Ep. 344 Lipid Masterclass: A Deep Dive into Our Cardiovascular Needs with Dr. Thomas Dayspring 

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Dr. Thomas Dayspring is certified in internal medicine and clinical lipidology. He is a fellow of the American College of Physicians and the National Lipid Association. He joins me today for the second class in our series of Lipid Masterclasses.  

In today’s class, Dr. Dayspring shares valuable insights on cardiovascular health and lipid management. We dive into the complexities of cardiovascular disease, focusing on lipoproteins, atherogenesis progression, and its implications on myocardial infarctions (heart attacks). He explains the mechanisms of ApoB invasion into arterial walls and discusses the critical importance of finding competent healthcare providers, particularly for women navigating the perimenopausal to menopausal transition. He also gets into the limitations of bikini medicine, and we tackle pertinent issues surrounding hormone replacement therapy, including potential side effects and clinical observations. 

Dr. Dayspring has a wealth of information to share today, and we have several additional masterclasses coming up to follow this class. Be sure to tune in for those episodes.

“Cholesterol is essential for all the cells in our body. But the one tissue it is not essential for is the arterial walls.”

– Dr. Thomas Dayspring


  • How lipids get transported, and how energy gets produced in the body
  • How the liver prevents fatty liver tissue from building up
  • Dr. Dayspring explains the process of lipolysis  
  • What is the role of LDL particles in atherosclerosis?
  • How the buildup of plaque in arteries can lead to blockages, causing heart attacks or strokes if left untreated
  • Why high cholesterol needs to get diagnosed and treated as early as possible 
  • The importance of HDL cholesterol in immunity and oncogenesis
  • Why ApoB is essential for lipid panel analysis
  • Why women need comprehensive medical care, especially during menopause

Connect with Cynthia Thurlow

Connect with Dr. Thomas Dayspring


Cynthia Thurlow: [00:00:02] 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] This is the second class in the Lipid Masterclass with Dr. Thomas Dayspring, who is a fellow of both the American College of Physicians and The National Lipid Association and is certified in both Internal Medicine and Clinical Lipidology. Dr. Dayspring joins me again, and in the second segment, we are talking about what is cardiovascular disease as well as lipoproteins, the progression of atherogenesis, the impact on ischemia, infarcts, which are myocardial infarctions, which are heart attacks, how does ApoB invade arterial walls, and what are the labs and the significance of them? How do we treat ApoB with both lifestyle and pharmacotherapy? The importance of finding the right competent provider, especially as a woman is navigating the perimenopausal to menopausal transition, as well as changes that he observed in clinical practice and why bikini medicine does not appropriately treat women’s needs, and lastly, we talk about some of the issues related to hormone replacement therapy and potential side effects. I know you will enjoy this conversation as much as I did recording. Again, this is the second conversation with Dr. Dayspring and we have several additional masterclasses coming.

[00:01:59] And so, for the benefit of listeners, let’s talk about what is atherosclerosis? You mentioned ASCVD. We used to call it cardiovascular disease, coronary artery disease, vascular disease. Let’s talk about what it is, because it is very different than how I was talking about ASCVD when I was a new nurse practitioner. Even as a new nurse, I worked at a premier kind of hospital in Maryland that did a high volume of cardiac caths. We saw a lot of coronary artery disease. We understand it better now, but let’s help understand and define what exactly this represents. 

Dr. Thomas Dayspring: [00:02:34] Yes, because if we really all understood it, we could put those invasive cardiologists out of business and they could get into preventive cardiology, where you would save a hell of a lot more lives than trying to fix those already– It is still fixable, thank God, if you do not diagnose this early in life. But yeah, it’s all prevention. So, everything we’re talking about today, even when we started to define lipids, ultimately this becomes important because there is one place in the human body– I tell you cholesterol is essential for all the cells in our body. But the one tissue it’s not essential for is the arterial walls in our body. Arteries are the blood vessels that carry plasma away from the heart to supply tissues. And of course, our veins return unwanted stuff back to the heart and actually to the liver. And the liver can redecide. What to do again?

[00:03:26] So, cholesterol, I told you, is going to be in one of these lipid transportation vehicles. I’ve told you a lot of the story of the HDL so far. There’s a little bit more to tell, but this is a good time to tell you about the other family of lipoproteins. ApoA1 is the structural protein for an HDL particle. There is a blood test called ApoA1. If you order it, we used to think, “Oh, you’re counting HDL particles,” but I already explained, because there could be one, two, three, four or five ApoA1 per HDL particles. ApoA1 is a very poor indicator of HDL particle concentration. It’s a blood test that nobody needs to order anymore because you get more information from looking at other lipid lipoprotein metrics. So, let’s talk about the other family of lipoproteins.

[00:04:16] I’ve already hinted that these big chylomicrons come out of your intestine, but there’s a very big lipoprotein that comes out of your liver, which is like a smaller version of a chylomicron and that would be the VLDL, very low-density lipoprotein. Now, obviously, these are much bigger carriers of lipids than our HDL particles. That’s why they tend to float more in the centrifuge tube. But they have to have a very big structural protein to unwrap the huge amount of lipid molecules they carry. And that apoprotein is called apoprotein B. And there is only one ApoB per member of the ApoB particle family. And that is kind of cool, because we could ask the laboratory, give me an ApoB concentration. 

