Ep 494: We Got Cholesterol All Wrong–The Most Shocking Truth About Heart Disease Risk You’ve Never Heard with Dr. Thomas Dayspring
- Team Cynthia
- Aug 22
- 40 min read
Updated: Sep 1
I am deeply honored to reconnect with Dr. Thomas Dayspring, who joined me in 2024 for an immensely popular five-part series. Dr. Dayspring is certified in internal medicine and clinical lipidology. He is a distinguished fellow of both the American College of Physicians and the National Lipid Association.
Today, we have the first episode in a new series of conversations with Dr. Dayspring, in which he will share more of his perspective and answer more questions from listeners. In our discussion, we review the basics about cholesterol, triglycerides, and lipoproteins, exploring the factors that contribute to the development of cardiovascular disease, the significance of ApoB and Lp(a), and the risk factors for younger women. We also dive into the limitations of traditional allopathic medicines, and Dr. Dayspring shares his views on lipids, lipid changes in menopause, specific ways to address ApoB, some of the challenges associated with statin therapy, and more.
Dr. Dayspring brings a wealth of experience and expertise to this discussion, and you are sure to find this series as invaluable as the last.
IN THIS EPISODE, YOU WILL LEARN:
Dr. Dayspring revisits the differences between cholesterol, triglycerides, and lipoproteins
What atherosclerosis is, and why it is concerning
Dr. Dayspring explains the structure and function of lipoproteins
The role of ApoB in lipoprotein particles and its significance in atherosclerosis
Some of the risk factors for lipid abnormalities in younger women
Lipid changes that occur as women transition from perimenopause to menopause
Dr. Dayspring shares his take on statin therapy
Ways to address high ApoB
Dr. Dayspring’s suggested goals for ApoB therapy
““The incidence of insulin resistance is exploding.”
– Dr. Thomas Dayspring
Connect with Cynthia Thurlow
Follow on Twitter
Check out Cynthia’s website
Submit your questions to support@cynthiathurlow.com
Connect with Dr. Thomas Dayspring
Cholesterol Balance Sterol Report Interpretation (1).docx:
I was contacted by a physician yesterday because he thought he had a rare case of “PHYTOSTEROLEMIA,” a lipid disease originally called sitosterolemia. My reply to him serves as a quick “teaching” of how to properly interpret the sterol panel. Tricky report to interpret.
The numbers depicted and colored bars on the left side of the graphic are actually a ratio that is of interest to epidemiologists, but has little use in evaluating individual patients. In that section of the report, BHL takes the sterol measure in umol and multiplies that by 100 (to convert to mmol) and divides that product by total cholesterol in mmol. It is actually a sterol/total cholesterol ratio. On the right side of the report, they do report the sterol “absolute” value in mg/L. The absolute value, not the ratio, is what you use to evaluate individual patients.
Usually, phytosterols cannot be absorbed by enterocytes, and there should be minimal concentrations in plasma. Any phytosterols that make it into the enterocyte via the NPC1L1 sterol influx transporter should be immediately effluxed out by the ABCG5/ABCG8 sterol efflux transporter (a heterodimer). If there is a loss of function of ABCG5/G8, the phytosterols (and cholesterol) will not efflux back to the gut lumen but rather will enter chylomicrons and gain systemic entry. Likewise, if ABCG65/G8 are not effluxing phytosterols out, they are also not effluxing cholesterol back to QUT lumen – thus resulting in hyperabsorption of cholesterol. The levels in the case at hand are high enough to suggest this patient has some heterozygous loss of function of the ABCG5 or G8 gene. If the LOF were homozygous of either ABCG5 or G8, the patient would have the extremely rare phytosterolemia condition – the absolute sitosterol or campesterol concentrations would be in the 20-30 mg/L range.
Note - theoretically, any elevation of one of the many phytosterols in plasma can be called “phytosterolemia,” but the disease, classically called sitosterolemia, is now called phytosterolemia and is limited to those with extreme levels of phytosterols
What really needs to be looked at to diagnose hyper/hypo absorption or synthesis is the absolute concentration of each sterol (shown in the column on the right of the report). Sitosterol and campesterol are two different phytosterols that normally should not be absorbed. In this case at hand -
The sitosterol concentration is 4.3 mg/L, which is the 92nd population percentile cut point -- Significant hyperabsorption
The campesterol concentration is 5.9 mg/L, which is the 90th percentile cut point -- Significant hyperabsorption
Both of those elevations indicate there is significant hyperabsorption of cholesterol. It is theoretical in that the degree of phytosterolemia matters
In this case, although hyperabsorption of cholesterol is present, the apoB is well controlled by atorvastatin at 56 mg/dL, and since apoB is the goal of therapy, nothing more necessarily needs to be done. Note the synthesis markers (lathosterol and desmosterol) are low, as expected on a statin.
Lathosterol absolute concentration is < 0.8 mg/L which is <20th percentile population cutpoint
The desmosterol is 0.8 mg/L, which is the 20th percentile cutpoint.
Despite the significant reduction in cholesterol synthesis, the bar graphs are green, suggesting normalcy. Reality is that there is significant hyposynthesis of cholesterol synthesis in this patient. Normal markers would be a level between the 40th and 80th percentile (1.2-4.7 lathosterol or 1-1.5 desmosterol)
In many cases, when a statin significantly inhibits cholesterol synthesis, there will be a reflex hyperabsorption of cholesterol, which is likely what has happened in the case at hand, at least in part explaining the increased phytosterol concentrations.
If further apoB reduction was needed, ezetimibe would be the drug of choice. But with apoB being fine, one does not necessarily have to treat the hyperabsorption. If the patient is known to have ASCVD, then for a variety of reasons, one might want to reduce phytosterols (there is a debate if they are also harmful) and use ezetimibe despite the good apoB. A patient like this should be told to avoid any phytosterol supplements.
One other salient point – One never wants to suppress cholesterol synthesis too much with a statin, because statins are the only lipid-modulating drugs that can suppress brain cholesterol synthesis; they may also be over-inhibiting cholesterol synthesis in the brain (the only source of cholesterol in the brain is synthesis). Low desmosterol is a biomarker that correlates with cognitive impairment and AD. When one hits ~ 20th % or less concentration of desmosterol, other ways of lowering apoB should be considered – ezetimibe, bempedoic acid (active only in the liver), and PCSK9i do not lower brain cholesterol or its synthesis (plasma lipoproteins cannot cross the blood-brain barrier and deliver cholesterol to the brain).
Transcript:
Cynthia Thurlow [00:00:01] Welcome to Everyday Wellness Podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.
