Transcript: Test (Dyslipidemia) Episode ID: 232 Generated: 2026-09-04 08:27:25 ------------------------------------------------------------ [00:00] (Music) Male Announcer: Welcome to HelixTalk, an educational podcast for healthcare students and providers covering real-life clinical pearls, professional pharmacy topics, and drug therapy discussions. Female Announcer: This podcast is provided by pharmacists and faculty members at Rosalind Franklin University College of Pharmacy. Male Announcer: This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified healthcare provider. Female Announcer: And now, on to the show. (Music) Dr. Sean Kane: Welcome to HelixTalk episode 198. I'm your co-host, Dr. Kane. Dr. Khyati Patel: And I'm Dr. Patel. And the title of today's episode is Lp(a), ApoB, and CAC: Navigating the 2026 Dyslipidemia Guideline Alphabet Soup. Dr. Sean Kane: So Dr. Patel, I'm sure you've heard that there are some new lipid guidelines that were recently published and we're going to be talking about those from the ACC/AHA. They're the 2026 guidelines on the management of dyslipidemia today. Dr. Khyati Patel: You know, this episode could not have come earlier enough, Dr. Kane, because I could not escape hearing about these guidelines. It's been everywhere. So we are so happy to finally talk about it. But before we jump into the guidelines and how they were updated and stuff, maybe we can present a quick clinical case that we can apply the findings or the updates of these guidelines. Let's say you have Rodney, who's a 54-year-old male. Past medical history is significant for controlled hypertension, newly diagnosed with type 2 diabetes, and obesity with a BMI of 35. His antihypertensive and antihyperglycemic therapies are optimized, but overall ASCVD risk reduction still needs to be addressed. The most recent fasting lipid panel shows total cholesterol of 198, LDL of 128, triglycerides of 201, and HDL of 27. So we're kind of looking at that mixed dyslipidemia picture here. His family history is significant for mother having a type 2 diabetes and hypertension, and father having hypertension, heart failure, and an MI at the age of 47. His dietary habits are improving because he is consulting a dietitian, and he has started to work out, aerobic activity. Denies any tobacco, alcohol, or substance use. And so really the big question is, if you have a patient like Rodney in front of you, how would you calculate the ASCVD risk and what's the best approach to manage that risk? Dr. Sean Kane: Yeah, and really the intent of the 2026 AHA/ACC guidelines is to kind of help answer some of those questions. So importantly, this retires and replaces the 2018 guidelines. So really not that old, but old enough that probably we needed an update. And it should be noted that these are the dyslipidemia guidelines, not the blood cholesterol guidelines. So focusing on, you know, abnormalities of the lipid profile overall. And we do have a link to the reference in the show notes. And just like all of our guideline updates for HelixTalk, we're not going to cover all 123 pages of the guidelines. We've kind of picked out the most important or salient points. But if you want to dive into it, you can go to our show notes at helixtalk.com. Again, this is episode 198, and kind of get as deep as you want to go on those guidelines. Dr. Khyati Patel: Yeah. And then for clinician use, they also have that guidelines at a glance link that we would put in our show note as well. Really it kind of highlights those top 10 recommendations that stem out versus this 123-page document is really detailed. But the overall strategy, Dr. Kane, the guidelines are embracing is earlier and lower for longer. So start treatment early, lower the LDL as much as possible, and then continue the treatment as long as possible. Lifelong screening has been emphasized, you know, starting from pediatric years. Intensive LDL goals, so yes, the goals are back. And then earlier initiation of treatment and ongoing monitoring as well as titration, appropriate titration. Dr. Sean Kane: So along the lines of kind of screening and earlier treatment is a newer recommendation related to how we're going to assess someone's 10-year risk of a future ASCVD event. So back in 2013, we had the pooled cohort equations to estimate the 10-year ASCVD risk. And in 2023, a newer equation was published called the PREVENT ASCVD equation. And this was recommended by the new hypertension guidelines that we covered back in episode 193. And again, same organization, ACC/AHA, not surprising that they're also embracing this for the dyslipidemia guidelines as well. Dr. Khyati Patel: And then kind of differences from that pooled cohort equation to this PREVENT calculator is that the age starts early. So instead of 40, it starts at age of 30. It goes a little bit beyond that, you know, 75 years of age, so you could have patient up to 79 years of age. The biggest change here is that it does not include race as a covariate. And that was probably a bigger talking point when we were talking about race-based medicine in general. However, it does include new metrics such as, you know, putting a BMI, if you have that available, putting patient's eGFR, because they want to accurately capture those CKM, the cardio-kidney-metabolic issues that are coming in. So it kind of captures that better here. [05:10] Dr. Sean Kane: And there are also optional metrics. So optional meaning that if you have these, it improves the quality of the prediction equation slightly, but if you don't have them, you don't necessarily need them. And those three optional ones are a social deprivation index, which is based on the patient's zip code. And that relates to like within that zip code, what is the typical income, the typical education level, things like that. Also an A1C and a urine albumin-creatinine ratio. So again, if you have those, you can add those in as part of the prediction, but if you don't have those, you don't need them to generate a 10-year or even a 30-year ASCVD risk. Dr. Khyati Patel: Besides these differences, I think there is another very important difference that PREVENT calculator brings compared to the pooled cohort equation. Dr. Sean Kane: Yeah, so, and we'll talk about the thresholds later, but in the dyslipidemia guidelines, they say that the pooled cohort equation overestimated risk by about 40 to 50% on average. Because of that, we have newer, lower thresholds because the PREVENT equation is going to be 40 to 50% lower on average in terms of that 10-year ASCVD risk. I feel like this was kind of like an "oops, like our previous equation we used for more than a decade overestimated by 50%" and we kind of didn't talk much about that. I'm a little bit surprised this wasn't a bigger deal. I guess it's good that we're using a more accurate equation, but it does kind of indicate or highlight the fact that these are truly estimates, like very rough estimates. It's not like if you have someone at 7.4% ASCVD risk that that's dramatically different than a 7.6% ASCVD risk, because in truth, these are very rough estimates to kind of guide decision-making processes, not to be very black and white. Dr. Khyati Patel: And all the while, the additional things such as BMI and A1C, you know, that information can be incorporated. Know that some of the other risk factors are not included, such as a pertinent family history of premature ASCVD. So you, the point goes to say is that