top of page

Ep. 527 HRT Changes Your Lipids More Than You Think – The Surprising Truth About Menopause & Heart Disease with Dr. Thomas Dayspring

  • Cynthia Thurlow
  • 2 days ago
  • 36 min read

ree

I am honored to have Dr. Tom Dayspring join me again today for another AMA session. He and I have done eight podcasts before, and this is a continuation of our last Ask Me Anything episode. 


Dr Dayspring is an esteemed expert on internal medicine and clinical lipidology. He is likely one of the most influential worldwide lipid experts, so I am thrilled to have him back with me to dive into various topics related to listener questions, including the impact of hormone replacement therapy on lipid changes, methods of administration, and why bioidentical hormone replacement therapy is preferable for managing both menopausal symptoms and lipid health. We discuss medications, including PCSK9 inhibitors and GLP-1s, as well as intermittent fasting, lipids, and cardiovascular disease risk. We also examine how heart disease develops gradually, over time, the impact of stress and lifestyle, and Dr. Dayspring shares the labs he recommends beyond traditional lipids, ApoB, and LpA. In our discussion, Dr. Dayspring noted that he was not in a position to speak about GLP-1 therapies or microdosing. Since I received many questions from listeners on those topics, I will host a future solo AMA to address some of their concerns.


Today's conversation with Dr. Tom Dayspring is truly invaluable, and I trust you will walk away with valuable insights you can share with your healthcare providers. We created a PDF - cynthiathurlow.com/lipids -  specifically for listeners that outlines key labs to discuss with your providers and questions to ask them to help you advocate for your own health and your family members' health.


IN THIS EPISODE, YOU WILL LEARN:

  • Why being physically fit does not always eliminate the risk of heart problems arising

  • How ApoB and cholesterol contribute to heart disease over decades

  • Why the early testing of risk factors is essential

  • How chronic stress increases the risk of heart disease 

  • How high cortisol affects insulin sensitivity and glucose regulation

  • How stress impacts endothelial and nitric oxide function

  • The link between low Omega-3 levels and heart problems

  • How insulin resistance degrades heart health

  • How high homocysteine levels can impair endothelial function and contribute to cardiovascular problems

“Chronic stress is a major contributory factor to heart disease.”


– Dr. Thomas Dayspring

Connect with Cynthia Thurlow  


Connect with Dr. Thomas Dayspring


Transcript:

Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness Podcast. I'm your host, nurse Practitioner, Cynthia. 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 is a continuation of a previous Ask Me Anything with Dr. Tom Dayspring. As I've mentioned before, I've done now eight podcasts with Dr. Dayspring and he is an esteemed expert on Internal Medicine and Clinical Lipidology. He's arguably one of the most influential lipid experts not only within the United States, but worldwide, and I'm very honored to have him back today to dive into topics related to listeners questions including the impact of hormone replacement therapy on lipid changes, how the route of administration as well as the type of hormone replacement therapy, specifically bioidenticals are preferred for managing not only menopausal symptoms but also lipids, specific medications including the PCSK9 inhibitors and new therapies, the role of GLP-1s and intermittent fasting, and very transparently, Dr. Dayspring indicated that he did not feel like he was in a position to be able to speak about GLP-1 therapies and/or microdosing. For listeners, because there were so many questions that came in, I will do a separate AMA just with me and I will address some of these specific concerns.


[00:01:44] We then went on to speak about lipids and cardiovascular disease risk and why heart disease is actually a fairly slow process, the impact of stress and other lifestyle measures and recommended labs beyond the traditional lipids, things beyond ApoB and Lp(a). Again, a truly invaluable conversation with Dr. Dayspring, one that I will hope you will garner great insights and information that you can take back to your providers and stay tuned. We do have a PDF that we have created for listeners that will help you be able to not only discuss lipids with your providers, but also ask for specific labs that may be of benefit to you and your family members.


[00:02:32] How does menopausal hormone therapy properly influence lipid profiles? We've danced around this, but is there a better route of administration based on the research? Meaning, is it better to take oral estrogen? Is it better to take transdermal estrogen? Is the information still not-- is the research not yet there to provide those recommendations? I'm leaning towards probably that we're not there yet. It's probably some clinical expertise along with what we know.


Dr. Thomas Dayspring: [00:03:04] It's always the case. We're never there yet because we’re [audio cut] as smart as we should be. There are certainly big differences on the transdermal administration of estrogen rather than oral as to what lipid change you might modulate. Once again, no matter what route you're going down, there could be individual responses. Of course, we've spent a lot of time talking about how loss of insulin sensitivity and acquisition of insulin resistance is a big cause of lipid abnormalities. In women where that can be addressed with hormonal therapies, you're more apt to see subtle changes in lipoproteins perhaps in a direction you want to.


[00:03:43] So, the thing is oral more than transdermal, but the oral agents that you can use for menopausal hormone therapy and certainly when you get into that lower dose birth control before that, there's wide differences in the amount of lipid changes you can have. You just have to go on what you're doing if you're using oral and repeat it. Oral estradiol is going to be more potent on improving ApoB than transdermal is. I will tell you-- and transdermal probably is not going to do much to HDL cholesterol also where oral estradiol or other estrogen ends, but what estrogen or what any lipid-modulating drug does to HDL cholesterol draw no conclusions. We've spent most of this podcast talking about it's ApoB that you got to get down.


[00:04:31] After you start whatever hormonal therapy, you're always going to keep an eye on ApoB because that's the driver of-- whether you're on hormone therapy or not, but that's the one you want to look at. Obviously if I could improve insulin sensitivity in a woman with an oral hormone therapy, you might see the triglycerides, but that depends a lot. It depends on the dose of oral estrogen. As you start using bigger doses of oral estrogen, you can aggravate triglycerides, you can actually create small LDL particles. Lower dose oral estrogen is-- I always liked a 0.5, I believe.


Cynthia Thurlow: [00:05:07] Say 0.5 or yeah, 1 mg.