[00:00:29] Today, I had the true distinct honor of reconnecting with Dr. Tom Dayspring. As you may recall, we had an incredibly popular five-part lipid series in 2024 and he returned today in person in my home podcast studio to dive into more of listeners questions and interest and to give you some perspective. Dr. Dayspring is certified in both internal medicine and clinical lipidology and he is a distinguished fellow of the American College of Physicians and the National Lipid Association. And as always, he brings a wealth of experience and expertise to our discussion today.
[00:01:06] We reviewed the basics about cholesterol, triglycerides and lipoproteins, things that contribute to the development of cardiovascular disease, the significance of ApoB and Lp(a) as well as risk factors for younger women and this is particularly important because I think there are not an enough clinicians that are educating our younger patients about some of the risk factors for developing heart disease. We also discussed limitations of traditional allopathic medicines, view on lipids, lipid changes that we see in menopause, in particular ways to address ApoB as well as goals. Additionally, some of the challenges to dealing with statin therapy and so much more. This is the first in a series of discussions with Dr. Dayspring. I know that you will find these to be as invaluable as you did last year.
[00:02:01] I feel particularly appreciative and grateful that Dr. Dayspring lives in my area and that we can have these conversations with greater frequency.
[00:02:13] Dr. Dayspring, I can't tell you how appreciative and grateful I am to have you here today. And the fact that we are both from New Jersey and we both live in the same city to me is just serendipitous.
Dr. Thomas Dayspring: [00:02:24] So, it's incredible. We've done podcasts before and I'm so thrilled to be in person with you and see that your nice smile and voice. So, we'll have some fun today.
Cynthia Thurlow: [00:02:33] Absolutely. And I have to tell you that my Everyday Wellness community really resonated with your message. I always say that I think a lot of my listeners really love the science and they'll sit through it and they love to learn. And so, I sit very gratefully saying to be able-- to have another conversation with you and be able to facilitate the learning process, but also do some listeners questions. And I jokingly tell you before we started recording that there were so many that I tried to pick themes because of course it's impossible to go through all of them. But we'll do that towards the end of the conversation today.
Dr. Thomas Dayspring: [00:03:06] Now look, I love speaking to enlightened audiences, which is certainly yours, because that's where hopefully we can spread the best information that are going to be useful to a lot of people.
Cynthia Thurlow: [00:03:17] Absolutely. And I thought it would be helpful. Obviously, listeners can go back to those original five podcasts for a deeper dive into these topics, but I thought it would be helpful just to do a quick refresh, talking about differences between cholesterol, triglycerides and then actually looking at the lipoproteins, those are the carrier molecules that are in our bodies. I think it's important just to start the conversation because I think many individuals, even frankly some healthcare providers, may lump all these entities together. And they are distinct-- They're each distinct on their own, with their own kind of pros, cons, benefits to our bodies. And as we navigate perimenopause into menopause, there's a lot that changes with our lipids.
Dr. Thomas Dayspring: [00:03:59] Indeed, it's a complex topic, but it's a fascinating topic. A little basic biochemistry is involved, but great news about lipids as we're talking about-- it is the biggest risk factor for the global leading cause of killer atherosclerosis. But it's entirely treatable if your lipid abnormalities, if you have them, are recognized. And the sooner in life they're recognized, the better is going to be the outcome, but very treatable abnormalities. So, if premenopausally woman was fine, but postmenopausally things have changed, you address it at that stage. If she had abnormal lipids at age 20, you address them at age 20.
Cynthia Thurlow: [00:04:39] I think for a lot of individuals there's been a knee jerk reaction that every lipid abnormality, and I'll just put it in air quotes because it runs the gamut, “That every lipid abnormality requires a statin.” And the one thing that I really appreciate and value about your work is helping us understand there's a time and a place for medical therapy. There are what I would refer to as, you know, if you've got high Lp(a), which I'm sure we will talk about, this is a genetically mediated issue. About 20% of us have a high Lp(a). I happen to be one of them. Both of my kids have also inherited that as well. So, we're on top of this.
[00:05:18] I know I'm like, thank you, parents. Both my parents bestowed that upon me, exactly, exactly. But helping people understand, so let's talk a little bit about lipoproteins in terms of before we start talking more about specifically ApoB and Lp(a), because again, I think a refresher on what these are and why we need to be asking for these tests is certainly very helpful. I think most of my listeners are very familiarized with the traditional lipid panel, total cholesterol, HDL, LDL, looking at triglycerides. That's helpful, but that's just one piece of the picture.
Dr. Thomas Dayspring: [00:05:54] Yeah. So, the basic science is, I always like to start off saying the disease we're worried about is atherosclerosis, which is ubiquitous pretty much. That is a deposition of cholesterol in your artery wall. If you don't have cholesterol deposits in your artery wall, you do not have atherosclerosis. So, it doesn't take a genius to figure out, well, God, for the people who have that, how did the cholesterol get in the artery wall? It's not like the artery started over synthesizing cholesterol. That doesn't happen. So, cholesterol, you mentioned triglycerides. They're like a bunch of fatty acids stuck together. They're in this category of organic molecules called lipids and their distinguishing characteristic is they're not soluble in water.
[00:06:36] So, the problem is our plasma is pure water. So, how the heck do lipids travel around our body in the plasma, that's a chemical impossibility. But evolution solves impossibilities. So, whenever in our distant, distant past, evolution had to invent water soluble lipid transportation vehicles. And it was an easy fix because proteins pretty much are soluble in water. So, if we take globs of lipids, oil droplets, so to speak, but we wrap them with a protein, lipids plus a protein is a lipoprotein. So again, one of my rules is lipids go nowhere in the human body unless they're a passenger within a lipoprotein particle, as we call it. Now, lipoproteins are not a molecule, it's a macromolecule full of thousands of lipid molecules, at least one structural protein, many other proteins and other molecules that tag along for the ride.
[00:07:32] So, lipoproteins, obviously, if you have cholesterol in your artery wall, there must be certain lipoproteins that have the ability to leave plasma, crash that endothelial barrier, enter the artery wall, and then they're a foreigner in this environment. So, in comes the immune defense system, the white blood cells, macrophages that start ingesting these cholesterol-carrying lipoproteins. All of a sudden you got a bazillion what we call foam cells, macrophages full of sterols, cholesterol, they stick together, plaque and plaque can evolve into things you really don't want to happen.
[00:08:10] So, it's a lipoprotein-mediated disease, atherosclerosis. So, God, the past 50-60 years, for the most part, physicians have been measuring lipid concentrations, the cholesterol, the three fatty acids stuck together, which is a triglyceride molecule, and those are the two primary lipid concentrations. They look at what was never taught, and there's no sense even teaching it until lipoprotein tests involved where everybody could order lipoprotein tests if they wanted to, is to say, well, we have this cholesterol concentration or we have that triglyceride concentration. Their guesstimates or surrogates of do you have the wrong type of lipoproteins or do you not?
