Daniel Einhorn, MD, Amitabh C. Pandey, MD, Douglas W. Triffon, MD um Okay every panel um we're gonna now do our Q. And A. Were actually a touch a bit ahead of schedule. Uh And the good thing is we have a lot of questions. Um So they've been coming in clearly um your talks have been great and I think I've induced a lot of those questions. So you guys ready. Um Okay so we're gonna go ahead and jump right in the first one is the left every question from this morning. It's gonna be for dr Einhorn. There was a question about what is the optimal a one C for cardiovascular health? Maybe a piggy back to that could be you know maybe they were. It was kind of a broad question. But would you target a certain level for your patients? Uh you know as far as a one C. Is concerned. So do you want to comment on that from an endocrinology perspective dr Einhorn, it's actually straightforward. You can think of a one C. Like LDL um It's fairly linear right into the normal range. The lower the better in terms of outcomes cardiovascular in particular. Um So that's for, you know, long term health. Um In the short run, the only reason the question might come up and just say well if it's too low, You know, my dad to get hypoglycemic or so, but that's not a function of the a. one c. That's a function of therapies that the person on diabetes would be on. So we try very hard to avoid insulin. We try to never use a funnel your areas. So for not using therapies that cause hypoglycemia, there is no the hippo is not a concern if you are using insulin or so fondiaria high. A one C will not protect you from hypoglycemia is very important. In fact, patients with higher A one CS because they are in poor control overall tend to have more hypoglycemia and more severe hypoglycemia with consequences. So the better A one. So you can get the better the key in terms of the level has to do with trying to avoid therapies that cause hippo. Okay. Great. That was very helpful. Thank you. And there's a piggyback question to that and I think you answered it. But I just want to make sure I get this question out there because it was specifically asked. Um it's about hypoglycemia and the S. G. L. T. Uh two inhibitors and the GLP one agonist. Um as far as you know, starting those meds in the non diabetic patient, do you worry about hypoglycemia? Is that something that you really need to watch and counsel your patients about? You? You do not have to worry about hypoglycemia? Okay the methods of action won't allow that when you ever hear of these associated with that. It's because the patient was on insulin or honest will finally RIA. And that's what caused the uh the hypo with the S. G. L. T. Two's. Again one pill once a day. Any time there's you feel lower and a higher dose. There's really three that are in common use, MPA can or the majority in sparse iga and in Marikana, those are the most common ones used. Um The only thing for a cardiologist I would be aware there is some diuretic effect of the S. G. L. T. Two is because you're losing glucose in the urine and so you're losing water with that. Um And and and some sodium. That really only lasts acutely for about a week to 10 days. This is your christian Mendy talk about this after about a week to 10 days you come into steady state and there really isn't an issue however, for that first, especially the older patients that first week or so you may want to cut back. Oh that's a loop diuretics or some other significant diuretic. So they will be more in the first week to 10 days. Uh That's about the only admonition for those, the GOP one's there's low dose, you step up slowly like med foreman. And if that's just a matter of G. I tolerance now that there's oral versions of GLP ones, you cardiologist don't have to worry so much about what it means to prescribe injectable therapies with your ps canines. You know PCSK nine, you know that you know those are very easy to work with. Two. Okay um I have more questions for you but we're going to shift to the other panelists um just to keep them engaged. So dr trip in. Um there was a question about your practice and culture scene and a patient that's had it in my um you know, they come and seen you after, they're seeing you afterwards. Have you started to incorporate that into your practice? Are you measuring cRP levels if they're elevated? Are you starting culture sing? So the question is incorporating CRP measurement and then coaching in the practice. And there's some great studies in circulation where they looked at, not just CRP as a biomarker at 30 days post in my but super sensitive component anti pro BNP, you know, an HS CRP. And the surprising data is you need to normalize all three of those by 30 days post in my And you need more intensive therapy for all three. So, again, we talked about dual targets, but triple targets. And so the answer to that question would be yes. I have some patients who have multiple recurrent events in their own PCSK nine inhibitors and their benefit from driving their LDL lower is small. Again, I use that. You prevent software and at risk models and I can see g there's not much more to gain. And I put the kolzig in the algorithm and said, wow, 30% drop in risk. And so these frequent fliers where I think the crp is in residual high after that 30 day mark. Then I I have been putting people on about several and to date surprisingly, I've seen very little problems. Again, I'm sensitive to the quota seen statin interaction. I'm gonna make sure I want a lower dose of a non three a four statin. You gotta watch renal disease quote seen as excreted through the kidneys. You've got renal disease, you're not going to use it. So there are some dues and domes, but I think it's very good on reducing recurrent acute coronary syndrome. Very good on reducing him I and stroke. And we don't know about mortality. We don't know about non cardiovascular mortality, but in these frequent flyers with high residual risk. But nothing else to treat. Yes, I will start them now. You can edge further and you go into, you know, Sandeep stalk. Wait, obesity and CRP are highly correlated diabetes and Crp highly correlated. Try let's see if the high court. So you put them on an S. B. L. T. To you get him to lose weight. Crp may drop to there are other angles to treat this culture scene is not, you know, the