[SPEAKER_04]: This is to a large extent in your control, and you should feel empowered to treat this with lifestyle, adjustments and, you know, everyone's genetics are a little bit different, and so some people have different thresholds for what you can get away with and what you can't and all of those things in life isn't fair, but
[SPEAKER_04]: for patients when the triglycerides are really high.
[SPEAKER_04]: To me, it's like a call to action.
[SPEAKER_04]: And if there's ever kind of a siren call for you should take control of your own health, very high triglyceride level, it's just like the biggest call to action that you could possibly have from a lipid perspective that's not a heart attack.
[SPEAKER_04]: And for some reason,
[SPEAKER_04]: The high triglyceride levels to me is the thing that patients actually respond to in a way that they don't respond to crazy high LDL levels.
[SPEAKER_08]: That's Dr. Greg Katz, a cardiologist at NYU.
[SPEAKER_08]: Welcome to the core.
[SPEAKER_08]: I am Thy Pearl's podcast bringing you high yield evidence-based pearls.
[SPEAKER_08]: I'm Dr. Schreitre Betty, and I'm joined by.
[SPEAKER_08]: Hi, I'm Jim and Hong, Chief President at UT Southwestern.
[SPEAKER_06]: And I'm an annual GRI, a PGY3 internal medicine resident also at UT Southwestern.
[SPEAKER_08]: Awesome, and we are talking about severe hyper triglycerideemia today.
[SPEAKER_08]: This episode was made possible by an independent medical education grant from the National Traclyceride Association.
[SPEAKER_08]: And I've got to say, I think what I didn't expect before going into this research and interviews that we did for the episode is how much I just learned about triglycerides in general.
[SPEAKER_08]: And I think I've told countless family members about the various teaching points.
[SPEAKER_08]: I think it's something that triglycerides are part of the lipid panel that I don't think doctors intentionally ignore, but it's just kind of this extra thing, and then there's also so much focus on the LDL.
[SPEAKER_08]: And I think a lot of our patients, though, are really interested on triglycerides.
[SPEAKER_08]: And so I think to set up our learning and to make sure we're getting the most out of it, I said to all of you one of my colleagues at the wonderful Dr. Adam Strauss.
[SPEAKER_08]: He told me, but I remember, in case he had, that's going to help us walk us through our
[SPEAKER_03]: Yeah, so this was a 59-year-old gentleman with a history of depression, alcohol dependence and insomnia, and he'd actually had a primary care visit a few days earlier at which time a lipid panel was checked just for a routine monitoring, and then he comes in five days after his appointment after having had an alcohol binge with triglycerides of
[SPEAKER_03]: about 1600 and abdominal pain, nausea, and vomiting, at which time he was found to have a cute pancreatitis.
[SPEAKER_03]: And then, from that emergency room, he was initially admitted to the ICU where he was treated with an insulin drip and had improving symptoms and improving triglyceride level down to 388.
[SPEAKER_03]: And then, upon leaving the ICU was started on a fibrate, as well.
[SPEAKER_08]: Oh man, I have so many questions, but of course, I think the first thing as an internist is wondering, could we have prevented this awful complication of elevated triglycerides?
[SPEAKER_08]: I've actually dug back into this patient's chart at a few days prior.
[SPEAKER_08]: This person, as Adam had mentioned, had gone to their primary care doctor and the lipid panel had a triglyceride that came back around 488, so it closed that 500 number and just hadn't been followed up on at that time.
[SPEAKER_08]: And so,
[SPEAKER_08]: In thinking about could we have prevented it?
[SPEAKER_08]: We set down with Dr. Seth Bomb.
[SPEAKER_08]: He's a preventive cardiologist, a clinical lipidologist, and a chief medical officer at Floresh Research, and the past president of the American Society for Preventive Cardiology, and he has some really good teaching points on this.
[SPEAKER_02]: Lipopriting lipis is what hydrolyzes the triglycerides, and lipopriting lipis is saturated at a triglyceride level of about five or six hundred.
[SPEAKER_02]: Well, that means is, if you have a patient sitting around with a triglyceride of 4, 5, 600, and the patient goes out and needs a terrible meal, within minutes the triglyceride can be, you know, well over 1000.
[SPEAKER_02]: So the risk of pancreatitis will increase as the triglycerides increase.
[SPEAKER_08]: Wow, I did not realize how quickly triglycerides can bury just in a few hours of eating, french fries or a burger, and that points really stuck with me since learning about it.
[SPEAKER_08]: Yeah, and the other really big teaching point is about like a routine life pace.
[SPEAKER_08]: Like a routine life pace breaks down triglycerides and saturates at levels around 500.
[SPEAKER_08]: And when the triglycerides increase as above that 500 threshold, then the most simplest sense to get all this badness in the blood like animal microns, creating a lot of complications.
[SPEAKER_08]: And so, hopefully as a takeaway, none of us feel comfortable if that trickless ride is less than 500, right?
[SPEAKER_08]: We should have alarm bell for multiple reasons that will go over.
[SPEAKER_08]: But one of them being that just one fatty meal can make that triglyceride shoot up 30-50%.
[SPEAKER_08]: Let alone an alcohol bond on top of it.
