Dr. Talreja discusses the 2026 standard of care for treatment of dyslipidemia with new screening guidelines and advanced therapy options.
Thank you guys for joining bright and early. On Tuesday morning, Amy tells me this is the last official grand rounds of the year. I'm, I'm joining Salvatore Carbone today, and we're going to talk about. Nutrition and the new lipid guidelines. What prompted this is I actually just gave a talk at the at the diabetes and endo group meeting, the Turning the Tide's 15th annual session, and I had a request from a number of people to present similar information here in the cardiology conference. So we're going to talk about the 2026 lipid guidelines. We're going to focus really on going beyond the statins. I, of course, have to say statins are first line therapy, but we're going to go a little bit beyond that because I think everyone in this audience knows that. These are my relevant financial relationships and disclosures. There's nothing I'll be talking about in an off-label fashion today. So in my daily life, the two clinics I sort of subspecialty wise find myself spending time in are the Lipid clinic and the TAVR Clinic, and they're set from a provider perspective. They're such different environments. In TAVR Clinic, you know, 2011 we did the first TAVR here. We're now 15 years into the maturity of that therapy. It's a You know, 6th, 7th generation equipment, we have a lot of options like we never had before. Patients come to structural heart clinic really excited and eagerly wanting a TAVR. Now many of them have moderate AS or they're asymptomatic, and they don't need a TAVR, and they're sorely disappointed when we tell them we have a great therapy that they really don't need it yet, at some point they will, and we'll keep in close touch. Lipid clinic is the exact opposite. I have a great therapy in terms of statins and other lipid lowering therapies that I'm excited to deploy for patients in clinically indicated and guideline-driven treatments, and a lot of the folks referred into that clinic don't want the therapy. They know there are a lot of potential things they've read that are negative about the therapy, and it's just such an interesting contrast between those two. Um, What we know from many years of experiences and multiple trials and guidelines and expert opinion is that the magnitude and the duration of LDL exposure ultimately is the final determinant of the level of ASCBD we face. So it's a simple equation of LDL levels multiplied by time and years equals total plaque burden, which correlates with ASCBD. The reason that's important is we hopefully will all be lucky enough to enjoy many years. That part of the equation we don't really want to change in a downward fashion. So the only way to decrease total plaque burden is to lower LDLC exposure over those many years of lifetime we hopefully enjoy. Of all the boards I've taken, the American Board of Clinical Lipidology, I think, was the most nitpicky and specific. And what we know is with the lipoprotein particle zoo, the atherogenic particles that are found in plaques at autopsy are largely these LDL and remnants and precursors of it, LDL, IDL BLDL remnants. We also have HDL, which is helpful, but no pharmacologic therapies have really shown us the ability to improve that, and we have chylomicrons and their remnants and VLDL which tend to be more involved in hypertriglyceridemia and disease states around that. Recently there's been increasing attention to LPA, and it bugs me that the terminology we use is contaminated from years of sort of lumped on additional namings of particles that make no sense. Just a quick reminder, AOB bearing particles, the way I think of AOB is it's a protein on the surface of the LDL particle. And NIDL and VLDL, it's on all the atherogenic, um, particles, and it's like a ribbon on a package. There's only one AOB per, um, LDL, for instance, and so you can measure AOB levels directly. AOB 100 is the particular one that's on LDL, VLDL, and IDL, the arogenic particles. Some APO. AB molecules are coupled with this extra moiety that makes them LPA, a more oxidizable form of AOB. There is also AOA, which has nothing to do with LPA. It's in fact the ribbon that's tied, the single particle that's on the exterior of HDL. So confusing terminology, but LPA is a more atherogenic form of AOB, which is on the particles that we're concerned about, and we can directly measure both LPAA, which is now finally recommended in the guidelines, and we can measure AOB levels and AOA. AOA on HDL is more confusing because while there's one ribbon on every LDL, there can be anywhere from 2 to 4 ribbons on HDL and HDL is a more complicated story. So this year in 2026. We finally have a consensus guideline between all the groups. Up until this year, the ACC, the NLA, the AHA, the ADA, and other groups had separate and discordant lipid guidelines, and it was always frustrating because you found yourself kind of making it when we created our lipid clinic guidelines, we had a potpourri of pieces we thought were the most appropriate from each of those. But finally in 2026, we have a consensus guideline. Many of you have asked me what I think of this guideline, and the answer for the nerds out there is that this is the Is the holy grail. This is the one guideline to rule them all and in prevention bind them as a nice allusion to the Lord of the Rings. And I'm going to very quickly move through this guideline. I want to have Dr. Carbon and I both talk about the state of nutrition, lipids, and cardiac rehab, and to fit all that into an hour, especially a plus 100 page guideline, means I have to move quickly and simplify a little bit. One of the first big differences is the idea is screen earlier, check regularly, aim for lower LDL, and treat longer. Screening is now recommended at 2 to 4 years of age if patients have a strong family history of premature ASCVD. I think our pediatricians are adapting to that. My wife's a pediatrician. They are starting to do this a lot more, but we're not there yet. Then screen at ages 9 to 11 to identify FH and other lipid disorders. So that's routinely, not just in high-risk patients. Then we screen again when patients hit their adulthood, and hopefully, by age 19, they've already had one screen, but they should have another one, and then we recheck typically at least every 5 years. LDL goals have been set downward. We're back to goals. The last ACCHA guidelines said get a 50% reduction, and they were well-intentioned. It was based on how the trials were designed and what, you know, what we ultimately think. Nowadays, the idea is targets are great for patients and physicians. I