Management of Dyslipidemia

Hi, I'm Derek Angus, the senior editor of JAMA and host of Healthy Dialogue, a new podcast from the JAMA network. Join me as we go beyond the latest discoveries with nuanced, in-depth conversations with the world's leading experts to explore the most pressing issues in health and health care. On trends in autism diagnosis, to private equity acquisition, to AI, and much, much more, visit JAMANetworkAudio.com or search Healthy Dialogue wherever you get your podcasts to subscribe. Hello and welcome to our listeners around the world. You're listening to the JAMA Clinical Reviews podcast. Thanks for joining us. I am Dr. Philip Greenland, a senior editor at JAMA, and a professor of preventive medicine and cardiology at Northwestern University Fineberg School of Medicine. Today, we will be discussing dyslipidemia, evaluation, and management. And you can find a link to the article in this episode's description. I am joined today by Dr. Amber Johnson. Welcome Dr. Johnson. Can you tell the audience a little bit about yourself and your interest in this topic of dyslipidemia, evaluation, and management? Sure. Thank you. I'm happy to be here. Thank you for having me. My name is Amber Johnson. I am an assistant professor of medicine at the University of Chicago, where I practice as a general cardiologist and preventive cardiologist. I have a clinical practice where I see patients and clinic. And the majority of time I spend doing research, I do a clinical research, studying mostly social determinants of health and how they affect outcomes in different preventive strategies for preventing coronary artery disease and cardiovascular disease. Thank you for that background. You and your colleagues have written a guideline synopsis for JAMA on the topic of dyslipidemia. And before we get into the details of the recommendations from the guideline, can you just comment about the source of the guideline and the importance that you attach to the guideline itself and maybe your comments about how objective you consider the guideline to be? Sure. So this guideline statement is reflective of the 2026 guidelines on the management of dyslipidemia, which is a report from the American College of Cardiology and the American Heart Association, as well as a number of other organizations. It was published in March of this year, 2026. And it's an update from their prior version from 2018. I put a lot of importance to these guidelines as a cardiologist, as a preventive specialist. These guidelines really help us to think about risk factors for cardiovascular disease and ways that we can prevent them. Some of the new things that came out this year, which I know we're going to get into, is how we can think about lipid lowering therapy and how best to do that for different patient populations. Another interesting thing is that although I'm an adult cardiologist, these guidelines also talk about children who are at risk for atherosclerotic disease and thinking about how we can best risk stratify them. I think that the guidelines are objective and myself and my colleagues have reviewed some of those markers of objectivity. And so we in our guideline statement, we talk about how the guidelines have established transparency, the writing group and what the writing group consists of. There's diversity amongst the authors of the guideline, including cardiologists, internal medicine physicians, geriatricians, surgeons, pharmacists, dieticians, and so on. And because of that, we have rated that the developing group composition is rated at a level of good. And so we look at good, fair, poor, and across the board, they've pretty much been good. The one thing that we rated the group as being maybe more in the fair category is just with updating. And it's so hard. There's so much new data coming out every few months it seems and looking at different markers. So it sometimes is hard to keep up with the latest as these guidelines are being written. And so that's one area that we can talk about as some of the levels of evidence that maybe aren't as strong as what we would hope to see and as more data develop over the course of this year and the next several years. We will probably see new guidelines coming out in the next few years just talking about additional markers that we can use with stronger levels of evidence to support them. Oh, that's terrific. We'll try to come back to that later in the conversation. So were you a member of the writing group? No, I was not. One of my colleagues from the University of Chicago was a member of the writing group, but I myself was not. Okay, very good. So your summary is an objective view of how the guideline appears to the cardiologist, general internist, general medical community. Yeah, I would think so. I will also say that my co-authors include a lipid specialist from the University of Pittsburgh, Dr. Anum Saeed, as well as Dr. Andrew Davis, who is a general internal medicine physician. And Dr. Davis really kept us on task about, okay, so what would the general internists want to know about these guidelines so that we didn't get too into the weeds with our synopsis. And I think that helped us to provide a statement that is objective and hopefully helpful to a general audience. Okay, great. So let's get into the details of the guideline. What would you consider to be maybe the most important of the take-home messages? It's hard. These guidelines had a lot of top messages. And when you look at the document itself, they do a pretty good job of what are the top 10 things that they would call their take-home messages. And others have published what they feel their top 10 things are. But what we summarized as our selected recommendations were five things. We really tried to keep them at the five things that had the highest level of evidence, the most support from randomized controlled trials. And so that the class of recommendations were level of evidence A for each of our recommendations as our selected recommendations. So for example, one thing that I think is really important to highlight is how the guideline is using a risk stratification tool that allows us to think about one's 10 and 30 year ASCVD risk. And so, aphorosclerotic cardiovascular disease can be predicted in terms of risk of 10 years. And traditionally, and up until this guideline, we were using risk tools that would predict 10-year risk. And most of us were using the pooled cohort equation. More recently, we've seen with the hypertension guideline and now with the lipid guideline, we are now being encouraged to use the prevent ASCVD risk calculator for various