Hi, my name is Mark Binaca, and on behalf of the American College of Cardiology, I want to welcome you to this panel discussion around peripheral artery disease. This is a CME activity really focusing on diagnosing peripheral artery disease and ongoing risk stratification. And I'm joined today by just the most amazing panel of colleagues, friends, and experts here where we're going to have a discussion around this really critical topic. Just for a moment, I want to show our disclosures. And then I want to just go around the panel here and do some introductions. So my name is Mark Binaca. I'm a cardiologist and vascular medicine doctor at the University of Colorado School of Medicine. Dr. Gutierrez, do you want to introduce yourself? Thank you, Mark. My name is Tony Gutierrez. I am from Duke University Medical Center. I specialize in interventional cardiology and vascular medicine. Thanks Tony. Dr. Hamburg. Hi, I'm Naomi Hamburg. I'm a cardiologist and vascular medicine specialist, and I'm at Boston University School of Medicine. So glad to be here. Thanks, Naomi. Great. And Dr. McNeil. Hello. Hello. I am on faculty with you, Dr. Binaca at University of Colorado School of Medicine. I am a research scientist specializing in communication science, as well as health disparities and health inequities, as well as cardiovascular disease. Great. Thank you, Dr. McNeil. And Dr. Pollack. Hi, my name is Amy Pollack. I practice cardiovascular medicine at the Mayo Clinic in Florida. Wonderful. And while this is an ACC activity, I just want to acknowledge that there's great representation from American Heart Association here as well with Dr. Hamburg, who leads the PVD Council, and Dr. Pollack, who has led a tremendous effort in PAD awareness. So I think we're going to touch on many of those topics in our panel discussion here. So I want to spend the first part of our discussion talking around diagnosis of peripheral artery disease. And we know it's underdiagnosed. We know that patients don't present in a typical fashion, and there are confusing, conflicting guidelines about should you test or screen or should you not? So I'd love to hear your personal wisdom about what you do when you see patients or what you do in the clinic or how you might advise folks when it comes to diagnosing peripheral artery disease. Who are the patients you worry about? What are the kinds of symptoms that sort of catch your attention? And maybe we'll just go in order on the screen here. And I'll start with Tony. Go ahead. Mark, that's an excellent question. I would say there are certain subgroups of patients that I am particularly concerned about. As you know, patients with diabetes, chronic kidney disease, also, in particular, if patients have had, already have a diagnosis of atherosclerotic disease in another vascular bed other than the leg. So if they had a prior MI or a stroke, these are the patients that I'm always kind of worried about and asking what their symptoms are. Great. Thank you, Tony. And Demetria, what are your thoughts here? So I really like what Tony said here. What I will add when you're thinking about the types of patients that you are most concerned with, the only thing that I'll add to what Tony mentioned is race. We all know when we're talking about cardiovascular disease, particularly peripheral arterial disease, that Black American patients have a significantly higher not only incidence but worse outcomes when it comes to this disease. So the ask is to also consider when you have the sort of the perfect storm of the traditional risk factors, those that we know to look for, that we also think through and consider race as well. Great. Thank you, Demetria. A really important point. Maybe Naomi, then, if you want to comment, maybe comment a little bit on your experience in terms of how people present with PAD. What are the kinds of symptoms that you sometimes hear about? Yeah, that's really important. We think when we're in medical school, we often learn about classic intermittent claudication. So we have the case where we have a patient who walks, gets cramping in the leg, and that goes away when they stop. But we know now from a whole series of studies that many people who have obstructive peripheral arterial disease present with atypical symptoms. And what do we mean when we say atypical symptoms? And I think we mean a couple of different things. One is that people describe what's happening in their legs in different ways. So people can describe having tiredness, heaviness in the legs, not being able to keep up, and not really sure why. And then the other is that a lot of times these are patients who are older and they have overlap disease. So they have different reasons to have leg pain. So they may have diabetes and have peripheral neuropathy. They have spinal stenosis. And so we have people who say that their legs hurt, and they may hurt for a whole series of reasons. And we really need to delve into whether obstructive peripheral arterial disease might be an important component and a component that helps us think about how to better treat them and to prevent worsening. Thanks, Naomi. And maybe I'll just ask you a follow-up question there. In the guidelines, and based on some trials that have been done in the past, there's this notion of symptomatic and asymptomatic PAD. I know that's been challenged more recently, that really, if it's truly PAD, there's no asymptomatic patients. What's your view on that? Yeah. Great question. Well, I think it's about really making sure that you're fully asking the questions. So when we talk