And basically, you’re counting all of these ApoB particles that might be floating in the plasma at the time you did the venipuncture. All right, again, just for accuracy, it’s a minutial thing that doesn’t affect clinical lipidology, but the intestine produces these monstrous chylomicrons, the major lipid component in the core there. Yes, there is some cholesteryl ester there. That’s the cholesterol you absorbed and the enterocyte stuck it in the core of the chylo after esterifying it, so it’s cholesteryl ester. But most of the lipids that the enterocyte are putting in your chylo are the triglycerides of course. So, it’s a gigantic triglyceride filled molecule, but there’s a lot of absorbed cholesterol in it also, but trigs predominate.

Because it’s a gigantic balloon, the surface has an immense number of phospholipids on it because it takes more phospholipids to create the surface of a big balloon and a little tiny balloon like an HDL. All right, so the enterocyte actually transiently releases that chylomicron into our lymphatic circulation, and it travels up, up, up from our anatomy. Most people and layman, if you’re listening, the lymphatic vessels empty into the venous system up in the neck, and all those intestinal chylomicrons join the bloodstream, the junction of the lymphatics and the blood vessel system. Now, what is the purpose of a chylomicron? Deliver triglycerides. Who wants triglycerides? Well, what happens when certain cells get triglycerides? There are lipases that cleave the triglycerides into fatty acids, which can enter through the cell membrane. And what does the cell do with fatty acids? It oxidizes them.

[00:07:02] And every time you lop off a carbon molecule from a fatty acid, you create ATP, the energy of life. If I had to ask you, guess what cells require the most energy. They’re the tissues that move a lot, our muscles. And I think we all have a muscle in the center of our chest that is contracting every second or so, and it needs a lot of energy to keep moving like that. No energy, no muscular movement, big trouble. So, the chylomicrons are triglyceride delivery vehicles primarily. So, they rush up to tissues that express an enzyme called lipoprotein lipase just like the gut did. So, if this big chylo shows up at a muscular cell, skeletal muscle or a cardiac muscle, lipases are expressed, fatty acids are created, and they enter through the cell membranes, and they undergo beta oxidation, creating ATP.

[00:08:00] Now, what happens to the chylo as it loses all these triglycerides? It shrinks, didn’t give up any cholesterol. It doesn’t deliver cholesterol to muscle cells or the heart. They can synthesize all their own cholesterol. They don’t need cholesterol, but it becomes a much smaller VLDL that is now triglyceride poor and cholesterol rich. They’re called remnants. Now, look, they’re still way bigger than IDLs, VLDLs, or LDLs, but they’re basically carrying cholesterol but a lot of cholesterol molecules. To put it into perspective, an LDL particle, if you’re measuring cholesterol, LDL cholesterol is the major component of total cholesterol. But that’s only because it hangs around several days, whereas the chylos and VLDLs disappear but a typical LDL particle carries about 2100 to 2500 molecules of cholesterol. You would say that’s all. Remember the HDLs? They carried 45. But what does a chylo [unintelligible 00:09:01] or the VLDL carry? 6000, 7000, 8000, 9000 molecules of cholesterol. Thank God, there aren’t a lot of these.

[00:09:09] But what happens once the chylo has delivered its trigs? And by the way, when it shrinks, what breaks off of the surface? Phospholipids. Now they can’t circulate in plasma, they’re a lipid. Evolution gave us a particle that scavenges phospholipids. So, once phospholipids are released from chylos and the same thing is going to happen to VLDLs in a minute, they bind to something called phospholipid transfer protein, PLTP. And what does it do with all these triglycerides? Remember I told you the little HDL is sucking cholesterol out of cells and it’s getting bigger, bigger, bigger. What does the HDL need on its surface? Phospholipids. Where does it get it? Phospholipid transfer protein takes the phospholipids off of chylos and VLDLs and rushes them down and say, “Hey, little baby HDL, you want to get bigger? Here’s some phospholipids for your surface.”

[00:10:01] It’s unbelievable how evolution evolved lipid transportation. But anyway, in a normal circumstance, the chylo would give up its triglycerides. It’s now only carrying absorbed cholesterol and makes a beeline for the cell that has the most receptors that can clear it, the liver. And what does the liver grab to anchor a VLDL remnant and pull it in which all its cholesterol, which the liver will do something with. It has a specific receptor for chylomicrons called a LDL receptor-related protein, LRP. And that is looking for two things on a chylo that it can attach to with high affinity.

[00:10:40] The ApoB on a chylo, interestingly, has 48% of the molecular weight of the big ApoB that the liver manufactures for VLDLs and LDLs. It’s a truncated ApoB, but it’s still big, big particle. So that’s called ApoB-48 because it has 48%. And that receptor is fine tuned to recognize and grab ApoB-48. So that receptor will clear chylos preferentially. The second protein that chylos carry multiple copies of that binds to the LRP is apoprotein E. Everybody knows about ApoE but they relate it to the brain. But it’s super crucial to triglyceride-carrying lipoproteins, because as they lose their trigs, the ApoE changes shape a little bit, and it assumes a shape that the LRP can bind to and pull it in. And this is why the half-life of a chylomicron is measured in minutes. It’s plasma resonance time is an hour or two.

