uh less commonly used, but something that I use for my high risk patients to check. Um it's a, it's a protein that's embedded in both L D L and V L D L and has been shown to have a strong correlation with AO uh heart disease. Um and lipoprotein A or uh LP Little A is, is how I uh how I like to say it is, is also a form of uh L V L associated with uh April lipoprotein A which is attached to April lipo protein. B, um, what's interesting about LP Little A is that it is, um, mostly genetically determined and, and it's fairly stable over a patient's life. Um, I see providers, um, some providers check LP Little A, you know, once a year. Um, there's actually no data to support, uh, doing that. Um, because again, it's, it's something that's stable and, you know, genetically mediated. So if it's elevated, um, when you first check it, it's probably gonna be elevated with maybe some variation. But um you know, that's how it's been studied. Um is, you know, it's a marker that's um stable for the lifetime. And um it's associated with um elevated cardiovascular risk. And what's important to know is that elevated LP Little A is uh the, the risk with LP Little A is independent of L D L. So you could have a person with a normal L E L and elevated LP Little A. And that person we, we understand is, is at elevated uh cardiovascular risk. Um So these are some of the, some of the basics we all know about. We also know, you know, in general, uh especially as a cardiologist. I, I like to espouse the, the concept of lower, lower L D L is typically better. Um you know, rarely see, you know, L V L s, you know, less than 10 rarely. Um So we typically try to get, get the L D L lower, especially for the high, highest risk people and we'll talk more about that um measurements. So uh there, there's uh uh uh an equation to calculate L D L C or L D L calculated L D L. Um This is typically calculated for us uh by our labs. Um uh What I think is uh important to remember is that uh L D L does not typically change much um when or after someone eats. Um And so fasting, we oftentimes order fasting uh L D L s fasting lipid panels. Um The data does not uh show necessarily that there's a difference in L D L significant difference between uh fasting and nonfasting L D L s. Um And, you know, similarly, uh fasting and nonfasting measurements of triglycerides and H D L, you know, there's not really any been shown to any be any difference in prognosis. Um But, you know, we, we still do often check uh fasting lipids. Uh Even though even though uh you know, there's not a lot of data showing that there's a benefit in, in fasting over nonfasting. But um what, what we do see is that there can be a, you know, impact uh particularly with a high fat meal um on triglycerides. Um So triglycerides, if, if you have someone who has a very high triglyceride levels and uh level and, and you know, that was unexpected to you, you know, might be, might be reasonable to, to repeat a fasting uh uh lipid panel to, to reassess that. So, you know, why do we care about lipids? Of course, we know that uh as, as we said earlier, lipids, um particularly some of these um uh lipo protein molecules like L D L, um you know, have a strong correlation with uh acle heart disease. Um in general, an L D L less than 100 corresponds with lower risk. Um And actually, you know, it, there's actually language in the guidelines. Um uh that uh uh a 1% decrease in the L D L can correspond to a roughly, you know, 1% reduction in, in cardiovascular risk. So that might be something if your parent, your, if your patients uh want to are, are into numbers and wanna wanna uh know about these types of numbers that might be something to communicate. Um And there are cutoffs with regards or, or uh I I, yeah, cutoffs in terms of A O B A protein B and um LP little A, you know, A O B greater than 1 30 LP little a greater than 50 corresponding with higher risk. Um So, um how do we assess risk aside from um um uh the lipids? And this is, this is uh what I'm tasked to sort of review with, with the audience. Um We, we know about um risk calculators um which take into account, not just lipids but um other factors and this is uh the, this calculator off of the American College of Cardiology website is the one that's referenced um by the AC C American College of Cardiology American Heart Association Guidelines. Um So this is the one I use. Um um and probably the, the the audience is familiar with this one. You can go on the AC C dot org website to find this. Um And it takes into account as we all know, limits age, patient, age, patient gender, um ethnicity, um and blood pressure among other things. Um Do you remember? And this is, you know, a situation that I encounter with patients sometimes is this risk calculator? Really um uh should be used for patients between the age of 40 and 79. Um It actually doesn't let you if you, if you input a person, you know who's 30 years old, I don't, I don't think the calculator actually will generate any data. Um So, do you, do you remember that? So um that calculator has actually been, you know, it's, it's been known or, or, or, or found to overestimate risk um uh cardiovascular risk. And so uh this, there is this other calculator that I oftentimes use uh for risk assessment. Uh the mesa risk calculator based on uh the MESAS series of studies, MESAS ending with the multi ethnic uh study of aosis um you know, pioneered by uh Matt Budo um and colleagues down in Los Angeles. Um And this calculator incorporates the uh cal coronary calcium score. Um And so as, as the audience probably knows, uh you know, coronary calcium scoring can be something that can be used to um uh reclassify or shall we say declassify uh risk or, or put someone in a lower risk group that um originally, if you just use the AC C um risk calculator um might overestimate risk. But for example, if, if someone had um you know, elevated L D L but actually has