about asymptomatic disease, we're usually talking about that in the context of an epidemiology study where we're measuring people's ankle brachial index, which is a way to be a very sensitive way to know whether there's decreased blood flow in the legs. I think in the clinical setting, again, we need to be careful about making sure that we ask about these more atypical kinds of symptoms. And also, it's interesting over this pandemic time, how much activity people really are doing. So the symptoms related to peripheral artery disease are symptoms that come on when people are exerting themselves and have an increased demand in their muscles for blood supply that's not able to be matched due to the obstruction. And so as people have become more sedentary, I've noticed that there's not as much reporting of symptoms, but that doesn't mean that they're not functionally limited. So really trying to figure out what it is that people do in their lives and what happens when they're walking. Do they have stairs in their home? Are they doing any of their own shopping? How much can they do and what happens when they do it? Great. Well, thank you for that. And really the art of history taking when you have vascular disease at the top of mind, which I think obviously we all want to think about for the patients at risk, as you described, Tony and Demetria. And so maybe, Amy, now I'd like to get your views on the overall question, and then maybe you could take us through a little bit of your approach to diagnosis. So once you're in the room with the patient and either they have the risk factors or symptoms, what are your thoughts about how to make the diagnosis? Absolutely. No, this is a great question. And in fact, we were talking about this on rounds this morning. I'm on the inpatient service, and we were talking about the importance of asking our patients to take their socks off or taking their socks off. And I'm in Florida, so it's flip-flop season, so it makes it a little easier. But for folks that don't have patients living in flip-flops, it sounds silly to say, take your socks off, or we need to do that, but to do a really good foot exam. So I think that is a call to action to make sure that we're looking at our patients' feet, not only to examine their pulses, their dorsalis pedis, and their posterior tibial, but also doing that visual inspection to see if there are any poorly healing wounds or ulcers or hair loss, something that's also going to go along with PAD. And then certainly doing the rest of our thorough cardiovascular exam and completing our pulse exam. But I think really honing in on that foot and distal pulse exam is really critical. Great. Well, thank you, Amy. And tell us about what a dependent rubor is. I mean, it's one of these counterintuitive things, right? So the patient's sitting on the exam table, and the feet are red. Doesn't that mean they have plenty of blood flow? Right. So you're absolutely right to bring this up. So that's certainly a sign of more critical disease in this kind of chronic critical limb ischemia. And I think that in terms of that spectrum of PAD that we can see in the examination room, it may be anything from just a, you can still feel their distal pulses, but it may not be quite as robust. And if somebody has that exertional leg symptoms or a change in their functional capacity, like Naomi was talking about, doing ABI testing, vascular lab testing to evaluate, to diagnose PAD. And then certainly if somebody has symptoms with poorly healing ulceration or that dependent rubor or elevation pallor where you're lifting their foot up and then it's turning white, that's certainly a sign of much more advanced PAD. And then the timeline to confirming the diagnosis and having a treatment plan really needs to be much faster. I just wanted to pick up, Mark, on what Amy was talking about being on the inpatient service. And so we were talking a lot about who, but I think we could also talk about when. So when do we think about peripheral artery disease in our patients? And I'm sure Tony thinks about this too, doing interventions. We know that there's a lot of overlap between atherosclerotic disease in different territories. People who have coronary disease have peripheral artery disease. And the really interesting thing is we might just say, well, it's systemic atherosclerosis, but people who have disease in different territories may have different prognostic outcomes and may benefit from different treatments, which I'm sure we'll talk about during this session. So I think a lot about making sure we ask when people are coming in with their myocardial infarction and they've gotten their treatment, maybe not in the initial period, but as we're thinking about making sure we take a thorough history, asking about peripheral artery disease symptoms then as well. Great point, Naomi. It's always an opportunity when you have someone in the hospital. And like you said, as we get into risk stratification, helpful in terms of understanding the risk. Excellent point. Now, Tony, maybe just coming back to you for a second. So Amy talked about taking the socks off, doing the pulses, the exam. What's your approach in the clinic? Do you do an ABI right then and there? Do you send people to the vascular lab? And then maybe comment, what if someone comes back with a normal ABI, but just a classic story? What do you do then? And what if they come back with a high ABI? Is that good news? So Mark, these are all excellent questions. I think one of the things that I've learned being an early career is that the first thing I