Dr. Thomas Dayspring: [00:05:10] Yeah. If you're going to have to take a progestin with it, I would prefer a non-androgenic progestin. That's obviously Prometrium or progesterone is the ones you'll get into. It's not going to change too much with oral estrogen might be doing. I'm an oral estradiol guy in my days with progesterone. It raised the question, “Hey, if we're getting progesterone through an IUD” now obviously I wasn't putting in IUDs. They were coming to me already having them or so. Then you can dance around that and see what you're-- no matter what oral concoction you're going to use, follow the lipids. I think even on the last podcast I am not a proponent of conjugated equine estrogen.


Cynthia Thurlow: [00:05:57] Me neither.


Dr. Thomas Dayspring: [00:05:58] Medroxyprogesterone acetate, so I have to tell you to really watch your lipoprotein profile after that.


Cynthia Thurlow: [00:06:07] Well, for many listeners if they don't know Premarin, which is what you're talking about, conjugated equine estrogen, I believe there is over 40 different kinds of estrogen and it's pregnant mare urine. It was the best of what was available many years ago, but now we have better options for women.


Dr. Thomas Dayspring: [00:06:25] By the way, I have to introduce the topic because I was very much involved with the development of raloxifene when it came on the market. For women who aren't going to use the hormone therapy for whatever reason and it's not a universal therapy for there are certain women who probably shouldn't go down that route, but the raloxifene was the first SERM developed primarily to prevent osteoporosis and reduce vertebral fractures.


[00:06:51] There was big hope when raloxifene came to market. It is a pretty significant lore of ApoB, even a little bit more so than oral estrogen. In fact, one of their big trials is multiple outcomes of raloxifene evaluation that is more of a bone mineral density and breast cancer. What does raloxifene do to both of them? It’s going to help the bones and it reduces breast cancer.


[00:07:11] But obviously, it was thousands of women that had lipid profiles on all. We were following LDL cholesterol and it was a very favorable response. Due to my arm twisting they measured ApoB in all the women too. It's not quite as good as ezetimibe, but you can get a 10% lowering of ApoB, which is a little more than oral estrogen. If you are a woman who has a SERM indicated and I was the author of the lipid changes in the multiple outcomes of raloxifene evaluation, we did the ApoB data and the triglyceride data in there, and it was favorable. If a SERM is right for you, raloxifene is in-- there are newer SERMs that have surpassed Evista as it was then.


Cynthia Thurlow: [00:07:55] Hmm.


Dr. Thomas Dayspring: [00:07:56] But it was so seemingly beneficial to what raloxifene was doing to lipids and lipoproteins that Lilly decided to invest a lot of money in a randomized, blinded, controlled cardiovascular outcome trial. This is a trivia question. There's been so much criticism at all these cardiovascular outcome trials. In the early days, no women got in them. Then they started to put a few women in them. But here's my question, and I'll stump everybody for it. [Cynthia laughs] Name the one cardiovascular outcome trial in the history of the world that only enrolled women.


[00:08:32] I believe it was like 9,000 of them and nobody knows what it is. It's raloxifene. It was the [unintelligible 00:08:37] raloxifene use for the heart. That's what their trial was. They believed because of what it did to LDL cholesterol and what I taught about ApoB that there's a good chance this is going to be cardioprotective. At that time, the estrogen data was coming out, the hardest trialing stuff that was scaring people away. They thought, “Boy, we'd have a big advantage over estrogen if we could prove we reduce heart attacks.” Turns out the trial was no. It didn't hurt anybody, but it did not reduce cardiovascular events. In posthoc analysis in the primary prevention cohort, the women would have-- it didn't see that beneficial. That's just hypothesis generating data. I just wanted to drop in the raloxifene.


Cynthia Thurlow: [00:09:24] Thank you.


Dr. Thomas Dayspring: [00:09:25] For most people, women are going through menopause. I would encourage estrogen therapy nowadays, especially if you're symptomatic. One of the downsides to raloxifene is it can aggravate certainly the vasomotor function. Yeah, it can help your breasts, your bones, your ApoB a little bit but you don't want to take if--


Cynthia Thurlow: [00:09:41] You're having a lot of vasomotor symptoms.


Dr. Thomas Dayspring: [00:09:43] Not helping your vagina.


Cynthia Thurlow: [00:09:45] Yeah. Because there are a lot of women that listen to the podcast that are breast cancer survivors. Maybe they're not yet at a point where their clinician will consider HRT therapy. Although that is now, Dr. Corrine Menn is a good example of someone who's a breast cancer survivor and now talks openly about the research surrounding utilization of HRT in cancer survivors. Maybe there are people listening who aren't yet at that point where they're having that discussion. This might be an option for them. Thank you so much for interjecting that.


Dr. Thomas Dayspring: [00:10:17] The one last thing we were ignorant of at the time, but remember that's anti-estrogen sort of therapy, it's not a super potent anti-estrogen but it's doing density estrogen receptors. One wonders if you stayed on it forever. Estrogen as we now know is crucial for the brain. I think if you're on raloxifene or another SERM, it might be good for X number of years,


Cynthia Thurlow: [00:10:17] Yeah. A time period.


Dr. Thomas Dayspring: [00:10:45] I don't know that you should stay on that forever. Perhaps there's been further data published on SERMs in the brain. If there is, I don't know it, but that would be one worry about.


Cynthia Thurlow: [00:10:52] Yeah, absolutely, without a question. Thoughts on PCSK9 inhibitors. I know there's these monoclonal antibodies. You've also talked about estradiol as a weaker PCSK9 inhibitor. For people that are listening-- maybe their provider has mentioned this might be appropriate therapy for them. I think the concerns that I hear from patients is expense if their insurance doesn't cover it. In some instances, they've been told by their insurer, “Oh, you have to have failed other medical therapies which aren't even equivalent to the monoclonal antibodies.” What are your thoughts here?