[SPEAKER_02]: One of the theories is that there are such large particles that they can't make it through the small vessels and the pancreas, they get lodged, they get open, you know, they'll pancreatic, enzymes start auto-digesting because there are areas of clogging, if you will.
[SPEAKER_02]: You know, that's one belief.
[SPEAKER_02]: It's not 100% known what that triglyceride induced pancreatitis, what the pathophysiology is.
[SPEAKER_08]: I can really picture that, and in particular, it's going to be the triglyceride gray than 500 milligrams per decelerate, that's going to really carry that increased risk of pigory tightness.
[SPEAKER_08]: And of course, the higher those triglycerides are, the higher the risk of pigory tightness.
[SPEAKER_08]: Yeah, and in addition to that, if you do have a patient with packer of tightness because of triglycerides, just know that their risk of organ failure and mortality is going to be higher,
[SPEAKER_08]: and other common causes of pancreatitis, and once someone has had an acute pancreatitis episode, the threshold for recurrent pancreatitis can be reached out even lower thresholds of triglycerides.
[SPEAKER_08]: Yeah, that's fascinating, that even lower triglyceride levels can make someone shoot into the
[SPEAKER_08]: All right, so that's all about the risk of pinker tides with elevated triglycerides.
[SPEAKER_08]: Bleschiff gears, and talk about another important organ of the body, and maybe your guys' favorite organ, the heart.
[SPEAKER_08]: Yeah, my favorite organ, I think people think, of course, triglycerides are associated with a lot of confounders, like obesity, metabolic syndrome, and diabetes.
[SPEAKER_08]: Things we already know are associated with increased risk of cardiovascular disease,
[SPEAKER_08]: Yeah, you know, great question.
[SPEAKER_08]: And so when we sat down with our discussions, we asked, are there other direct ways that triglycerides can make people more likely to have cardiovascular events?
[SPEAKER_04]: it's that when the triglycerides are high, you usually require more LDL particles and more atherogenic lipoproteins to carry around the cholesterol and the triglycerides through your body and so it's atherosclerosis risk through the traditional means and when triglycerides are high, it usually means that
[SPEAKER_04]: LDL cholesterol is underestimating somebody's cardiovascular risk related to lipo proteins.
[SPEAKER_04]: Just think like if you need more particles because you have to carry around all these triglycerides and so you need more trucks to carry the cholesterol because they're filled up with all this other stuff.
[SPEAKER_08]: So ultimately with a lot of triglycerides in the body, there needs to be a lot more trucks to carry them.
[SPEAKER_08]: And it's just like a traffic jam in the Budbessel causing inflammation.
[SPEAKER_02]: There is also some evidence that triglycerides can be pro and flammatory in order to themselves.
[SPEAKER_02]: So even though they're not part of the plaque, right?
[SPEAKER_02]: So when you make a plaque, it's cholesterol, they're triglycerides on in there.
[SPEAKER_02]: Well, it's triglyceride in the vicinity, like the increasing inflammation.
[SPEAKER_08]: So that inflammation then is the nightest where that lipid containing junk to build up on the vessel walls.
[SPEAKER_08]: And now, when I counsel patients on cardiovascular risk, I think I'll drop this picture of an inflammatory traffic jam.
[SPEAKER_08]: Yeah, nice.
[SPEAKER_08]: Yes, there's so much going on there and how could we simplify if our patients is really important.
[SPEAKER_08]: So to summarize what I'm taking away when it comes to risk of severe hyper-triplecydeemia, I think I was humbled to learn how quickly triglycerides can translate a shoot-up after a fatty meal, alcohol, and so the next time I see a triglyceride in the triple digits, especially in that 500 range, I think I'm going to do a better job in my counseling and management, which we will cover a lot more in depth in Pearl 3 and Pearl 4.
[SPEAKER_08]: And then with the risk of the triglycerides being elevated, especially over 500 milligrams
[SPEAKER_08]: Yeah, and it's not just the 500th threshold we care about.
[SPEAKER_08]: As a boarding cardiologist, I do want to emphasize that patients who are sitting at our elevator targets are level above a hundred and fifty to a hundred and seventy-five do experience high cardiovascular risk that needs our attention.
[SPEAKER_08]: But now that we talked about the risk of these trice glycerides, when we do see trice glycerides, and a level that raises our eyebrows, we learn from our discussions which should first rule out a few things, in addition to the genetics which we'll get to in profile, and then see if we need any acute management.
[SPEAKER_06]: So we sat down with Dr. Elliott Brinton and endocrinologist and the president of the Utah Lipid Center in Salt Lake City.
[SPEAKER_01]: hypothyroidism screen for a treated if it's present.
[SPEAKER_01]: Protein Eurea, the products syndrome, is a cause of high triglycerides.
[SPEAKER_01]: Sissimical quirk was of course, will cause triglycerides.
[SPEAKER_01]: So if they're taking predies on on a daily basis, try to figure out how to deal with that if you can.
[SPEAKER_01]: And a psychotic agents can cause both obesity and high triglycerides together.
[SPEAKER_01]: So somebody's taking the newer and a psychotic meds,
[SPEAKER_01]: She's got a way to deal with that if you can, maybe refer them back to their psychiatrist and see if there's something you need to do.
[SPEAKER_06]: Okay, so we would need to roll out thyroid issues, nephrodic range proteinuria, hypercortisolism, like incushing disease, is the patient on part in his own or dex himethosone, or even on an anti-cycotic agent that can contribute to disability media.