like targets. I like a goal I'm trying to achieve, a finish line. So less than 100 for any Prevent ASCVD, less than 10%. We'll look at this. Frankly, the goal is now less than 100% in almost anyone that anyone in this room would touch. Less than 70% if the ASCVD risk on the Prevent score, which is the new favored tool, is greater than 10%, if they have a family history, if they have diabetes, if they have a calcium score of greater than equal to 100, and less than 55 for the vast majority of patients we're taken into the hospitals, doing PCIs on that have clinical risk factors that put them at high risk. The recommendation is to check lipids every 4 to 12 weeks after any dose titration or adjustment in medications, and there's a recognition that while many of the trials end at age 75 or 80, that there is good data to suggest use in Octa and nonagenarians. This is a great therapy around. Um, uh, Salvatore, we'll talk more about this, but the Life's Essentials 8s reminds us, any good lippitox should remind us, diet, physical activity, stress reduction, treating blood sugar and weight, following blood pressure, quitting smoking, and sleep are really important and critical parts of managing dyslipidemia. In the current era. Our schedules are so compressed we don't often have a good time to do this, but I'm hopeful that in partnership with EVMS and our rehab programs, we can do a better job of this in the time. Obviously there's a huge benefit to individualized risk benefit discussion with patients in a clinical world that moves as fast as ours does, where we're overbooked and have long waiting lists. I think this gets short shrift a lot of the time, but it's important to recognize the value of this, and we're trying to come up with systemic tools to make this more available, especially to the sickest patients. I would have a call out that cardiac rehab is a great place that picks up what we often don't have time to do around this. The reason it's so important is we know that mortality directly correlates with improvements in physical activity. We see a, a huge difference, and the greatest drop is from doing nothing to doing just a little bit of physical activity. The Centeralipid Clinic currently follows the Pritikin plan. We obviously had the orange plan in the past. This is an intensive cardiac rehab program, and I'm gonna skip on because I know Salvatore is gonna talk a little about it, and I know we talked about this when we did the last grand rounds about a year ago. That was run by our nursing team, Elizabeth Vick, and I'll talk more about this group in a in a moment, but they've done an amazing job really systematizing a lipid approach, and that's continuing to grow. So when we look at lipid lowering agents, we have a growing armamentarium. Statins are far and away the first line of therapy. We have over 50 years of data showing excellent improvements in outcomes. All the, all the collaborations of the trials and each individual trial consistently show benefit. Benefits in hard clinical endpoints, while there have been concerns about potential side effects, and some of those are real, remember back to the 4S trial, where the simvastatin, Scandinavian simvastatin survival Study studied 4,444 patients with simvastatin versus a standard of care therapy, and 8% of patients complained of muscle uh complaints. In the on-treatment group, but in the placebo group, 6% of patients complain of muscle complaints. So while it's real, and while we need some of these other therapies to help us, uh, statins really are the first line therapy. We talked already about the guidelines, they lay out very nicely that we need to document, they currently recommend a standard non-fasting or fasting lipid profile in the absence of hyperlipidemia or severe disorders of LDL a non-fasting profile is fine. Um, when family history, uh, is present or premature ASCVD or a known, uh, significant level of elevation of triglyceride metabolism, that's when we really need the fasting lipid profile. So if fasting is an obstacle, don't worry about it, just get a non-fasting lipid profile. We've typically use the Friedwald equation. There are more complicated equations. I'll show you. The Martin Hopkins equation and the Samson NIH equations are now preferred based on the guidelines. We're working at discussions to convert Centera over. This is for the nerds in the audience. This is the more detailed explanation of what those are. The real problem with the Friedwald equation is elevated triglycerides skew it so that the LDL looks low when it's really not. The other equations are more complicated but less susceptible to that. All right, the other ancillary risk markers that are being discussed nowadays are also doing direct measurements of apolipoprotein B, especially in patients we're not certain about. It's a more accurate measure of the actual LDL concentration in the body. It's not just the concentration, it's actually the total burden of LDL that exists. Also, we'll talk more at the end of the talk about screening with LP. Little A, that's now recommended and we commonly see elevations a little, uh, of LPD little A. There's a higher incidence of cardiovascular events. Uh, I know for years I followed a, um, very intelligent young lady who had a stroke early in life with an elevated LPA diagnosed a decade ago. We still have no direct therapies for lowering this. We'll talk about it later, but, um, more is coming. The now preferred calculator is the Prevent ASCBD risk calculator. It's available online. We're working on building it into the Centera system. It takes into account the factors on the right, which are both modifiable and non-modifiable risk factors, and increasingly cardio metabolic clinics, which again we'll hear more about in the primary care conference coming up in a few weeks, there is emphasis on CKM diseases and following urinary albumin creatinine ratios. The new guidelines set a lower level for low risk. We're increasingly treating patients. This is the correlation with the previously recommended pooled cohort equation. I think Prevent is now clearly the tool we want to use preferentially, and the idea is within every, every lipid panel draw, every year, every 5 years at least, we want to reclassify patients as low risk, which is 0 to 3% of cardiovascular events over 10 years. Borderline is 3 to 5%. 