[00:11:40] So, that’s why you will only find chylos if you’re looking for them in a postprandial state. You start drawing blood three, four hours after somebody ate and you’re looking for ApoB-48, you’re not going to find any because they’re gone. Evolution wanted them, get this damn energy, these triglycerides to the muscle cells ASAP, and then get the cholesterol to the liver, then we don’t need you anymore. So that’s how chylos come and go. Give us a very wonderful way to transport energy and absorb cholesterol. For people who have genetic defects that they can’t catabolize these triglycerides and then chylos, these monstrous chylos float around your plasma forever. These are people who have triglyceride levels of 15,000, 20,000, 30,000. The primary genetic defect that does that is a lipoprotein lipase deficiency. As you might, you can’t hydrolyze the triglycerides.

[00:12:34] Thank God. It’s pretty rare and it’s present with you at birth. These are children who, if it’s not diagnosed early on, they start getting acute pancreatitis at ages 1, 2, 3, 4, 5 because that level of trig, that monstrous protein can’t invade your artery wall, but it can invade your pancreatic cells and destroy them. The fatty acids are tissue destructive, so pancreatitis is a big, big worry in those. Thank God we’re now developing better ways of treating that. But even now, the primary way to treat such infants is they just can’t eat saturated fat because that’s what creates the triglycerides that overload these chylomicrons. So, people who reckon these kids are on low-fat diets day 1 or month 1 or else they’re going to, ultimately if you weren’t astute enough to check lipids early in an infant, you would certainly check them as they got their first episode of pancreatitis in a little infant. You’d know that’s wrong. That’s in a slide. 

[00:13:33] So, that’s the chylos but those muscles need a lot of energy and maybe chylos can’t even deliver enough trigs. So, evolution gave us a big lipid-producing organ called the liver. So, the liver is full of fat. It can make it de novo. It gets fatty acid and trigs delivered to it. So, the liver can take any extra triglycerides, fat, that it does not want, because why wouldn’t the liver want to accumulate fatty acids? You would get a fatty liver that’s not good for survival of the liver long term. So, the liver says, “Uh-oh, I got a triglyceride pool here. I’m going to enwrap them with ApoB. But the ApoB is ApoB-100. It’s the full ApoB molecule.

[00:14:14] I’m going to stick some cholesteryl ester in there to make it a nice circular particle, and then I’m going to shoot it into the arteries. And here come the VLDLs. Now, by the way, a chylomicron, if we’re measuring its diameter when it’s full, can be 200 to 300 angstroms, 200 to 300 nm/L. A VLDL, the biggest one that comes out might be 140, 150 nm/L. So, you can see it’s like half the size of a fully blown chylomicron, but it’s still pretty big. It’s carrying a lot of triglycerides, and it basically does what the chylo does. It makes a beeline for muscles that are expressing lipoprotein lipase, cardiac, skeletal, and it’s another supply of triglycerides.

[00:14:59] By the way, on the surface of chylos and VLDLs is a protein that has tremendous affinity for the express lipoprotein lipase. It’s called apoprotein C2, apolipoprotein-C2. Chylos and VLDLs carry almost 100 molecules of C2, and that makes them rapidly bind to the lipoprotein lipase. But chylos have more C2 than VLDLs and that’s why the plasma resonance time and the half-life of chylos is so, so short. But once they’re done, then the VLDLs start binding and keep supplying energy. By the way, the half-life of a VLDL particle is not in minutes, but it’s a couple of hours. Plasma resonance time is like six hours, and then they’re mostly gone. But look, you could check your triglyceride level at 9 o’clock at night, and you’d still get a triglyceride level.

[00:15:49] But if you have the perfect body that, Cynthia, just your trig level would be 30 or 40. If you did it right after a meal, if your trig was 30 or 40 at baseline, it might go to 70 or 80 after a meal. If you do a postprandial trig and it’s much above 70, 100, God forbid 150, you know you have delayed metabolism. That’s called lipolysis of your triglyceride-carrying particles. They’re ApoB particles carrying cholesterol. You don’t want to extend their half-life, and we’ll tell you why as we get down to the LDLs. So now, interestingly, when the chylo delivered its trigs, it was rapidly cleared by the liver. The VLDL, when it delivers its trig is more slowly cleared. It doesn’t have ApoB-48 on it. So, the LRP, it does have some ApoE, but less molecules than a chylo. So, it does get cleared at the liver quickly, but not as quickly as a chylo, but way more quickly than what’s coming.

[00:16:46] So, let’s say a VLDL has delivered its trigs. It’s now only carrying cholesterol, didn’t deliver any cholesterol, and it’s circulating through your body. So, it’s going to circulate through the liver, and the liver is going to grab it by recognizing ApoE. It’s got a couple of ApoE molecules on it, or more importantly, ApoB-100. And we have a very specific liver receptor that grabs ApoB like fly paper grabs flies, and that is called an LDL receptor. The one for chylos is LDL receptor-related protein. This is the actual LDL receptor. Bingo, but the chylo is back in the liver with a little bit of triglycerides it’s still carrying, but all of the cholesterol it’s still carrying. And believe it or not, as that VLDL was circulating around, it actually gathered some more cholesterol. People are saying, what?