[SPEAKER_08]: Yeah, and so of course there will be a more exhaustive list of secondary causes in our show notes, but I'm glad we mentioned medications because that's exactly one of the things I was playing in Adam's story.
[SPEAKER_03]: and then also actually he had been started on Cira Quill which can have a role in trackless or hyper trackless or Idemia related pancreatitis.
[SPEAKER_03]: So someone did their homework and I see you I think and realize that that should maybe be stopped.
[SPEAKER_08]: So after we rule out secondary causes that might be contributed to those high triglycerides, let's just very briefly talk about acute management.
[SPEAKER_08]: This is particularly related to severe hyper triglycerides related to pancreatitis.
[SPEAKER_08]: And on yet, you looked into this more in-slunter, plasma exchange, what did you find?
[SPEAKER_06]: So, first things first, what we may reflexively do is make the patient NPO, and this can be really effective.
[SPEAKER_06]: It can reduce the triglycerides by up to 50% within the first 24 hours.
[SPEAKER_06]: And to really hammer this home, we learn and purl one that triglycerides rise rapidly.
[SPEAKER_06]: They can also fall pretty quickly with just making the patient NPO.
[SPEAKER_08]: Nice context there.
[SPEAKER_08]: What about insulin drips?
[SPEAKER_08]: Positive exchange.
[SPEAKER_08]: Honestly, have never seen these done per se, but I think would be good to run through really quickly in case it's mentioned.
[SPEAKER_06]: I agree, it's a bit of a gray area for me as well.
[SPEAKER_06]: When I looked, there isn't clear guidance as to who may require an insulin drip.
[SPEAKER_06]: The endocrine society practice guidelines really don't recommend the use of routine insulin drips for patients with severe hyper-tragostride related pancreatitis if they don't have diabetes.
[SPEAKER_06]: Of course, if they have diabetes and they're hyper glycemic during the admission, it can definitely be offered.
[SPEAKER_06]: But of course, it does require close monitoring, Q1 hour glucose checks, and so it depends on the unit and or nursing staff and all of the factors there as well.
[SPEAKER_08]: Definitely, and then what about plasma exchange?
[SPEAKER_08]: Is there a level of triglycerides that you might see that you're like, okay, and to reach for this?
[SPEAKER_06]: So not a trigostrial level per se, but usually it would be used in patients who have refractory severe acute pancreatitis.
[SPEAKER_06]: So thinking about the patients with shock who are really not getting better.
[SPEAKER_06]: But again, this is a bit of a gray area as well and different institutions may have different practice patterns.
[SPEAKER_06]: I will say there hasn't been much evidence supporting a direct benefit in terms of morbidity and mortality in patients with pancreatitis related to severe
[SPEAKER_08]: Now let's get to know.
[SPEAKER_08]: So if we're playing this all together, it sounds like in the acute management, and I think just in general, we should always try to be ruling out secondary causes.
[SPEAKER_08]: Seeing their meds, are they on a steroid?
[SPEAKER_08]: Is there any anti-cyconic that can be contributing?
[SPEAKER_08]: And could be switched possibly if the outpatient doctor thinks it's okay.
[SPEAKER_08]: Is there cushions, cortisol at play, thyroid, and so on?
[SPEAKER_08]: And then more acutely in the inpatient setting, make this person and PO.
[SPEAKER_08]: It can really help make the triglycerides go down.
[SPEAKER_08]: It's up to, you know, 50% the first 24 hours.
[SPEAKER_08]: And then when it comes to pancreatitis related to those triglycerides above 500 or so, an insulin drop if the patient has diabetes can help reduce those triglycerides.
[SPEAKER_08]: And then, yeah, if it's a really sick patient refractory shock, you could consider plasma exchange.
[SPEAKER_08]: But when you pull that lever, when our things not getting better enough,
[SPEAKER_08]: All those questions are still not clear.
[SPEAKER_08]: Okay, so after the immediate things are addressed, we then get to shift our thinking about the long-term management of these patients who have elevated triglycerides.
[SPEAKER_06]: And of course, before we get into the medications, let's get into the most important part in my opinion.
[SPEAKER_06]: How do we counsel these patients about their lifestyle?
[SPEAKER_08]: Yeah, definitely my favorite part.
[SPEAKER_08]: And of course, who better to talk about counseling than the wonderful Dr. Greg Ketz, whose voice you might recognize from our Beyond Journal Club segment?
[SPEAKER_04]: I talk to patients, I tell them that your triglycerides are really high, triglycerides are concerning.
[SPEAKER_04]: It's fat in the bloodstream.
[SPEAKER_04]: It can be toxic to a bunch of organs, your pancreas is the one that's most characteristically at risk from it.
[SPEAKER_04]: But it's also problematic because it tells us about your long-term heart disease risk in some ways.
[SPEAKER_04]: And then we'll get into triglycerides are super responsive for most people to the things that we do.
[SPEAKER_04]: how much we move, what we put in our bodies, and it's also really responsive to medications.
[SPEAKER_04]: And so like, ultimately, most people need a combination of medications plus lifestyle interventions to get things under control.