reasons that we don't necessarily have to get into. But one of the interesting things and very useful things about the prevent calculator is it allows us to look at 10-year risk as well as 30-year risk for developing ASCVD or aphorosclerotic cardiovascular disease. The reason why that 30-year risk is important is because there may be some populations for which, some patients for which we calculate a 10-year risk. And maybe it's not high or maybe it's intermediate, but when we look at the 30-year risk, that may actually change our management for lipid lowering therapy or for targeting outcomes of therapy. We know that the duration of time at which people have dysliplidemia increases their lifetime risk of developing disease and in the long term can predict cardiovascular outcomes. And that is one of the major things that we highlighted with the synopsis statement. Let me ask you also about the age of the people that are recommended for risk prediction. Was it changed in the new guideline? It was. So again, with the prevent calculator, we are able to use it starting at age 30, which is an update compared to looking at starting to risk predict at age 40. As we've seen in clinical practice, it used to be a challenge where we had someone who was younger than 40 and we were unable to accurately calculate their risk. So now we have a little bit of a better idea for adults who are age 30 up. We also in this guideline have recommendations for children and so doing a screening lipid panel starting at age 9 and then considering repeating that around age 19. Okay. Thanks, that's really helpful information and some new things that people are going to to have to get used to in clinical practice. What about any recommendations that they had about lipid lowering therapy? Anything new there? So with regard to lipid lowering therapy, the guideline this year has updated some recommendations about which therapies are considered level of evidence A and recommendation level one. Those continue to include statins, azetamib, PCSK9 inhibitors are listed with more support this year as well as bempidolic acid as being considered for maybe an adjunctive therapy for those whose LDLC does not reach target or perhaps are unable to tolerate statins as their primary therapy. Are there other medications that one would consider and the guidelines do go over what those options are? However, the data do not support their use as first line therapies. What about the targets of therapy that LDL levels that the new guideline recommends? Are there any changes there? There are some changes, yes. And the changes should be thought of within the context of the level of someone's risk. So for individuals who are at higher risk for ASCVD, those would include people who have already had clinical ASCVD. And so in the past we would consider that as secondary prevention. One of the things that I really appreciate about the guidelines this time is they help us to think about the populations and the continuum of risk that people may have. And so we can think about people who have clinical ASCVD. And so those are people who have had an ischemic stroke or perhaps an MI or peripheral artery disease in the past. We can also think about people who have subclinical ASCVD. And so our risk that we will assign to people with subclinical ASCVD is a little bit higher than perhaps we would have assigned in the past. And so therefore our treatment goals are a little bit different. And then even for primary prevention groups, we've been thinking about how other comorbid conditions can increase risk more so than what we perhaps had been thinking about in the past. And so in talking with some of my primary care colleagues, there tends to be a little bit of a surprise that so many people are recommended to be at lower goals. And that's because we have the data to support that having conditions such as chronic kidney disease or having conditions such as hyper-triangleceridemia at younger ages, those put people at a higher risk category. And so to answer your question, for depending on one's risk, so for our individuals who are at very high risk or high risk, our LDLC goal is less than 55 milligrams per desolate year now. We can also think about dyslipidemia beyond just LDL and perhaps that's a topic that will come back to, but we can have treatment goals aside from just LDL. We can think about non-HDL cholesterol. We can even measure other markers like APOB that will help us to think about what our targets should be as we are initiating people on therapy and then monitoring their outcomes over time. Okay. Thank you. I'm very grateful. Want to ask you about the recommendation concerning measurement of Lycoprotein Little A? Can you talk about that a little bit? I'm really excited about Lycoprotein Little A. It's something that I think a lot of cardiologists have had in their practice for some time. And so it's nice to see that this guideline statement is now supporting that. So the recommendation is that for adults who you are screening for risk of ASCVD, all of them should have at least one Lycoprotein Little A checked in their lifetime. So why is that reasonable to do it just once in their lifetime? Well, because at this point, we don't have any treatments that can lower Lycoprotein Little A reliably. There's been actually some decent data to suggest that PCSK9 inhibitors may lower Lycoprotein Little A. Stattons may actually increase Lycoprotein Little A. And so because there's not great data on what we should do in terms of serial measurements, it's really important to at least check once so that can help us to establish what one's risk may be. And then that helps to guide the conversation about what lipid lowering treatment may look like for that patient. So how would that be incorporated into the overall risk assessment or is this an addition to the overall risk assessment? This is an addition to the overall risk assessment. Right now, our risk calculators do not include the Lycoprotein Little A level in determining risk. And so in addition to perhaps checking a prevent ASCVD score, we would also check a Lycoprotein A. There may be some patients for whom their Lycoprotein Little A increases their risk based on the guideline. And so for example, what we consider elevated is a Lycoprotein Little A level greater than 125 nanomoles per liter or 50 milligrams per desolate. So if your number is at or above that cutoff, that would be considered a risk enhancer that would be used in consideration in addition to the prevent ASCVD score. And so that may help to frame the conversation a little bit more, especially