0% intermediate risk is 5 to 10%, and high risk is greater than equal to 10%. Using this classified, personalized, reclassified framework, we will treat more patients than we did with the previous guidelines. For the lowest risk group of patients, lifestyle modification is recommended. For everyone else, we start thinking early about whether they have risk enhancers and whether they would benefit from pharmacologic therapy on top of aggressive diet, lifestyle, exercise treatment. The highest risk patients are those that have had multiple ASCVD events, or have had at least one event, and we'll talk about what an event is nowadays it's clearly anything where we've revascularized a patient, including uh diagnosis, but not revascularization, where we put them on medical therapy, um, even when the FFR is normal. Calcium scores have come into play, and high risk conditions are increased age, defined as the low level of greater than equal to 65, cabbage or PCI, current smoking, diabetes, history of CHF hypertension, or LDL greater than or equal to 100, despite maximally tolerated statin plus azetimi. Risk enhancers very briefly are um related to age, to demographics, to uh to ancestry, polygenic risk if known, LPA greater than equal to 125 on our current measurement techniques, elevated HSCRP, elevated triglycerides, um. Cardiac kidney, metabolic syndromes, higher LDLs, and also reproductive risk markers. There's a lot on that in the new guidelines. Premature menopause, preeclampsia, gestational diabetes, gestational hypertension, or preterm delivery are all considered risk enhancers that would make us push for more aggressive targets. All right, primary prevention, a lot on this slide. My goal is not to go through all of these algorithms in detail. Um, it's worth looking at at some point, but the idea is very early on, we're starting moderate to high intensity statin therapy and aiming for these goals we've talked about already. When we can't get there, we have additional therapies including. Including azetimib and increasingly the push is to go to PCSK9 inhibitors and further therapies we'll talk about earlier to really get patients to goal. A lot of our patients really need to be on that therapy. Unfortunately, the cost has come down considerably. We have more options we'll talk about, and approval is a lot easier. That's the primary prevention group. Secondary prevention, um, the guidelines talk a lot about in detail. Again, the goal is high intensity statin therapy, not intermediate, now high, to achieve both an LDL reduction of greater than 50% and an LDL goal of less than 70%, and later we'll talk about the less than 55% goal. Note that the guidelines didn't completely drop the 50% reduction. The reason to leave it in there is when you have a patient that comes in with an acute MI and their LDL is 90. You want to get them below half of that, a 50% reduction, or let's say they come in at 65, you really wanna get a 50% reduction and get them down to the 30s based on the guidelines. There's additional discussion about additional agents including azetimi PCSK9 inhibitors, um, vapidoic acid, and we'll talk about further therapies as well. Um, secondary prevention in, uh, in patients with very high risk, you all know, is LDL less than 55 and that greater than or equal to 50% lowering, um, and here, because we have to worry about triglycerides, we either need to check the triglycerides or use the surrogate of non-HDLC of less than equal to 85 is what we're targeting, and we'll talk about how we get patients there. You see the guidelines have a lot of class one and class 2A indications. The, the knowledge base these are based on is very robust in this era. Severe hypercholesterolemia is an LDLC greater than 190. Um, it's a very high lifetime risk of ASCVD even without other risk factors, and I see less of these patients nowadays, but there were many a decade ago that were arguing, even though my LDL is 200, do I really need to be on therapy because I feel good and I haven't really had any problems. We should always look for secondary causes. These include inappropriate diet. Especially ketogenic type diets or high saturated fat diets. These can often help with weight loss, but the unintended, uh, consequence is poor lipid uh results, hypothyroidism, CKD, nephrotic syndrome, steroids, etc. Once we've excluded secondary causes, the goal is max tolerated statin and very quickly and aggressively move into additional therapies. There's increasing use of family history and. Coronary artery calcium scoring to help identify these patients, and here we see the first appearance in the guidelines of inclycerin on top of, or, or as opposed to um PCSK9 inhibitors. Also another very effective therapy. The Orion trials to look at endpoint reduction are ongoing, which is the only reason this isn't yet a class one indication, but as a 2A indication, inclycerin has a useful role in our therapies as well. This is those two guideline sets, and what I like compared to the older guidelines is you can see they're very linear. Uh, you start with your statin and then you move down and quickly escalate to other therapies. All right, diabetic patients are higher risk than most. The studies looked at patients typically ages 40 to 75, but in my opinion, these guidelines appear to any age group, um, even, even pediatrics and certainly elderly patients who want to aggressively get them on statin therapy early. If they're not, uh, tolerant of statin, then think of additional, uh, treatments. And if you can't get their LDL less than 70, then move to high intensity statin. Um, for the first time in the guidelines here, we see additional thoughts because diabetic folks often have high triglycerides about therapies for elevated triglycerides. If their triglycerides are 150 to 500, you wanna consider um omega-three supplementation, and that's based on 2 out of 32 trials in the, um, in the omega-three space that have both shown benefits with icosopentanyl ethyl um substitution. Additionally, we wanna lower LDL further and especially if a patient's very young, even if their numbers aren't as bad, we really wanna get them on therapy aggressively because we know that most diabetics will ultimately, uh, suffer cardiovascular disease, and that's the leading cause of death in that population. That is a lot. I have moved quick, but the reason is because I know a lot of the audience really kind of already knows this, and it's consistent with previous guidelines, just a little more aggressively stated to titrate early. Diabetics, there are risk enhancing factors for as well, that's long duration, more than 10 years for a type 2 diabetic, or 20 years for a type 1 diabetic that would push us to more aggressive earlier therapy. Albuminuria, again, recognition of that CKM syndrome, um, decrease in GFR, retinopathy, neuropathy, or evidence of PAD as, uh, espoused by an ABI of less than 0.9. That one's included, whereas a lot of other measures that aren't because