[00:08:57] But once we have lipoprotein tests, the lipids take a big backseat to it. And certainly, if you really are interested in this disease, and you should be because it's likely going to be on line one of most of our death certificate, hopefully later rather than sooner, you really have to step up to-- yeah, you're going to always look at the lipid concentrations, but you'd be far smarter ascertaining your risk if they're abnormal, far smarter knowing what your goal of therapy should be if you're measuring lipoprotein concentrations.
[00:09:30] So, now it just comes down to what are the names of these proteins that are enwrapping these particles. And this is where it gets a little more advanced. Because we have two families of lipoproteins and one family, and people know them by their more common names, is very low density. Most people have never heard of intermediate density that's sort of in between those two things. And everybody knows the high-density lipoproteins. Well, the first three I mentioned, VLDLs, IDLs, and LDLs, they share the same structural protein called apolipoprotein B. ApoB for short. APO, not APO [crosstalk] [Cynthia laughs]. It's APO, whatever. Spell it right and you'll get it.
[00:10:16] And the cool thing is on every VLDL or LDL there is simply one ApoB peptide. Perfect laboratory measure ApoB for me, I'm counting the number of VLDLs and LDLs that are floating around somebody's plasma at the moment the blood test is done. And the important thing to know if you're getting ApoB is you're going to factor in something called plasma residence time a little bit of a complex feature. Once the liver or the intestine which manufactured these particles, shoot them into plasma, how long do they stay there before they're cleared? Well, however long they stay, that's called the plasma residence time. Well, VLDLs, Chylos, that are the ApoB particle that comes out of your intestine delivering absorbed lipids, they're gone in a couple hours. VLDLs are gone in four hours. LDL particles hang around three, four, five days.
[00:11:12] So, if you do measure ApoB, yes, it is VLDLs plus IDLs and LDLs, but 95% of them are LDL. So, in essence, ApoB is an LDL particle test. Now, if you told me what your LDL cholesterol level was, if it was high, I'm going to say, I'll bet your ApoB is high. Wouldn't bet your life on it, but likely it is. And if you would say, “No, I have a perfect LDL-C, I say, “Well, probably your ApoB is okay,” but I sure as heck wouldn't bet your life on that because there is this concept called discordance, where as good as LDL-C correlates with ApoB in a lot of people, a lot at the times. But there's 20-25% of the population where those two metrics do not correlate.
[00:12:01] And when they do not, ApoB rules, that is the accurate biomarker. You dismiss LDL cholesterol as not helping you at all. So, if you understand this discordance, as that's disagreement is called, the only way to know you or I have discordant lipids versus lipoprotein concentrations is to measure both, or just measure ApoB, since that's the one that always rules. But most people are always going to get a lipid panel plus an ApoB. So that's the story. And just a word about the other family of lipoproteins, which are the high-density lipoproteins. They're much smaller than the LDLs or VLDLs. But there's an interesting little side bit to that.
[00:12:45] Why are HDLs so small? And why are the LDLs bigger and the VLDLs are ginormous. Well, what do VLDLs carry, LDLs carry, but not as much but HDLs never carry, triglycerides, which is a pretty big lipid molecule because it's got three fatty acids stuck on a glycerol backbone. So, if your purpose in life is to traffic VLDLs, triglycerides, energy for muscle cells, storage for adipocytes, you got to be a big dump truck. LDLs, they're a byproduct of VLDLs half of the time, their mission is not to carry trigs. There'll be some leftover trigs. So that's why they're much smaller. They're primarily carrying cholesterol.
[00:13:29] The HDLs never carry triglycerides other than a couple of molecules, and thus they don't need to be very big because they got cholesterol in them. And they carry a lot of stuff on their surface that's not inside the particle. So, your high-density lipoproteins, the structural peptide is not ApoB. There is no ApoB on an HDL particle. It's another apoprotein called apolipoprotein A-1. And I say capital A because I never wanted you to confuse it with apoprotein little A, which we will talk about.
[00:14:03] So, an interesting, the HDL is very small, but ApoB is the largest apoprotein that the body makes for those known molecular weights, 550 kilodaltons. ApoA-1 is the smallest apoprotein that the human body makes. It's like 40 kilodaltons. So, you need anywhere from 2 to 3 to 4 to 5 ApoA-1 particles per baby HDL particle because it's so small. Even though the HDLs are small, they were-- And an HCL starts off little, but it does get bigger as it acquires cholesterol. So, they have a lot of ApoA-1 on. This is why ApoB is a great way to count LDL particles. But ApoA-1 is not a very smart way to count HDL particles because you don't know how many copies of ApoA-1 are per HDL. So, that's the ApoB story, and that's the ApoA-1 story.
[00:14:59] And it concludes with the only particles that can crash your artery wall and do that illegal dump job of cholesterol in your artery is the ApoB family, 95% of which are LDLs, which is why the cardiovascular community spends so much time talking about LDL metrics of which ApoB is the best one. And what makes an ApoB particle decide to be an illegal dumper or return to the liver where it's supposed to be going, it's particle number. And once we exceed a certain concentration of LDL particles, ApoB particles, they're going to go in. Now, they don't go in overnight. This process occurs over years and decades. That's the good news about atherosclerosis. If you discover your risk, it's not like unless you're at the end stage, it's not going to knock you off tomorrow.
[00:15:50] You have a lot of time to reduce those concentrations and halt the entry into the artery wall. So, it's a very slow process, thank God. And this is why the current mantra in preventive cardiology is the sooner you recognize ApoB abnormalities that's when therapeutics come into mind. Now, it doesn't have to be drugs necessarily, the lifestyle unless you're a total nightmare who's already had an event, that's lifestyle plus drugs. But in most other cases, you're going to give therapeutic lifestyle a chance. Is the patient going to do it? Have you advised the patient on the right lifestyle? And sometimes that's a little tricky, depending on individual differences.
[00:16:33] And you would go X number of months to see did I get the ApoB to where it has to be? If not, then you start to consider pharmacologic therapy. And everybody thinks statins are a great drug if you need them. But there's many other drugs available. If we were in 1990 doing this podcast, it'd be statins or we're done. But now we have so many great ApoB-lowering options. So, even if you can't take a statin, if you absolutely refuse to take a statin, I've got other tricks up my sleeve that are just as good at lowering ApoB. So, it's a little easier now to do it. But anytime people even, “Oh, he's just some statin lover.” Anytime you've ever listened to me, I've always started off with therapeutics and every guideline says this too. Guidelines are not pushing drugs down anybody's throat. If you need a drug, it's lifestyle plus drugs. And not anybody but the highest risk, it's let's do lifestyle for a while and see.
[00:17:32] And you know more than I that everybody swears, “Yes, I'll do that lifestyle and they do for two months, three months, and when you see again six, oh, I forgot or I don't like that lifestyle.”