[00:17:37] Okay, so, by the way, if a VLDL is returning cholesterol to the liver. It certainly didn’t deliver cholesterol to any cell in your body. You would have to say part of the function of a VLDL is reverse cholesterol transport and it is. And nobody was ever taught that the ApoB particles work with the HDLs on getting cholesterol back to the liver. All right, but now as the VLDL is docking at the hepatocyte because it wants to attach to the LDL receptor, uh-oh there’s another– hangs out with the LDL receptor. It’s called hepatic lipase. It’s not so much a triglyceride, it’s a phospholipase. It loves to hydrolyze phospholipids on the surface, so as the VLDL and by the way, it’s a smaller VLDL. So, it’s called the VLDL remnant. It’s cholesterol rich, triglyceride poor.

[00:18:28] Some of the VLDLs actually undergo additional lipolysis, hydrolysis of remaining triglycerides and surface phospholipids. And so, the VLDL actually shrinks and becomes a higher density particle because it’s lost lipids. It becomes an IDL, an intermediate-density lipoprotein. So, the IDL still has a molecule or two of ApoE on it. It’s certainly got ApoB 100. So, it’s not long lived for the world because the LDL receptor is going to grab it. But some of the IDLs at the liver undergo additional lipolysis by this hepatic lipase. Now, when you shrink an IDL a little bit, the ApoE backs off. So, the only protein left is ApoB-100, but it’s a much smaller particle now because it’s lost some triglycerides and phospholipids, its density is higher. So IDLs, they transform into LDLs, low-density lipoproteins. 

[00:19:30] Now, you would say, well, okay, the LDL will be instantly cleared by the LDL receptor. No, what does the LDL not have that the IDL had? ApoE. So, the clearance of LDLs, which can only be done by an LDL receptor, grabbing ApoB-100 is much slower. IDL half-life is again half an hour. They’re gone in 2 hours. The LDL, which has much slower receptor-mediated clearance, hangs around for two, three, four or five days. Now remember, there is one ApoB on every VLDL, IDL, and LDL. So, if we ask the lab give us an ApoB level. In essence, we’re measuring VLDLs, IDLs, and LDLs that are floating around.

[00:20:13] But because of the much longer plasma residence time of LDLs to 95% of an ApoB level that a lab reports to you, is actually an LDL particle concentration, your VLDLs and IDLs are a minuscule contributor to total ApoB. Chylos don’t contribute at all because of their very short plasma residence time. And most of the time, we do these panels fasting, where there would be no chylomicrons. So ApoB we’re going to talk about is the blood test everybody needs. But when you get an ApoB level, you’re basically getting LDL particles. And what’s an LDL particle? It’s basically a collection of cholesterol, very few triglycerides wrapped by one ApoB. It’s a super cholesterol rich particle. Where is the last place you want an LDL particle to invade your arterial wall? Because if it enters there, the ApoB on the particle sticks rapidly to the connective tissue.

[00:21:11] In the intimal layer, the connective tissue is full of molecules called proteoglycans, looks like the fly trapped on fly paper. They’re stuck. A few may break off and exit back to the plasma, but most do not. They’re trapped. Now, once they’re trapped there, they’re not supposed to be there. Our immune system goes into play as if a bacteria invaded your body today. Immune cells would go and attack it and try and kill it. Well, so once ApoB particles in the artery wall, the arterial wall sends out signals, “white cells help.” They’re chemotactic proteins for white cells that are expressed on the endothelium of the artery wall. And they start pulling in monocytes and ultimately other white blood cells that are floating around T cells and B cells. And once in the arterial wall, a monocyte transforms into this big gobbler called a macrophage. 

[00:22:04] And as the ApoB particles are sitting there, bound to proteoglycans, and they’re right next to one another, they start to aggregate. The phospholipids on their surface change positions, and they start sticking to each other. And now, all of a sudden, you got multiple LDL particles congealing. That’s called LDL aggregation. Like, the first step of atherogenesis is the ApoB particle invading the arterial wall. Second step is aggregation, but then those phospholipids, once they aggregate those particles, phospholipids are highly amenable to oxidation. Many of the fatty acids in the phospholipids have double bonds, very prone to oxidative forces. So, if you have reactive oxygen species in your artery wall, and because of our lousy living, we have lots of them there, they start oxidizing these congealed LDL aggregates, and then you got a monstrous collection that gets pulled into the macrophage. 

[00:23:00] Now, when you have all these sterols invading the macrophage, it’s called a sterol-laden macrophage. They were discovered in 1914 by a Russian scientist, Anichkov, who was overfeeding rabbits cholesterol and rabbits hyper-absorbed cholesterol. And he was looking at their artery walls, because rabbits get atherosclerosis, especially if you’re drowning them with cholesterol in the diet. And he had beautiful drawings of all. He didn’t know what they were, but they’re, in retrospect, foam cells in the artery wall. Now, overtime, these foam cells, these macrophages, fill with these cholesterol, they start attracting. It’s a whole inflammatory mess that goes on. Smooth muscle cells are pulled in, they transform into abnormal smooth muscle cells. And over time and we’re talking decades here, you develop plaque.