only game in town. So I might say gee let's just get him in cardiac rehab. Let's get you mentioned, let me send him to stand deep and let him lecture them for an hour so you can get some weight loss, get their crp down all that's you know, been helpful. Yeah. I mean again I share with everybody my passion for lifestyle medicine and thank you for bringing that up. I think that all of this does come back to that. And I I personally, my practice use these biomarkers to drive that conversation. You know, a lot of our patients don't want the meds, they want to know what they can do and and it's a partnership. It really is. And I think you use the meds, but you also use these biomarkers to really help drive that conversation and help impact the lifestyle changes. Thank you for bringing that up. Okay? And there's another question gonna follow up with you dr trip. And it was on ceremony levels. You mentioned the residual risk when you have low LDL but high ceremony level. So what do you do to treat that you've got a patient with? Okay, so you've got this high sierra minus 11. Your patients Cholesterol is 10, is LDL is 10. What are you doing? Well We we just published an abstract showing that four g of epa a lower ceremonies, 38%. We have been using that in clinic and it works like a charm. We also, according to the Med Peds studies, is a great paper in Lancet where they showed that that mediterranean diet with four tablespoons of olive oil does inhibit inter Lukens. I'll 60 NF alka are decreased. And we're seeing again, I want to look at our experience and actually get a formal number. But the Lancet paper showed total protection from serra modes in five year follow up in these people. So we have evidence that it works. So I will personally use four g of E. P. A. With mediterranean diet. And I've seen ceremonies go from 11 to 2 and so I'm very confident now PCSK nine inhibitors lower ceremonies, Mayo clinic just reported that statins lower ceremonies zita might lower serra minds. I think five rates lower serra minds. So there are many ways to treat this. But I've been using the epa mediterranean diet. Great success so far. And so that is one option that works. Okay. Great. All right. Thank you. Okay, Doctor Pond, a question came in about differences in sex with apologetic risk scoring. So men versus women, can you make a comment about that? I think that's a very good question. Yeah. Absolutely. So again, unfortunately, we're tied to the data that we have. Right. So most patients that are um in most of the domestic data sources that we have erIC study may, so we're not um typically are not going to be very diverse as far as gender go. So there's gonna be much more men than women there in those studies. But we do know that there are um if you look at the data for men versus women, generally speaking PRS is slightly higher in men, um you know, in my mind, it kind of becomes a question, is it because of the limitations of the data set and we just don't have enough information yet? Or is it something that's truly there? If you look at the traditional, classic data that we have from the wrist ratifying scores that we have Framingham and whatnot. Obviously men are at risk factor in that. And so it's likely that it does in priest based off of gender alone. Okay. Great. Um, and thank you. And another another question. Uh, I seem to to see this a lot anytime anybody talks about genetics and it's about kind of the the opening pandora's box on, you know, do you have the, you know, the fear of if they have the genes about genetic counseling and then also about like, life insurance and other effects that people get fearful of when they when you start going down that route. I see this question come up a lot. And we got another question about it. So, um, can you make a comment about that? Yeah. So, I mean, it's definitely something that's very important to discuss, right? That's why you want to increase the knowledge and comfort that patient that physicians and providers have so they can make those accurate discussions with the patients. Um, you know, the nice thing about the project risk force is that it is a relative risk, right? So you're not giving them actual genetic information. You're saying that your risk falls at a higher level compared to population based cohort. So that I think is something that is useful in the fact that you're not saying that you have something that is going to be detrimental and this is a particular gene and you're going to pass it on to future generations and that sort of thing. But it's another tool like you were mentioning and we've been hearing all day that you can use in that discussion with the patient to say, hey, You have these risk factors. One of those is also genetics, you're at an 80% risk compared to some other people. What can we do to try to mitigate those risks? And I think that's something that's very important. The insurance part I think is something that still involving, right? Unfortunately for the insurance system that we have here, it is something that we always have to take into consideration um because of pre existing conditions and how that's going to be defined and what sort of things will come in the future from that. So I think part of the reason why P. R. S. S. Have not really caught on and there's not a lot of integration into E. M. R. S. Is to try to prevent a lot of that from going on. So if you even if you look at the my jean rank out study, It was done through a partnership with 23 and me. So 23 and me runs these panels for ancestry, but they're running the same sniff panels that can be used for identification of cardiovascular risk. Right? So you have patients go out and do 23 and me. You have them do the cheapest asset because they run the same chip. They give you back different levels of information And then you can use that data through the partnership that set scripts research in 23 and me to get that risk for. Well that makes it very very convenient actually. So that's cool. Alright. So okay we're gonna pivot back to DR Einhorn. Um There is a question about you mentioned that both the G. S. G. L. T. Two meds and the GLP one meds are indicated for cardiovascular risk. So if you've got a patient with cardiovascular risk, what you go to, which one do you choose? Like how do you make that choice? So