Cynthia Thurlow: [00:17:44] Yeah. It can be a big-- I mean, I think for a lot of patients it's not realistic for them to make too many changes all at once. That's number one. And I always say, “I would never ask a patient or a client to do something that I myself can't do.” So, there are things I'm like, “This is a deal breaker. I'm not willing to do X or Y.” However, you bring up some really good points. Number one, for many, many years, we as clinicians were very focused on that traditional lipid panel. Every single person listening needs an ApoB done and an Lp(a) at least once. And I'm going to keep emphasizing this statistic 20% of us have genetically propensity for having high Lp(a). And we'll talk more about Lp(a).
[00:18:31] What's interesting to me is when I look at ApoB levels and I'm sure you do this, you have a gestalt, you're like, their level’s too high even if they do everything right, lifestyle wise, we're not going to be able to get that therapeutic. And there's no shame in taking medication. And I always say, “I've been on Zetia and that has been life changing for me in terms of looking at lipids,” at least as a starting point. With that being said, when people are listening and they're thinking, okay, I'm going to go to my healthcare provider, I'm going to ask for an ApoB. I'm going to ask for an Lp(a). Before we even think about that, when you were still working directly with patients or younger women, what were some of the risk factors? Like causal reasons that they would be at greater risk.
[00:19:15] Like you would be thinking, okay, this person has lipid abnormalities. I have to be even more proactive addressing this than, let's say, someone who's 50 years old with no risk factors that we're looking at.
Dr. Thomas Dayspring: [00:19:27] Yeah. And this is something that has evolved big time. Because if you went back to what I was telling a woman in 1988 or 1995, it'd be a little different today. Because in that era, believe it or not, we knew almost nothing about women in atherosclerotic heart disease. My generation of physicians, and it's five decades since I graduated med school, we're pretty much taught women don't get heart disease. So, zero in on your men and [Cythia laughs] that was a silly belief. It was funny even in my residency, internal medicine, and I liked cardiology. I spent virtually every elective in the CCU or the CATH unit because I just found it was evolving and it was fascinating. But there was never a shortage of women in the coronary care unit.
[00:20:10] So, what is this mantra that women don't get heart disease are all the exceptions in Paterson, New Jersey and the rest of the world. So, obviously that was silly and that's evolved, but it took a long time, I was just telling you before. All of the initial lipid modulating trials for the most part would not enroll women. They were just-- especially younger women, but even in the older women, they were writing them off and the younger women, they were afraid this lady might go out and get pregnant. We don't know what this drug might do to pregnancy. So, no company doing research on drugs wanted to enroll women. Later on, they started to thank God. So, we got the catch-up data with women that we have now. But here's what we now know about women.
[00:20:53] You don't want to know what I might have been preaching back in the dark ages there. So, I mean, you do your basic screening lipid panel, if you're coming to me, you're getting an ApoB automatically with it. But most docs are probably just doing-- If I see an abnormality of LDL cholesterol or very high triglycerides, I have to presume you have a genetic abnormality. And again, it's the leading cause of atherosclerosis. So, you're 25, you're 35, I should wait till you're 70 or 65 before I might want to treat you. Some of them are the women who are in the CCU that are just alluded to. So, no, I would say, “Well, it's the genetic thing going on and you could try doing genetic tests.”
[00:21:40] Half of the things, you don't even find the genes because we don't know the full gene. And lipids can be controlled by a lot of minor SNPs, so you check the major SNPs, you see nothing. But all the minor SNPs she's inherited is what's generating her particle abnormalities. So, once again, the levels exceed a certain threshold, you decide lifestyle, and if it doesn't work, drugs. But we now know, are other very important risk factors for women. First of all, the incidence of insulin resistance is exploding. Not every woman has a BMI of 20 nor does every man. So, there's a lot of insulin resistance in the community. A big risk factor that may drive trigs a little bit. Probably not to a scary level, but somebody who understands IR would recognize a trig of 130, 120. I better look further into this. So that's going on.
[00:22:37] There's no shortage of women with polycystic ovarian syndrome, basically a high insulin resistance scenario where they get the same type of lipoprotein abnormalities. But we also now know you have to want part of the integral history taking in a woman when you first see her is the pregnancy history. And even the menstruation history. At what age did you start menstruating? Have you ever been pregnant? If so, have there been any miscarriages along the way? If you did carry, were there any hypertension of pregnancy? Anybody check trigs during pregnancy? Eclampsia, preeclampsia? And not only do they put the little baby at risk for the pregnancy, but they are big forecasters that down the road this woman is going to be a high-risk woman. Keep a close eye on this woman as you're following her over time.
[00:23:33] And there's just many other pregnancy risk factors that I've forgotten even to mention here that you better have a checkoff list when you're doing the initial history. How many pregnancies did you have at what age was your first pregnancy on? All of these things, as you are surmising, have things to do with your hormonal balance and stuff which are tied right into lipids and everything. Did you breastfeed or did you not breastfeed is a nice protective way to ward off future heart disease. More and more women are doing that back in the day, I don't know, for the longest time women were not doing that at all, but still not every woman is or not every woman can.
[00:24:15] So, there are reasons and that would just be another little risk factor to pay close attention to this woman herself. And hypertension would be a coexisting risk factor just as important to lipids to the development of cardiovascular disease. It's not a lipid, but they team up together to do awful bad things and everything. So, those are just some of the things you would look at. And then later, as all right, she is in menopause whatever, standard age is 51. But as you know, there's a wide confidence when women start having menstrual irregularities or hormonal imbalances, the so-called perimenopause which can be variable at different ages in women. Things start to change there.
[00:25:04] If you haven't paid attention to lipids before, then that's another opportune time to watch a multitude of women's health risk factors for other diseases too and everything. We were talking before women-- long before their menopause, most women are getting regular mammograms. And then we've known it for a while, but it's really come into play now. Most radiologists are finally attuned to this. And sometimes you see faint calcifications on a mammogram, and they were all written off as nothing. Unless they were the type of calcifications that look like certain types of breast cancer warnings, but they would be ignored.
[00:25:39] The radiologist sometimes would mention it on a report, but the primary care doc and even the gynecologist would pay no attention to that. You've got calcium in your breast. That's calcium in the arteries in the breast. Guess what other arteries you might have calcium, meaning plaque in, your coronary arteries, your carotids, upstairs in the brain. So that should be a big red flag for a woman who says, “What doctor what are these calcifications here?” And if he doesn't know, your listeners will know now that they better Google that in a big hurry and say, maybe I better pay more attention to whatever cardiovascular risk factors I mentioned.