[00:23:46] And ultimately, if that plaque keeps getting bigger and bigger and bigger, it’s going to extend into the lumen, obstructing the diameter of the lumen. If it obstructs it enough beyond 75% occlusion, you don’t deliver blood and oxygen. That’s called ischemia as you know. God forbid that blockage closes the artery, nothing gets through, you infarct the tissue and if it’s the heart, myocardial infarction, that happens less and less nowadays. What really happens is this nest, this volcano, full of sterols and inflammatory molecules. It’s like a volcano. It erupts. And if it erupts through the endothelial barrier, all the guck coming out of the plaque interacts immediately with the coagulation system, which wants to seal off the volcano. But what happens? You develop a thrombus, a clot. If it’s a little clot, it causes some ischemia, God forbid it’s a big clot, you infarct. That’s atherogenesis in a nutshell.

[00:24:44] You and I know, though, thank God, you can’t have a bad meal today. Raise your ApoB level, and you’re going to die tomorrow. This takes decades of the ApoB particles invading the arterial wall. See, this is why even kids who are born with familial hypercholesterolemia and have very high ApoB levels and LDL cholesterol levels. They don’t get heart attacks when they’re five years old, but they start getting them when they’re 20 and 30 years old, depending on the severity of their ApoB level. The only exception to that rule is the poor little babies who absolutely pick the wrong mom and dads. They inherit evil genes from both. That’s called homozygous familial hypercholesterolemia. As infants, when they’re one and two years old, their LDL cholesterol is 300, 400, 500, 600– 

[00:25:34] And these are actually kids, if that’s not recognized, actually get infarcts at age 5, 6, 7 and 8. Fortunately, nowadays that’s recognized more and more. Pediatricians are starting to check lipid levels much earlier in life. Sometimes, the parents know they have familial hypercholesterolemia, so they would alert the pediatrician. God, I hope I didn’t pass any genes down to my baby. And a wise pediatrician would check lipids very early in life there. But that’s basically the story. I’m going to just wrap it up. I hinted to VLDLs actually gather cholesterol in their short plasma residence time, but so do LDLs in their several day. And now you’re going to find out why they gave us LDL particles. Remember the HDLs that have sucked all the cholesterol? And now they’re big, buoyant HDL particles full of cholesteryl ester. 

[00:26:27] They bump into LDL particles, but also some VLDL particles because they’re- And by the way, we all have 28 more times HDL particles in our plasma than we do LDLs or any other ApoB particles. So, even though they’re small, we got so many HDL particles. And as they bump into the LDL particles, we have what’s called a lipid transfer protein that HDLs carry in and it gets expressed. It’s actually a protein tube that penetrates the ApoB particles, most of which are LDLs. But some are LDLs, and the HDL transfers its cholesteryl ester into the LDL or the VLDL. And that’s why evolution made LDLs hang around for so many days. Its primary purpose is not to deliver cholesterol to any tissue. It basically does none of that. 

[00:27:22] It takes excess cholesterol out of the HDL, and the LDL or the VLDL returns cholesterol to the liver, completing the reverse cholesterol transport process. Now, look, the HDL also has the ability to go back to the liver and delipidate and get rid of its cholesterol. But half of it is given to the LDLs. So, this very complex thing and we were just taught reverse cholesterol transport. We all were just taught HDL is bringing back cholesterol to the liver. We got to reexplain it. Yes, HDLs are super important. They get the excess cholesterol out of the damn cells, but they give it to the ApoB particles to bring back to the liver. So, when an ApoB particle brings cholesterol back to the liver, an LDL or VLDL, that is called indirect reverse cholesterol transport.


[00:28:10] If an HDL brings it back to the liver, that would be called direct RCT. Total RCT is a sum of direct and indirect. I hate to make things more complicated, but these LDLs and HDLs can also return cholesterol to your intestine, which takes the cholesterol from them and exports it to the gut lumen, so we can excrete it fecally. So, you can see there are many avenues of lipid transportation in the bloodstream. And I dare anybody to come up and tell me whatever your HDL cholesterol is, whatever your LDL cholesterol is right now, what are your LDL and HDL particles doing? Lipid concentrations tell us a lot. Basically identify, but they tell you nothing about the functionality of what the heck the particles are doing in your blood. 

[00:28:56] I’m going totally wrap this up by saying HDLs don’t give all their cholesterol to LDLs and VLDLs. They give a lot. By the way, that transfer protein is called cholesteryl ester transfer protein, CETP. There are people who are born with loss of function genes. They don’t make CETP. What do you think their HDL cholesterol is? 180, 190 because the HDL can’t get rid of the cholesterol by giving it to the– can’t transfer cholesterol. Interestingly, that gene is associated with longevity, so it’s kind of cool. And this is why, for years, pharma has tried to develop a CETP inhibitor, all of which have failed. Well, the last one, it worked, but it didn’t work that good, and it hung around the body forever. So, Merck never brought it to market. That’s the anacetrapib.