these are really rough estimates and then patient's risk assessment should involve looking at those risk factors, the risk-enhancing factors, etc. Dr. Sean Kane: Yeah, so given that the older 7.5% threshold that we had historically was an overestimator, inflated because it used the pooled cohort equation, using the new PREVENT equation, we now have new thresholds. And the new thresholds are 3, 5, and 10%. So if a patient's 10-year ASCVD risk is less than 3%, we call that low risk. Between 3 and 5%, it's a borderline risk. Between 5 and 10%, it's an intermediate risk. And then 10% or greater is a high-risk patient. Dr. Khyati Patel: Dr. Kane, I'm not sure if you came up with this mnemonic, but there is an easy way to remember the 3, 5, and the 10% threshold. Dr. Sean Kane: So AI helped me with this one, to be honest with you, but the mnemonic aid is "triangle hand bowling". So triangle, there's three sides to a triangle, and that is the initial threshold of between low risk and borderline risk. There's five fingers on your hand, so that is the threshold between borderline and intermediate risk. And then at 10%, there's 10 bowling pins. So 3, 5, 10, triangle, hand, bowling. Those are the three thresholds between low, borderline, intermediate, and then high risk. Dr. Khyati Patel: And this is where the recommendations in the guidelines kind of come in at the kind of language they have used. So like if the risk is the borderline risk, which is 3 to less than 5%, then the statin or the LDL lowering therapy, quote unquote, "can be considered". But if it's the intermediate, which is 5 to less than 10%, then it "should be considered". Dr. Sean Kane: And if we go back to the pooled cohort equations from 2013, where our main threshold was 7.5%. And I understand that between 5 and 7.5% it was kind of that "can be considered" threshold, but if you're picking the 7.5% from the older guidelines, that is now the 5% from the newer guidelines. So historically that 7.5% treatment threshold is now a 5% treatment threshold using the PREVENT equation. Dr. Khyati Patel: So that's a, that's a drastic change. The other change that is that the goals are back again. NLA kind of stuck with the goals the whole time. AHA, ACC kind of steered away and now we are back to the goals again. Dr. Sean Kane: Yeah, so really if you think about what our goals are for most patients, there's basically three tiers. So we have a moderate intensity tier, we have a high intensity tier, and then we have like an extra high intensity tier, I guess. So the first tier is people who you're trying to decrease their LDL between 30 and 49% and their LDL goal is going to be less than 100. And the way that you would do this primarily is using a moderate intensity statin. Dr. Khyati Patel: So these are going to be individuals whose PREVENT ASCVD score is that less than 10%. They don't have the family history of dyslipidemia or additional ASCVD risk factors. And we'll talk about the CAC score, but the CAC score is between 1 to 99. [10:05] Dr. Sean Kane: So then for a higher risk patient population, we would want their LDL to drop by at least 50%. And for those patients, and these are all like higher risk people. So for the first tier, it's an LDL goal less than 70, which we've kind of always had that. And then for the extra high risk patients, they have an LDL goal of less than 55. Dr. Khyati Patel: So to kind of differentiate what population, patient population we are looking at here for those who you could consider LDL goal of less than 70 would be those with the PREVENT ASCVD risk score of 10 or more. Heterozygous familial hypercholesterolemia, have additional ASCVD risk factors, maybe they have diabetes with risk factors related to diabetes, and the CAC score is 100 or above. Dr. Sean Kane: And then that less than 55, that's again for our highest risk individuals. These are going to be people with a history of multiple ASCVD events or an ASCVD event plus multiple risk factors. They have severe hypercholesterolemia. They have a CAC score greater than 1,000. So again, our very high risk patients, we would target a really low LDL of less than 55. Dr. Khyati Patel: And I think this goal of less than 55 is sort of not new with the ACS guidelines that came out in 2025. They had suggested to consider that goal of less than 55 and these guys finally took that. Dr. Sean Kane: And we should just make a nod to the fact that European guidelines have had these lower LDL goals for a while. And now the European guidelines even have lower goals than 55. So maybe in 5, 10 years we'll be talking about LDLs less than 40 or something like that. But for right now, the American guidelines, the lowest threshold goal is less than 55. Dr. Khyati Patel: And it's kind of like pushing that NLA's, you know, lower for longer is better and kind of aligning with the European as well as the NLA guidelines that the, you know, bottom line is that the goals are back. Dr. Sean Kane: And I think it's worth highlighting for patients that have these really low LDL goals, you can't generally get there just with a statin. So because we have these lower LDL thresholds or goals, we're probably going to need to expand the use of these non-statin therapies more often to be able to achieve the LDL targets that we're looking for. Dr. Khyati Patel: Right. And while you do that to lower LDL, which is the first goal of the treatment, you gotta also work on some other ASCVD risk factors, right, that are modifiable. So lowering the blood pressure, you know, losing weight, smoking cessation, all of those things together is going to pay off, not just treating the, the lipid numbers. Dr. Sean Kane: Now, Dr. Patel, another big update that I know pharmacy students are going to be really excited about is that we have new numbers to memorize besides our LDL goals. Dr. Khyati Patel: And those are our non-HDL goals and our ApoB goals. So let's talk... Dr. Sean Kane: Yeah, and I think we have to talk about what exactly are non-HDL and ApoB. And non-HDL, I think intuitively just makes sense. It's well, it's your cholesterol, not your HDL, which we just need to talk about that for a second. So what, what exactly is a non-HDL cholesterol? Dr. Khyati Patel: That's overall your total cholesterol minus the HDL, that kind of becomes your non-HDL. We know that HDL is our good cholesterol, right? H, I tell students to remember H, high. You want to, you know, keep it as high as possible. But that one is a good cholesterol. All the other cholesterol, all the other lipoproteins are atherogenic. One or the other way increase the risk of ASCVD events. Dr. Sean Kane: So what are some examples of these non-HDL particles besides LDL? Dr. Khyati Patel: Yeah, so we have obviously, you know, the LDL, but triglycerides, as well as some of the VLDL, which is the very low density lipoprotein, or IDL, which is intermediate density lipoprotein. They're kind of somewhere in between the HDL and the LDL on the spectrum of the mix of how much protein they have versus how much lipid component they have. Dr. Sean Kane: So Dr. Patel, is this something that a pharmacy student or a pharmacist would calculate or is it provided by a lab? Is it something special that needs to happen? Dr. Khyati Patel: Yeah, so you get your fasting lipid panel. You have your total cholesterol, your other lipoprotein values, that includes HDL, LDL, VLDL. You basically take your total cholesterol and minus the HDL, and that's a simple