did here in North Carolina is get to know my patients. What scenarios would these symptoms come out? Here in North Carolina, everybody seems to have a house on a large property. So they usually tend to get their symptoms when they're walking that half a mile to their mailbox. And everybody likes to do their shopping at a large grocery store, such as a Walmart. That's when the symptoms come up. And you bring up an excellent question as far as like, what do we do first? You know, my go-to still is the ABI. You know, I can either do it in clinic. It's pretty easy to do. It's easy to teach. And if I have a high index of suspicion, I'll also go ahead and get ultrasound studies. But you also brought up a great point that, you know, what if the ABI is normal? A lot of times you can just go ahead and get a treadmill study for the exercise ABIs, which is something that, you know, it's a classic board questions for internal medicine. Great. Thanks, Tony. Yeah. The stress test of the legs, right? And then that high ABI, that non-compressibility, you know, you need the TBI to know if you've got disease there. So that's super helpful. Now, the next part of diagnosis I want to talk about, because obviously you're all experts and you think about this all the time, but we know that there is a dramatic underdiagnosis of PAD. And Dr. McNeil, to your point earlier, that some of that is particularly burdensome on different populations and different races. And so what, where are some of the gaps and what do you do in your institutions to try to improve diagnosis in terms of educating your trainees, in terms of trying to raise awareness with other clinicians and other practices? What are some of the things that you're thinking about in terms of gaps and ways to address them? And maybe we'll just start in the same order here, Tony. Go ahead. So, you know, I think I was brought up earlier that as a minority myself, when there's two groups, African-American and Hispanics, particularly Puerto Ricans and Mexicans, when they come in, it is something that I absolutely go above and beyond to ask questions because I feel like they usually do present, just like the data says, they present very advanced disease. So I will go out of my way to ask them questions specifically about their legs. And a lot of times, you know, they will tell you, they won't say, hey, I'm having classic claudication, but they'll say, hey, my legs give out for some reason. They're just giving out more than usual. And that's kind of what I do to go ahead and just initiate the conversation. But I also tell them and say, hey, have you ever heard about this disease? And do some teaching, some points of, especially if they were smokers, so that they can at least go back to their communities and go ahead and do awareness. Are also our organization here. We also do some outreach to local communities, and we've begun to go visit churches and certain locales just to go ahead and spread the word about PAD. As all you know, everybody here on the panel is a champion for awareness, PAD awareness. Well, thanks, Tony. We're really highlighting just being awareness of some of these disparities. It helps us to do a better job maybe of eliciting. And Demetria, I really want to hear from you. You lead groundbreaking research in this area. I know you're doing a lot of interviews and research trying to understand why there's this gap. What have you learned? Yeah, yeah. Thanks, Mark. This is sort of the greatest issue I think that we have, particularly around this disease is, you know, we want to sort of give it the umbrella definition of sort of awareness and lack of awareness. And I think that that's on both ends. And when I say both ends, I think from the patient side, but also from the clinician as well as the healthcare institution side. Why do I say that? Because there can appear to be a greater or shall I say a discrepancy between which diseases, if you will, get greater attention until, right? So until you have the catastrophic, unexpected amputation, you know, no one knew and no one saw it coming. And so that's a problem, right? When you're talking about removing someone's limb and it was a surprise, that's what we don't want, right? That that is unfortunate for everyone. And so I really like what Tony said in terms of education and awareness. And one of the things that we have to find out is that all institutions are not created equal. When you see how one institution works, that's how that one institution works. They are all not calibrated the same. They do all not have the same resources, support, staffing, et cetera. So when we simply say things like, oh, just get an ABI, right? From institution to institution, it's not as simple as, oh, just get an ABI. Some of them may not be able to be done in clinic. If they are done in clinic, it's only, you know, one or two MAs, if you will, that are able to do it. They may have to be referred out. Again, that adds to the time, which I believe my colleagues Naomi and Amy both spoke to, is that you don't want to have this long length of time that you're waiting to see what are we doing here? You want to try to get to the root of what's happening as expeditiously as possible. So I think that that's kind of one thing. The other piece that Naomi brought up, which I think is just also something to think through, is overlap disease. I was speaking with a colleague who mentioned that a patient ended up being diagnosed with ABI but never thought of it, only thought of it because it was through a telemedicine visit, but the patient took a picture of their