Dr. Thomas Dayspring: [00:11:29] Technically PCSK9s are not your everyday lipid-modulating therapy. By itself it is the most potent ApoB-lowering therapy one can go on. If you're a multimillionaire and you have a high ApoB and you want to go on a drug that pretty much has no side effects that have been seen so far, be my guest, take a PCSK9 inhibitor. For most people it's now reserved because it's still a very expensive drug, $600 a month if you pay for it, reserved for people who are in the highest risk categories.


[00:12:02] Because then you might get a third-party payer to say yes, we'll reimburse you for a PCSK9 because you've been on a statin, you've been on ezetimibe and either you can't tolerate then and then you would qualify for-- or you have not got to go with those cheaper generic therapies that most people are put on to start with. That's when you might be able to qualify for a PCSK9 inhibitor. Traditionally, it's reserved for people who are in the highest atherosclerotic risk categories, people with existing coronary disease for sure, if you've had an event, a bypass, a STEMI or stroke, you better have a reason why you're not on a PCSK9 inhibitor then.


[00:12:44] We look at ApoB. Most doctors look at LDL cholesterol. The third-party payers look at did your initial drugs-- did your LDL see the goal? You're in trouble if it got your LDL-C to goal, but it didn't get your ApoB to goal to talk. “Hey, third party payer, look at my ApoB sometimes.” “Oh, don't look at that.” That retards the use of PCSK9 inhibitors too. How they work, they're injectable drugs. Now there are two classes, the first two that have been on the market the longest and they came on within a month of each other on the market are monoclonal antibodies which have to be injected subcutaneously. It's in an autopen, very easy to stick yourself. You press the button and it takes about three seconds to inject it into your thigh or your subcutaneous tissue and your abdominal wall. It's antibody that attaches to your LDL receptor.


[00:13:38] When PCSK9 is floating around, it attaches to PCSK9. I've already told you, if you inhibit PCSK9, your LDL receptors recycle. So you have way more residence time of your LDL receptors and that's how they lower ApoB. There's a short interfering RNA drug called inclisiran, Leqvio is the brand name. By the way, the monoclonal antibodies are Praluent, alirocumab or evolocumab, Repatha are the one. I think Repatha has the biggest share of the market. But the inclisiran is interesting because after you inject it goes into the liver. It's attached to a protein and will only go in your liver, not in any other cell in body. You're not putting PCSK9 in your brain or other places where maybe it shouldn't be. It's only in the liver where it inhibits PCSK9. So, your LDL receptors give to live another day.


[00:14:31] The cool thing is the first dose, three months later you get a second dose, and then it's every six months thereafter. This is good for busy people on the fly. Maybe they don't want to stick themselves every two months. Maybe they're traveling all the time. They don't want to be caught the in these pens around. It's an attractive PCSK9. It's a little less potent in the monolith but it's really pretty good. There are ones in development that are probably a once-a-year injection and there's also in developing oral PCSK9 inhibitors so stay tuned for them. Patients given the option usually choose for oral medications and it'll be very liver specific also. We'll see. So that's the PCSK9 story. The average is that you're going to go on statin ezetimibe.


[00:15:19] You and I know, we like to check “Are you a hypersynthesizer, hyper absorber?” before deciding on either one of those drugs. But if I can't get your ApoB to goal because and you're in a high-risk category. I got another synthesis inhibitor bempedoic acid but why not jump to the big guy PCSK inhibitor and you could probably make the case to a third-party payer if you have not got at least to an LDL-C goal. Good luck talking to them about ApoB.


Cynthia Thurlow: [00:15:47] Let's talk about GLP-1s. I know that they're very popular. I know there's probably-- research will be coming out. We know that they can be helpful for insulin sensitivity and for a lot of people helping to reverse metabolic issues. Do you have any thoughts just anecdotally as a clinician about potential impact long term if we look at research in the future that might be helpful?


Dr. Thomas Dayspring: [00:16:10] It's very funny, they have a long story. We started out with weaker GLP-1 receptor agonists than what we have now. But as somebody who is totally involved with the scourge of insulin resistance and for much of my life I was a rather overweight guy dealing with insulin resistance. As soon as the first GLP-1 receptor agonist came on the market I went on liraglutide which is Victoza. People will recognize that name, Byetta was probably the first one that came on the market. Because I just believe with my bit of study and what they were showing us at that time, this is probably something I want to be on. Because I was already using metformin. I had never crossed the glucose threshold for prediabetes back then and certainly not diabetes.


[00:16:58] But I was at the end stage of insulin. I knew sooner or later my glucose is going to go up. My mom and dad had old age diabetes. I was predestined to have it. The data was good enough early on. Then I'm just going on Victoza and I was on that for a decade probably or so and took-- and just around the belief that it was going to be good for the cardiovascular system and was going to delay the onset of type 2 diabetes by improving insulin sensitivity in my cell. Of course, many many years later the liraglutide publishes its coronary outcome trial where it did reduce heart attacks in MACE and everything. I just jumped on that bandwagon ahead of time. I'm glad I did.


[00:17:41] I think it's one of the many reasons that have kept me out of the CCU. We previously talked about the PCSK9 inhibitors because I am totally statin and even ezetimibe intolerant due to myalgias. I was on a PCSK9 inhibitor rapidly when they first came out, I remain on them today. I think between the PCSK9 inhibitor and the GLP-1 receptor agonist, now I didn't stay on Victoza at a certain point when newer more potent GLP-1 receptor agonists came along. I think it was around 2015-2016 I followed the intermittent fasting hypocaloric diet advised by my dear friend and colleague Peter Attia. I lost 70 pounds very rapidly with that regimen and I adhere to it strictly. In retrospect was it all the hypocaloric? How much does the one-- my intermittent fasting was five days a month, basically 300-400 calories.


[00:18:44] I got used to it. I did it for four years and kept it up. COVID came along and a lot of things happened. I don't know, I just-- It's a tough diet to stay on. So like all too many diets people do use them for a certain amount of time. So, I started sneaking off of it, not doing a five-day fasting and sneaking in more calories than I ordinarily did. My weight started to sneak up. By that time, we had the more advanced higher dose Semaglutide on the market. I went on Wegovy and knocked off 40 pounds again very quickly and I since remained on it to that day. This is how the third-party payers drive you nuts.