it's inexpensive and easily available. Again, with diabetics, this is the guidelines set, just very quickly, what I'm pointing out again is there's almost no diabetic that shouldn't be on a statin very early in their cause, especially those of us that cardiologists and vascular surgeons and cardiothoracic surgeons are getting involved with. Um, and, and the guideline goes on again to say add additional therapy early on the right side. Uh, it specifically calls out a number of them, for example, ezetimib and PCSK9 inhibitors, and the addition of omega-three supplementation on the left side if their non-HDL is high or their triglycerides are greater than equal to 150. And in the time to come, I'll talk briefly about hypertriglyceridemia and newer therapies for those with the really high triglycerides greater than 500. Next, a condition we probably don't, uh, adequately identify is both heterozygous and homozygous familial hypercholesterolemia. Any person with an LDL greater than 200 at any point, we should think about heterozygous FH. This is an autosomal dominant genetic condition where the LDL receptors or something in that complex isn't working correctly. Genetic testing can be done for those patients. And we actually have the ability in the lipid clinic to do free genetic testing for a a subset of these patients, so something to think about. We really wanna aggressively treat these patients, um, they probably should be referred to a lipid specialist. They clearly need to be on max tolerated statin therapy. They, they almost always require the addition of, of additional therapies we talked about. And then you see the first mention of evanucumab, um, that's also called Efkiza, it's not. Generic name, if they have elevated levels, then patients with homozygous FH, not heterozygous, but homozygous, have this additional therapy, and also laidipide is a therapy we've used for many years. I would say in my mind, evanucumab comes a little bit ahead of lamitipide, but it's in addition as well. This is how evanucumab works. To me, it's a fascinating alternate mechanism. This is a vast simplification of the earlier slide I showed you. But the idea is when our livers produce VLDL and secrete it, the lipoprotein lipases and endothelial lipases break down some of the elements of it and ultimately produce VLDL remnants, then IDL then LDL. Typically, we use statins and benpatoic acid and PCSK9 inhibitors to increase uptake of LDL through those purple LDL receptors as we loop around back to the liver. The problem is in familial hypercholesterolemia, and with homozygous you have even worsening of this, the LDL receptors simply don't work. So instead, there's an LDLR independent clearance mechanism, which the green arrow points to, and that is the LDL remnant receptors. Evannuumab is an injectable, it's a once monthly one hour infusion. That dramatically up regulates this VLDL remnant receptor activity pathway, and as a result, even with broken LDL receptors that these homozygous FH patients have, we can reduce their LDLs by about 50% with evanucumab, great therapy. This is the pivotal clinical trial that showed the gray placebo group and the red on treatment group. The group that received evanucumab had about a 50% reduction, which was sustained over time. You see that after the uh the investigational portion of the trial in the open label portion, which went out to almost a year, that those patients who were originally on placebo and were able to then switch over and get active therapy again had. Roughly 50% reduction. So my ask of everyone is, if you see homozygous FH patients, LDL is greater than 400 at any point, please send them in, because while it can be, um, you know, it takes a little more time to pre-auth and so forth and monitor, we are delighted to help with these patients in the lipid clinic. The guidelines then call out um measurement of subclinical coronary atherosclerosis, and I'll pull up all the slides. I think we as a practice are increasingly using this, so it's coronary artery calcium scoring, and of course, we have a lot of modalities to look, we have PET coming, we have um for, for the right patients, some of the other therapies that identify. Plaque are everything from CT's where we're looking at AI augmented approaches to try to identify plaque, even when we're not getting cardiac related tests on patients. But then we also have obviously coronary CT scans, we have cardiac catheterization, we have stress tests through echo and nuclear and just exercise-related testing. There's a whole panoply of trials that will show us the presence of subclinical coronary atherosclerosis, and I think those tests are truly life-saving when applied in correct fashion. It's interesting. Look how coronary artery calcium score of 1 to 99 already starts us thinking about starting moderate intensive intensity statin therapy. To me, when I see those patients that are not interested, getting a um a CRP and a CAC is a very useful, quick and easy, inexpensive, relatively inexpensive first set of paths that tells. if they need to be on something, and again, coronary artery calcium score of 0 is the only level which isn't mentioned in the guidelines set. Once you start getting higher and higher, you really wanna think about additional testing, about additional lipid lowering, and again, I'll keep my comments brief just in this period of time, but I think this is important to bring up. Again, I'll keep comments brief, but increasing guideline recommendations in patients with chronic kidney disease. Patients with kidney disease are mostly going to have, uh, cardiovascular endpoints as a that result in mortality. So we really want to be aggressive early on with these patients. Um, they wear out valves, they wear out coronaries. They just need aggressive therapy, and they're at high risk. Older adults, because the trials have often excluded them, uh, some, some guideline sets have ended, including this one at 80 years, but this guideline set goes further to really say that even when patients are greater than 75 or 80 years, it's reasonable to continue or even initiate statin therapy. I'm a stronger believer in this. This is the one part of the guidelines that I feel is. Dramatically underdone, and the reason is they wanted to be very evidence-based and unfortunately the number of randomized trials that included older patients is limited. There certainly is trial data, but honestly, I, I personally think both those two A's should be class 1 indications and if they have a reasonable life expectancy, we really want to initiate therapy and continue therapy. All right, moving on, we've spent a lot of time talking about LDL