a zero coronary artery calcium score, um that person probably would be reclassified from a, you know, a higher risk group to a lower risk group given AAA zero coronary artery calcium score. Um And so this, this calculator um can be used to help um with that and we'll, we'll talk more about coronary calcium in a second. Um So we, we've talked about lipids, we've talked about risk assessment and, you know, at the core of this, I of course, have, you know, have to put in the slide about diet and exercise, which is which we all know, we, we all counsel our patients about and this, this first line is um a quote from the guidelines um from 2018. Um of course, a heart healthy lifestyle is crucial and something that we need to um emphasize to our patients. Um One other tips that uh I'm sure the audience uh may use, you know, uh consultation to nutrition or diet counseling can be helpful. Um Some of my patients ask me to, to refer them to a, uh, dietician. Um, I, I usually don't have enough time to go over someone's diet, but, um, in, in detail, in great detail. But uh, oftentimes that's what patients only want to talk to me about is what should I eat, how should I eat and how much should I eat. Um, and of course, you know, we all know about the, the CDC, the physical activity for Americans guidelines. Um you know, AC C also espouses this the 150 minutes of moderate to vig too vigorous physical activity a week or 75 minutes a week of um high intensity physical activity. Um These are, these are numbers that I um talk to my patients about because patients like numbers in general. Um So, so speaking of primary prevention for heart disease, um so this is from the guidelines from 2018. Um uh it's a busy slide but um we, we all know the gist of, of primary prevention. Um But uh you know, if, if we were to sort of boil it down, um you know, looking uh looking at age groups, you know, the, the folks younger than 20 you know, we're mainly counseling lifestyle changes and assessing or um screening for uh familial hyper cholesterol Leia. Um the the group, you know, 20 to 40 years old. Um again, lifestyle um checking lipids, of course, um screening, screening for familial uh hyper cholesterol Leia. And, you know, if they're, if, if they have significant risk, you know, if they're L B L s above 1 60 the guidelines um suggest, um considering a stent. Um, you know, for the most part, at least for most of my patients are, you know, between or above the age of 40 and, you know, those are the patients uh with which, you know, you start to think about, you know, uh a 10 year uh uh as a risk assessment, um checking their L D L and, and really, you know, discussing, you know, medical therapy if, if uh if indicated. Um So in terms of the risk calculator, you know, we all know about, you know, putting, putting um putting patients into these pocket buckets, um you know, low risk, intermediate, high risk, um and these numbers, these percentages we, we can get from the calculator. Um and uh that impacts our, our, our assessment of whether a patient should be on statins or not. For example, uh probably our, our biggest uh decision point um uh statin statton in initiation. Um And uh you know, you know, oftentimes our, our patients are in the middle, I mean, if it, if they're, if they're low risk, you know, or, or if they're very high risk, then it, you know, our decision may become quite straightforward, but, you know, in the patients who are borderline or intermediate, those are the more, you know, challenging patients um and that's where the coronary calcium scoring comes in. Um you know, and, and as I, as I mentioned earlier, you know, this can help um you know, reclassify someone's risk um higher or lower. Um So, I mean, if you have a person who has um we talked about a calcium score of zero, but if you have a patient who has a calcium score of a, you know, 1500 you know, usually their L D L probably would be elevated. You're probably gonna put that person on statin therapy, a secondary prevention, you know, someone who already has a diagnosis of, of heart disease, um you know, probably, you know, I as a cardiologist will be seeing these patients. Um but uh you know, just for the sake of time, I I can sort of this uh speed through this one but, you know, you know, most of these patients will be on statins um to, to, to keep it short. And um you know, we're, we're really aiming for greater than 50% L D L lowering. Um And uh our goal L D L would be less than 70. Um and actually in, in the European guidelines, there is language based on data that says that if, if someone's at extreme high risk, you know, goal L D L would be less than 55 actually. Um But that's not yet in the uh um us guidelines. Um and this is a busy side, but just to expand on the um uh question of, of a high risk uh sorry, not at very high risk or at very high risk. And that's where the branch point here with this, with this algorithm comes in um very high risk patients, you know, have some of these conditions, you know, for example, recent um heart attack, recent stroke, um uh high blood pressure diabetes. Um these are, these are a lot of my patients. So, so, um so essentially a lot of my patients end up on statins if they're, if they're in a high risk category, um, diabetes a little bit on, on diabetes in a time check here, diabetes and, and uh heart heart disease, you know, class a recommendation, you know, uh moderate intensity statin therapy is indicated and, and you don't even need to do a one year, uh sorry, a 10 year um uh risk assessment. Um they're, you know, they're, they're based on guidelines. They, they should automatically be on moderate intensity statin. Um, class two a recommendation is if, if uh if, if their 10 year um heart disease risk um is, is extremely high, then, you know, you can bump that person up to a high intensity standard. Um um another sort of uh smaller group is severe or familial