equation. Dr. Sean Kane: So it's not like a special assay that needs to be run. It's just subtracting two numbers and you're good to go. Dr. Khyati Patel: Yep. The current lipid panel should satisfy this requirement. Dr. Sean Kane: So as I mentioned, we're going to have to memorize some new numbers. Is there a cheat code here in terms of what our non-HDL goal is if we already know what our LDL goal is? Dr. Khyati Patel: It's usually 30 points above what the patient's LDL is going to be. So if your patient's LDL goal is below 100, the non-HDL goal will be below 130. If it's that less than 70 LDL goal, that non-HDL goal will be less than 100. If it's below 55, the non-HDL goal will be less than 85. [14:57] Dr. Sean Kane: So kind of nice that if you just remember the rule, your LDL goal plus 30, that's your non-HDL goal. The other thing to know is that we optimize for LDL first. So we're only thinking about our non-HDL goal once we've figured out and achieved our LDL goal. And once we've done that, then we say, okay, is our non-HDL goal at goal or not? And if it's not, then we should do something about it. Dr. Khyati Patel: Right. And I have to say that that non-HDL part, which is that triglycerides, the VLDL, the LDL, they kind of play along the same lines of things and requires non-statin, non-LDL lowering therapies to get to goals. So we'll talk about that in a later on too. Dr. Sean Kane: Would you say that's mostly lifestyle modification versus drug therapy? Dr. Khyati Patel: Um, it also requires looking at the patient's triglyceride levels and stuff. But yeah, lifestyle modifications are going to be heavily recommended for those patients. And then if the triglyceride levels are really elevated, we could also consider a therapy. Dr. Sean Kane: So then let's talk about ApoB, which is one of our alphabet soup items. This is fairly new in terms of a guideline recommending a specific threshold or goal. What exactly is ApoB? Dr. Khyati Patel: So I think before we even get started, we need to understand what is LDL-C. That C part, it basically means cholesterol. When a lab gives us the LDL value, it's the mass of the cholesterol, which is the weight of the cholesterol. It doesn't give us the how many particles of LDLs that are in a patient's blood sample. Dr. Sean Kane: So then if a patient had like a bigger or a smaller LDL particle, then your cholesterol amount would differ, but the number of particles would potentially not differ. Or in other words, not all LDL sizes are created equal. Sometimes they're bigger or smaller, that can change the ratio of the size versus the number of particles that you have. Dr. Khyati Patel: And then remember again, back to the basics, lipoproteins are made of, as the name sounds, lipid components and protein components. The protein part of the lipoprotein, kind of think about a lock and a key component. It's made of a certain shape. And when the LDL particles attaches to the hepatocytes, it needs to fit in. That key needs to fit in the lock. And if that ApoB is not fitting in the lock properly, then LDL processing would not happen. So really it's that one lipoprotein that's ApoB and this is what gives our LDL, IDL, VLDL its function. It doesn't work without it. Dr. Sean Kane: So each, let's say LDL particle is going to have one ApoB protein on it. And that is what gives the functionality of the bad cholesterol, the thing that is atherogenic. So when we're measuring cholesterol, we can either measure the mass of the cholesterol in LDL, or we can measure the ApoB count basically. And it is described in milligrams per deciliter, so it's still a concentration, a weight per volume concentration, but the lab is literally measuring the particle count as opposed to the size of the LDL cholesterol. Dr. Khyati Patel: And then this is where the discordance or discrepancy kind of comes in. And that has to do with the weight as we talked about, right? You have one LDL particle that weighs 10 nanograms, but you can have two LDL particles that will each weigh 5 nanograms. So total weight comes out to be the same, but you have one extra LDL particle, that one extra LDL particle is depositing in your arteries. Dr. Sean Kane: And the thought is that the higher number of particles is probably bad in terms of if you have twice as many bad particles hitting your, your arteries that are then getting embedded into the arterial walls and causing atherosclerotic lesions, that that higher number of particles is probably bad. Obviously just having a high LDL is bad as well. And this isn't just theoretical. Something that I came across, Dr. Patel, as we were kind of preparing for the episode is something called small dense LDL or sdLDL, which is like a subclass of LDL, which is basically there are patients where their LDL might be at goal, but because the LDL particles are smaller and denser, they have a lot of these particles. So their LDL cholesterol looks okay, but they have more particles than what would be considered normal. Dr. Khyati Patel: Right. And I think back in the day when we were calculating or estimating the LDL using the Friedewald equation, the new guidelines are actually recommending using a different equation like Martin-Hopkins. If you're using that new equation, then you can reduce the discordance between the mass of the LDL versus the ApoB particle count. Dr. Sean Kane: So then are there any patients that are more likely to have a bigger discrepancy between the particle count, the ApoB, and then the actual cholesterol mass, the LDL cholesterol? Dr. Khyati Patel: Yeah, I think it's identified that patients who have higher triglyceride values, so above 200, patients with diabetes, or LDL less than 70, they are tend to going to have those small dense LDL particles. Dr. Sean Kane: So just like with non-HDL cholesterol goals, we do have ApoB targets, but we're going to worry about the ApoB target only once we've achieved our LDL goal. So achieve your LDL goal, after that you can worry about your non-HDL and your ApoB. [20:12] Dr. Khyati Patel: Right. So I think the current recommendation when it comes to ApoB is to measure ApoB, which is a class 2a recommendation, in adults who are already on lipid lowering therapy. In particularly, as we mentioned, these patients are going to be those with type 2 diabetes, they have CKM syndrome, elevated triglycerides, to help guide what is that residual ASCVD risk and then decide whether treatment intensification is needed. So ApoB is not recommended to help initiate lipid lowering therapy, but it's to whether we need to tweak it further or not. Dr. Sean Kane: And then there's a class 2b recommendation to measure ApoB to decide if you want to start a lipid lowering therapy in an adult or not. So a little bit lower strength of recommendation, but it could be something to consider as well. Dr. Khyati Patel: Yeah. Dr. Sean Kane: More numbers? Dr. Khyati Patel: More numbers. And hopefully they made it really easy for us, Dr. Kane. Dr. Sean Kane: Never. Dr. Khyati Patel: Okay, so we have three LDL goals. Tell us what would be the ApoB goal based on that LDL threshold. Dr. Sean Kane: So it's not a magic formula like, you know, add 30 to get to your non-HDL goal. At lower levels of LDL, the ApoB goals are the same as the LDL goals, but then they start to differ when LDL gets to 100. So let's say your LDL goal for a patient is less than 100, the ApoB goal will be less than 90. Dr. Khyati Patel: So close, but not