[SPEAKER_04]: And so for this patient, ultimately, like we gave her a home work assignment for a week of, you need to walk, you can't have a sip of alcohol, you can't have any dessert and you need to bring you a food diary and then we'll sort of make adjustments based on that.
[SPEAKER_08]: Yeah, and in talking to him, I just loved hearing the stories he had, of the numbers of patients he's had, who had severe hyper-trickness or ademium, and he really zooms into their lifestyle.
[SPEAKER_08]: For example, I really recommending, you know, over 7,000 steps a day.
[SPEAKER_04]: And so this was notable because this woman was like, I have my phone on me 100% of the time.
[SPEAKER_04]: And I looked at her step count over the last, I don't know, like month.
[SPEAKER_04]: She averaged like 900 to 1000 steps a day.
[SPEAKER_04]: There were plenty of days where it was triple digits and she hadn't broken a thousand.
[SPEAKER_06]: man, there were plenty of days when I might not have even broken a thousand steps, particularly when I was studying for step.
[SPEAKER_06]: I wonder, I wonder how my drag goals rise are doing back then, I mean, no, same.
[SPEAKER_04]: And so if you take somebody who does not do any physical activity,
[SPEAKER_04]: and you give them the homework of they have to go for a 20 minute walk after every meal that they have.
[SPEAKER_04]: I've had quite a few patients who have 50% reductions in their triglyceride levels from doing that.
[SPEAKER_04]: And, you know, like, when you give somebody homework like that, they're probably going to be a little bit more careful about what they're eating for their diet and how long that persists and whether they do it when they don't have to see me in two or three months.
[SPEAKER_08]: get it's fascinating to me how powerful giving patients homework can be.
[SPEAKER_08]: I think for some people they really need that prescriptive language to make that change.
[SPEAKER_06]: Another recommendation of course is to have a low-fat diet.
[SPEAKER_06]: I found it helpful to talk about this with Dr. Robert O, a clinical professor and family medicine that's Stanford.
[SPEAKER_06]: He's written into the issue that when we recommend the low-fat diet patients tend to fill in the gaps with refined and processed carbohydrates.
[SPEAKER_05]: And so you can go over that, but you have to make sure it's low saturated that and you have to make sure that you have higher protein and not of these refined carbohydrates, but you have to cut the sugar out the half to cut the alcohol off.
[SPEAKER_05]: So, most people will shy away from low car for whatever reason.
[SPEAKER_05]: I think I have a bad name, but that's the one if you look at the studies.
[SPEAKER_05]: It's looked at there's a couple of articles and look at all the macro and nutrient composition.
[SPEAKER_05]: The lower car ride rate, the better.
[SPEAKER_05]: You have a better weight loss and you have a better with trigostrite profile.
[SPEAKER_06]: So the teaching point here is that, of course, recommending both a low fat diet and a diet that's lower in processed carbohydrates, refined carbs and simple sugars.
[SPEAKER_06]: These excess carbs are converted by the liver and to fatty acids.
[SPEAKER_06]: And of course, those fatty acids are then assembled into triglycerides and secreted as VLDL.
[SPEAKER_06]: If we really want to nerd out, we also know that high carbs can also lead to insulin resistance, which then reduces triglyceride clearance as well.
[SPEAKER_08]: Um, and there is so much here, and so to summarize a lifestyle counseling, what I'm taking away is really coaching patients on how responsive their truckless rides can beat a lifestyle.
[SPEAKER_08]: And really prescribing to them, you know, avoiding any alcohol, refined carbs, sugar, a low-fat diet, you know, as much aerobic exercises they can get, weight loss, and the idea of tracking can be really helpful in having them come back on the sooner side.
[SPEAKER_08]: All right, so in addition to counseling on lifestyle, we also need to talk about medications.
[SPEAKER_08]: For example, Adam's patient, you know, hit that patient's checklist where I was still sitting at 388, even at a fasting level, a few days into the hospitalization, and mostly being NPO.
[SPEAKER_08]: And again, I like have to remember that idea that, you know, just one fatty meal in this patient, because saturate his life protein life pace, right, above 500 or so threshold, and hopefully not set him back into their great Titus.
[SPEAKER_08]: Yeah, that's such an important point.
[SPEAKER_08]: Well, before we get into mess though, in this initial visit, it may be a solid for a future you to get a fasting triglycerid level, and Dr. Brenton touches a little bit on this.
[SPEAKER_01]: I always prefer fasting.
[SPEAKER_01]: And the reason is, it has less noise.
[SPEAKER_01]: Triggless rice, fasted or fed, are going to vary by 20 to 30 to 40 to 50%.
[SPEAKER_01]: And if you think about that for a minute, our triglyceride lowering drugs have efficacy in that same range.
[SPEAKER_01]: So you've got a problem with signal to noise, where the signal and the noise are in the same range.
[SPEAKER_01]: So how can you figure out if somebody is getting better or worse on a given medication?
[SPEAKER_01]: Do you have one time you measure them fast?
[SPEAKER_01]: You're going to the next time non-fasting.
[SPEAKER_01]: Or if you measure them twice non-fasting, and in one time it's been six hours, and they have very little fat, or the second time it's been two hours, they had a lot of fat.
[SPEAKER_01]: In either case you're going to have a huge difference in terms of kind of microns.
[SPEAKER_08]: And yes, different people can have different practices with having patients come back for a fasting lipid panel.