hyper cholesterol Leia class one indication. If you have a person who has an leo of 220 you know, that person probably has um heterozygous familial hyper cholesterol Leia. And they, you know, based on the guidelines should be on um high, you know, maximally tolerated statin therapy and ideally high intensity stat. Um So, and we'll get, get more into sort of the nuances of that in a second here. Recommended medical therapy. I don't have to go into too much detail because you all know this but statins, statin statins or first line therapy. Um and then, you know, next line is, is uh is Edom or, or Zia um really fibrates and NIACIN are really further down the, the, you know, recommendation chart. Um they can target and be used for triglycerides. Um There is language um for the um um which targets uh which is an I I I ethyl uh molecule with high levels of EPA um has been shown in randomized clinical trials and it is, it is approved for hypertriglyceridemia. Um Lovaza which is a, you know, a branded uh form of Omega three ethyl um has high levels of EPA and DH A. Um I I, I don't use it as much. Um um but that's, that's in the guidelines as well and P CS K nine inhibitors, which, which are, you know, frequently used for high risk atherosclerotic disease patients. So, uh you know, I think it's important for us to know about high, moderate and low intensity statins. Um uh for the sake of time. Uh you know, I, I, I won't spend too much time on this, but, you know, high intensity statins we know are, are considered uh a tort and Sutin and don't forget, you know, dose, dose matters. Um, you know, when we're talking about high risk patients, um you know, you're, you're talking about at least 40 mg of a statin and at least 20 mg of the. Um I, I'll, I'll, you know, briefly go over, you know, these other lipid therapies which the audience may or may not be familiar with, which uh and these therapies I sometimes use and these are actually, you know, approved therapies, uh Ben, Ben do acid um which inhibits L D L production in the liver. Um uh This is a newer L D L agent um in C ran which was uh just uh approved, I think uh F D approved a year or two ago. Um actually a um small interfering R N A agent um and actually has very strong uh in my opinion, uh strong data, it's an, it's an injection um once every 3 to 6 months. Um So that may be something that can change the landscape a little bit. Um And Juxtapid is a very rarely used medication for familial uh typically um homozygous um hyperlipidemia. Um We try not to, you know, I try not to recommend over the counter, recommend uh over the counter um Omega three or fish oil really not uh not in the guidelines and not really shown to be clearly beneficial patients still take them. But um I, I, I, I let them know about the positives of data. Um So these are the guidelines, um the 2018 guidelines on management of lipids that I encourage folks to look at, you know, there's a 2019 set of guidelines on primary prevention, um skip this slide for the sake of time. And you know, and the, the final topic is coronary calcium scoring. And just want to emphasize uh these, this topic of how um uh how the, the how of the prognostic benefit um of, of coronary art calcium. So this is a study um looking at coronary calcium scores in both men and women, um women on the left men on the right. But um and you can see that, you know, um you know, the blue lines which are the corneal cal calcium scores of zero and this is tracking mortality. Um um looking at the difference between corneal calcium of zero versus corneal calcium of 400 especially in the women, you know, on the left uh panel, you can see, you know, this very significant difference between um uh the coronary calcium, um the high and the low cord or high and the zero coronary calcium groups showing that this can be a very strong uh predictive uh uh marker even going out 15 years as you see this study um does. And this is, this is a um also a a registry study including a lot of patients, one on the east coast, one on the left, uh uh uh a west coast, um thousands, tens of thousands of patients also showing, you know, remarkably, you know, the top line um in both studies, registries is the coronary calcium score of 0 to 10, you know, even going out five years, you can see mortality is almost, um, you know, uh you know, minimal like So, so Kaplan Meyer curve, um uh you know, almost, almost um very little rates of mortality in patients who have minimal coronary calcium. Um And I think this is my final topic. Um What about a familial hyper cholesterol Leia uh uh and zero coronary artery calcium score. Um And that's actually a situation that I encounter uh not infrequently a patient who has an L D L of 200 but then they end up getting a coronary calcium score and it's zero. What do we do about that? Um So, you know, this study from fairly recently showed that, you know, almost half of patients with heterozygous familial hyper cholesterol Leia had coronary calcium scores of zero. Um And this was another study looking at again, familial hyper cholesterol Leia, heterozygous hyper cholesterol imia patients, you know, usually, you know, L E L S 1 92 100 to 10, you know, if their coronary calcium scores zero, which is the uh red line, their survival free rates um from major adverse cardiovascular events is, you know, almost 100% that they do really well. Um So, you know, even though the, the guidelines say if you have a patient, um who has, you know, severe hyper cholesterol Leia, um guidelines say, well, you, that person should be on a statin, you know, if you do end up assessing a coronary, coronary calcium score and it's zero, then, you know, that may be a situation where you can say, you know, you probably don't need a statin. Um I think that's it, it's 8 28. So um that's my, that's my talk. I know uh um this is a review review for, for, for all. So love to hear if there are any questions.