exactly the same number. Dr. Sean Kane: Exactly. But then when you get to LDL goal of less than 70, then your ApoB goal is also less than 70. And same with the LDL goal of less than 55, your ApoB goal is less than 55. So not terrible to memorize it. You just have to memorize that your ApoB goal is going to be the same unless your LDL goal is 100, then it's a little bit different for an ApoB goal of 90. I wish they would have just allowed it to be 100 as well to make it easy, but they didn't. So there's a small difference there, but the 70 and 55 are the same LDL and ApoB goals. Dr. Khyati Patel: Right. And again, as emphasized before, you know, we're going to try to get to that LDL goals first before we chase these other goals. Dr. Sean Kane: Well, so we talked about a lot of risk factors, residual risks and stuff. We have to keep in mind that these lab values and the cholesterol numbers we have are sort of rough estimates and there is chances for a lot of error. And this is where clinicians always talk about this is like, do I have my patients fast for their lipid panels versus non-fasting? So what's the difference between the two? Dr. Sean Kane: So the guidelines are pretty clear that you only need to fast if your triglycerides are more than 400. And Dr. Patel, I'll just be honest with you, when I have my annual physical, they make me fast and I fast even though I know it doesn't matter. And it's one of those like dogmatic things in healthcare that people just assume that you need to fast. But if your triglycerides aren't really high, and 400 is really high, fasting doesn't matter. It's clear that you don't need to, but it's very commonly done. Dr. Khyati Patel: Right. I think more and more clinicians and practices are opening up to the idea of non-fasting labs. This guidelines are definitely recommending doing either. But in order to get an accurate lipoprotein panel, fasting assessment is preferred in patients who have history of elevated triglycerides, so above 400 as you said, Dr. Kane. But also those who have family history of dyslipidemia or premature ASCVD, or if they've had any suspected disorder in that triglyceride metabolism in general. Dr. Sean Kane: And then the other thing to think about too is, and there's good literature on this, that your LDL and your HDL, if you were to check it multiple times in let's say a week period, the total error from a lab error, from your diet, from just morning versus evening, the total error is plus or minus about 10%. So let's say that someone had an actual LDL of 75, plus or minus 10% would be as low as 68 or as high as 83. And I think that really emphasizes that in addition to our ASCVD estimate being an estimate, even like obtaining that cholesterol lab panel, there's a lot of like variability to that that you shouldn't get worked up of plus or minus a couple here and there from your LDL or your HDL. These are just general rough guidelines to help guide therapy. Dr. Khyati Patel: Right. And again, remember if somehow because triglycerides were really high and patient was, you know, tested non-fasting, instead of using that direct LDL, which sometimes is used as that reflex lipid panel order, or that Friedewald equation to calculate the LDL, they're now recommending to use either that Martin-Hopkins equation or Sampson's NIH equation instead to measure the LDL estimate. Dr. Sean Kane: So Dr. Patel, for those other two estimates, are those things that the lab would do for you or would a clinician have to do that by hand? [24:50] Dr. Khyati Patel: Dr. Kane, I think it's going to be another math number to crunch on the clinician's part. So currently, as I'm aware, the labs are not going to use this equation. Dr. Sean Kane: So then kind of continuing with our alphabet soup, we mentioned lipoprotein(a) or Lp little a. And the new recommendation here is that everyone should have Lp little a measured at least once in a lifetime in adulthood. So where is this coming from? This is a class 1 recommendation. That's a pretty strong recommendation. Dr. Khyati Patel: So Lp little a has been all over my, I don't know, feeds if you will, or, you know, conference talks or updates and whatnot. This is actually a risk enhancing factor and it really helps break the tie to start the therapy if it's unclear. This is a particular type of lipoprotein that is expressed on the LDL. And about 20% of the population is known to have this elevated Lp(a). The current lipoprotein lab that tells you what the patient's LDL is does not tell you what the Lp(a) is. That's a separate lab you have to do. And this percentage or this level doesn't really change. And so once in a lifetime assessment is recommended. Dr. Sean Kane: So it's primarily genetics driven versus your diet and lifestyle. And pharmacy students love numbers, so there's actually two numbers to memorize here. And it depends on how the lab is reported. So if it's in nanomoles per liter, the threshold is 125. If it's in milligrams per deciliter, the threshold is 50. So above 125 or above 50 is the threshold that means that you are at an elevated risk of ASCVD. So to put a number to it, at that those thresholds, the risk of ASCVD is about 40% higher. So 1.4 times higher if you are above that threshold. But it's a linear relationship. So if your Lp little a is really, really high, then that means that your ASCVD risk is that much higher than someone who has a normal Lp little a value. Dr. Khyati Patel: And as you mentioned, Dr. Kane, this is genetically driven. So the current therapy that exist don't really modify the Lp little a, which is sort of discouraging. But good thing to know is that there are plenty of agents in the pipeline that are going to help target the Lp(a). But we just have to wait and watch. So what do we have available right now? The recommendation is to really go after those modifiable risk factors that are contributing to ASCVD risk. As I mentioned earlier, control the blood pressure, reduce the weight, exercise, smoking cessation, all of those things are going to be helpful. Dr. Sean Kane: So we should note that PCSK9 inhibitors do reduce lipoprotein little a by about 25%. So not amazing, not nothing. And Dr. Patel, as you mentioned, there are some drugs in the pipeline that have pretty profound impacts on reducing lipoprotein little a, but many of those newer drugs in the pipeline haven't really shown cardiovascular benefit yet. So even once we get them on the market, we still want to know like, are they able to reduce your ASCVD risk versus just making your lipoprotein little a number better. Dr. Khyati Patel: One more number to memorize, Dr. Kane. We're going to move on to talking about coronary artery calcium scoring, also known as CAC. Now, this scoring is not new. This was recommended in the 2018 guideline update as well. It's just that it wasn't utilized as much. The growth has been there and uptake has been there, but this guideline is really kind of pushing it, especially to measure that residual risk. So really what coronary artery calcium scoring is, it measures the amount of calcium that is deposited into an arterial plaque that is a subclinical atherosclerosis, hasn't become like that angina or MI just yet. Dr. Sean Kane: And we should note that this is radiation, so you're getting a CT scan, but you don't get contrast. So it's a non-contrast CT, probably takes 5 to 10 minutes to actually do once you're in the CT scanner. And you get a number. And the