management, and it kind of sounds to the average cardiologist out there like the answer is just, you know, put everyone on statin, and if they don't get to a pretty darn low number, you pick 1070, 55 based on the risk, then add other therapies, at a. Ami, add phampadoic acid, add PCSK9 inhibitors, think about inclycerin and screen for FH in the highest risk patients. And there are certainly other therapies that I haven't listed in there, but those are probably the ones that appear most prominently in the guidelines. Now we're gonna talk about elevated triglycerides. Um, three recommendations in adults with persistently elevated triglycerides greater than 150, we really wanna think about what's going on. We wanna manage and look for secondary causes. The most common is gonna be simply diabetes, hypothyroidism is on the list as well, um, excess sugar intake, especially just prior to the test, poor diet, huge contributor, um, a lot of other things on the list we talked about earlier. We wanna be thinking about aggressive therapy if they have concurrent ASCVD and LDL is greater than or equal to 55. And if they have persistently elevated triglycerides, we really wanna think about omega-three supplementation as we talked about. So simply, we wanna identify and manage secondary causes first, discuss alcohol intake, diet, physical activity, and improve weight management. If we can get them within range, and really truthfully, even 150 is high, the normal numbers should really be less than 100 and and probably significantly less than 100. Once we initiate therapy, we want to think about monitoring their response to it, and here's where fasting levels are important, and the guidelines call out the strongest recommendation on omega 3 supplementation specifically. When adults have triglycerides greater than or equal to 500, again, we wanna do all the same thought process early on, what we wanna think about is managing not only cardiovascular risk, but risk of pancreatitis as well. And so typically we've been, uh, in a traditional approach, if their LDL is greater than 500 and they have a fasting, uh, hypertriglyceridemia with some sort of elevation of risk, we early think about adding a statin, and then there are other therapies like fibric acid, and while niacin isn't used much anymore, it can help with lowering triglycerides as well. More excitingly, if we screen patients for FCS, familial chylomicromia syndrome, this is more and more common, and I see a lot of referrals now with patients with triglycerides anywhere from 1000 and really even 800 is where I start to worry about this, but 800 up to a few 1000. Certainly we've traditionally used things like fibric acid, omega-3, and niacin. Uh, more recently, there are dedicated therapies. Again, Olozarsan is one that we are excited about, um, in our area, the pivotal trials went on. This is an AOC3 ASO anti-sense oligonucleotide. Again, this is gonna be injectable therapy, but we basically have a complement to the mRNA that's created to create AOC3, which is one of the enzymes involved here. The by injecting this anti-sense oligonucleotide, it couples with and then degrades the mRNA that these patients' bodies are making for the AOC3 um um complex. When you block it, we see that there's an increase in triglyceride-rich lipoprotein hydrolysis, so we use natural mechanisms to clear it. There's an increase in triglyceride rich lipoprotein clearance, so we break it down and we clear it, and this results in decreased plasma triglyceride levels and a decreased incidence in acute pancreatitis. There are not yet studies that have finished out looking at cardiovascular endpoints, but those are in process now. The bridge trial of this therapy, and there are others coming as well, looked, it was a nice randomized controlled trial, and you can see very significant reductions of approximately 50% that occur very early on in patients who have olosarsan added in. Again, the indication is FCS, so these are the really high triglyceride patients, but this is another group we're happy to see in lipid clinic and get them on therapy. Let's talk briefly about elevated LPLA. For many years, I thought, why check this? And the reason is, while it is a risk adjudicator and would tell me to treat to lower LDLs, very often there's not a dedicated therapy, and so there wasn't really anything to do besides lowering LDL. The guidelines have really caught up and finally say let's. Go ahead and check it if they're elevated, and we check it in all individuals, typically once in their lifetime. It tends to be one of those tests that shouldn't change a lot. I have seen a couple of exceptions to that where patients have radically different numbers, and those are often difficult to explain. That'll be something that'll be more data coming on. If they have clinical ASCBD and they're not at goal, very early we move to PCSK9 inhibitors. There are no currently FDA approved indications for LPA reduction, but we do know that we have a number of therapies that significantly lower LPA, although they are not indicated for this specific endpoint. So, so when you pre-op, for example, inclycerin or PCSK9 inhibitors, saying you're trying to reduce LPAA actually doesn't help at all. You gotta really specify that you're reducing LDL. Now you may be setting more aggressive LDL targets because of elevated LPAA, and fortunately. LPA will often go down. You can see by different amounts. Unfortunately, it's fairly disappointing what happens with statins, so really in these patients, early on, I'm moving to these additional therapies we talked about. Um, there is more coming on the horizon are a number of, uh, agents that are gonna specifically target lowering, um, LPLA at CRT and at ACC. There was discussion of ongoing trials, and those trials continue to go on. Uh, we don't have endpoints yet, but it's anticipated that within a 12 to 24 month period, the. First endpoint trials will come out and everyone's optimistic and hopeful that we'll reduce endpoints by actually specifically targeting this, but we don't know that as yet. So, one last time, my disclaimer is this slide is showing us what is the LPA reduction with these therapies that are indicated rather for lowering LDL, not necessarily for LPA reduction. Why does this matter? To me? Uh, this is 2006. We saw the asteroid trial, and I think these images are what made me get excited about getting into the space and boarding in lipidology. We can absolutely see plaque regression. This is a six month pre and post. You see IVIS of a vessel which is targeted to see baseline and follow up six months later on aggressive lipid lowering with Crestor 40 mg, rosuvastatin. You