[00:19:28] I was on a third-party payer Medicare Advantage plan which was covering the Wegovy and the carrier dumped its Medicare-- It was actually this year I had to go on anew and they would not cover Wegovy. On a little bit of an interesting thing because I tried to make the case, I do have chronic stable coronary artery disease and it does reduce MACE. But they went and looked at the study where Wegovy, the high-dose semaglutide reduce ASCVD and they said they excluded diabetics from the regimen. I wasn't really a diabetic but I couldn't make that case to them, but they turned around and said “But you could go on high-dose Semaglutide, Ozempic.” It’s the same things as Wegovy.


[laughter]


Cynthia Thurlow: [00:20:16] Exactly.


Dr. Thomas Dayspring: [00:20:16] That's how idiotically-- So, I'm on the Ozempic high dose now. Obviously, I'm a believer in them but since then of course there's all sorts of trials coming in showing us benefits with renal disease, more with atherosclerotic heart disease, maybe dementia. We don't have the final stuff but all the preliminary starters and why would it not? Because it's improving insulin sensitivity. So why wouldn't it improve every insulin resistant associated pathology or so. Even if I had to pay for it myself, I'd never go off it now because I got to keep this brain going. I'm an old man now at 79. I'll be 80 next year and you see how much I love to keep trying to teach what I know and pass it on to everybody.


[00:21:06] So, if GLP-1 receptor agonist can help my brain, I think they probably do. I'm going to continue to do it, along with my scrupulous slippery slope. Now what do they do to other things and lipids? That cannot, you know nothing to hone about what they-- There's a little bit of improvement in the lipid numbers. I don't know if that’s why they reduce heart disease? I think it's more related to what they're doing, insulin sensitivity, and even a subtle change in lipid can't be bad. I don't think people should be prescribing them as lipid drugs per se. Find out who your insulin resistant people are, certainly your overweight people who are and hopefully you can get them qualified because just like the PCSK9, they're even more expensive.


[00:21:54] I don't know when I look at what deforms that my third-party carrier sends me, they quote that the Repatha is what I said around $600 a month they had to pay for it, but the Ozempic was 900 some dollars a month. Now there's other ways of getting this and I don't know, but if you want the prescription drug, it's going to cost you. I know even the makers that I've talked about will give it to you at $500 a month or $400 and some people could afford that.


Cynthia Thurlow: [00:22:23] They're still making money. [laughs]


Dr. Thomas Dayspring: [00:22:26] I know from all drugs that basically cost pennies to make. Yeah, the markup is [unintelligible 00:22:30]. Now you and I also know the billions that they had to put in research trying to develop this. But I would think at a certain point you’ve recouped that. Cut people a break and you'd still make a ton of money if more people could use your drugs. I never understood how I call them the bean counters, the economists that advise pharmaceutical companies how they figure they're just still much in a hurry. Maybe they think somebody's going to invent something better next week and all of a sudden nobody will use our drug. There are complexities that go into deciding this. That's the story as much as-- and I don't keep off with the GLP-1 receptor literature other than what I recited off the-- But the trials I have done are just-- And I'm happy because I'm on one.


Cynthia Thurlow: [00:23:18] Yeah, it's interesting. My mom was on Byetta over 10 years ago and initially it was just menopausal females, seen some changes in insulin sensitivity, and she was on that for many years and felt like for her at the level that she was at, still working full time at a very stressful job, it allowed her to maintain insulin sensitivity and felt like she was able to avoid some of the sequelae of full-blown diabetic related issues. But, thank you so much for sharing your story.


Dr. Thomas Dayspring: [00:23:48] That's a good thing. Even GLP-1 receptor agonist have been around for a long time. It's not like they invented them last week. We don't know what the downstream effects are. They've been around for a long while.


Cynthia Thurlow: [00:23:58] Absolutely, absolutely. It's interesting, maybe listeners know this or not. Yes, it costs a lot of money to bring drugs to market, but what I find interesting is I cannot think of another drug in my adult lifetime that I think has the potential to impact so many people. We talk about these high-level concepts around disorders that are associated with loss of insulin sensitivity. Then I have colleagues and we're not going to dive into this because there isn't any research around this right now. It's been more anecdotal experiences, microdosing these drugs and some of the benefits people are seeing with autoimmune conditions and other types of things. But I do think that the potential exists that could be-- I think the GLP-1s are going to go down as a really impactful drug class.


Dr. Thomas Dayspring: [00:24:49] The one thing I should mention you again, you know way more about this than I do. There is a potential study shown perhaps some loss of muscle mass with these drugs too. If you are on them, you should be doing [unintelligible] building exercises.


Cynthia Thurlow: [00:25:04] Absolutely. Strength training, adequate protein intake, for sure. I think that goes along with appropriate prescribing. The providers, whoever is prescribing these for their patients should be having that conversation. What I think is interesting is [laughs] I just watched, I don't know why, I watched a documentary one of the streaming services and it was talking about patients who were no longer able to get the drugs through their insurance companies and now they were going to compounding pharmacies or online resources and some of them were even reconstituting them. For listeners that aren't familiar with that term generally when these drugs come to you, they're ready to just pull out of the syringe and use. In these instances, patients were having to use distance distilled water to reconstitute powder to be able to use the drugs.


[00:25:46] So, I always say ultimately you want to work with a licensed medical provider and you want to make sure you are working with someone that's going to be able to appropriately counsel you about making sure you maintain muscle mass because that is so, so important. Making sure you're eating the right macronutrients. Obviously, we aren't going to dive too much into this, but I think that's part of the proper prescribing practices that providers should be using.


[00:26:10] Okay, what do you wish every midlife woman and her clinician understood about lipids and heart health? If you were just writing a script, what would be the thing?