first in the sequence maybe ultimately less important than they really make sense to use together. Um So we always started, you know, one thing at a time obviously um if the if the picture is more towards you know, a chf kind of patient um then the STL T two s are absolutely the ones to start with. If it's a page to might especially benefit from weight loss. Uh And with that there's more uh glycemic reduction and other um triglyceride reduction etcetera. Then the GLP ones are the strongest that we have. And you will you will be hearing by the way about some very strong GLP one, some high doses of these as remarkably effective weight loss agents getting weight loss of 15 20% plus. So bariatric surgery level weight loss from the GLP ones to Zepa tight, which is a combination GLP one and G. I. P. Has consistent greater than 20% weight loss and and consistent a one CS that drop into the fives. So there's some really very interesting compounds in the pipeline to just amplify everything that we've said today. Alright that's that's that's great to hear. Um So um and then a follow up is you know, not to call you out on what you personally using your clinical practice. But do you have a go to favorite for both classes and kind of what your way of starting it there. There was a question about kind of like how do you start like obviously start low, go go then go up from there. But what should go to write? You know it's idiosyncratic because it depends whatever insurance will cover. I'm good. That's you know that's number one I'd say the most data is now with with that with Far Siga and Guardians. Okay because they clearly have shown themselves in the heart failure um patients and the overall cardiac effect patients there there is good weight loss with them. They're easy to tolerate. Most of the worries I should say that were at one point attached this class, people talk about things like amputations and that those are just gone. Those are just non issues um anymore. Um so that it's really very easy to live with. So so I'll usually pick, you know, one of those deadliest. It's the three and the same thing with the with the GLP ones. Whatever the formula will cover, I'm happy. Usually you'll pick a once a week formulation just re interview. So that's genius. Epic. Or to elicit e and for that person who just doesn't tolerate them well with which happens like with Metformin then that's where the by durian, the eggs, any tied may come in. So at least you'll get some benefit in a tolerable formulation foreman. Used to be hard to tolerate. Then we all got very comfortable with the doubts, relatively easy to tolerate. The same thing will happen with these meds. Gotcha, gotcha. Okay. All right, that's great. Very helpful. Critical information. Thank you. Um And then one last question we have. We don't have much time but it's gonna be productive trip in. Um It's it's this concept of are we testing too much with all these biomarkers? Are you you know, is it is it a good idea to routinely get these, you know, crp levels and particle numbers etcetera on our patients routinely? Do you get him stabilized and say maybe once a year. What's the what's your thought on that? Because there is this concern about the cost of adding to the cost of health care. Right. So the question is, you know, which biomarkers have the most value and which should be routinely tested? And again, it depends on the risk of the patient and so forth. But in my first talk we went through the literature made a strong argument that cholesterol content has failed as to be adequate risk prediction. We need to move to particle numbers. So that's sort of the biggest bang for our buck. I know Allen Sneiderman is calling for Appleby to be in the guidelines, no longer calculated LDL. So I think you've got to push the, you know, the in chronology pissed you know, hats off to Daniel, you've got Appleby on your guidelines. You know, the cardiologist don't. But so I think one of the things is we need to move from calculate LDL to either Appleby or LDL particle that I think in studies from Harvard, they showed a a 300 point higher LDL particle than LDL increase your risk three full 300%. So some of these small discordance can be very powerful over 10 years. So I think number one cholesterol content LDL calculated isn't comprehensive, needing new to more comprehensive targets. Now in terms of hierarchy, we know that anti pro BNP. Well, first of all, calcium score is number one how hazard ratio of nine Anti pro BNP would be next high sense of your troponin T. So if you wanted to have a hierarchy, that would be it again, LP little a once in your lifetime if you've got the risk collagen risk once in your lifetime, all of these things I think will modernize our treatment and so for me to pull back and try to minimize testing, I think the future is going to be algorithms incorporating all of this. Again, we need to make it cost effective. And that's true and I do particle number every visit and it is an issue because it's not covered by insurance. The guidelines haven't incorporated it and that's lagging. I think if if we get up will be in more guidelines that's going to be paid for. So you know the societies can foster some of the costs being covered and we really need their help to put this in the guidelines. So but I don't see us going back to less testing again, everything I showed in both lectures is that we need more because our risk scoring is poor. We miss a lot of people. So we need these bio markets, we apologetic risk all of this to be additive and integrated and to really an ai artificial intelligence software program where we can be so much more sanguine on who we treat aggressively and who looks like any treatment but actually doesn't benefit. So again, it's a long when it answer, but the future is not backing away from the testing is try to consolidate it into a platform that's that's reasonably priced and again, sentient by guidelines that will make it covered. Okay, well, thank you. Um we are we actually are right out of out of time. I'm going to bring dr cork in here to end it, but I just want to thank the panelists. You guys this afternoon was super exciting. It really gave us for what we were looking for. Thank you very much, guys. That was a really great discussion from all present. Thank you.