[SPEAKER_08]: It's an extra plastic.
[SPEAKER_08]: Some people want to see what they're non-fasting triglycery lives at, but when the triglycerys are getting into that severe range and you're thinking of starting on medication, getting a fasting one really definitely helps to see that impact of that medication without too much noise, whether or not they have been out of chips or some Ben and Jerry's before getting abs.
[SPEAKER_08]: But yes, I love all the tips to help future you interpret the impact of medications.
[SPEAKER_08]: Alright, so when we, when it comes to medications, what do we got on the table and how much does it really help?
[SPEAKER_08]: There are three big buckets we're going to talk about, statins, omega-3s, and 5 rates.
[SPEAKER_08]: And maybe let's start with the most familiar one to a lot of us, statins.
[SPEAKER_01]: How do we prevent ASCBD in our patients with high-tragal storage?
[SPEAKER_01]: Well, believe it or not, we're gonna do is use a statin.
[SPEAKER_01]: Now you go away in a minute, statin's lower LDL, they don't lower triglycerides.
[SPEAKER_01]: Well, in a person with normal triglycerides, they, whatever their percent LDL lowering is about half a squad for triglycerides.
[SPEAKER_01]: So you're using a high intensity stat and you get a 50 to 60% LDL lowering, you have a 25 to 30% triglyceride reduction.
[SPEAKER_01]: That doesn't mean that triglystroidlorine goes down a lot more, but what it means is that you're going to get as much triglystroid reduction as you do well the L-L-L-L-L-L.
[SPEAKER_08]: So in general with statins, we can expect patients to drop their trigosterized by 10 to 30 percent, but at higher levels, we can have an even greater degree of reduction.
[SPEAKER_08]: Awesome.
[SPEAKER_08]: And just to say that loud, the 2018 AHA AC cholesterol immune guidelines do say, start a statin if your patient is between 40 and 75 years old and has persistent moderate lead elevated trigosterized.
[SPEAKER_08]: So that's a fasting trigosteri greater than 175 to 499 milligrams for dusk heater.
[SPEAKER_08]: Or, if they have severe hyper triglycerides, so that's the Korean than 500 milligrams of desoliter, with a 10-year ASU degree than 7.5%, and the reason here is yes, you get a little bit of triglyceride lowering, but more so it's about decreasing their overall cardiovascular risk at these states.
[SPEAKER_06]: Right.
[SPEAKER_06]: So let's talk about other options as well because in addition to that ASCBD risk reduction, those patients who have really high triglycerides in the triple digits, especially greater than 500 milligrams per desoliter, are going to need more than just a statin.
[SPEAKER_06]: So another option is phenophibrate.
[SPEAKER_04]: phenophibrates probably the medication that has the largest evidence-based that at lowers triglyceride levels.
[SPEAKER_04]: And anecdotally, it just seems really effective at lowering triglyceride levels.
[SPEAKER_06]: and looking at the evidence, you can actually expect a 30 to 50% reduction in triglystrods when you start being a vibrate.
[SPEAKER_06]: Sounds good.
[SPEAKER_08]: Alright, tell me about Omega 3s.
[SPEAKER_08]: I mean, my dad takes fish raw supplements because of some random WhatsApp video that was sent to him and I don't know maybe that's helping, and so was one of the three that you mentioned.
[SPEAKER_04]: Omega-3 fatty acids also do a really good job of lowering triglyceride levels.
[SPEAKER_04]: It's related to how they impact lipoprotein lipase and that's a very easy add-on.
[SPEAKER_04]: And if you look at the whole premise behind reduce it, which was the trial adding Bissapa to stand in a care lipid lowering therapy, was that it helped to clear the triglycerides and it helped to treat these patients who had residual triglycerides.
[SPEAKER_05]: So reduced it was a pretty large trial.
[SPEAKER_05]: These are patients with type 2 diabetes or other cardiovascular risk factors.
[SPEAKER_05]: And they already were on a statin, which is prepared for it to understand.
[SPEAKER_05]: And they had trigoceride levels above 150.
[SPEAKER_05]: So that was kind of an exclusion criteria.
[SPEAKER_05]: And so these are high risk patients already on a statin.
[SPEAKER_05]: And their trigoceride levels are up.
[SPEAKER_05]: And then they offered them in randomized fashion
[SPEAKER_05]: or BSTP, the number needed treat was 111, so one person, 111 person treated and have one cardiovascular or mortality benefit, which is pretty decent if teeth and numbers, considering they already on a statin already.
[SPEAKER_06]: So that's a huge finding that Omega-3 supplementation had a 25% reduction in major cardiovascular events.
[SPEAKER_06]: And for those like me who like numbers, these Omega-3s can lead to about a 28% triglyceride reduction when you get to those doses of three to four grams at EPA or a
[SPEAKER_08]: Cool.
[SPEAKER_08]: And what these Omega 3s want association to possibly keep in mind is that they did find increased rates or hospitalizations for a trophy relation in the Omega 3 group.
[SPEAKER_08]: And this might be something to watch out for especially in patients who may have poor cardiac substrate.
[SPEAKER_06]: Yeah, that's definitely something to be cautious about.
[SPEAKER_06]: I'm also wondering if patient or like in the case of Shreya's dad is go for the counterfisch oil sufficient or should we be transitioning everybody to a prescription strength?