Dr. Thomas Dayspring: [00:26:19] It was pretty easy. Atherosclerosis is the leading cause of global morbidity and mortality. Global, that means across the planet. It's a scourge. We all want to live as long as we possibly can. The mantra is you want to have a lot of health span to go along with your longevity. It's no fun being 90 if you're babbling in a nursing home or something. You want to, at 90, be able to enjoy your great grandkids and interact with your family and all the good ways that being alive is so wonderful about. Peter talks about, I think, the four or five horsemen that you really have to attack and prevent before you get down that route.


[00:27:02] But number one that he always talks about is, we got to take out atherosclerotic heart disease and then we can start going to the other horsemen there. He has said it many times, and God knows I have. It is so easy to take atherosclerotic heart disease in the overwhelming majority of people who don't have some bizarre nightmare genetic lipoprotein abnormality. Even nowadays, there are drugs different than what most of us will have used that can help those people. There is no reason to ever die of atherosclerotic heart disease, be admitted to the CCU, wind up with a bypass or a stent.


[00:27:40] As long as you adapt what is now being called primordial prevention, recognize early in life that while you have some of the causal risk markers or risk factors, and you even have a bunch of risk markers which pile on top of your causal risk factors, and the sooner in life you recognize them and start taking good care of them. Lifestyle first. Unless you are a genetic nightmare with [unintelligible 00:28:07] levels and if whatever lifestyle is deemed appropriate for you does not get you to the ApoB, go right back there and you know what? The LDL-C, non-HDL, but ApoB is the best. You restore that to-- You don't have to make it totally blow away, but you restore it to a healthy level. That is your best way to eliminate atherosclerotic heart disease. It's a totally preventable disease.


[00:28:35] I feel so bad on the news, you hear this celebrity, that celebrity died young. They had a heart-- a massive heart attack. That just means nobody was ever looking at the risk factors or if somebody was looking at them, they didn't understand them. Totally preventable death. Some of them are Lp(a), but there's even plenty of things we can do to those people. And locally, if you pick up the Richmond Times and you look at the obituary column and you see the age group and I just-- They're not all cancer deaths. Some of them are atherosclerotic heart disease, which is a total tragedy when somebody, man or woman, is dying in a third or fourth or fifth decade and their families are still young. Oftentimes they're the income producers in those families. Tragedy and totally preventable. I think-- that's why I'm doing the podcast for you, Cynthia.


[00:29:29] You get out there to educate so many people and your listeners will know how to take that pathology off the table. It's a cholesterol caused disease, but it's the ApoB particles delivering the cholesterol. The only way to keep cholesterol out of the artery wall, the culprit is to get rid of the delivery trucks, the ApoB particles. We do that by enhancing clearance at the liver LDL receptors. Every single drug that we use outside of the drugs related to the homozygous FH folks and everything which the run-in-the-mill people will never use. We can lower ApoB almost everybody to where it has to be. It's so easy.


Cynthia Thurlow: [00:30:12] It's so important. It's interesting. I was watching The Biggest Loser documentary. I'm a documentary person. I just like to learn. One of the trainers who I think was in his maybe late 40s, essentially had a sudden cardiac death event. This is a very fit guy who trained other people for a living. I think he was in the ICU for days before they're able to revive him. He talks about how he assumed because he was so healthy that it couldn't possibly be something he needed to worry about and how many patients I took care of. I had-- There was a very long trail ride that people would ride bikes on in Washington D.C. that was close to where one of the hospitals I worked at. There were so many men who were out riding their bicycle.


[00:30:57] They were cyclists and they have a heart attack while they're riding. I remember saying to my husband, I came home one day and I said, from now on, you have to make sure I know exactly where you are when you are riding your bike. So that if something happens to you and you suddenly stop moving, I know what I need to do. But how many of these patients said to me that was such a wake-up call. People that were in a position of-- they were very influential whatever industry they worked in and they just took for granted because they were physically active that it couldn't possibly happen to them. I think that there is this misconception that you have to be metabolically unhealthy. That's not always the case.


[00:31:34] There's any number of athletes, world class athletes who have coronary disease. There's several baseball players who have dropped dead, same in every sport. Yet they're world class athletes. Because they do have more serious ApoB problems younger in life. As bad as ApoB delivering a cholesterol is, it takes years and decades to build up. That's why we don't have heart attacks when you're 14 unless you have homozygous where your ApoB has been in the stratosphere the moment you're born. It takes 30, 40 years. That's why most heart attacks in men are in the 40s and 50s and women, it starts in the perimenopausal and they start to catch up. But for decades they've been developing this plaque and it had somebody recognize that and the easiest way to recognize that early in life is not imaging.


[00:32:27] For the most part it's ApoB, blood pressure, of course, God forbid, smoking, and insulin resistance and attacking them. Therapies early in life other than the extreme levels are lifestyle. If you can do it, great. If not, then we go down the pharmacologic approach after discussion and there are tests to do ahead of time to even judge which might be the best ApoB-lowering pharmacologic approach you should use. It's again, tragedy after tragedy that should never happen.


Cynthia Thurlow: [00:33:00] I agree and it's interesting. It is something that whether we're building greater awareness around this, it is just more talked about on social media or in the news. This is why it's important to test these things early so you know what your risk factors are. What is the impact in your clinical opinion of stress on not only metabolic health, but our risk for developing disease long term?


Dr. Thomas Dayspring: [00:33:27] I think it's in the category of major risk-


Cynthia Thurlow: [00:33:30] Yes.


Dr. Thomas Dayspring: [00:33:30] -for virtually every pet of those five horsemen that you're going to come down for. It can't possibly help you because if you're in a chronic stress situation, you're just changing a lot of the milieus in your body when your immune system, certainly your hormonal changes-- It's recognized as a major contributory factor to major adverse coronary vessels. Your sympathetic nervous system is going like crazy. Your adrenal gland is pumping out stuff that you don't want pumped out. So, it's a big factor. I don't know if I was lucky or unlucky back then because that was nothing we would even consider back in the day there because nobody was teaching us that how horrible this could be. We just saw it.


Cynthia Thurlow: [00:34:12] Well, let’s deal with it.