see, the atheroma area is 10.6 millimeters in the baseline study and is reduced to 6.99 millimeters squared in the post-treatment study at just 6 months. The lumen increases by over 20%. Interestingly, most of the difference is in the atheroma, and when we look at, uh, specific plaque morphology, what we know is there may be a higher ultimate plaque calcium level. But the soft plaque, which is really what seems to be the uh part that causes acute cardiac and cardiovascular events, is significantly reduced, and that's concordant with the data I left out of this, that, you know, again, huge, huge meta-analysis, as well as each individual trial, generally so shows something like a 25 to up to 35 or 40% reduction in hard clinical events like stroke, MI, and death. So while many of our patients and media reports are skeptical of statin therapy and lipid lowering in general, many patients come to us, of course. A decade ago they were worried about things like cancers that could come from statins and joint side effects. Now they tend to be more worried about diabetes and memory problems. Again, the most aggressive trials of looking at PCSK9 lowering of statin, the neurologic substudies with very careful analysis, albeit over short time periods, but showed no neurologic adverse events. For the rare patient, they've convinced me maybe they've had something and we've backed down on therapy, but the guidelines are showing us increasingly we can go lower and lower and lower, and genetic studies in the population show patients who are living through childhood and adulthood with in utero, uh, genetic defects that cause very low levels of LDL in the single digits. So clearly the levels we Americans have. And most, uh, most developed countries are excessively abnormal. It's just they are kind of the norm because of our diets and lifestyles. Getting down LDLs, I celebrate when I see LDLs in the twenties, honestly. A lot of patients ask, can I back down? And that's a complex discussion because we have limited data to address it, but there's certainly good safety data for reasonable time periods now in that group. One other thing I wanted to mention is um. Centera has created a lipid clinic. The folks that are part of this, and I'll show them in a second and give them credit for it, have gone on to iterate and have developed the next level. So we started with the one lipid clinic out of Virginia Beach. Elizabeth Vick hosted that clinic. We've increased it, and this has been a QPI metric that we've achieved routinely for the last 3 years, where our nurses are the Drivers of this, they will do titration protocols. The physician still specifies what the goal is, what's the indication, and so forth, but they'll titrate so we don't just start a low dose statin and not see the patient for another year. Currently, that clinic is only an SCS clinic because it's very underpowered, so any SCS provider can refer a patient in for dose titration. The next evolution of this that our team has independently come up with, and it's incredibly impressive to me is the idea that just like we have a Coumadin clinic, maybe we could use a team with nursing and pharmacy together to make that a larger, more available clinic. Again, this is in the early stages, and I'm sharing something that is really in its early thought stages, but to me that's brilliant. And the real heroes behind this are the folks battling dyslipidemia in a galaxy near you now. You can see this is Allison Derry. Amy Hoggart, Elizabeth Vick, who actually presented a grant rounds with me a year ago on this topic, and Amy Coleman and many more that deserve credit that I don't have time to put in. But you know, a celebration of the May Star Wars folks out there, they're doing an amazing job. So a lot, a lot of data. If I were summarizing my final slide, the 2026 ACCHA guidelines are the best set out there, and not just ACCHA, they're with other groups as well. This is the final consensus we have. The idea is we do CPR on patients. Let's do our CPR of the lipid world, which is assessing them and keeping on reassessing them and and figuring out this framework of calculating, personalizing, res. Classifying, we want to aggressively treat. The current targets are less than 70 and less than 55 for the vast majority of patients we're seeing. LPA measurement at least once in a lifetime for folks. And if there's uncertainty, making sure we're getting fasting lipid profiles when triglycerides are high or when we're uncertain and using APO-B as a tiebreaker. All right, that is a ton of information in a short space. I'm delighted to answer any questions at the end and to have anyone reach out by email or uh in basket or anything else. I'd like to take time now and introduce my friend and associate, Dr. Salvatore Carbone. He's going to take over and talk about some exciting work going on as we see increasing growth in this collaboration between EVMS, ODU, and Centera. I could talk for longer than we have for this talk on Salvatore and what he's done, but he's an associate professor and program director of the new nutrition program at the Eastern Virginia Medical School of Health Professionals, an associate professor within the EVMS Division of Endocrinology and Metabolic Disorders and the Strelitz Diabetes Center and the Macon and Joan Brock Virginia Health Sciences at ODU. Prior to joining ODU in 2025, he was a tenured associate professor at BCU. He's a registered dietitian, nutritionist, and internationally recognized scientist. He's been named among the top 2% of scientists worldwide by Stanford University, most of the last decade and a recipient of the 2016 Mentored Clinical and Population Research Award from the American Heart Association and also the 2019 Career Development Award from the American Heart Association. And the 2023 Investigator Award from the Heart Failure Society of America. He's dedicated his career to advancing nutrition science and improving patient outcomes with a focus on heart failure, and I'm grateful for him joining us today. Salvatore, thanks for coming. Uh, well, good morning everyone. I hope you can see my slides and can hear me OK. Yes, they're on screen. OK, perfect. Uh, well, first of all, I wanna thank Doctor Tarija for inviting me to give, to be part of this, uh, uh, um, very, very interesting and timely, timely topic, and, uh, um, you know, I thank you also for, for, for this first. Uh, part of the presentation, it was really wonderful to see how much this space has evolved over the last few years, uh, and for the next 10 minutes, uh, what we'll, what we'll do is to really just go also through the new guidelines, but particularly focus on