[00:29:44] But right now, undergoing clinical trials is the latest version of a CETP inhibitor. And fingers crossed that it may work and so far in its early clinical trials, it’s looking real good. It’s called obicetrapib, so I think the fifth or sixth CETP inhibitor, but there’s great promise for it. 

Cynthia Thurlow: [00:30:05] It’s so interesting. 

Dr. Thomas Dayspring: [00:30:06] So stay tuned to that. That’ll be a future podcast. So, I hope I’ve explained, oh, the last thing, HDLs can bring it to the liver, they can give it to an LDL. But HDLs happen to be a major supplier of cholesterol to steroidogenic tissue, our gonads and our adrenal cortex that make adrenal cortisone and crucial hormones that come from cholesterol. So, those tissues make, under physiologic conditions, basically all the cholesterol they need. But under certain situations, stress or whatever, if your adrenal cortex needs to make more cortisone, it just expresses receptors that grab and delipidate HDL particles, SRB1, scavenger receptor B1. I think I’ve given you an indication on how complex lipid transportation by lipoproteins are. Atherogenesis, I’ve described to you. Perhaps the next question you’re going to ask me is, Tom, what makes an ApoB particle invade the artery wall? 

[00:31:04] Because if it didn’t do that, you couldn’t have atherosclerosis particle number. It’s pretty much a diffusion process. Once your LDL particle number ApoB exceeds a certain level, and remember, it’s over decades, it starts invading the artery wall, and atherogenesis slowly but surely begins. The higher your ApoB, the more quickly atherogenesis occurs. The FH kids, they get heart attacks at 20. Most of them get heart attacks at 50 or 60 because it took a little longer for our ApoB level to cause the heart attacks. But it’s simply particle number, so you could measure ApoB cheap, affordable, done at every lab in America at least. There is a more sophisticated test using nuclear magnetic resonance, or ion mobility transfer, that can give you an LDL particle count by itself. Basically, LDL particle count is ApoB, so any of those measures will work. 

[00:31:57] Quest uses ion diffusion mobility, which reports the LDL particle number. LabCorp, Boston Heart, Cleveland also would give you the nuclear magnetic resonance, the NMR, lipoprotein concentrations, and total LDLP is the most important number you get out of them. There’s other metrics they give you, but total LDLP and ApoB is basically what you need. What don’t you need? HDL cholesterol or ApoA-1, because there are too many ApoA-1 molecules per particle, so it gives you no usable information. HDL cholesterol, it’s such a dynamic process where it’s gaining and losing, gives you no information. HDLs are super crucial lipoproteins, not because of the cholesterol they carry, although that’s important. It’s the proteins they carry. There have been almost 200 proteins described that you will find on the surface of some HDL particles.

[00:32:51] Now, each one carries three or four proteins, but, as I said, quintillions of HDL particles. And it’s the proteins that determine what we call the functionality of the HDL particle. Is it doing good things to the artery wall? Is it doing bad things to the artery? That’s called dysfunctional HDLs. Some of these proteins are anti-cancerous, so HDLs are involved with the immunity with oncogenesis. Some of these proteins kill bacteria, so they’re involved with immune– You get an infection someplace, HDLs– You ever notice if you, you shouldn’t do it, but if you did a lipid panel and somebody went in acute crisis, an infection, their HDL cholesterol is low because the HDLs are being destroyed at the infective sites by delivering proteins that helped our immune cells. So, HDLC is cool, but it tells us nothing. 

[00:33:42] But I can tell you when, go back to that, your brother-in-law, who has a low HDL cholesterol and high triglycerides. “Hey, if he’s got high trigs, his liver is making too many VLDLs that become too many LDLs. His liver is even overproducing LDLs, his ApoB is through the roof. So, the poor man’s best way. If you don’t want to order ApoB, and you’re just starting with a lipid profile, if you see a high triglyceride HDL/cholesterol ratio, you order ApoB. It’s going to be ugly when it comes back. So, low HDL cholesterol is just a signal of insulin resistance and your ApoB level is much higher than you want it. And therefore, the proper treatment to anybody with high ApoB including those with low HDL cholesterol, is to lower ApoB through lifestyle, and, if necessary, if your risk is disastrous enough, through pharmacology. 

[00:34:33] And if we all did that and this is why ApoB measurements earlier in life, because they go out of whack sooner than those LDL cholesterol. The triglycerides, even that takes a long while to go up. First, you’ll get insulin going up, and then postprandial insulin first, then fasting insulin. But all of this metabolic mess is occurring in these people. So, I’ll take a deep breath, and you can ask me more questions. 

Cynthia Thurlow: [00:34:55] [laughs] No. There’s so much here to unpack, but it helps explain why this is a complicated business, why, in many ways, it’s my opinion that we have taken a complicated process and tried to just take a total cholesterol, HDL, LDL, and triglyceride and make that the whole story. And really, what you are identifying here is it’s one step in the process, and we need to look beyond those basic metrics. And you talked about the poor man’s ApoB. So, if you have a regular lipid panel, you can look at your VLDL, your LDL, your HDL, to get a sense of what your ApoB must be. But the ApoB is really where it’s at. This is something that, for me, I am exquisitely attuned to, not just because I’m a lipid nerd, but because I, through genetics, have a high ApoB. And we’ll probably, at some point, if not on this podcast, we will discuss my own lipids, because I think it’s important to be transparent and say I’m doing all the right things. And still, some of this is genetically mediated. 