Dr. Thomas Dayspring: [00:34:14] Relieve your stress. I would not train or equip to do that. Nowadays that has to be part of the evaluation. There's all sorts of effective approaches to controlling anxiety. Nowadays you don't necessarily have to see a full-blown psychiatrist. There are all sorts of groups that people and modalities that can calm people down. Some of the low-grade exercise modalities, some of the-- just so many ways to attack that. It has to be recognized as a major [unintelligible 00:34:45]. Unless you're really trained to recognize, it's easy to miss too because many patients are not going to, “Oh, you know--” some will tell you they feel that, but many will not. You have to recognize it or ask the type of questions that you pull that out of them. It's very big. I wish I could tell you, “Here's my ApoB [Cynthia laughs] [crosstalk] I control to handle that nowadays.


Cynthia Thurlow: [00:35:08] It's so interesting because I know that there's probably some mention of it during my medical training, but the longer I do this, the more I acknowledge that chronic stress, I think is one of the greatest risks for people developing, not just because the high cortisol and as you appropriately stated, impacts your immune system, impacts your gut health, but how high cortisol impacts your insulin sensitivity and your glucose homeostasis. For a lot of people, they just deal with chronic stress like it's no big deal. It's not until they get to perimenopause and menopause that all of a sudden they start to realize that chronic low-level stress over time no longer serves--


Dr. Thomas Dayspring: [00:35:46] Serves right into that endothelial health discussion we've had there.


Cynthia Thurlow: [00:35:52] Absolutely.


Dr. Thomas Dayspring: [00:35:52] Addressing your nitric oxide big time with that. Your blood pressure is a result of that the nitric oxide perturbations.


Cynthia Thurlow: [00:36:01] Yes, absolutely. If you could recommend-- So I know we've talked a lot about lipid markers, inflammatory markers, but if you could recommend three blood tests beyond our traditional lipid markers, what would they be and why? What do you think are three that maybe not everyone's thinking about, but if someone's listening and they're working with a clinician who's open to suggestions, I hope everyone is. Things that are important and impactful.


Dr. Thomas Dayspring: [00:36:29] I'll always start off by repeating the three lipid things. So ApoB, Lp(a) and triglycerides. Then you got a pretty good handle on your lipoprotein-mediated pathologies. What else do I have always looked at and more? Remember I worked for a biomarker lab for seven years that was analyzing virtually any biomarker you could think of. There's a bunch of them that are probably nonsensical, but the ones I think you need an inflammatory marker, the most tested over time is the C-reactive protein. By the way, they call it high sensitivity. If you say you've a rheumatoid arthritis where they're monitoring C-reactive protein, the activity of your disease, it's the exact same assay that you would get in [unintelligible 00:37:10]. It's just that they're looking at lower levels, but the assay is identical.


[00:37:16] There's no hs-CRP assay that's different from the regular CRP assay, but the numbers that worry you are different. You're going to look at high sensitivity C-reactive protein. The other most commonly used inflammatory markers, but I don't necessarily recommend them-- are Lp-PLA2 lipoprotein phospholipase A2. That's an enzyme that traffics with various particles, especially your Lp(a) particles, somewhat on small LDL particles that hydrolyzes the phospholipids on the surface of your particle after they enter the artery wall. When you hydrolyze phospholipids to fatty acids and lysolecithin, reactive oxygen species takes over and use it's step one of that inflammatory cascade in the arterial wall. The reason I don't like it anymore-- In a patient not on drugs, it's a useful inflammatory screen marker, as is CRP.


[00:38:15] But they thought it was so important and so much involved in the etiology of atherosclerosis that they developed two phospholipase potent inhibitors. They thought if we just inhibit Lp-PLA2, there'll be no inflammation in the artery wall, there will be no heart attacks. This is why you have to do clinical trials. [Cynthia laughs] Because the two big trials, they basically took Lp-PLA2 activity out of the picture and didn't reduce a single MACE. There's something that might have been thought to be a causal risk factor, but when you treat it and you lower it and nothing happens, it moves to the category of risk marker. It can help you, at baseline, identify people, but you can't use it as a goal of therapy to judge the efficacy of any therapy you're using because reducing it doesn't really matter.


[00:39:04] It's like we used to believe you had to raise HDL cholesterol and now trials show no, you don't. So, HDL-C is not a goal of therapy, not everybody realizes that. I think inflammatory markers-- The other one is myeloperoxidase. It's more of an immune system sort of marker. They do have studies showing it, relates to atherosclerotic heart disease. I've always believed that's a marker that labs like because again you can make money from it. [Cynthia laughs] The more inflammatory markers somebody-- So I don't recommend that anymore or do it. It's probably this-- We don't have studies showing if you inhibit that also you reduce MACE. Again, if you want to use it somehow as a pre and they're not on lipid-modulating drugs, you need a third inflammatory marker?


[00:39:55] Okay, but I wouldn't be following up and judging the success of your therapy as to what happens to it or so. But, there are a multitude of other markers I think are essential. I think you have to do the omega-3 index, that's red blood cell omega-3 and red blood cells are floating in your bloodstream. Omega-3s work in the body because they become an integral member of every cell membrane in your body including the noggin. But I can't biopsy any cells in your body and analyze them for omega-- but I can pull red blood cells out of your plasma which have a cell membrane that is full of the same phospholipids and that your cells throughout your body are. If we extract the red blood cells, pull out the phospholipids hydrolyze--


[00:40:39] Remember phospholipid is a phosphorus moiety head group with two fatty acid tails. If we hydrolyze the two fatty acids and just measure what fatty acids are in your red blood cells and you're going to get, all right here's the fatty acids there, they total up to 100% of the fatty acids. Now count the omega-3s, which are being because you're doing it by mass spec LC, you're actually measuring every fatty acid that's in there. If 5% of your total fatty acids are omega-3, your omega-3 index is 5%. Desirable is well above 8%. The neurologists who really want you to get DHEA up in the brain and other people even say-- we wouldn't be unhappy if you had a 10% omega-3 index.