every you're seeing that the one level may be high and that is perhaps discrepant to the other level that you're checking. Okay. Also wanted to ask you about the recommendation about coronary artery calcium measurement. I know that it's a different recommendation than we've seen in the past. Would you comment about that? The coronary artery calcium score, the way the measurement is determined is based on Agustin units. And then that is compared to similar age, sex and race cohorts. And so the score that you would get would tell you what's the likelihood that other patients like yourself, other individuals like yourself would have that same level. Because what we're using the coronary artery calcium score for now is also as a risk enhancer. So similar to the LIBO protein A, we can use that coronary artery calcium or CAC score. I think that that's a great recommendation to include. What we find though is by the time the coronary arteries have that calcification, we may be on the time frame for which we could have been more active in preventing the development of disease. That brings me back to the concept of checking for patients at younger ages and thinking about the 30 year risk. For our younger patients, we may not find an elevated coronary artery calcium. And so although I do agree that the coronary artery calcium is important, if it's high, then that's important to include and think about and would even classify someone more as a subclinical AACVD, as opposed to in the past, we might think of a primary prevention if they've not had an event yet. If someone has coronary artery calcium, then we know that they have disease. And so our risk prediction and our treatment targets are that much more aggressive. So that does still leave some room for our younger patients for whom their coronary artery calcium score may still be low. That doesn't necessarily mean that they're out of the woods. Great. That's really helpful. I have one more question for you and that has to do with shared decision making. Yes. And I know this is a big issue in the previous guidelines it's mentioned very strongly in the new guidelines. Could you comment about how you deal with that yourself in your own clinical practice? That's a great question. The more that I've been in the preventive cardiology space, the more I can see that sometimes there's a dichotomy of patients that I will interact with. For example, there are some patients who are worried they want to treat their cholesterol as much as possible and they'll do everything that they can. Whereas there are some patients who maybe they're not so worried and they take some convincing to achieve a heart healthy lifestyle and make the lifestyle modifications and add lipid lowering therapy to their medication regimen. And so there's a nuanced conversation that I will have with my patients that depends on what their goals are for their care. And from my perspective, especially having reviewed these guidelines, having reviewed the primary literature that more clearly help us to understand how dyslipidemia affects cardiovascular risk, I encourage my patients to pursue in addition to lifestyle modification, lipid lowering therapy. And I also try to set some expectations that sometimes it's not just a single medication, sometimes you need an elixir or a cocktail, a whole regimen of medications to get the lipids to where we need them to be. And so that all becomes part of the conversation with each individual patient and it does need to be nuanced based on the patient's background and their goals and again coming back to shared decision making as you asked. You mentioned one thing about updating and you said that that was maybe a limitation of the guideline. Is there one or two things that you would say you think are going to be just beyond the horizon now that we should be thinking about for an update? Definitely. Thank you for asking that. So my co-authors and I really toyed around with the idea of including APOB as one of our top recommendations. Right now the use of APOB as a target for therapy or as a risk predictor as we are starting people on therapy or talking about with their risk is APOB right now stands at a level 2B or 2A level. And we didn't include that in our selected recommendations because it wasn't at a level one. However, I do think that as more data come out in support of monitoring APOB with therapy or perhaps treating to a target APOB, we may start to see that the level of evidence will be even stronger. And so right now we see that the guideline will say that an APOB target for our patients who are at high risk should be less than 55 milligrams per desoliter. We're sort of using that as an adjunct. In the future we may be seeing that as part of our central recommendations. Another thing that we're getting more data on and we're very hopeful and excited and Dr. Greenland I heard you give a talk about the trials for LIPOPROTEAN LITO-A. And we're hoping to see that LIPOPROTEAN LITO-A can become a treatment target and that there are medications that are available that we might be able to use to decrease risk even more so than our current regimen that we have. Okay terrific. Before we close is there any other thing that you want to mention that you think we haven't covered yet? Yes, I would say other risk enhancing features that are important and raised by the guideline this time around include high-risk patient populations. For example, people living with HIV, people with chronic inflammatory diseases as well as people who have had adverse pregnancy outcomes such as preeclampsia. And so for these patient populations it's important to have a nuanced consideration of their risk factors and risk enhancing factors and to consider lipid lowering therapy even at earlier ages than would the risk score suggest? Okay well I think we've covered a lot of territory about this new guideline and the overall approach to assessment and treatment of dyslipidemia and I really want to thank you for spending time with us today. I am Dr. Philip Greenland and I've been speaking with Dr. Amber Johnson about dyslipidemia assessment and treatment. You can find a link to the article in this episode's description. This episode was produced by Daniel Musisi at the JAMA Network to follow this and other JAMA Network podcasts. Please visit us online at JAMANetworkAudio.com or search for JAMA Network wherever you get your podcast. Thanks for listening. This content is protected by copyright by the American Medical Association with all rights reserved, including those for text and data mining, AI training and similar technologies.