foot and their toe. And her response was definitely alarm that we had PAAD here, right? And so that is sort of how that started. And so we just kind of talked through what that looked like, because she said, you know, I wouldn't have originally thought of that to name his point, he had overlap disease, he had prior back surgeries, and other things going on. So that wasn't the first sort of line of thought around that. So I think that that's something else to consider. But then also the communication piece. And when I say communication, I liked what Tony said when he said, hey, a lot of my patients, they live on large tracts of land. And so they may walk half a mile to their mailbox, they may they go to these larger grocery stores. So what does that look like? So I think that when you're talking about or talking with your patients, and you're understanding, okay, well, they walk and then pain ensues, it may be helpful, particularly from a functionality perspective, to understand what when they're saying I walk, what does that mean for them? Where were they walking? How long were they walking? What were they doing? So all of that gives you information and real nuggets to help you kind of investigate what's going on. Oh, fantastic. Thank you so much for that input. And obviously a lot, lot to learn there for all of us. So Naomi, you you know, you work at a fantastic institution, long legacy of vascular medicine, and you have, you know, a lot of different populations that you treat. But how do you still see heterogeneity in terms of your colleagues and trainees in terms of their thinking of PAD and diagnosis? And how do you work within your health system to try to improve systematic detection of disease? Yeah, I think that, you know, wherever we are, we're all busy clinicians. And so I think that it's and there's a lot on our plate when we're thinking about managing our patients. And so we want to try to have some, some, I think some simple pieces and simple questions that we're talking about that that are going to be multifunctional for our providers. And some of this is a lot about what does it look like when you're walking, taking your shoes, taking your shoes and socks off. So really trying to do some simple education steps to have vascular disease incorporated into comprehensive care. I do think that there are other opportunities, in particular patient population. So we've talked about that patients with chronic kidney disease or patients with diabetes are at particularly high risk for having peripheral artery disease. So I think that trying to creating some collaboratives across particular high risk groups is important. And then working together. So we work a lot with our entire vascular care group, which to me includes podiatry, vascular surgery, interventional radiology. And we have done education to get all together. So we've done sessions at community health centers. We've done sessions for residents. We've done sessions in geriatrics and primary care. So really having a multidisciplinary educational approach, but I'm, I'm interested in whether other institutions are, are, you know, using kind of EPIC or other EHR systems to really identify people who might benefit from targeted evaluation. That's a great question, Naomi. I know there are some groups that are looking at that, you know, sort of what are the predictors and actually Sue Duvall had a paper a number of years ago, predictors of PAD and, you know, whether we could do a better job of popping up a flag and saying, Hey, you better, you better think about this patient who has diabetes or smoke or older age. And we know that the prevalence in those populations is so high. So I think that's a great, great point. I will say also, you know, to the point about amputation, I do think one thing that we do very well is identifying patients with advanced disease and ulcers as people who need to have early evaluation for peripheral disease. So I really think getting that message out is so critical to try to reduce some of the disparities that we see across the country where people are, where we have patients who end up with amputations without a thorough vascular evaluation to see if whether it could have been prevented. Great point. Yeah. Oh, sorry. I mean, yeah, please. Well, I was going to turn to you next. And I think maybe not just in your institution, but with your, you know, PAD Awareness Task Force and some of the idea around, you know, how do we even inform the population better? I mean, everyone knows what a heart attack and a stroke is, right? So what are your thoughts? No, absolutely. I think that this, you know, the co-panelists have said it so well that there's, and one of our other colleagues, Aruna Pradhan, always says that PAD has a PR problem. And I think that she's absolutely right. There's that lack of awareness, as Demetria said, both amongst the community, amongst patients at risk, and then still gaps in healthcare providers and clinicians. And I was going to mention just as tying on with Naomi's comments that I think with patients with diabetes, particularly who have diabetic foot ulcers, you know, half of our patients with diabetes with a foot ulcer are going to have underlying PAD. And so I think that there's, you know, there's so much that we need to do from that larger awareness perspective to then those more targeted, really high-risk populations, diabetes, chronic kidney disease, tobacco use, layered polyvascular disease, to really better diagnose our patients. And I think fundamentally, I think this group is so passionate about, we're