number of zero is what is normal, which means that you don't have any of that subclinical atherosclerosis and you're good to go. But any number not zero means that you have some degree of plaque formation. And the number goes up pretty high. Dr. Khyati Patel: And then Dr. Kane, one thing to also note is that these values are either specific numbers or they're, you know, above 100, you know, above 99, all that stuff, but also they could be percentile based. And that percentile is based on age, sex, race, etc. So it kind of gives us a comprehensive risk picture here. Dr. Sean Kane: And if you think about it, if you took like a 40-year-old, they shouldn't have very much plaque formation. But if you took a 70-year-old, they would have more, right? So age makes sense. So if you had a 40-year-old that had the plaque formation of a 70-year-old, that would not be good, right? So that's why we have kind of two numbers. So the first number is going to be the actual CAC score. And it goes up to more than a thousand. So between 1 and 99 is the abnormal, but on the lower end. Between 100 and 999 is like the medium end, still not normal. And then above a thousand is really bad. And we can also look at percentiles. So if you're less than the 75th percentile, that means that for your age, race, sex, that you are at least not as bad as 25% of the population, then that's okay. But if you're above the 75th percentile, it means that you're on the worse side for your age and things like that. So we look at all of those in terms of our degree of intensity or concern for that particular patient. [30:20] Dr. Khyati Patel: And I think that information will be used to decide whether patient needs to be on moderate intensity statin and what LDL goal we are looking at versus high intensity statins and maybe more of those intense goals. Dr. Sean Kane: Yeah, so to put a number to it, at that lower CAC score threshold, we're probably having an LDL goal of less than 100 unless other factors are present. If you're in that medium bucket where you're 100 to 999, we're looking at an LDL goal less than 70 probably with high intensity statin. And then if your CAC score is more than a thousand, that's pretty bad. And it doesn't really matter what percentile you're at, it's going to be a high percentile. You definitely need a high intensity statin and we're probably going to consider that most aggressive LDL goal of less than 55. Dr. Khyati Patel: So it definitely helps assess the risk and guide the LDL and non-HDL goals in men at least 40 and women at least 45 years of age. And then according to this guideline, it is recommended to be used alongside that PREVENT ASCVD calculator, the 10-year risk score, to use as a tiebreaker. And so this is where that shared decision making comes in. If the risk of ASCVD is not clear or maybe the patient is hesitant to start lipid lowering therapy, CAC scoring can be done to kind of say, hey, you, you have a subclinical disease that could become clinical, you know, in in future. Dr. Sean Kane: So a great example would be someone with a PREVENT score of like 4.5. Remember 3, 5, 10 were our thresholds and at the 5% mark is typically where we would initiate statin therapy. If that patient's less than 5, but their CAC score was elevated, through shared decision making, they may choose to initiate statin therapy because they have this subclinical atherosclerosis. Or if the CAC score is zero and they kind of don't want to take a statin, you might use that as a tiebreaker to not justify statin initiation. Dr. Khyati Patel: So one more thing in our toolbox for assessing the risk. And that is to consider the risk enhancers. Now, Dr. Kane, there is a list of risk enhancer provided into this guidelines. I think this list is not any different than what was in the 2018 guidelines. And really the advice here is to use these also as tiebreakers to decide when to initiate the lipid lowering therapy as an adjunct to lifestyle modification. So as I mentioned earlier, your PREVENT calculator does not include family history of premature ASCVD. That's a very strong independent risk factors for having a high ASCVD risk. And that's included as a risk enhancer. Dr. Sean Kane: And some other ones we already talked about, lipoprotein little a, if it's elevated, that could be a good tiebreaker. There's also good data for high sensitivity C-reactive protein, if that's more than 2. And that's an inflammatory marker, and inflammation is what is triggered or driving some of that ASCVD risk. So if that's elevated, especially if it's checked more than once and it's still elevated, that would be of concern and could be a good tiebreaker. Dr. Khyati Patel: Right. And then for example, obesity, impaired, you know, glucose tests, high triglycerides, low HDL, increased blood pressure. All of those were considered like independent underneath the risk enhancing. Now they have just put all of these under CKM bucket, that cardio-kidney-metabolic syndrome bucket. Dr. Sean Kane: And as we mentioned, there's a lot of other ones we're not going to go through all of them. The list is not that different from 2018, but these are our tiebreakers where if you're not exactly sure if you want to go more aggressive or less aggressive, you can consider these and that's part of shared decision making. Dr. Khyati Patel: So we kind of concluded, there was a lot to discuss here, Dr. Kane, in terms of like how we are assessing patient's risk. Again, try to incorporate a very comprehensive risk assessment and use some of these additional tests to tie break, right, the shared decision making and stuff. But once that's done, the guideline kind of tells us like how to approach the treatment from start to finish. And they have adapted this model called CPR, which is C stands for calculate that 10-year ASCVD risk score using the PREVENT calculator. P stands for personalizing the estimated risk. So add all of these things that we talked about, right? The ApoB, the CAC scoring, the risk enhancers, things that were not part of the PREVENT calculator. And then kind of reassess the or reclassify the patient's ASCVD risk. That's what the R stands for. And if need be, you can do the CAC scoring here and then reassess the treatment recommendations thereafter. So we're going to dive into treatment recommendations soon. Dr. Sean Kane: And you know, there are a variety of different groups that justify different treatment strategies or intensities just like the 2018 guidelines. The one that usually is first is familial hypercholesterolemia. So this is anyone with an LDL more than 190. So 190 or higher, they have a genetic reason for that in most cases. And for those patients, you're going to have to give them a lot of different therapies to get them down to their LDL goal. And unless they have other risk factors, their LDL goal is going to be less than 100. And that means that you're going to have to get there through a high intensity statin or a max tolerated statin, but very often you're going to need other non-statin LDL lowering therapies as well. And this is really no different than the previous guidelines. [35:34] Dr. Khyati Patel: Right. And then our other subgroup is patients between the ages of 40 to 75 with diabetes, CKD stage 3 to 4, or eGFR below 60, or those who have active HIV infection. This group formally in the 2018 guideline was just the patients with diabetes, but they've added the CKD group as well as the HIV status in here