[00:41:29] Unless you're a Japanese person eating the right type of fatty fish all day long, if you're in America, most are walking around with omega-3 indexes the 3% to 6%, 4% or low is associated with sudden death. The bicycle guy riding down the pathway drops dead. That might be one of the etiologies of this sudden whatever-- I think checking omega-3 index, and in Americans, most people are not going to be at that 8% or more, but it's easy to correct with the proper omega-3 supplementation. Now that's another whole lecture. What type of omega-3 products you might be recommending. There's all sorts of concoctions people sell and call it omega-3s that you probably shouldn't wind up taking. But omega-3 index would be another important blood test.


[00:42:16] Look, we've already mentioned insulin sensitivity. So, I love the LPIR score. If you want to do insulin levels, then they'll probably report a homa-IR score with it. I just think that's superfluous. You don't necessarily need that if you're getting the LPIR score, which is adjudicated against the insulin clamp studies. That's all you really need to do that. I mean everybody's looking at an A1c nowadays just to make sure, can I call you a free diabetic or a diabetic? Because that introduces a whole mother of the therapeutic avenues. Of course, those measures are important whether you want to do a glycated hemoglobin, which you know, hemoglobin A1c is, I meant, glycated proteins. That's a shorter interval. You could only have high glucose for a month and that test becomes abnormal where you got to wait three months for an A1c.


[00:43:11] So, check your whatever parameter of glycemic control, but don't rely on a glucose level, that's for sure. Then you get into things like homocysteine. I think there's plenty of evidence that homocysteine can certainly be one of those aggravators for the endothelial function we talk about. It's intimately related with nitric oxide production in the endothelial cells. So looking at homocysteine, understanding at what levels become dangerous, easy to correct with certain vitamin B therapies, especially if you use methylated vitamin B preparations, because it's really-- You got to put methyl groups in there to recycle the homocysteine cycle, the methionine cycle there. You have perfect functioning of those because a lot of important molecules come out of that cycle, including a lot of neurotransmitters and everything. I think homocysteine is unfortunately not checked a lot.


[00:44:09] There are people who check the MTHFR, that's your genotype that can predispose you and I think if your homocysteine is high enough, you know you're going to find some sort of MTHFR abnormality and some are more worrisome than the others. The MTHFR, what is it, 677 if you have the 2T alleles is especially worrisome.


[laughter]


Cynthia Thurlow: [00:44:31] Thank you parents.


Dr. Thomas Dayspring: [00:44:34] I know you love your parents, so [unintelligible 00:44:36] few genetic things.


Cynthia Thurlow: [00:44:38] [laughs] Yes.


Dr. Thomas Dayspring: [00:44:38] Luckily there are things you can deal with.


Cynthia Thurlow: [00:44:39] Yes.


Dr. Thomas Dayspring: [00:44:40] They didn't give you some terminal illness or something. So that becomes important there too. Do you know what I do especially first time I see you and living in the lipid world but every-- the overwhelming majority of people are going to come in are going to have lipoprotein abnormalities. You're not going to see a lot of hypo betas in your practice. You'll see some. So, there's a lot of things you want to check. On the presumption, if your ApoB comes back high, we may want to do something-- even with lifestyle there might be certain suggestions I make to you. So, you know, I'm a big advocate of ascertaining day one “Are you a hyper absorber of cholesterol? Are you a hypersynthesizer?”


[00:45:23] And it doesn't take a lot of imagination to know if you have a high ApoB and you're a hyper absorber, probably the best initial avenue to lower your ApoB is to block the absorption of cholesterol through certain lifestyle modulations or for sure ezetimibe if it becomes bad enough and people who are hyper absorbers tend to be the hyper responders to ezetimibe. You'll be shocked how much you can-- [crosstalk]


Cynthia Thurlow: [00:45:49] 50%. [laughs]


Dr. Thomas Dayspring: [00:45:52] Everybody thinks that’s a weak drug. Don't even use--


Cynthia Thurlow: [00:45:55] No, it's a great drug.


Dr. Thomas Dayspring: [00:45:56]  Because you're probably giving it to people who are hypersynthesizers where you do get a 5 to 10% reduction in ApoB but just the opposite. If I ascertain your ApoB is high and wow, the mile markers of cholesterol synthesis are out of whack. Your first line drug is a statin. If you for some reason know I absolutely refuse a statin or I once tried it and I can't take it then we do have the bempedoic acid which is a liver-specific drug, does nothing to muscles, does nothing to your brain. So, it's a safe way to inhibit cholesterol synthesis absorption. And remember they tend to be the hyper-responders to statin or bempedoic acid whereas they would be a hypo-responder to ezetimibe. The other thing we know-- So, if I see you are a hyper-synthesizer that doesn't call for high intensity statins.


Cynthia Thurlow: [00:46:52] This is so important.


Dr. Thomas Dayspring: [00:46:54] For a low intensity statin. Look, unless you're an ACS survivor or something. Okay, I'll probably give you a bigger dose stand. But even then I might escalate my way up the ladder combining ezetimibe with the lower dose. Because it's all about ApoB control no matter what it is. Trust me, there are no magical mystery effects of statins beyond lowering ApoB. Everybody talks about the pleiotropic effects. Please show me a trial related to outcomes that what a statin does to anything other than ApoB reduces MACE, zero, you will find nothing. Oh yes, in a rat it reduced this coagulation factor.


Cynthia Thurlow: [00:47:30] Not rats.


Dr. Thomas Dayspring: [00:47:32] In a human it improved this, so what. Just for ApoB, did any of that matter? I think going with the low-dose statin, which is likely to be the best tolerated if you're heading down the muscle, maybe not-- either low-dose statins in some people, one of them can cause myalgias. But you would know that very rapidly in most people within a few weeks, a few months they were going to become complaining of the muscle aches. You would say maybe a statin is not for you. We do have the other alternatives. I don't even go to you. In the old days when it was only statins, then we go to every other day, once-a-week statins, anything.

