Ep. 523 This Is Why Your Cholesterol Shifts in Midlife – The Best Strategies to Reduce Risk & Improve Vascular Health with Dr. Thomas Dayspring
- Cynthia Thurlow
- 2 days ago
- 41 min read
I am excited to reconnect with Dr. Tom Dayspring today. He joined me before for an extremely popular seven-part podcast series where we tackled topics related to lipids and the physiological shifts that occur as we transition from perimenopause into menopause.
Dr. Dayspring graciously agreed to return today for an Ask Me Anything episode, where we explore how lipids change as we navigate the perimenopause-to-menopause transition and discuss the significance of bioindividuality, inflammation, vascular health, and endothelial function in the context of changing estrogen levels. Dr. Dayspring also clarifies how visceral fat affects lipid levels, and we discuss testing for cardiovascular disease, the relevance of particle size, LPIR scores, and physical markers of insulin resistance.
Stay tuned for today’s valuable and fascinating conversation. I will share the second AMA with Dr. Dayspring later this fall.
IN THIS EPISODE, YOU WILL LEARN:
How estrogen loss impacts lipid metabolism in midlife
Shifts in vascular health that occur during the menopause transition
What makes endothelial function central to long-term health?
Why triglycerides matter more than you think
How variations in LDL particle size influence cardiovascular risk
What standard cholesterol tests could miss about your cardiovascular health
How inflammation can alter your lipid profile
How your genes and lifestyle shape your lipid profile
Markers women need to track over and above standard cholesterol tests
How menopause reshapes women’s cardiovascular risk profile
“Look at ApoB if you want the most accurate risk assessment.”
– Dr. Thomas Dayspring
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Connect with Dr. Thomas Dayspring
Transcript:
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] Today, I had the honor of reconnecting with Dr. Tom Dayspring, who has been part of an exceedingly popular series of podcasts. There are seven prior podcasts discussing topics related to lipids and shifts in our physiology as we navigate perimenopause into menopause.
[00:00:52] Today, he returned graciously to do an Ask Me Anything and we started off discussing how lipids change, navigating the perimenopause to menopause transition, the impact of bio-individuality, the role of inflammation, vascular health and endothelial function in the setting of changes in estrogen, how visceral fat impacts our lipids, testing for cardiovascular disease, the relevance of particle size, LPIR scores and physical markers of insulin resistance.
[00:01:27] As always, another invaluable conversation with Dr. Dayspring. Stay tuned for the second AMA that will be shared later this fall.
[00:01:41] Dr. Dayspring, it goes without saying, thank you again for coming back to tag on another podcast episode addressing listeners' questions, of which we got hundreds, not surprisingly, hoping that we can dive into some of these topics in a little bit greater detail for the listening community.
Dr. Thomas Dayspring: [00:01:59] That makes me happy because if you're getting that many questions, people are listening, and they're thinking, and they're interested in these topics. I am happy to continue to share knowledge with you.
Cynthia Thurlow: [00:02:10] One of my son's mother's friends actually has a chemistry degree and she said, "What I loved about the first series we did together was I had to go back to chemistry textbooks and relearn some concepts I had forgotten about." I look at it as exponentially helping people reinvest in their own education but also lead to greater advocacy.
Dr. Thomas Dayspring: [00:02:33] Sure. When you hear things, you do have to do a little study. If you want to get into lipids, a good biochemistry book on the shelf can really help you a lot.
Cynthia Thurlow: [00:02:42] Absolutely. We got specific questions in about six or seven different areas. We went over them together, so we're going to dive into some of these. What are some of the most significant lipid changes women experience as estrogen declines in perimenopause and menopause?
Dr. Thomas Dayspring: [00:03:00] It's a complex question because every woman is a little different. What may happen in menopause, the lipid metrics in one woman might be a bit different than another. Do they have underlying insulin resistance? Do they have a genetic lipid disorder that they've been dealing with all their life? What medicines might they be on? Are they using hormone therapy or not? The changes in lipids would be different in a lot of people.
[00:03:28] If you want to generalize, in general LDL cholesterol goes up a bit. Triglycerides can start to escalate a little bit, the lipoprotein (a) that we've talked about before can certainly go up as you lose estrogen. HDL cholesterol can be a bit variable. Again, it depends on what's underlying as to what might happen.
[00:03:52] It's not a dramatic change in HDL cholesterol, but we now know that HDL cholesterol really doesn't have a lot to do with HDL functionality. I almost don't care what happened to HDL cholesterol at menopause, I have to zero in on the other things. When I said LDL cholesterol goes up, my favorite and I think the most accurate biomarker, ApoB, tends to go up a little bit also, which is not desirable.