Dr. Thomas Dayspring: [00:36:01] Yeah. And I’d be happy to give you my lipid panel one day too, [Cynthia laughs] which is probably a bit worse than yours, but I have it under perfect control. 

Cynthia Thurlow: [00:36:07] Yeah, yeah. No and it’s interesting. It’s because of my ApoB that I started, because the lifestyle was already dialed in. It’s because of my ApoB that I actually started taking medication. And we’ll get to a point where we’ll talk about people that are hyperabsorbers of cholesterol, and I happen to be one of those. But let’s talk a little bit about ApoB. We know it impacts the arterial walls. We know if were to draw an ApoB on an infant versus a child versus an adult, like, where those numbers should be. So, if people are listening and they’re interested in getting the slab drawn, where are those numbers supposed to be? So, at birth, my understanding is between 20 to 30 mg/dL. Is that correct? 

Dr. Thomas Dayspring: [00:36:45] It is. 

Cynthia Thurlow: [00:36:46] Okay. And then as children, you know children progress 40 to 50 mg [crosstalk]

Dr. Thomas Dayspring: [00:36:51] By the way, just an aside here, because there’s so many people who panic when they see low ApoB or low LDL cholesterol. At that age, infancy, they are developing their most important organ in the body, which is super cholesterol rich, the brain. So, these kids having low LDL cholesterols and low ApoB have no problems with brain development. So, that reinforces something I dropped early. What’s floating around our plasma has zero to do what’s floating around our brain. And I want to certainly in the future, talk to you more about the brain. But don’t panic when you see a little baby with an LDLC of 25, that’s a normal kid, and that kid is probably going to develop into a normal brain, and everything’s going to work. Sooner or later, you’ve got [unintelligible 00:37:38] ApoB because it will hurt the artery walls, but not if it stayed 20 to 30. [laughs] No atherosclerosis in that kid.

Cynthia Thurlow: [00:37:44] Well, and I think it’s important to talk about where do we ideally want in someone who does not have insulin resistance, who is metabolically healthy, has known coronary artery disease, no diabetes, where do we want the ApoB to be as an adult? This is an important metric. So, here’s a pearl we’re introducing, because I want people to be able to walk away and say, “Okay, this is the metric I need to work towards.” 

Dr. Thomas Dayspring: [00:38:05] Yes, the laymen who are listening, if you run to your doctor on your next appointment and said you listened or you learned that ApoB is important and they want it, and your physician, clinician, whoever you’re seeing tells you, ApoB is not important, nobody measures it. I joke, run out of that office as fast as your legs will carry you. And finally, a practitioner who, before even making an appointment with a doctor, if you’re an adult, say, by the way, does the doctor check ApoB? And if the person answering the phone says, yes, you’re probably in good hands. Out aside, this is so crucial and so important, and the reason is, you could say, why can’t I just use LDL cholesterol? 

[00:38:44] Because especially for those in the insulin resistant world, but in others, all of a sudden, there are certain people where the LDL cholesterol does not correlate with the ApoB. The LDLC may look fantastic, but ApoB could be a nightmare, or vice versa. The LDLC could look scary, but the ApoB is good. No risk at all. So, the risk more closely follows ApoB than does any of these cholesterols or even triglyceride metrics you’re hearing about. They’re good guesstimates, but ultimately, you want the real test. Cynthia started off by saying, jeez, perhaps we’ll ultimately get into menopausal women, because at certain points in our lifespans, gender is obviously different. Things change. So, why doesn’t these little babies who have ApoB of 40 or 50, why doesn’t that stay 40 or 50 for their whole lives? 

[00:39:34] And whatever your ApoB is as a woman, when you go through menopausal transition, why does it start going out of whack? What forces might be at play? And the same with men. Why is it out of whack earlier in life, more in men than it is in women? So, everything we’ve taught you so far, we’re going to try and translate into it does change. And this is why you have to keep periodically repeating ApoB and lipid panels. It’s not just a one-time test in your life. And I hope we get into all these scenarios. Would you like me to explain what levels should be as we age?

Cynthia Thurlow: [00:40:10] I would love that. And then it would be helpful to hear from you, because I love and this is one of the reasons why I knew when I connected with you, I was like, this is my person that I know is designed to bring this information to my community was when you were in clinical practice in New Jersey, your specialty was looking at lipids and managing women in perimenopause and menopause. And you said to me, because these women have really been so poorly managed is probably an understatement. But I think after the Women’s Health Initiative in 2002, a lot of women were taken off their hormone replacement therapy. And we know that HRT can beneficial for helping to quiet inflammation, oxidative stress. And why, in particular, I wanted you to be the one to talk about it, because you had many, many years of clinical experience discussing this with your patients in particular. 