[00:26:16] Any of the things Tom just rattled off during pregnancy. Did I have any of them? And that's his ways of picking up atherosclerosis when you want to pick it up before the stent, before the bypass, before the [unintelligible 00:26:28], before the CCU admission. So, all little tricks like that, but that perimenopause is big. There's one other category of women who for one reason or another have premature ovarian failure. Sometimes it's chemical because they've had a cancer that they had to take, some potent drug that destroyed their ovaries. The moment that happens and their body is devoid of estrogen, they're in for a lot of trouble. Bones for sure, atherosclerosis for sure. So, cognition, those are things that provider ought to be looking very seriously at.
[00:27:05] And the lipids are easy because they're so identifiable and you can start treating them long before you might otherwise have to or so. And some women just get premature ovarian failure through autoimmune mechanisms or mechanisms not well understood, but a big red flag that she's going to be prone to some of the morbidities we just alluded to there. So, there's so much-- women's health and I like to brag. I have the distinction of being the first physician in the United States who is both Board Certified in Clinical Lipidology and by the Menopause Society as a menopause practitioner. Back in my day it was called the North American Menopause Society, now it's the Menopause Society. But I was number one.
[00:27:49] So, I was super interested in women and lipids. And I'll tell you why. Because as I did evolve into lipids in the 80s and stuff and I was still an internist then, so I'm seeing men and women plenty. And you'd be talking to the women and they often were seeing gynecologists too. And if they even wanted to discuss the harder lipids with the gyno. They-- [crosstalk]
Cynthia Thurlow: [00:28:12] Yeah, they don't want-- [crosstalk]
Dr. Thomas Dayspring: [00:28:13] They're into a prime. If talking to me would be great. But most primary, “No, you're too young. Oh, look at your HDL cholesterol. It's so good. You're nowhere you could ever get heart disease.” Fallacy, big fallacy for listeners today. I soon discovered women get such garbage advice among a variety of practitioners. You know, men in one ear out the other half the time. I so enjoyed talking to women, their intent, they pay attention, they listen, they'll work with you, they ask right questions. So, I just fell into a Well Women's healthcare practitioner.
[00:28:49] My practice in Jersey was called the North Jersey Institute of Menopausal Lipidology. Not that I had any shortage of premenopausal women, but I just enjoyed taking care of women. And so, once I decided that, I had to realize, okay, I do know the heart stuff pretty good, but I got to really start learning now more about the breast, the vulvar area, the bones and the brain. And I dump into that big time too. I've done tons of lectures on those morbidities too. I would always squeeze in some heart in my education, in my lectures. But I just love and you-- I again, one of my old sayings, and I'm sure a lot of docs probably use this.
[00:29:30] When a woman walked into my office, I'm not looking at a pretty face. I'm not staring at her boobs. I'm not wondering what's below the belt. I'm looking brain, heart, lungs, breasts, pelvic, abdominal bones, you can't just focus on one area because what you're doing may affect the other area. But that's kind of cool being somebody trained in internal medicine. They like the big picture. So, it's another reason I wound up where I did. None of this was by grand design. The things just happened that pointed me in right directions, but women are complex. But it's very gratifying when you find a woman who will work with you.
[00:30:11] Usually, you'll get pretty good results. I mean, you can't guarantee anything but a little preventative care with every aspect of all of those organ systems I just mentioned are easily diagnosed and therapeutics do exist, be they lifestyle or be they pharmacology, if they're needed.
Cynthia Thurlow: [00:30:28] Well, you were certainly ahead of your time because when I trained in medicine, 1990s, early 2000s, everything was siloed. In fact, I recall when I would round on cardiology patients on our service and my docs would say, “Cynthia, stop talking to the patient about X, Y and Z. Just call the specialist.” And I'm like, “But the patient's telling me about X, Y and Z. I feel a sense of obligation to address it. And so, it became this like reoccurring theme of stay in your lane. Don't think about anything outside of the heart, which frankly, I think the heart affects everything. I would say all the time you're not in a vacuum. If the heart doesn't work right, nothing else works right.
[00:31:05] But I think to your point, individuals could be listening and they're like, maybe I'm 35, I'm, you know, menopause is many years away. I don't need to worry about these things. And I was one of those people that had high LDL, high HDL. And because my HDL was so high, 70s, 80s, 90s, no one thought that they needed to think about anything. And yet brewing beneath the surface was high ApoB, high Lp(a). And I interject this just to say at the time we didn't know, now we do know. And I think it's really important for everyone to be advocating for themselves, to be asking for these tests and to work with a practitioner that's going to be open minded to have that conversation. Because these are tests covered by insurance.
[00:31:48] These are not integrated medicine tests that are unusual, that aren't covered, that you pay out of pocket for. I think it's very, very vital, especially as we are looking at navigating, you know, early perimenopause, post menopause and beyond. And think to your point about the CCU and seeing all these older females, how many patients I saw in the ICU that had massive heart attacks. We know women present later with heart disease because we take care of everyone else. Women tend to have more small vessel disease, which means for listeners stuff you can't necessarily stent or intervene on. The other thing is we know that loss of estrogen is so incredibly impactful on the body not just for brains, bones and heart, but every organ system in the body. It is a catastrophic downstream effect of this loss of estrogen.
[00:32:37] So, the patients I saw with the heart attack probably had some atrial fibrillation, would end up being septic. None of them at that time were on vaginal estrogen. We weren't thinking about the association of loss of estrogen in the genitourinary system. That would make women at greater risk for developing urinary tract infections, which would make them at greater risk for develop systemic blood infections, which in some instances can be life threatening. And so again, that's why I'm so grateful for these conversations.
Dr. Thomas Dayspring: [00:33:06] The estrogen story is funny too, because for years it was the bailiwick of gynecologists, internists never wanted anything to do with hormonal therapy. I always joke the worst fear of an internist is at 02:00 in the morning getting a call, “I have vaginal bleeding.” [Cynthia laughs] And so, Gynes were mega advocates of probably the wrong type of estrogen and the wrong doses of estrogen and then came these initial trials that started putting some fear of estrogen with the coronary artery disease and ultimately some information about breast cancer that got this promulgated a little bit. And then nobody wanted estrogen therapy, including the internists who still didn't want it. But even the guys were a little bit scared away from it, certainly patients.
[00:33:55] And now it's come full circle with reanalysis of some of these complex trials and newer trials that have come in. But for the right woman, estrogen is a wonderful drug. For the wrong woman, like any drug, it's the wrong drug. But you have to have somebody who understands the nuances of hormonal therapy and can take a part a woman's history, physical, risk factors and decide for you, great drug for you, uh-unh, we can't go there. So, it is a little bit complex, but what isn't in medicine, but the rewards are so promising, but it's back in at least, I think, I hate to say by those in the know, because I don't want to denigrate anybody, but if you haven't read about hormonal therapies, even, go get a guideline statement from the menopause society or so, and you're going to see they've revisited a lot of those areas and it's strongly indicated for a lot of reasons.