trying to reframe vascular disease so it's not just PAD in a silo by itself, but that it's cardiovascular disease as kind of three legs of the stool, where we're talking about somebody's heart health, their risk of stroke, and then their risk related to PAD, because it certainly is additive in terms of that polyvascular. And, you know, I had a patient just this past week who came in, he said, gosh, I just, I had coronary disease, but said that he felt that he was just aging, slowing down, and clearly had a change on his pulse exam and had a new diagnosis of PAD. And so we have an opportunity to really dramatically change our patients' quality of life and their outcomes by better identifying and diagnosing and treating PAD. So a lot of work to be done in terms of reframing that conversation about PAD and cardiovascular disease, both in the community, high-risk individuals, and then amongst healthcare clinicians from the trainee level through continuing medical education. So lots of work to be done and certainly committed individuals to work on it together. Well, fantastic points, Amy. And I like the three legs of the stool. I mean, they're not separate diseases, but in the words of Alan Hirsch, he used to describe it as metastatic atherosclerosis when you'd have multiple territories. And that got my attention in terms of the severity of disease, and the outcomes aren't much better. So I think you're right, the PR, we need to do more. You know, we've talked a lot about diagnosis, but I was hoping we could spend a little bit of time in the next 10 minutes or so on risk stratification. So you've made the diagnosis, you've identified peripheral artery disease, but just like every other disease state, you know, not everyone with PAD is at the same risk. And so how do you work to risk stratify your patients? What are the different biomarkers or historical elements that sort of catch your attention and maybe make you think that someone's at higher or just average risk or how you characterize them? And then how do you talk to your patients about that? So let's just go down the panel here. Tony, why don't you start? So as you probably, as you know, Mark, a lot of the work you started off in Boston, usually the patients that are really that kind of like alarm bells go off in my head when I'm talking about peripheral artery disease is if they have polyvascular disease, right? If they've already had a heart attack and then diabetes. Those are the two that really I will just go ahead and tell them and show them what the risks are. I have a few charts in my clinic and say, hey, unfortunately, because you have several competing risk factors, each of these can put you in a bad spot, increase your risk, but together, the risk is additive. And these are the people that I really try to do everything I can, every patient. But, you know, these are the patients that, you know, I try to communicate very clearly and say, hey, we have to do everything we can to minimize your risk over the next few years. Great. Thanks, Tony. So the prior MI, diabetes, it's not just part of the disease, they're synergistic. So that's a really important point. Demetria, what are your thoughts about sort of different, I mean, you mentioned race early on and other sort of markers that should sort of get people's attention for us. What are your recommendations in terms of risk stratification? Well, so I agree, obviously, everything with what Tony said, but something else that strikes me that's pretty interesting that we've seen in the literature, but I've also seen in person when I am working with several docs in clinic. And one of that is around even patients, I mean, obviously, you talk about prior MI, et cetera, but even patients that have had prior revascularization. There's, you know, I had an interesting story that I was discussing with a colleague around a patient that had had actually more than one revascularization. And the problem is it kind of came to the point where amputation had to happen. And the patient was unfortunately surprised by that because the patient thought, quote, no, you'll just fix me up like last time, thinking that sort of, you know, we could just kind of keep doing this. And, you know, what had to happen is they had to share, well, remember, we've been talking about what we had to do to try to avoid this. And, you know, and so again, I think that being able to communicate around where this could go is extremely important for the patient to really understand, but more importantly, to understand what the self-management piece looks like for them at home and to understand what their abilities are to engage in the self-management behavior, because oftentimes we'll say, or you make a recommendation and assume that everyone's speaking the same language if you say words like exercise or walk, and that's not necessarily true. You have to have a mutual understanding about what is expected, but more importantly, what can help delay disease progression and attempt to save that off. Great. Well, thank you, Demetria. Fantastic points. And Naomi, I'm just going to turn to you now. And so Tony talked about, you know, concomitant coronary disease and diabetes. Demetria talked about prior revascularization. What are your thoughts? And maybe you could comment on some of your studies. You had recent data at the AHA for patients with end-stage renal disease and PAD and some of their outcomes in terms of function. How do you think about other comorbidities? Yeah. Great question. So I think we're seeing this overlap pandemic of, you know, we see both