[SPEAKER_06]: Of course if it's covered by insurance and affordable for the patient.
[SPEAKER_01]: So, what about the dietary supplement omega-3?
[SPEAKER_01]: It's cheap, it's easy, it's there on the grocery store.
[SPEAKER_01]: I think I'm a giant bottle of it, start taking it.
[SPEAKER_01]: Well, there are several problems.
[SPEAKER_01]: Number one, they tend to have a lot of saturated fat.
[SPEAKER_01]: Number two, they tend to be oxidized.
[SPEAKER_01]: Number three, they basically always have a lot of DHA, so you're digging the whole deeper.
[SPEAKER_01]: So, please tell your patients, please never recommend dietary supplement omega-3, and please tell your patients that they're taking them to stop because it's not helping them.
[SPEAKER_08]: So the omega-3 supplements that patients can get over the counter actually have a variable amount of EPA and DHA.
[SPEAKER_08]: And so you're not sure exactly how much a patient might be getting.
[SPEAKER_08]: And then just for contacts that reduce a trial, the omega-3 used, it was prescription strength, omega-3 purified EPA, and no DHA.
[SPEAKER_06]: So I also want to bring up some really recent evidence, hot off the press.
[SPEAKER_06]: There was an RCT that showed that prescription strength though make a threes and patients on hemodial says reduced mace by about 43%.
[SPEAKER_06]: So in this trial, there wasn't really a baseline elevation in triglycerides for the patients on hemodial says.
[SPEAKER_06]: So theoretically, the reduction in mace may have been through a mechanism that was separate from triglyceride lowering.
[SPEAKER_08]: Not, it's yeah.
[SPEAKER_08]: And interestingly, in the fine print, if you look, it was a combo prescription, like a two-to-one ratio between EPA and DHA.
[SPEAKER_08]: So maybe we need to have more EPA for it to be effective.
[SPEAKER_08]: I think either way, the takeaway is when you're doing your MadRag to make sure it's not patients who are just buying omega-3s off the shelves.
[SPEAKER_08]: It sounds like the doses of EPA and DHA can be so variable.
[SPEAKER_08]: and that we are prescribing the Omega 3 that is, you know, whichever one it's the purified EPA or the one that's higher in EPA content.
[SPEAKER_06]: Definitely.
[SPEAKER_06]: Yeah.
[SPEAKER_06]: I think the prescription is really the only way to enter this.
[SPEAKER_06]: also just wanted to bring up nice and I think a lot of us learn about it in medical school as a part of the triglyceride treatment pathway, but really in practicality it's not in our toolkit even for severe hyper triglycerideemia.
[SPEAKER_06]: Not many people can really tolerate the medication especially with the side effect of flushing and it can also cause liver injury and there also hasn't been a clear cardiovascular benefit.
[SPEAKER_08]: Yeah, so sounds like we really have the statins, the phenophybrates, and the omega-3s to choose from.
[SPEAKER_08]: And so that brings us to a very important point, which is how do we choose, right?
[SPEAKER_08]: Is it side effector event, what really helps us decide to start this one versus that one?
[SPEAKER_08]: Yeah, so it's a question that comes up all the time in our clinic visits, and we really press our discussants on this, and honestly, most of them says, start with the medications that you are most comfortable with.
[SPEAKER_06]: And another point is that if you want to rapidly lower trigly strides, so for those patients who are at risk for pancreatitis, especially with the levels over 500, reach for the phenophibrates and omega-3, these medications are better for rapidly lowering the trigly strides and can give as much as a 50% reduction.
[SPEAKER_08]: Awesome.
[SPEAKER_08]: And even the ADA, the American Diabetes Association, has the explicit recommendation for anyone with a fast and trickless record in 500 to, you know, really reach for a phenophibrate or a high dose omega-3 fatty acid, and that's really a warranted to reduce that pain-grade tightest risk.
[SPEAKER_06]: And then there's of course, stands, which have less of an impressive triglyceride lowering footprint in terms of percent reduction, but do have that ASCVD benefit.
[SPEAKER_06]: And now we see that omega-3's also have that.
[SPEAKER_08]: Perfect.
[SPEAKER_08]: And so we talked about the importance of medications.
[SPEAKER_08]: Once their patients are on these medications, the other questions in clinic is when to bring the patient back and what to check in on during these visits.
[SPEAKER_02]: So I tend to bring them back more frequently when we're rapidly.
[SPEAKER_02]: So four to six weeks, let's say.
[SPEAKER_02]: So that's what I would do.
[SPEAKER_02]: So you're looking for frankly dramatic changes in those comorbidities.
[SPEAKER_02]: Is the patient doing something to lose weight?
[SPEAKER_02]: Has the patient started exercising?
[SPEAKER_02]: Is the diet better?
[SPEAKER_02]: Has the patient cut back at alcohol?
[SPEAKER_02]: And he medications that they were on that increased triglycerides have they've been changed?
[SPEAKER_02]: You know, things like that.
[SPEAKER_02]: So you're looking to see that there's been a significant change that would ultimately lead to a sustained reduction in triglyse words, not just the blood test that you're repeating.
[SPEAKER_06]: That was good space for repetition to what we talked about earlier on the podcast about all the things that may be contributing to that triglyse article.