[00:34:47] So, you just don't say, “No, we don't go there to hormone therapy because you want it.” That's silly. Funny, all the men are pumping in pills full of testosterone. [Cynthia laughs] Give a woman estrogen and you're a criminal, sometimes. So, it always evolves. But we're in a happy zone right now, I think, with most of the advice that we can give within a more coherent setting or a quick shoutout back in the day when this was evolving, two of my mentors with women in heart disease was Roger Blumenthal at the John Hopkins.
Cynthia Thurlow: [00:35:21] I trained with him.
Dr. Thomas Dayspring: [00:35:23] He did so much with the hormonal therapy in women, and I tagged on to him, even though I'm a bit older than him, not much, but a little bit. He was so bright. I love. And I used to attend lipid conferences at Hopkins and he was always part of it. But Michael Davidson in Chicago too, who's just a mega thought leader on it, we did a ton of the early estrogen trials. What type of estrogens cause what type of lipid changes? So, I learned so much from mentors like that. And I laugh because I'm older than both of them, but they taught me.
Cynthia Thurlow: [00:35:54] Well, fun fact, Roger Blumenthal. I did some of my training with him at Hopkins. So, Ciccarone Preventive Cardiology Center is what he-- that's like his big-- [crosstalk].
Dr. Thomas Dayspring: [00:36:03] Yes, it sure is. And it is patient-- Mr. Ciccarone [crosstalk] Hopkins.
Cynthia Thurlow: [00:36:08] Yep. And so just in a really, incredibly gracious, lovely thought leader and.
Dr. Thomas Dayspring: [00:36:14] And who's down there now? Aaron Mikoz, who's King Tut of that world, probably right now, that's probably the wrong appellation, but-- [laughs]
Cynthia Thurlow: [00:36:22] Yeah, yeah. So, let's talk a little bit, from your perspective, what are some of the changes that are happening with lipids as women are navigating this perimenopause to menopause transition? Because I think, for gosh, I mean, we get hundreds of questions, but it is so clear. Women will say, “My lipids weren't bad before, but now I'm in menopause and my lipids are horrible.” And why is this happening? So, there's definitely this estrogen protective virus.
Dr. Thomas Dayspring: [00:36:45] So, we don't have all the answers, but with lipids, I think there are pretty distinct answers. So, one, as a woman loses estrogen, one of estrogen's attributes, it's an insulin sensitizing drug. So, as estrogen goes by a woman is apt to become more insulin resistant. Well, insulin resistance, we could spend a whole podcast on how insulin resistance causes high ApoB and lipid abnormalities. So, insulin resistance is one you're just going to have delayed catabolism of the ApoB particles so they hang around longer. Production rates may be involved. Menopausal women tend to start hyper absorbing cholesterol. Your Chylos are bringing too much absorbed cholesterol to your liver. Your liver no longer manufactures what's called an LDL receptor, which is the tool that clears your ApoB particles from plasma.
[00:37:38] So, you're hyper absorbing. The liver doesn't want to get more cholesterol pulled out of your plasma because cholesterol above a certain amount can be injurious to any tissue. So, that's a big factor. But interesting enough, and it's been known for a while, but really coming into play, everybody knows PCSK9 inhibitors are the greatest player in the world nowadays because they are our most potent ApoB lowering drugs. And PCSK9 is a protein that actually catabolizes those LDL receptors. You don't want to catabolize LDL receptors. [laughs] You want as many as you can have to clear the ApoB particles to which they bind.
[00:38:15] So, if you make PCSK9, you have a very short half-life of your LDL receptors. Your ApoB is going to be high. And they saw in genetic studies, they evaluated two types of people who had genetic gain of function of PCSK9 and loss of function. If you have loss of function of PCSK9, they had very low levels of ApoB because their LDL receptors were not being catabolized at all. So, they went through life with ApoBs of 30 or 40, LDL cholesterols of 10, 20, 40. What didn't they get, heart disease.
[00:38:51] More importantly, what did not happen, any adverse effects of very low LDL cholesterol or low ApoB. So, the Genetic Mendelian analysis of it says you want lower ApoB. But then they discovered, “Oh, oh there are a few people who did pick the wrong mom and dads and they had gain of function of PCSK9.” Their LDL receptors were being destroyed as they were being formed. So, they had familial hypercholesterolemia.
[00:39:18] When you see that, you say “God, if we could only invent a PCSK9 inhibitor, we would turn everybody into loss of function of PCSK9 and do away with heart disease.” Long story short, that's exactly what happened. We have three PCSK9 inhibitors available to us now. They dramatically lower ApoB. All of their studies have been done in the super high-risk nightmares with existing coronary disease. But they have drastically reduced major cardiovascular events on regression studies. The plaque shrinks and everything. So why am I even teaching PCSK9? Because it turns out estrogen is a PCSK9 inhibitor to a lesser degree. It's not a Repatha, but nonetheless.
[00:40:01] So when a woman loses estrogen, all of a sudden PCSK9 is higher than it was. No wonder LDL cholesterol goes up. But remember, those LDL receptors are not only clearing LDL particles which do carry triglycerides, they're involved with clearing VLDL particles too. So, if all of a sudden, you're losing some LDL receptors, LDL cholesterol can go up and triglyceride, it'll be individually variant, could become abnormal too. Most of the trigs I think is insulin resistant related or so. So, those are the two biggest reasons right there that's going on that why should we be shocked? And some of those things are at play in those PCOS women who get those things earlier in life, they have big estrogen troubles and everything too, infertility.
[00:40:48] So, those are the things I can hang my hat on in the lipid world or so. And in addition to okay, she's in the menopausal year, no estrogen, losing a little [unintelligible 00:40:58], diets sometimes tend to get a little worse. The exercise trails off, so the lifestyle takes a dive also. So that compounds what's going on with your lipoprotein homeostasis also, if you're not doing the ideal lifestyle as much as you used to, and maybe you were never doing lifestyle, it's probably worse after men, of course, you're certainly less inactive or you're less active, not less inactive.
Cynthia Thurlow: [00:41:27] Yeah, it makes so much sense and it's interesting, I learned something new that estrogen is a mild PCSK9 inhibitor. I mean, [crosstalk] makes so much sense and for me, one of the things that, and I'm sure you're the same way or any clinician is like when you walk around and you view the world and you start to understand like what is happening to women as they're making this transition. Because I see people who were healthy, active, insulin sensitive, they go through that transition whether they're on HRT or not. And all of a sudden, they're incredibly inflamed, they become weight loss resistant, they're losing muscle mass, so they become sarcopenic, their sleep goes south, so their cortisol is high. I mean, it's sad that the one hormone that goes up in menopause is cortisol, so we become less stress resilient. It's kind of like the perfect storm.
