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 UCSF. 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 UCSF. 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 going to 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 lipoprotein, uh, molecules, and some of the most famous ones we know about are LDL, uh, LDL and, and as, as well as LDL is VLDL, very low density lipoprotein and low, low density lipoproteins. Why we care about these are, is, is that we know that they promote um the, the disease process of atherosclerosis, um, and that's been very clearly proven. Um. Um, non-HDL, um, is the combination of these two atherogenic, uh, uh, types of, uh, molecules. Uh, LDL and VLDL. Um, VDL, VLDL also carries, uh, triglycerides, um, and, uh, again, this, this combination of, of molecules we know as, as, uh, disease-promoting. Um, we also know about apolipoprotein B, 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 LDL and VLDL and has been shown to have a strong correlation with atherosclerotic, uh, heart disease. Um, and lipoprotein A or uh LPA is, is how I, uh, how I like to say it is, is also a form of, uh, LDL associated with, uh, apolipoprotein A, which is attached to apolipoprotein B. Um, what's interesting about LPAA is that it is, uh, mostly genetically determined and, and it's fairly stable over a patient's life. Um, I see providers, um, some providers check LPLA, 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 going to be elevated with maybe some variation, but, um, you know, that's how it's been studied. Uh, 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 LPA is, uh, the, the risk with LPAA is independent of LDL. So you could have a person with a normal LDL and elevated LPA 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 LDL is typically better. Um, you know, rarely see, you know, LDLs, you know, less than 10, um, rarely. Um, so we typically try to get, get the LDL lower, especially for the high, highest-risk people. And we'll talk more about that. Um, measurements. So, uh, there, there's, uh, uh, an equation to calculate LDLC or LDL calculated LDL. Um, this is typically calculated for us, uh, by our labs. Um, uh, what I think is, uh, important to remember is that LDL does not typically change much, um, when or after someone eats. Um, and so, fasting, we oftentimes order fasting, uh, LDLs, fasting lipid panels. Um, the data does not, uh, show necessarily that there's a difference in LDL, significant difference between, uh, fasting and non-fasting LDLs. Um, and, you know, similarly, uh, fasting and non-fasting measurements of triglycerides and HDL, 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 non-fasting. 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 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, uh, 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, lipoprotein molecules like LDL, um, you know, have a strong correlation with, uh, atherosclerotic heart disease. Um, in general, an LDL 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, a 1% decrease in the LDL can correspond to a roughly, you know, 1% reduction in, in cardiovascular risk. So that might be something if your parent, uh 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 AOB, Apolipoprotein B, and, um, LPAA, you know, AOB greater than 130 and LPAA 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 ACC American College of Cardiology, American Heart Association guidelines. Um, so this is the one I use, um, um, and probably the, the, the audience, uh, is familiar with this one. You can go on the ACC.org website to find this. Um, and it takes into account, as we all know, lipids, 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, do remember that. So, um, that calculator has actually been, you know, it's, it, 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 MSA series of studies. MESA standing for the Multi-ethnic, uh, Study of atherosclerosis. Um, you know, pioneered by, uh, Matt Budoff, um, and colleagues down in Los Angeles. Um, and this calculator incorporates the, uh, 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 ACC, um, risk calculator, um, might overestimate risk. But like, for example, if, if someone had, um, you know, elevated LDL 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 a, a, a zero coronary, coronary artery calcium score. Um, and so this This calculator can be used to help 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, I 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, dietitian. 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, ACC also espouses this, the 150 minutes of moderate to 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, uh, 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, uh, 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, um, you know, we're mainly counseling lifestyle changes and assessing or, um, screening for, uh, familial hypercholesterolemia. 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, hypercholesterolemia, and, you know, if they're, if, if they have significant risk, you know, if their LDL is above 160, the guidelines, um, suggest, uh, considering a statin. Um, you know, for the most part, at least for most of my patients are, you know, between, or, or above the age of 40. And, you know, those are the patients um with which, you know, you start to think about, you know, uh, uh 10-year uh uh uh risk assessment, um, checking their LDL 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 bucket, 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, statin 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 0, but if you have a patient who has a calcium score of, you know, 1500, um, You know, usually their LDL probably would be elevated. You're probably gonna put that person on statin therapy. Uh, 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, 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%. LDL lowering, um, and, uh, our goal LDL 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 LDL 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, uh, 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, 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, uh, in a high-risk category. Uh, diabetes, a little bit on, on diabetes and 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 you don't even need to do a one year, sorry, a 10-year risk assessment. Um, they're, you know, they're, they're based on guidelines, they should automatically be on moderate intensity statin. Um, class 2A 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 statin. Um, um, another sort of, uh, smaller group is severe or familial hypercholesterolemia, Class one indication. If you have a person who has an LDL of 220, you know, that person probably has, um, heterozygous familial hypercholesterolemia, and they, you know, based on the guidelines, should be on, um, high, you know, maximally tolerated statin therapy and ideally high-intensity statin. Um, So, and we'll get, get more into sort of 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, statins, statins are first-line therapy. Um, and then, you know, next line is, is, uh, ezetimi or, or Zetia. 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 VEA, um, um, which targets, uh, which is an icosaan ethyl, uh, molecule with high levels of EPA, um. It has been shown in randomized clinical trials and it is is approved for hypertriglyceridemia. Um, Lovaza, which is a, you know, a branded form of omega-three ethyl ester, um, has high levels of EPA and DHA. Um, I, I, I don't use it as much, um. Um, but that's, that's in the guidelines as well. And PCSK9 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, atorvastatin and rosuvastatin. 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 atorvastatin and at least 20 mg of rosuvastatin. 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. Uh, these are actually, you know, approved therapies, uh, ben benpadoic acid, um, which inhibits LDL production in the liver. Um, uh, this is a newer LDL agent. Um, inclioran, which was, uh, just, uh, approved, I think, uh, FDA approved a year or two ago. Um, actually, uh, um, small interfering RNA agent, um, and actually has very strong, uh, 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, andjuxapin 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-threes 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 paucity of data. Um, so these are the guidelines, um, the 2018, um, 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 of the prognostic benefit um of, of coronary artery 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, um. And you can see that, you know, um, you know, the blue lines, which are the coronary calcium scores of 0, and this is tracking mortality, um, um, looking at the difference between coronary calcium of 0 versus coronary 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 low 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 the 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, 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 5 years, you can see mortality is almost um. You know, uh, you know, minimal, like, uh, so, so Kaplan-Meier curve, um, uh, you know, almost, almost, um, very low rates of mortality in patients who have minimal coronary calcium. Um, and I think this is my final topic. Um, what about, uh, familial hypercholesterolemia, 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 LDL of 200, but then they end up getting a coronary calcium score and it's 0. What do we do about that? Um, so, you know, this study from, uh, fairly recently showed that, you know, almost 50% of patients with heterozygous familial hypercholesterolemia had coronary calcium scores of 0. Um, And this was another study looking at, again, familial hypercholesterolemia. Heterozygous hypercholesterolemia patients, you know, usually, you know, LDLs 190, 200, 210, you know, if their coronary calcium scores 0, which is the red line, their survival-free rates from major adverse cardiovascular events is, you know, almost 100%. Uh, 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 hypercholesterolemia, um, guidelines say, well, you, that person should be on a statin. Uh, 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 I'd love to hear if there are any questions.