microvascular disease and macrovascular disease a lot related to diabetes. And what do I mean by that? So PAD is, you know, disease in large vessels leading to decreased blood flow, but we also see patients have kidney damage related to their diabetes and hypertension and other risk factors. And when they go together, especially in patients who are on dialysis, these patients have really higher risk of amputation and other poor outcomes. And I think what we were looking at in this study also was functional. So we know that after revascularization patients who have chronic kidney disease or end-stage renal disease have poor outcomes, but we don't always think about what's happening in terms of the walking ability and people who are on dialysis and or have advanced kidney disease. And, you know, here too, it really looked like the patients who have PAD, there was a low rate of having classic claudication, a lot of leg symptoms and really poor functional capacity. So really important to think about these patients and think about whether there might be new treatments. I just wanted to pick up on one other comment about this self-management and self-care, really trying to think about how to work as a team with our patients. And, you know, we usually have this model where we ask people about like their risk behaviors, but really trying to shift that to thinking about self-care. What are the things that you're doing for self-care and how, as someone who's trying to participate with you as a physician or other healthcare provider, how are we going to work together to help you advance your care? And I just wanted to talk a little bit on that about smoking. We've mentioned diabetes and kidney disease, but I think smoking is often the forgotten risk factor and really important for PAD and thinking about how we can work together with our patients to make sure that we're referring for smoking cessation, thinking about all of the strategies for smoking cessation for our patients who have PAD and those who have polyvascular disease. Wonderful points, Amy. Yeah, we can't talk about PAD without talking about smoking, for sure. That's one of the key modifiable risk factors, so thank you. Well, Amy, we're going to end with you talking a little bit about your views on risk stratification and what are your thoughts? I mean, I think just echoing what our other panelists have said in terms of, I think, trying to identify the patients who are at higher risk with PAD, diabetes, polyvascular, chronic kidney disease, ongoing tobacco use, prior acute limb events in terms of who we might want to treat with antithrombotic therapy, with, you know, rivaroxaban plus aspirin, or who we might want to recommend being on dual endoplatelet therapy to help reduce cardiovascular events and limb events. So I think that risk stratification can help for who to augment medical therapy, potentially try to achieve a lower LDL cholesterol, adding a PCS-K9 inhibitor, and I think just underscoring what Naomi was saying about the tobacco cessation is just so critical for our patients, and I think echoing Dimitri's points about the self-care, that just really resonates. I mean, gosh, for all of us focusing on self-care as we're going into 2022, but definitely for our patients who have cardiovascular disease and just understanding that they need to be looking at their feet, they need to be controlling their blood sugars, assessing themselves for changes in their functional status. So I think having it really be that partnership and trying to empower our patients with an understanding of what they need to be, resources they may benefit from, and then tips for how to monitor their health at home. And I'll just end with, you know, I was, as we were on Browns this morning, I was talking about how, as I talk to patients with newly diagnosed PAD, I make sure to say that, you know, we need to be on the lookout for a leg attack. You know, just in the same way I talk to patients about their, who have diagnosed with coronary disease, we need to be on the lookout for warning signs of a heart attack and what to do about it. I think that that's really important that we talk with our patients about those warning symptoms of acute limb ischemia, chronic limb ischemia, what to do if they have an ulceration or sore. That way it's less of a surprise, because just to Demetrius' point that patients just aren't, tend to not be as informed about this. So they may not know that there's an urgent issue, really an almost emergent issue, unless we're helping to teach them about that. Well, fantastic points, Amy. And, you know, I think your point about a leg attack or acute limb ischemia, I mean, it's hard when you talk about preventive therapies, patients don't understand what they're trying to prevent, the gravity, especially when you're talking about risk benefit, so important. And I love the comments around partnering with our patients in self-care. I think it can be more, you know, clear, especially in 2021, 2022, as we all go through this pandemic together, just the notion of self-care. Well, listen, I want to thank all of you. This has just been a phenomenal discussion. I think for all the listeners here, hopefully you've learned something and enjoyed this conversation. I'm incredibly grateful for all the panelists for their time today and thoughts, and I've learned a ton. So thank you very much for attending this CME activity on behalf of the American College of Cardiology.

peripheral artery disease

diagnosis

risk stratification

underdiagnosis

awareness

education

patient communication