lifestyle, the lifestyle component, uh, and we will discuss a little bit about nutrition and then, uh, uh, quite a bit also about cardiac rehab and the and the role that you might have in the, for the treatment of your patients. I don't have any disclosures except that some of the tables you will see were developed with the use of AI, but I do take full responsibility for the final results. So this, in this slide, I just try to summarize all the major components of the of the new uh 202, 2026 uh guidelines for dyslipidemia, and as Doctor Theresa has already mentioned, there is a big focus, which was already emphasized in the prior guidelines on primordial prevention, so preventing those risk factors. In childhood and early adults and uh uh one of the questions is how do we do that? And obviously pediatricians and primary care physicians play a critical role in this. Uh, the new guidelines, what I like is that they provide some tools that we can use. The Life Essential aid, for those who are not familiar, was developed several years ago by the American Heart Association. And really looks at all different components of uh uh um uh all different factors that could uh contribute to an increased risk for the development of risk factors and then cardiovascular disease. Any of us can go online and use uh create a pro a profile and use Life Essential aid for us. Uh, I, I, I do it uh routinely and we can do it for our patients, uh, and the next thing of the Life Essential aid is then it will then provide. Uh, some dedicated some targeted, uh, guidance for based on the risk factors then that are, um, not, uh, adequately controlled, and so it provides very good recommendation also for, for our patients. Uh, for those who already have dyslipidemia, and particularly LDL related disorder, uh, the recommendation is, uh, um, the, the class of recommendation one, based on randomized trials is that adults and children with uh, uh, with and without ASCBD should emphasize the consumption of fruits, vegetables, nuts, legumes, whole grains, and fiber, and importantly, they should replace saturated and trans. Fat with uh healthy fats or unsaturated fats like mono and polyunsaturated fats that can be found in food like olive oil, canola oil, avocado, nuts, uh, fatty fish, among others uh and this is because these nutrients have been consistently associated with a decrease in LDL cholesterol, and I'll show you uh some data also in uh reducing hard outcomes in cardiovascular outcome trials. In individuals with overweight and obesity and also have they also have dyslipidemia, there's still a recommendation to counsel patients on reducing body weight. However, I also want to be realistic here and remember uh and remember that reduction in weight is uh is uh uh desirable in most cases, uh, but the effect of weight loss on LDL cholesterol lowering is not as pronounced as we might think. Uh, there's approximately one. Uh 0.3 mg per deciliter reduction LDL cholesterol for each kilogram of weight loss. So if an individual loses 10 kg, which is already a lot like uh over 20 pounds, uh, we should not expect more than 13 to 15 mg per deciliter reduction in LDL cholesterol, and I think this is important, an important expectation also for patients uh when their uh main target is LDL cholesterol. We can still reduce LDL cholesterol, even in absence of weight loss by changing diet quality. Uh, and I think this is a new addition to the guidelines. Obviously, as a dietitian, I'm particularly happy to see this, uh, the new guidelines, in fact, provide guidance on uh rec on when and how to recommend, uh, refer your patients to a nutrition specialist, a registered dietician, nutritional RDN. And there's a very strong recommendation here in referring all your patients with triglycerides greater than 1000 to an RDN uh to create an individualized treatment plan, uh, aimed at reducing triglycerides and reducing the risk for pancreatitis, and in fact, there are several studies showing that uh um. Medical nutrition therapy, MNT provided by a registered dietitian can reduce cholesterol can reduce triglycerides up to 40% in some cases 50%, even in the absence of pharmacotherapy, uh, so really it's very important for your patients to be referred to a registered dietitian. And uh importantly, dietitians will not only focus on reducing fat intake in patients with high triglycerides, but will also provide counseling on reducing and stopping alcohol consumption altogether, and also reducing added sugar consumption, which are often one of the main culprits of hypertroglyceridemia in in our patients. Uh there's also uh um a recommendation to refer your patients. Your patients with triglycerides less with lower than 999 and higher than 152 IDNs um and again trying to prevent that increase in triglycerides even further and possibly uh especially in presence of features of uh cardio kidney cardio kidney metabolic syndrome, uh, uh reduce the risk for cardiovascular disease. This is also a new addition of the of the new guidelines and I think very, very important uh uh because they uh they actually recommend against any dietary supplement uh or any over the counter uh um um. Uh, therapy that you could find, uh, because this is, this is not shown to reduce LDL cholesterol, triglycerides, they're inconsistent and limited data, so we should not recommend our patients any of the over the counter, uh, um, uh, medications, and if they are on any of them and there are no other indications, uh, it, it feels it would be very safe to stop them. Uh, with regards to, uh, LDL lowering, this is what we have, but do we have clinical data, clinical trial data to really support the implementation of specific data pattern, not only to reduce LDL, triglycerides, but also to reduce heart outcomes. Uh, and we have two major clinical trials that have been published over the last 12 to 15 years. Uh, on the left, we have the uh Predime study. This is a primary prevention study where patients were being randomized to a low fat diet, which at the time was being recommended by the American Heart Association. Uh, uh, 22 Mediterranean diet groups, one was being supplemented with at least a handful of nuts per day, and one was being supplemented with at least 4 tablespoons of extra virgin olive oil per day. And you can see here that by the end of the study, the Mediterranean diet supplemented with olive oil and nuts, uh, were associated with a 29% risk reduction for the composite primary endpoint of acute MI, stroke, or death from cardiovascular causes, and then more recently in the cardio. study, it was a secondary prevention study, so patients who already had an established ASCBD, you