as well. For these patients, at least a moderate intensity statin is recommended. If there are additional risk factors, then high intensity statin can be used. Dr. Sean Kane: And you know, there, we've always had good data for patients with diabetes. The guidelines do dive in a little bit deeper than the 2018 in terms of for primary prevention among people with diabetes, what are those recommendations? So now we have a younger age group of 20 to 39. The recommendation is to start moderate intensity statin if they have diabetes specific risk enhancers or their PREVENT ASCVD risk is 3% or higher. So those diabetes specific risk enhancers are things like they've had diabetes for a long time. So more than 10 years for type 2, more than 20 years for type 1. If they have protein in their urine, so a UACR of 30 or higher. If they have CKD, so an eGFR less than 60. If they have retinopathy, neuropathy, peripheral arterial disease, or other indicators that they are having some tissue or organ damage from their diabetes. Any of those things, especially if you're 20 to 39, we should be more aggressive in that patient population. Dr. Khyati Patel: In patients who are 40 to 75, again, moderate intensity statin is recommended for most. But if we have higher risk, so if the PREVENT ASCVD risk is 10 or more, or if patients have quote unquote multiple ASCVD risk factors, then high intensity statin is recommended. And I have to say, Dr. Kane, this is the area where the guidelines kind of left it unclear as to what they mean by multiple ASCVD risk factors. So I had to dive into the ADA guidelines. Dr. Sean Kane: What did you see in the ADA guidelines? Dr. Khyati Patel: So according to ADA guidelines, the multiple ASCVD risk factor definition is having one or more ASCVD risk factors. What are they? Older age, hypertension, dyslipidemia, smoking, CKD, or obesity. So nothing different than all the stuff that we have already talked about. Dr. Sean Kane: And of course, this is not to be confused with the diabetes specific risk factors or the risk enhancers or any of the other lists that we've come up with. This is a separate list of other risk factors to consider that are very similar to kind of the other factors that we've discussed. Dr. Khyati Patel: Right. So if they have more than one of these, one or more, then they should receive high intensity statin. Dr. Sean Kane: So Dr. Patel, just to clarify, so in people with diabetes, when we say multiple ASCVD risk factors, diabetes counts as your first one, and then you need another thing, just one more thing, hypertension, smoking, obesity, whatever. And then that constitutes multiple risk factors where you'd be, if you're older, 40 to 75 in that high intensity bucket, to be more aggressive in those patients. Dr. Khyati Patel: Yeah, absolutely. And this, that is because diabetes increases the ASCVD risk by twofold compared to those who don't have diabetes. Dr. Sean Kane: And then finally, among primary prevention for people with diabetes, if the age is greater than 75 years of age, it's basically shared decision making with a consideration for moderate intensity statin. And a lot of this deals with the fact that as people get older, we just don't have a lot of clinical trial data among like 85-year-olds in terms of if they take a statin, does it help them live longer, prevent heart attacks and strokes? It probably does, but you have to have enough time to live for that for you to derive benefit. So a lot of this is involved with how are the side effects, are you okay with taking a statin, the life expectancy of the patient, things like that. But it's nice to see that shared decision making is an emphasis for those greater than 75 years of age for primary prevention if they have diabetes. Dr. Khyati Patel: So talking about primary prevention, we're going to jump into that category, but we're going to talk about patients who don't have diabetes, who are between the age of 30 to 79 years, and who do not have that primary LDL elevation. Dr. Sean Kane: So among those patients, if their PREVENT ASCVD is less than 3%, then you could consider a moderate intensity statin only if the LDL is pretty high, between 160 to 189. Dr. Khyati Patel: In patients who have that borderline PREVENT ASCVD risk, 3 to less than 5%, they could consider moderate intensity statin. Again, shared decision making should be discussed, especially if they have presence of risk enhancing factors. And this is where also the CAC score can come in play as a tiebreaker. So if that comes elevated, they should definitely go with moderate intensity statin. [40:21] Dr. Sean Kane: And then remember our older 7.5% threshold is now our 5% threshold. So if the PREVENT ASCVD risk is 5% to less than 10%, the guidelines say to start at least a moderate intensity statin or a moderate to high intensity statin if they're on the higher end of that risk range. And generally speaking, we're looking at LDL goals of less than 100, LDL reduction of 30 to 50%, which would be moderate intensity statin territory. But you could justify that higher intensity, so a high intensity statin with a lower LDL, if they have more of those risk enhancers or other reasons to justify a more intensive therapy. Dr. Khyati Patel: And then based on my interpretation of the guidelines, they also said that if, if on the spectrum of 5 to 10, if your risk is like closer to 10, then you probably want to go with the higher intensity instead of moderate. Which was interesting. So it's a range. Dr. Sean Kane: And then that really gets us to the last one of if you're more than 10%, you should have a high intensity statin with an LDL goal of less than 70. Dr. Khyati Patel: So the discussion we've had so far are patients who haven't had an ASCVD event. So they're all kind of considered in that primary prevention category. The guidelines has updates regarding the goals for the secondary prevention, and then talking about when it's the best time to employ our non-statin agents. Dr. Sean Kane: Yeah. So just like previous guidelines, if you've had an ASCVD event, you should have a high intensity statin. Really at this point, the question is, do you want an LDL goal of less than 55 or less than 70? And the vast majority of patients are going to end up with an LDL goal of less than 55. And the guidelines, they call this patient group "at very high risk", which means that you've had two or more ASCVD events, or you've had one ASCVD event and two high risk conditions. Dr. Khyati Patel: And those high risk conditions are age of 65 or above, having done a revascularization procedure like a CABG or a PCI, patient smoking, they have diabetes, congestive heart failure, hypertension, or if their LDL is above 100 despite being on maximum tolerated statin plus ezetimibe. Dr. Sean Kane: And as I mentioned, most of the patients will fall into this category because on average, people tend to be a little bit older when they have their ASCVD event, or they have diabetes or hypertension, things like that. So it's not hard for many of these patients to end up with two high risk conditions after an ASCVD event. But in the minority of patients, if they don't have any of those things, the guidelines would say an LDL goal of less than 70 if they don't meet those criteria. Dr. Khyati Patel: So as you mentioned, Dr. Kane, earlier, getting to the goal of less than 55 is hard just with statins, especially if they're not able to tolerate those high intensity