[00:48:12] But nowadays with ezetimibe and bempedoic acid being around-- because remember when you start going to alternate-day statin, especially if your ApoB is high, you're not going to get ApoB to goal, you’re going to have to add ezetimibe to it anyway but the low-dose statins. Often, I've put it on my social media many times. The [unintelligible 00:48:32] from rosuvastatin 5 mg gives you a 38% ApoB lowing. Now that's a generalization, not everybody, some people a little more, some people a little less. That probably has to do with how much you're absorbing, but 38% reduction. Now I go to the gorilla statin, the biggest dose and you start getting up at the 40th, approaching 50. You had quadruple the dose to get up there and you just introduced potentially more side effects, maybe the insulin resistance.


[00:49:04] In a person predisposed, insulin comes on a little sooner. So why go there if you don't have to? I'm just a bigger advocate. We all know with ApoB nowadays it's not arguable. Every ApoB-lowering drug we've mentioned in mighty discussions, you have FDA approval outcome studies that they reduce MACE. So, you can't go wrong with any of them if at the end of the day you're looking to reduce heart attacks, strokes and bypass since they all do that. But how much they do that relates to how much they lower ApoB. We're right back to whatever stepwise therapy or whatever monotherapy you're going to use. ApoB is your goal of therapy. You're going to get there or you're not. With whatever regimen you're using, then you need something else added to the regimen to get there.


[00:49:53] This is not rocket science anymore to understand lipoproteins and to control it. I often, for these people who keep insisting I got to use the high intensity statins on everybody, there's any number of studies that if you take the lowest dose of the statin and you add 10 mg, the only dose sold of ezetimibe to that statin, you get the same ApoB, LDL-C lowering as the 80 mg or 40 mg dose dependent on which-- Rosuvastatin 5 plus ezetimibe is equal to rosuvastatin 40. Atorva 10 plus ezetimibe is equal to Atorva 80. Please, which would you rather be on Atorva 80 or Atorva 10 plus little ezetimibe? You also know and people follow me on social media know, ezetimibe is a drug that can be dosed intermittently. 10 mg is what the FDA approved, but 5 mg is like 80 to 90% the same efficacy. When it was a branded drug, one way to save the patient money was just every other day or every third day and you push your following ApoB and if it works, you're saving a lot of money. Now it's a generic drug. So, it doesn't matter for the most part.


Cynthia Thurlow: [00:51:11] That's why I don't worry if I miss a dose. Like if I have a day where I forget to take my Zetia, I'm like, “Ahh, not a big deal, I'm covered.”


Dr. Thomas Dayspring: [00:51:18] The good news, your LDL particles at the half of two to five days, missing one or two days isn't going to screw you up too much. [Cynthia laughs] You don't want to miss it more than a week or 10 days, that's for sure.


Cynthia Thurlow: [00:51:28] Yeah, no, no. This is again, a truly invaluable conversation. Please let listeners know how to connect with you outside of the podcast. Obviously, we will have all the links to a lot of the research that we have touched on today as well as links backed to our other conversations that we've had in the past.


Dr. Thomas Dayspring: [00:51:46] I'm pretty responsive on social media. I've been told by the people who know, there are a lot of people have more followers than-- even you, Cynthia, than I do on my social media, which on X I'm @Drlipid and on LinkedIn, it's Thomas Dayspring, MD. On LinkedIn, when you ask to connect, I pretty much only do it if you're a medical professional. That doesn't mean MD or DO. You're a nutritionist, you're anything, you're a radiologist, you're you working, you're in medicine, so you interact with patients. I'll connect with you there. So, that's the best way.


[00:52:24] If you give me a coherent message on either those things instead of irresponsible message, [Cynthia laughs] I'll later retreat the answer or link you to some-- I am very responsive. Because of that, people who know and these are people in industry who monitor social media big time because it's everything nowadays. I have been told that I am the number one global social media influencer on lipids. Not that I have the most followers, but people really believe what I say and they respect me and they trust me. More apt to read what I say they should do or perhaps follow my-- that's a high honor. I never knew that, but the people who monitor this stuff and are paid to monitor it by industry, who wants to know who do we?


[00:53:13] This is why-- you know my bio, I've done 4,000 lectures in all 50 states, a bunch of other countries, but yet through podcasts like yours and others, Peter’s, Simon Hill’s, I reached infinitely more people than I did collectively in those 20 years of flying the globe and going to every little podo town. I shouldn't say that because I loved every town. I did have the opportunity to visit, this is a wonderful country, we lived it. Social media is where it's at today. The great thing about that, because of my old bones, my bum back, I'm not one who can run through airports at warp speed like I used to gathering my three and a half million frequent flyer miles back in the day. [Cynthia laughs]


[00:54:01] I avoid airports like the plane now, so I don't travel anymore because it's just too hard. Airports are a bigger mess than they used to be, but through social media it is-- I can just get my voice out there. I like to do a lot of podcasts. I pick and choose and I get so many invites. You turn down a bunch because I'll check these people out and [Cynthia laughs] maybe who else they've interviewed, so I don't go here. Obviously, you're high on the list of-


Cynthia Thurlow: [00:54:27] Oh, thank you.


Dr. Thomas Dayspring: [00:54:27] -the influencers. The cool thing now is I can drive right. It is- [crosstalk]


Cynthia Thurlow: [00:54:33] I know, I know in person. Absolutely. [crosstalk]


Dr. Thomas Dayspring: [00:54:37] -Zoom into somebody, they work and they work pretty well, but in person.


Cynthia Thurlow: [00:54:42] Absolutely. I feel so grateful. I think I reached out to you over LinkedIn and I remember thinking, “He can't possibly be from the same part of Virginia that I'm in.” I felt like it was very serendipitous. I'm so grateful for your time and your kind words. I know my community loves you, and so thank you for all the work that you do.


Dr. Thomas Dayspring: [00:55:00] It's my pleasure. Total joy.


Cynthia Thurlow: [00:55:05] Awesome.


[00:55:06] If you love this podcast episode, please leave a rating and review. Subscribe and tell a friend.



bottom of page