Dr. Thomas Dayspring: [00:41:01] No. So important. Cynthia is right. When I left practice in New Jersey in 2012, moved to Virginia, because I became part of biomarker laboratories down here. I was getting to be an older man. So, sooner or later, you got to leave practice. But anyway, as I evolved my practice, I did evolve into women’s healthcare. And it was certainly lipids, but it was every aspect of a woman. Her bones, her breasts, her pelvic organs and the reason why is because for whatever reason, I was very interested in that. I used to joke, well, ultimately, I was married to a menopausal woman, so I had to make sure everything was good with her. That’s not a joke to even use anymore, but it worked in my day.

[00:41:43] But anyway, what Cynthia says, I notice, and I would because I evolved into, I’m caring about, they were getting such crappy care all over the place. And their doctors were not talking to them about all the multiple issues. And, you know, again, one of my New Jersey jokes, when a woman walks into your office and you’re a physician, it’s not just her breasts and her vagina that you have to be cared about. The woman has a brain, the woman has a heart, woman’s full of arterial blood vessels, woman has joints. So, you have to. If you’re going to say, I care for women, you better know the total woman. And when this started to evolve, even a lot of gynecologists started, “Oh, I’m changing my practice to women’s clinic.” But they just looked at the breasts and the pelvic. They didn’t look at the brain or the arterial wall for sure.

[00:42:32] Many of them have evolved into doing that just now. Good luck finding them. But I stumbled into that world because I felt bad for the women, because you’d get talking to women, and I’m there. “Hey, I’m your internist. I’m doing blood pressure. I’m checking your lipids.” By the way, has anybody talked to you about bone density? Has anybody talked to you about your emotional well-being, what, is their dementia in your family, blah, blah, blah. By the way, even gynecologists sometimes get into sexual functioning of a woman. This is also important. And I don’t know, but I stumbled into that world. At the time, I stumbled into it.

[00:43:05] There was a new organization forming at that time called the North American Menopause Association, and they were a group of scientists that were actually, “Hey, we’re going to start.” There are thousands of women. The baby boomers are all turning into menopausal woman right now. So, it’s a big issue. We got evolved, actually started the journal Menopause. They were the people who, a wonderful journal, you unfortunately know about. But anyway, they actually started a board examination for menopausal healthcare, and they actually started their Borgo Organization before the National Lipid Association started their American Board of Clinical Lipidology Certification. So, I jumped right into NAMS and I passed the menopausal board certification. 

[00:43:47] And a few years later, when the lipid board came, I passed that, of course, and I’m very proud for, there’s no monument to me anywhere, but I’m the first clinician in the world who was certified by both NAMS and the American Board of Clinical Lipidology. So, I immediately changed my business card. I have to scan you and send, it was called the North Jersey Institute of Menopausal Lipidology. And I just felt I was doing so good to women. My staff hated me because that meant at least an hour, hour and a half discussion with every woman. And that’s not a way for an internist to make a lot of money. Luckily, I evolved into education, so I had an educational income that allowed me to spend so much time with women. But there is so much to discuss and it’s become 10 times more complicated even when I was one of the early people in this field.

[00:44:37] One of the things I’m proud of, I ultimately became a subeditor of The Journal of Clinical Lipidology. And I obviously did a ton of peer review or asked other people, but I also did several peer reviews for the journal Menopause because Isaac Schiff, who is an editor, whenever there was a lipid issue, “He often Tom, would you review this article?” A lot of gynecologists in that organization, so I felt so good to do that. But anyway, that’s how I stumbled into that world. And sadly, even today, if you’re a woman, really good luck getting good comprehensive meta– It’s better than it was. But you have to be proactive, you have to search. 

[00:45:13] Not only do you have to ask your doctor, you know what ApoB is, but I’m a woman. Are you going to evaluate my brain? Any cognitive things that might predispose it? What things in the mammogram other than you squeezing them, tell me anything. The pelvic exam, what issues, it all has to be addressed. We did have that studies that all came into play in the late 90s. Before that it was a religion that if you were a woman, you had to be on estrogen. Even back in the days before we knew they were getting unopposed estrogen for God’s sakes. And that’s not a happy ending for your uterus. But ultimately progestins were invented and they came on board. But the bones, who was looking at bones? Your spine is going to be crooked when you’re 80 years old, who cares when you’re 40 years old? We don’t have to worry about that. Yes, that’s the opportune time to work. So, that was an issue.

[00:46:06] The whole pelvic floor was just another issue. And that is addressed differently than what you– if you’re going to use estrogen, you’re doing systemically. But if you don’t know this, you can’t do it. The last joke I’ll make is– so Gynes were all estrogen and they slowly evolved into knowing, “Hey, estrogen is a great drug for the right woman and it’s not the right drug for another class of women.” So, you obviously have to figure out who that’s for. The problem with hormone replacement therapy or menopausal hormone therapy as it’s now caused is internists want nothing to do with it. The biggest panic phone call an internist can get is I’m a woman with vaginal bleeding.

[00:46:45] Oh my God. So, they just– They don’t want to even discuss those important parts and few are going to prescribe appropriately hormone therapy during the menopause transition where maybe use a high dose OC and then evolve into menopausal [unintelligible 00:47:01]. It’s just, ugh, so frustrating and I feel for women. They really do, as do you. And you know this as well as I do. You just introduced this, so important. 

Cynthia Thurlow: [00:47:13] If you love this podcast episode, please leave a rating and review, subscribe and tell a friend.