statins. And that's where the guidelines bring in the non-statin agents and and when can they be initiated. Dr. Sean Kane: Yeah, and those non-statin therapies are in no particular order, ezetimibe, PCSK9 inhibitor as a monoclonal antibody, PCSK9 inhibitor as a small interfering RNA drug, and or bempedoic acid. So we have kind of a variety of different options with different levels of evidence and rationale to pick one over the other between those different options. Dr. Khyati Patel: Yeah, and I do want to emphasize that the inclisiran, which is the small interfering RNA for PCSK9, that one's kind of recommended as a secondary to the mAbs, just because we don't have the CVOT data out yet. Dr. Sean Kane: And Dr. Patel, I think it is worth just mentioning, as we have kind of touched on a number of times, especially for people with an LDL goal of less than 55, it's really hard to get there without some of these therapies, if not multiple of these therapies. So because of the guideline change, I think we're going to see a lot more ezetimibe use, probably bempedoic acid use, and then maybe these injectable therapies as well. Dr. Khyati Patel: Right. And we're going to kind of review those in a in a minute or so too. But overall, the monitoring of the therapy didn't really change. They're saying after starting the therapy or changing the therapy, 4 to 12 weeks to do a lipid panel again to see if we have reached those LDL goals, or if the patient needs any further improvement and titration in the therapy. But they're also saying to continue monitoring these patients every 6 to 12 months thereafter. Used to be like 12 months usually once they get to the goal. This is a continued monitoring because again, kind of going along with that longer, lower for longer type of a motto, they want to make sure we are titrating therapy appropriately. [44:50] Dr. Sean Kane: So then Dr. Patel, we've kind of covered many of these LDL lowering therapies, but why don't we just briefly review some of them. So obviously statins, we've talked about that a number of times and we actually had a whole HelixTalk episode 180 on statins. But what are some of the key points that aren't different from the guidelines but are just worthy of highlighting again? Dr. Khyati Patel: Well, then we have three categories of statins. The high intensity which lowers LDL by about 50%, the moderate which lowers it by 30 to 50%, and we have the low intensity which is less than 30% reduction. Really we don't really start anybody on the low intensity. They may be on a low intensity because that's the max tolerated statins. But really think about the statins, they give you about 6% or more LDL lowering if you double the dose, which isn't a lot. So if you started somebody on a 40 milligrams of atorvastatin, going from 40 milligrams to 80 milligrams is not going to lower LDL by that much. You're going to have to bring in the non-statins at that point. Dr. Sean Kane: And then, you know, although we want LDL to get better, the main reason we're doing it is for ASCVD risk reduction. And the best benefit that we've observed in clinical trials is with statins. So depending on the intensity and the patient group and things like that, we're looking at something like a 30% reduction in ASCVD events in the future by taking a statin, which is our best bang for our buck. And the main benefit is going to be with the high intensity that gives you more LDL lowering. And this is atorva 40 or 80 or rosuva 20 or 40 milligrams per day. Again, there's a variety of other statins that we have for moderate and low intensity as well. Dr. Khyati Patel: Right. And then the second agent that is geared towards LDL lowering is ezetimibe or Zetia. This one lowers LDL by about 20%, so not as impressive. However, the ASCVD risk reduction is also not that impressive, about 6%. The benefit here is that it's once a day, it's oral, and it's cheap because it's generic available now and tolerated pretty well in combination with statins. Dr. Sean Kane: Yeah. And then another oral therapy, which is a little bit newer, is bempedoic acid or brand name is Nexletol. We actually talked about this in episode 119. Like ezetimibe, it decreases LDL by about 20%. And you might be wondering, well, can you have both ezetimibe, which is oral, and bempedoic acid? And you can. And the brand name is Nexlizet, which is a combination therapy. And you get about a 40% reduction in LDL. We do have clinical outcomes data with bempedoic acid. It reduces ASCVD risk by about 13%. So I'd be careful kind of comparing apples to oranges. They're different patient populations, different trials. The main thing to know is that you do get an ASCVD reduction with both ezetimibe and with bempedoic acid. Dr. Khyati Patel: Yeah. And then PCSK9s are another one. We have the mAbs, which are the evolocumab, Repatha, or alirocumab, which is Praluent. And then we have that small interfering RNA, which is the inclisiran, the brand name is Leqvio. Dr. Sean Kane: And these are sub-Q injections. They are really effective for reducing your LDL. We're looking at like 50 to 60%. And they also reduce ASCVD risk in the clinical trials. It's about 15% with the monoclonal antibodies. And inclisiran, the clinical outcomes data is pending. Probably soon we'll know, but for right now, as you mentioned, Dr. Patel, the monoclonal antibodies just have a higher level of evidence because they have demonstrated the clinical outcomes benefit. Dr. Khyati Patel: Right. So so far our discussion was about LDL lowering drugs and like where patients fit in for LLT therapy, which is lipid lowering therapy. That's the first goal of treatment. We go after the LDLs and after that we go after non-HDLs and the ApoB goals and whatnot. But there are some patients who would still have the mixed dyslipidemia, aka they may have high triglycerides. And the guidelines kind of are recommending what to do for those patients too. Dr. Sean Kane: And I can't highlight this enough. When you have a patient with an elevated triglyceride, the number one thing is lifestyle management. So we're thinking about diet, specifically having a lower caloric intake in addition to a lower fat intake. Physical activity. And the big one is going to be alcohol reduction and obesity management. So by addressing those factors, that's going to be the vast majority of the benefit that you're going to get for many of these patients. But not everyone is going to be successful in losing weight, changing their diet, being more physically active, but we at least have to start there. Dr. Khyati Patel: Right. And as you said, Dr. Kane, these things may not overtly impact their triglycerides, especially if there is a genetic component of why their triglycerides are elevated. But all of these are modifiable risk factors for ASCVD reduction. So by doing that, at least we are reducing overall ASCVD risk if not triglycerides by number. [49:32] Dr. Sean Kane: And the guidelines are clear that if a patient has a reason to be on a statin regardless of their triglyceride, you should do the statin first because statins do have some benefit with triglycerides. It's just not that we're using it specifically for the triglyceride. But once you've started the statin, if they're appropriate for it based on their LDL, and you've done the lifestyle modifications, if the triglycerides are still greater than 150 or elevated, that's when we're thinking about triglyceride lowering drug