Dr. Thomas Dayspring: [00:42:13] Yeah. We mentioned one or two markers, but as you said, it all related. You change one, you change another, and they all depend one another. They're all supposed to be acting in homeostatic synergy together. And you screw up one, all of a sudden-
Cynthia Thurlow: [00:42:25] Oh, it's a domino.
Dr. Thomas Dayspring: [00:42:27] -another one, and that screws up another one--crosstalk]
Cynthia Thurlow: [00:42:30] Absolutely.
Dr. Thomas Dayspring: [00:42:32] Whatever diseases are going to manifest, they'll start manifesting sooner.
Cynthia Thurlow: [00:42:36] Yeah, absolutely. So, I think again, it goes back to like, what are the things we need to be looking for. You've given us a lot to think about. I'd love to spend a little bit more time talking about ApoB, largely because you've already mentioned that our liver loses the ability to clear this as we are making this menopausal transition. When we're talking about ways to address high ApoB, and when I'm thinking high, there's a woman that I'm working with right now and her initial ApoB was 178. And I said to her upfront, I was like, “You're going to need charts, you're going to need medication.” There's no question. We can talk about-- [crosstalk]
Dr. Thomas Dayspring: [00:43:11] Your problem.
Cynthia Thurlow: [00:43:12] Yeah, I was like, we can talk about lifestyle, we can talk about all these other things, but you clearly need medication. Let's move on to this cholesterol balance. So, let's talk about ways to address high ApoB, starting from lifestyle first and then obviously there's more to it than that.
Dr. Thomas Dayspring: [00:43:27] So, listen, if you have high ApoB in 99% of the cases, it's because all of a sudden, your liver is not clearing those ApoB particles as readily as they should be. And that is totally dependent on what we just were talking about these LDL receptors, which is a protein the liver manufactures. Once it's made at the protein-making apparatus, it migrates to the surface of the liver cell that interacts with plasma. I always joke it for people who know what the ADAMs family is. Remember, there was that thing that came out of the bounce and it would grab things. Well, an LDL receptor is a hand that's sticking out of the liver cell, reaching into the plasma. And it's structurally engineered that the curvature in the LDL receptor is engineered to recognize a small component on the ApoB peptide.
[00:44:20] On the ApoB, it's called the LDL receptor binding domain. On the LDL receptor, it's called the ApoB binding domain. So, if you have the proper-sized ApoB particle and you have a non-defective LDL receptor, they lock up and it pulls it into the liver. Now the LDL receptor grabs the whole LDL particle, pulls it in, and it enters a little vesicle called an endosome, which rapidly gathers a whole bunch of proteolytic enzymes, lipolytic enzymes that destroy the LDL particle into cholesterol, fatty acids, phospholipid components, amino acids from the peptide and then the liver does whatever it wants with those molecules. If you're lucky, those proteolytic enzymes do not destroy the LDL receptor.
[00:45:11] It is released from the lysosome, as an endosome with enzymes is called, and it migrates right back to the surface of the liver cell and does it again. Over a few days, it does it numerous times. It recycles, so to speak, if and only if you don't have a lot of PCSK9. Because if you had PCSK9, the LDL receptor gets destroyed with the LDL particle and it can't recycled. Oh oh, lot less LDL receptors, lot less of what's called clearance, the ApoB-- [crosstalk]
[00:45:42] So that's an important concept, An LDL receptor grabbing an ApoB particle, pulling it in, is called clearance. If you had defective clearance, your ApoB level is going to be high because the particles continue to float around. And they're only going to float around so much because if they keep floating around, the number is going to go up. They cross the threshold that they can cross the endothelial barrier and you know what the consequences of that are.
[00:46:07] So, next step is, okay, what tells the liver to make LDL receptors or don't make LDL receptors apart from PCSK9? And it's very easy. The liver is like the master regulator of cholesterol balance in the human body. We call it homeostasis, is the big word. But it's really regulating things to make them physiologic so they don't hurt anybody. So, what determines whether a liver wants cholesterol, in which case it'll manufacture more LDL receptors and clear more ApoB particles or the liver says I don't want any more particles because too much cholesterol in any cell will crystallize and kill the cell. In the liver, excess cholesterol contributes to NASH, fatty liver. So, the liver is not interesting in overloading itself of cholesterol. It will just stop clearing particles. If that was happening, one reason why people with ASH have high ApoB.
[00:47:02] So, if you understand that concept, you would say if I could only deplete the liver of its cholesterol pool. And it needs cholesterol to make bile acids. It fills HDLs which deliver cholesterol to steroidogenic tissue and adipocytes. And I need cholesterol for my own cell membranes if I'm a hepatocyte. So, I need X amount of cholesterol. So, if it doesn't have enough, it acquires it. If it's got too much, it stops acquiring it. Well, how does the liver acquire cholesterol if it needs it, turns on the genes that promote cholesterol synthesis. So, huh-huh.
[00:47:41] So, if I really wanted to deplete the liver of cholesterol, I might decide let's deplete cholesterol synthesis in the liver. Now, the obvious answer is prescribe a statin or bempedoic acid, a somewhat weaker cholesterol synthesis inhibitor. But there's certain nutritional things I might advise too, and I'll get to them in a moment. So, that would be one thing. And then ii could deplete the liver of cholesterol with the statin, with the bempedoic acid, the liver needs cholesterol, got to make bile salts for tonight's supper. It will grow more LDL receptors and they grow them very quickly. It doesn't take long for-- there's something called the nuclear transcription factor that recognizes their cholesterol deficiency. And they go right in and turn on or turn off the genes that are controlling all of this or so, so is there another way of depleting the liver of cholesterol.
[00:48:35] Intestines stop absorbing so much cholesterol. All of a sudden, the chylomicrons are not doing their job. They're not delivering adequate amounts of cholesterol to your liver. Cholesterol deficiency in the liver, no problem, I'll just grow more LDL receptors. Well, we can't tell our chylomicrons-- How do we tell our chylomicrons not to deliver cholesterol. We block cholesterol absorption in the gut. Hello, ezetimibe, [unintelligible [00:49:01]. And there are some supplemental ways or lifestyle ways you can enhance absorption of cholesterol also, but the pharmacologic way is ezetimibe. Ezetimibe depletes the delivery of absorbed cholesterol to the liver. The liver says, “Oh, my God. Hey, gut, you didn't send the cholesterol up. I'll just-- Don't worry, I'll make more LDL receptors.” That's how ezetimibe lowers ApoB. You grow more LDL receptors, you might say, I believe you mentioned a woman who had both hyperabsorption and hyper-synthesis.
[00:49:33] Well, then I use a little cholesterol synthesis inhibitor with a little cholesterol absorption inhibitor and you really upregulate LDL receptors or if you really just had a lower ApoB so much in the case you just mentioned, you might go with combo therapy day one and the last thing. So, that's how the cholesterol synthesis inhibitors and the absorption inhibitors factor in. But we were talking about these PCSK9 inhibitors. So, if I could inhibit PCSK9s, whatever LDL receptors your liver cell is now making would live longer and longer. They recycle more and more. Big ApoB benefit.