can see how the Mediterranean diet group, which was being supplemented with extra virgin olive oil here, uh, was associated with almost a 30% relative risk reduction for the composite of uh major cardiovascular events, which included MI, revascularization, ischemic stroke, peripheral artery disease, and cardiovascular death. So really remarkable data to show that very simple. Intervention here were associated with remarkable and clinically significant improvement in uh uh heart outcomes. Interestingly, in both studies, there was an increase of extra virgin olive oil consumption to almost 5 servings of olive oil per day. Uh, keep in mind that both the studies were done in Spain, so whether we could replicate this in the US, uh, it's not, uh, uh, um, you know, it's not been done yet. Uh, however, over the years, inspired by this study. And uh uh over 10 years of work we've done when I was at BCU in heart failure with preserved ejection fraction. Uh we recently received funding with Dr. Tarija, both of us serving as co-principal investigator on the study uh through the Centeria Foundation and Spark, which is a grant mechanism that allows collaboration between ODU, EDMS, and the Centera uh to do the OLEA HF study and specifically we're looking at patients with heart failure, with reduced eject. fraction, uh, with an LDF less than 35% who are being referred to cardiac rehab as part of standard of care, and they, they will be randomized to uh to with a 2:1 ratio to either consuming 4 tablespoons of extra virgin olive oil or more, or standard of care for 3 months, and we're hoping that by adding extra virgin olive oil, we can further enhance uh functional capacity, uh, improvement achieved with cardiac rehab alone. We are doing this in collaboration with other researchers, Dr. Galkina here at ODU that is focusing on inflammation and immune function, uh, Dr. Summit Katarpal, who's a physician scientist at UVA who's doing targeted metabolomic and targeted epidemic, and Dr. Singh here who's a postdoc in my lab and is focused more on movement, behavior, sleep, and more recently, uh, also on cognitive function to, to determine whether olive oil can improve any of those outcomes. Uh, I always emphasize the importance of healthy nutrition, but I also want to remember everybody that as Doctor Torres has already mentioned, that there are also dietary patterns that can make your cardiovascular risk, uh, uh, significantly worse, and the ketogenic diet is a clear example where you see in this, uh, uh, case series, a dramatic increase in LDL cholesterol, doubling in LDL cholesterol, uh, when individuals started on a ketogenic diet, which goes with normal normalization of LDL cholesterol when patients stop the ketogenic diet. Uh, this is another study that I think it's small but uh mechanistic, but I think very, uh, very important. It was a randomized controlled feeding study, and controlled feeding means that the participants were provided with meals by the study team. And this was a study of 24 women that were following a 4-week ketogenic diet, uh, and then followed by a 4 week controlled diet, and just within 4 weeks of ketogenic diet, these women experienced an increase in in LDL cholesterol by 70 mg per deciliter, and every single woman in the study actually experienced an experienced an increase in LDL cholesterol. So currently, we really don't have enough evidence to support the use of a ketogenic diet, and I personally recommend against it unless uh um uh part of uh, unless this is part of our uh clinical trial. I will go fast here, but I just wanted to let you know that in addition to lipid lowering, we do have other simple strategies can, can make a difference in uh um in patients' lives and patient outcomes. One of those is salt substitute, this is, this is the results of an SAS study, a randomized controlled trial, where really the only intervention uh was to switch regular salt uh to uh sole substitute. Uh, made of, uh, that included some potassium, and you can see dramatic improvement in cardiovascular outcomes, uh, without increasing hyperkalemia, and these are allowed to be included in the guidelines, the hypertension guidelines last year to prevent and treat, uh, blood pressure and hypertension, uh, potassium basal substitute are now being recommended, uh, but always keep in mind that, um, if you have patients who have already have a high risk for hyperkalemia, potassium should be monitored closely. Uh, we do have the new 2026 guidelines also recommend exercise training, and, uh, this is extremely important because we do now have data to support the use of, uh, uh, uh, multi-domain rehabilitation programs, um, uh, namely cardiac rehab, uh, and this is because we have on the last, this is an infographic from uh uh meta-analysis showing that cardiac rehab improves, um. Reduces cardiovascular mortality and improves health related quality of life, and it is cost effective, and then on the right you have the results, very recent data from the pipeline trial where, where a multi-domain rehabilitation program was associated with a 43% relative risk reduction uh for the cardiac rehab compared to standard of care for the primary endpoint, which was a composite of cardiac. Vascular death or unplanned unplanned hospitalization for cardiovascular causes within one year. So very strong data to to uh support the use of cardiac rehab, particularly the ones like the ones that we have at Centara that is not only focused on exercise but also focused on uh on nutrition and uh and overall um improvement in lifestyle behaviors. Uh, we do have indications and uh CMS coverage here in this table for different conditions. Uh, uh, in our studies we're focusing on patients with heart failure with reduced CF, uh, but there are so many other indications, uh, with very strong cluster of recommendation and level of evidence, uh, that are, uh, CMS covered, uh, and so I hope that many of your patients will be referred to, to, to this very important tool. And then finally, uh, I just wanted to do some self-advertisement, uh, we're starting a nutrition. Program here at ODU and we have our 1st 4 students in a master's program starting in the fall in August, and this is going to be a fully online master's program. Currently we don't have one in Virginia, so we're particularly excited to lead this uh and uh uh I'll be happy to answer any questions for those who are particularly interested in the program even outside of this talk and with that I'm going to stop and uh I know that doctor. T and I will be happy to take uh take any questions and again thank you for, for the invitation.
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