therapy. Dr. Khyati Patel: Right. So then we're going to look at whether patient has a history of cardiovascular disease or has diabetes. And if that's the case, we're going to look at that EPA only fish oil, brand name is Vascepa, because that has shown reduction in ASCVD risk. Dr. Sean Kane: And obviously if someone's had ASCVD events in the past, they're at higher risk than someone that hasn't, which is why we're picking that preferentially. But if someone doesn't have a history of ASCVD or doesn't have diabetes, then we can pick either a fibric acid, so primarily fenofibrate, or a prescription omega-3 fish oil, which could be EPA only or the EPA/DHA, but still prescription strength. We're not messing around with the OTC stuff, which tends to not have as much concentration, they have to take more pills per day, things like that. Dr. Khyati Patel: So why don't we go back to our patient case? And I like the CPR approach you mentioned in terms of how we approach a patient with dyslipidemia, in terms of how we're addressing their dyslipidemia. So the first one was C for calculate the risk. And the guidelines say that you could do a PREVENT ASCVD score, and it wouldn't be wrong to see if that score was more than 10%. But that patient had diabetes. So because they have diabetes, you actually don't need to do the PREVENT score and you could kind of skip it and then look for other risk factors that they have. Dr. Sean Kane: And it wouldn't be wrong to do the risk calculation if you, if you needed to, but you're looking for the risk of 10% or more. And then we kind of move on to the P part, which is personalization of the risk. So this patient has diabetes, doesn't have the ASCVD event, but does have those quote unquote multiple ASCVD risk factors. So the patient has hypertension, dyslipidemia, and obesity here. So they definitely qualify for that multiple risk factor category. And not to forget all of those things kind of also go under the CKM. Plus there is that premature history of cardiovascular disease. So father had an MI at the age of 47. So this is definitely an independent increased risk of ASCVD. Dr. Khyati Patel: And you certainly could look at a lipoprotein little a in addition to all of the other risk factors that you've already mentioned. But at this point, I'm kind of sold, Dr. Patel, on a high intensity statin for the patient. You don't really need to do a CAC score with the coronary artery calcium score unless there's some reason that the patient really didn't want to initiate statin therapy. But given diabetes plus multiple, multiple risk factors, the high intensity statin would be our initial step here. Dr. Sean Kane: Right. So kind of reassessing the treatment. I know you are sold on high intensity statin, Dr. Kane, but off the bat with that diagnosis plus age, the LDL level, you know, at least moderate intensity statin. But with all the things that we mentioned, personalizing the risk, this patient really does qualify for the high intensity statins. Those are our rosuvastatin 20 to 40 milligrams or atorvastatin 40 to 80 milligram. And then this patient's LDL goal of course would be less than 70 and the non-HDL goal would be less than 100. Dr. Khyati Patel: And then if we wanted to, we could potentially check the ApoB, which would again be less than 70 because it matches the LDL of less than 70 in this particular case. And our goal is that we want to drop that LDL by at least 50% with our high intensity statin, again to achieve that LDL less than 70. Dr. Sean Kane: Right. And then if Rodney starts that treatment today, in 4 to 12 weeks we'll ask to repeat the lipid panel. And if the LDL is not at goal, then definitely other non-statin agents like ezetimibe or the PCSK9 mAbs can be considered promptly, so without delay. Dr. Khyati Patel: Or bempedoic acid, right? Dr. Sean Kane: Yeah, that works too. Dr. Khyati Patel: So then once we're at that LDL goal, that's when we're thinking about non-HDL, we're thinking about triglycerides, maybe ApoB, things like that. Again, also re-emphasizing lifestyle modifications, thinking they have diabetes, so we might need to address their A1C or fasting glucose, things like that, that by addressing those other things and weight loss if it's appropriate, might also help with the lipid panel as well. Dr. Sean Kane: Right. And then outside the scope of this guideline, when we are talking about ASCVD risk reduction, fixing dyslipidemia is like one piece of the puzzle. We are still looking to reduce risk by maybe identifying if patient qualifies for antiplatelet therapy. And given this patient's age, diabetes, and multiple risk factors, according to the ADA guidelines, this patient is a candidate for a small dose aspirin, if not tolerated, a 75 milligram clopidogrel. Dr. Khyati Patel: And we haven't even talked about the patient's blood pressure, if that is elevated at this stage, things like that. So there's a variety of other risk factors that we should be considering. Dr. Sean Kane: Yep. [54:30] Dr. Sean Kane: So Dr. Patel, why don't we wrap it up with this 123-page guideline into just a couple key take-home points. I think the main one that probably is going to make most of the news and make most pharmacotherapy lectures update their slides is going to be the PREVENT ASCVD equation, which is now replacing the pooled cohort equation from 2013. This is how the guidelines are asking that we calculate 10-year ASCVD risk. And it is the triangle, hand, and bowling pins of 3%, 5%, 10% for our thresholds. The previous threshold of 7.5% for really promoting statin therapy is now at 5%, that it is recommended that if you're above that 5% that you really should be thinking about a statin. Dr. Khyati Patel: Right. And in order to do a more comprehensive risk assessment, in addition to that 10-year ASCVD estimate, clinicians should also consider using the Lp little a, you know, those are the kind of your risk enhancers, the coronary artery calcium scoring as a tiebreaker whether to start the treatment or not. Dr. Sean Kane: And then we have LDL goals of less than 100, less than 70, or less than 55 depending on risk. But now we're also going to be thinking once we've achieved those LDL goals about non-HDL cholesterol and ApoB goals, which again, those are secondary goals after you've achieved your LDL cholesterol goal. Dr. Khyati Patel: And as we mentioned with that lower LDL goal, statins alone are not going to be enough and we're going to need non-statin therapy to reach those goals. The recommended non-statin therapies include ezetimibe, the PCSK9 monoclonal antibodies, the PCSK9 small interfering RNA like inclisiran, however this one is secondary to PCSK9 monoclonal antibodies, and the bempedoic acid. Dr. Sean Kane: So for the listeners, again, in our references on helixtalk.com, episode 198, we do have a reference for the 2026 ACC/AHA guidelines if you want to see the guidelines in all their glory. And we also have show notes from today as well. So with that, I'm Dr. Kane. Dr. Khyati Patel: And I'm Dr. Patel. And as always, study hard. (Music) Male Announcer: If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five-star review in the iTunes store. Search for HelixTalk and place your review there. Female Announcer: To suggest an episode or contact us, we're online at helixtalk.com. Thank you for listening to this episode of HelixTalk. This is an educational production, copyright Rosalind Franklin University of Medicine and Science.