[00:50:10] In the nightmares of the world, it might be triple combination therapy, a statin, ezetimibe, and a PCSK9. Somebody-- you're just [unintelligible [00:50:19] ApoB, but in the stratosphere there-- You don't start three drugs at once. Of course, you'll go lifestyle and then if you need, you'll add the drugs. But if you're not getting to the goal, you have to keep adding. I get so annoyed at physicians or clinicians tell a patient, “Well, we did pretty good. We're not going to push our luck.” No. Okay. Just let her go get atherosclerosis, heart disease down the road. Why wouldn't you push her luck? The therapies, trust me on this and there's many ways to double check me. The lipid therapies we're talking about, you have to know the side effects of every possible drug anybody's going to prescribe.
[00:51:01] But considering these are not cancer chemotherapies, the downside is virtually nil to PCSK9 inhibitors. For the most part, a little bit with a statin, far less with ezetimibe, almost none with bempedoic acid. And even if there are some side effects with statins, and there are not in the majority of people, no, but in some, yes, but they're all recognizable. So, even if we went down the statin route and we see everybody knows and some glucose may go up, some aminases in the liver may go up, some may get muscle aches, albeit a minority. If we saw that, we would revisit the statin therapy and try and work around it or say no, you're just one of these humans who just can't take a statin like Tom Dayspring. And so, he's moved on to other drugs.
[00:51:50] But you just don't say, “No, I'll never use it because you haven't done your homework on any of these lipid modulating drugs. So, it's basically restoring cholesterol balance to your liver by understanding that cholesterol balance is what regulates the LDL receptors that do the clearance of the particles from your plasma.” And last but not least, every particle that your liver clears is one less that can wind up in your artery wall.
Cynthia Thurlow: [00:52:16] And that's a way to think about it. And I always love when you talk about statins, you emphasize that most of the benefit comes from the lowest doses. This is something that in clinical cardiology we oftentimes are starting highest doses.
Dr. Thomas Dayspring: [00:52:30] And part of this was pharma design. But in the early days, they knew lower is better, but they really wanted to prove even more is better. So, we're not going to waste our time with low-dose statins in these clinical trials. We're going to just start you on the megadose. And they did them and they worked and [unintelligible [00:52:45] went down. So, that became evidence-based medicine. You have to write a gorilla statin, it’s my adjective for high-dose statin. When anybody who's ever studied the pharmacology of statins knows, yes statins deplete cholesterol synthesis in the liver. The liver will manufacture LDL receptors, but almost all of that LDL receptor upregulation comes with the baby dose of the statin.
[00:53:13] And that's why if I use 5 of Rosuva, I get 30%-35% low. But then every time I double the dose of Rosuva 10, 20, 40, I get another 5, 6% ApoB-- [crosstalk]
Cynthia Thurlow: [00:53:24] This is very important.
Dr. Thomas Dayspring: [00:53:25] Yeah, so, but I do get more and more side effects the more I put, even though they're minor, as I said, I would rather not deal with them at all. But you go starting everybody on the highest dose statin day one. First of all, people read this stuff, they don't even want to take them. So, they're probably not even going to comply with that prescription in today's world. But they're more apt to be the side effects and you're never going to get them to ever trust therapeutic decision again because drugs cause misery. So, you're going to get in far less trouble with the baby dose. And pretty much my mantra is now if that baby dose and with Rosuva that's 5 mg, with other statins it's a little higher. But you're not starting with maximum dose of whatever statin you prefer is if the five, if the baby dose didn't give me all the LDL receptors, hello, ezetimibe, hello, bempedoic acid if they can afford it or if they're in the higher risk category where they're third-party payer. well, likely just the hello PCSK9 inhibitor.
[00:54:27] And I believe the new guidelines are going to address this big time because the experts now know we're just scaring people off of statins because of this [unintelligible [00:54:35] and cardiologists still pound the table, “I will not prescribe anything but a high-risk statin.”
[00:54:41] And again, I'd get a second opinion big time, preferably with a lipidologist or even a primary care physician or clinician who understands this stuff. I just told you how slow atherosclerosis is. It's not that if you don't start your gorilla statin today, you're going to die next week. You have months if not years to get these things under control. So, please. Now, I will make the caveat. If you just had an acute coronary syndrome last week and you come out of the hospital all right for a year or so, you push your high-dose statin and then we'll fine tune your therapies. But we're not talking that, we're talking primary care here where or even a little bit of secondary care where you've had a stent or somebody did an image on you and they see coronary disease, you got time to play, so I don't know that you need the gorilla statins. I think they're doing more harm than good. They are going to kill me for saying that-- [crosstalk].
Cynthia Thurlow: [00:55:35] No, no, I mean, I can remember that the expectations of what we were writing for and I wrote for thousands and thousands of tens of thousands of prescriptions for statins over the years. And I would sometimes say to my colleagues, I was like, “Listen, if this is a not a STEMI or a non-STEMI, someone who's had acute coronary syndrome has just had a myocardial infarction, a heart attack. We've got a little bit of time to play with this. And I always found that going low and slow, I got better patient buy in. We would talk about potential side effects, we would discuss, when the Jupiter study came out, that threw everything into a tizzy because then all of my patients were like, “Am I going to develop diabetes?” Then that caused more anxiety and I was like this isn't helping. And so, I think that there has to be a degree of judiciousness when we're having these conversations.
Dr. Thomas Dayspring: [00:56:25] And you know, even that data, until we started using these bigger doses of statins, the rosuvastatin, 80 mg of it, we didn't even know diabetes was a risk factor of statins because we were using lower dose Pravachol, simvastatin. And it took a long time for the community, the trials to recognize, “Hey, X number of people do get in some resistance on statins and it's dose dependency.” Then you have to change your approach once you understand, “Oh boy, we didn't notice 10 years ago, but we know it now.”
[00:56:56] So that has to alter thinking and sooner or later you have to abandon level 1 evidence when we now know and it's unarguable that all you have to do is use an FDA-approved drug or lifestyle and get ApoB to goal and heart disease goes away. How you do it is irrelevant-- Now again, the ApoB nightmares are going to require pharmacological therapy, but lesser degrees might not. They might go step wise with your therapeutic--
Cynthia Thurlow: [00:57:28] If you love this podcast episode, please leave a rating and review. Subscribe and tell a friend.
geometry dash is a community favorite clicker title. Navigate unpredictable columns, earn stars, and compete with fans everywhere today!
One of the most addictive elements of Drift Boss is its high-score chase. Every run becomes a competition—not just against others, but against yourself. Beating your own record feels rewarding, and seeing improvement over time makes you want to keep going.