[SPEAKER_08]: So if we were to summarize if three typical medications were reaching for when it comes to triglyse rides, there is one more that
[SPEAKER_08]: It's really an art, right, in terms of which one's to start and how many do you start at once, depending on how the triglycerides are and how that motivated that patient is in terms of lifestyle.
[SPEAKER_08]: But the ones that have an A, C, B, D reduction is going to be our statins.
[SPEAKER_08]: And now more data is coming out about the Omega 3 and it's in particular the prescription strength Omega 3's higher doses three to four grams a day and with more EPA content.
[SPEAKER_08]: And then the ones that rapidly lower the trace glycerides, especially when we are worried about the risk of pancreatitis, fetal hybrids usually first line, they can also reach for omega threes too.
[SPEAKER_08]: All right, so most of these cases with high triglycerides are associated with metabolic syndrome, alcohol use, other things, but as Greg mentioned, everyone does have different genetic supply.
[SPEAKER_08]: Yeah, so the reason to watch out for these different genetics applied is because the treatment is completely different for some of the genetic syndromes.
[SPEAKER_08]: There are two big buckets.
[SPEAKER_08]: The first we call FCS for a familial calomicronemia syndrome.
[SPEAKER_08]: The other form is MCS, the metabolic form, and that we call mixed calomicronemia syndrome.
[SPEAKER_08]: They can be a muffled, but Dr. Seth Bomb and Dr. Elia Brintin takes us through this beautifully.
[SPEAKER_02]: In FCS, first of all, it's an ultra-rare disorder, right?
[SPEAKER_02]: It's present somewhere between one and let's say 10 people per million to two.
[SPEAKER_02]: FCS has certain classic patterns of presentation, classic findings.
[SPEAKER_02]: They are not necessary though to make the diagnosis, right?
[SPEAKER_02]: So you can be off on one or two of these things, it's still at FCS.
[SPEAKER_02]: So it's a mono-genic disorder, there are five genes that are typically involved.
[SPEAKER_01]: It is, most often, a defect in the lipoprotein lipase gene, LPL, that reduces the activity.
[SPEAKER_01]: In fact, generally, these people have, you know, zero to 20% of normal lipoprotein lipase activity.
[SPEAKER_01]: So, FCS means what?
[SPEAKER_01]: You generally have Kalimakranemia since we're very young.
[SPEAKER_01]: It often presents in neonates, or young children, or preteens or teenagers.
[SPEAKER_08]: Yes, people with FCS have a genetically-determined low-activity of fiber-routine lipase.
[SPEAKER_08]: When you don't have as much fiber-routine lipase, you lose your ability to break down Kylo-microns.
[SPEAKER_08]: So people with FCS presents, with guy-high-charges rise that are persistent regardless of fasting or not.
[SPEAKER_02]: If you do genetics on a patient and the patient does not have the evidence of those mutations, it does not mean that the patient doesn't have FCS.
[SPEAKER_02]: Right?
[SPEAKER_02]: If you find them, the patient has it.
[SPEAKER_02]: If you don't find them, you still have to consider the diagnosis.
[SPEAKER_08]: So it turns out genetic tests missed a certain number of people who behave like FCS, but do not have a detectable mutation with our genetic panels.
[SPEAKER_08]: Yeah, and hold that thought about genotypers' phenotype we'll come back to that in a second.
[SPEAKER_08]: Let's talk about the other genetics at play, the MCS patients, and just to be clear, this is technically a patients who's fasting trickless rides where you're then 800 and 80, and this is what the observed kind of tipping point where we see chylo-microns developing in the blood.
[SPEAKER_04]: For every case that you see, there's probably 500 cases of it's just metabolic syndrome and it's just elevated triglycerides related to an imbalance between somebody's lifestyle and what their genetics want their lifestyle to be.
[SPEAKER_08]: So, sounds like MCS is much more common and makes me wonder when we are a value in a patient and clinic and we just, you know, most likely there can be MCS or is there something else we're looking for when those triggers are over 80 to make us suspect okay this is FCS versus MCS.
[SPEAKER_02]: So phenotype always trumps genital, okay, so that's one thing you think about.
[SPEAKER_02]: You look at the individual and there are certain things you go look for what's the age of onset.
[SPEAKER_02]: Well, you know, when I was 30 years old, I was told I had a very high triglyceride, so it's young, it's not terribly young, but it's young.
[SPEAKER_02]: That favors FCS over MCS.
[SPEAKER_02]: Patience body habits is the patient over way to obese.
[SPEAKER_02]: If the patient's over way to obese, favors MCS, FCS, typically thinner.
[SPEAKER_02]: You look at whether or not the patient has any secondary causes of severe hyperdragals ready in me.
[SPEAKER_02]: Diabetes will be the typical one.
[SPEAKER_02]: metabolic syndrome, central obesity, you know, other like underlying rheumatologic disorders or medications that might cause it hormonal medications, atypical anesthesiocotics, so you go through this list and go up to the space to have any of these features.
[SPEAKER_02]: You ask about things like abdominal discomfort guys, you have periodic abdominal discomfort because that could be a sign that there's like a low grade pancreatitis if you will work.
[SPEAKER_02]: Are there cognitive disorders?
[SPEAKER_02]: Do you feel like you're in a foggy state frequently?
[SPEAKER_02]: Do you miss a lot of work?
[SPEAKER_02]: Those favor FCS, okay?
[SPEAKER_02]: What were prior triglyceride levels if you have access to them?
[SPEAKER_02]: If they were all over a thousand, and the patient doesn't have any of these other causes that would be associated with MCS, you're really looking at an FCS patient.
[SPEAKER_02]: What about response to triglyceride lowening therapeutics?
[SPEAKER_02]: So you say, have you ever been given a fibrade or a statin for triglyceride lowening or omega-3 fatty acids?
[SPEAKER_02]: Yeah, they didn't work at all.
[SPEAKER_02]: Start favoring FCS over MCS.
[SPEAKER_02]: They're variable in MCS, though.
[SPEAKER_02]: So you still might have a poor response.
[SPEAKER_08]: These are all very important clues that help us identify patients with FCS.
[SPEAKER_08]: And this brings us to an important question, so why do we want to identify FCS?
[SPEAKER_08]: The presence of FCS has significant implications for treatment.
[SPEAKER_08]: FCS tends to not respond well to traditional lipid lowering therapies like statins and fibrates and omega-3s, because often these therapies require working like routine lipase.
[SPEAKER_08]: And for a very long time, patients with FCS really didn't have much therapeutic options except for a very old that diet for a lifetime.
[SPEAKER_08]: But now we have some good news.
[SPEAKER_01]: December of 2024, finally, the FDA approved the first drug for FCS, and that's what is arson.
[SPEAKER_01]: It's an anacinous organucleotide that blocks APOC3 production.
[SPEAKER_01]: An FCS, you get a 50% triglyceride lowering.
[SPEAKER_01]: Well, that's a miracle for an FCS patient, because there they have so few treatment options.
[SPEAKER_01]: And that's enough to reduce pancreatitis by roughly 80 to 90 percent, and that is amazing.
[SPEAKER_07]: that is really amazing for patients with FCS.
[SPEAKER_07]: And now we have Olosarsin and Plosassurin.
[SPEAKER_07]: In clinical trials, Olosarsin lower triglycerides by about 43% compared to Plosipo.
[SPEAKER_07]: And Plosassurin achieved about 59% reduction in triglycerides compared to Plosipo in patients with FCS.
[SPEAKER_07]: So that gets me thinking, you know, if somebody walks in with really elevated triglycerides and a phenotype of FCS, do I need to send off such an early testing or not?
[SPEAKER_01]: One other thing I will say, I do not bother to genotype patients who have persistent telemicronemia and or either the clinical functional FCS or what would ultimately be
[SPEAKER_01]: FDA does not require this, and a majority of patients who have what looks like typical FCS have this clinical or functional FCS, and not genotypic.
[SPEAKER_01]: So in a majority of cases, you will quote, prove yourself wrong by failing to genotype them as FCS.
[SPEAKER_08]: So for the most part, our discussions had mixed practices for sending off genotyping.
[SPEAKER_08]: Dr.
[SPEAKER_08]: Bomb did say that he would send off genit existing for FTS if the phenotype fits because it may have implications for familial screening.
[SPEAKER_08]: Exactly.
[SPEAKER_08]: And with that, we will end with one final word from Dr. Seth Bomb.
[SPEAKER_02]: But to say that, I think we need to look at triglycerides differently nowadays, that we need to have in the SHTG population, we need to have a sense of urgency where previously we didn't have that.
[SPEAKER_02]: And it's for a couple of reasons, one, it's for the acute panhutitis risk.
[SPEAKER_02]: and especially in view of the saturation of like a protein lipaceite around trackless around 500.
[SPEAKER_02]: These people are at much higher risk than you think they are for a cute package.
[SPEAKER_02]: And the other is ASCVD.
[SPEAKER_02]: I mean, it's still the leading cause of death in the United States.
[SPEAKER_02]: And I think, you know, anything we can do to diminish the risk would be valuable.
[SPEAKER_02]: So that would be it.
[SPEAKER_02]: You know, pay attention, take it seriously and do what you can to
[SPEAKER_08]: All right, and that is a wrap for our episode today.
[SPEAKER_08]: If you got some value from this podcast, our ask is to please send it to one other colleague who could also use a nice aha moment.
[SPEAKER_08]: I know I had a bunch myself.
[SPEAKER_08]: Hmm, same here.
[SPEAKER_08]: And thank you so much to our peer reviewers, doctors, Aki Damod, and Dr. Michael Shapiro.
[SPEAKER_06]: Thank you to Dr. Navigos Weiss for the Epi Company and graphic.
[SPEAKER_06]: And as always, we love sharing feedback.
[SPEAKER_06]: Please email us at hello at quarrympodcast.com.
[SPEAKER_06]: Opinions expressed our own and do not represent the opinions of any affiliated institutions.
[SPEAKER_06]: Thank you, and take care.
[SPEAKER_08]: Is there a trigrosite trick?
[SPEAKER_08]: Why is trigrosite so hard to say today?
[SPEAKER_08]: I know.
[SPEAKER_08]: Oh, I know.
[SPEAKER_08]: Is there a trigrosite trick?
[SPEAKER_08]: Try, gliss, or try, gliss, or gliss.
[SPEAKER_08]: I'm having trouble to, like, many hours and...