Cynthia Thurlow: [00:04:18] It's interesting because I learned through you that very often when you see a high LDL, you can also see a concomitant high ApoB. For a lot of listeners, because we got so many questions around this, many said things like, "My provider noticed that my LDL has started to creep and they want to start a statin." I think we would agree that before we even think about medical therapy, we're getting a full picture. So really looking at the ApoB and Lp(a) because those together can allow you to see what the next step should be.
Dr. Thomas Dayspring: [00:04:53] We have to be cognizant of the fact that LDL cholesterol and ApoB usually have a pretty high correlation. When one's up, so is the other. When one isn't, neither is the other. But in upwards of 20 or even a little bit more percent of people, they're what we call discordant. One's up, one's low or vice versa. In those cases where they don't really agree, ApoB rules. Your cardiovascular risk follows ApoB. You can dismiss the LDL cholesterol in that case.
[00:05:27] This is why you have to do ApoB. You could get away with LDLC in a lot of cases, but you would miss the ones who have discordance. They're typically the ones where the triglyceride has started to escalate a little bit above physiologic triglyceride levels. There are reasons why, if you want to get into it at some point in the podcast, we can, because it changes your lipoproteins in the way they're cleared or not cleared.
[00:05:56] ApoB rules [laughs]. Even non-HDL cholesterol, which is better than LDL cholesterol as far as correlating with ApoB, there's X number of people who have discordance between non-HDL cholesterol and ApoB. If I have the best tests and I got some two pretty good tests, if I'm really going to have to advise a woman or even a man, I need an ApoB.
Cynthia Thurlow: [00:06:18] Absolutely. Now, this is a test, I just keep reemphasizing this, covered by traditional insurance, is not an expensive test. Everyone should know their ApoB and their Lp(a). I will continue saying this to reemphasize the importance of it. I think that there's a lot of focus on LDL, triglycerides, and HDL and I would make the argument that if you have high triglycerides, and I define high differently than most allopathically trained providers-
Dr. Thomas Dayspring: [00:06:47] That’s true. Yeah.
Cynthia Thurlow: [00:06:49] -I would say greater than 70. You have work to do, irrespective of what you are hearing at your office visit. We used to say under 150 was fine. By that point, as we've discussed in other podcasts, you're very likely dealing with some degree of insulin resistance.
Dr. Thomas Dayspring: [00:07:05] I’m sure. That's the 75th percentile in the population. You don't want to be in that neighborhood with a triglyceride or any metric level for goodness sakes. Yes, a physiologic trig, as you've just pronounced, is under 70 mg/dL. Really, 30 or 40 mg/dL if you're in total perfect health.
[00:07:26] The problem is when trigs start to escalate a little bit, it changes your lipoproteins, especially your LDLs, which is the predominant ApoB particle in plasma, which diminishes their clearance at the liver, the LDL receptors and that means LDL particle concentration, ApoB. There are parallels. As triglycerides escalate, you got an ApoB problem. I see an ApoB of 130 and I'm worried, but an ApoB will tell me how much I really have to worry about.
Cynthia Thurlow: [00:07:58] Yeah. I think that's important and it’s interesting. I'm in several Facebook groups with other physicians and nurse practitioners. At least once a week, there is a clinician-- a well-meaning clinician in this group that is talking about, I see on paper, an insulin-resistant female and they're focused on hormones, which are certainly very important, but the lifestyle piece really needs to be addressed. When I'm looking at triglycerides of 250, 300 or higher, the first thing you can do is low-hanging fruit. It’s like, okay, “Let's talk about your diet. Let's lean into those metrics” because that can make a big difference before medical therapy is even started.
Dr. Thomas Dayspring: [00:08:36] Look, no matter what lipid or lipoprotein disorder you have, other than Lp(a) where nutrition doesn't seem to move that metric, all of the ones we're talking about, trigs and ApoB, lifestyle is always the initial therapeutic agent. If you are in the nightmare class, you've had a stent, a bypass, your metrics are so darn high, yes, it's lifestyle plus a pharmacologic agent.
[00:09:02] But nobody-- I think I mentioned it the last time I was accused, "Oh, you're pushing drugs, pushing drugs.” Yes, for the right person. I don't want drugs in the drinking water to control lipid disorders that so many people have. Depending on your degree of risk, it's always appropriate to start with a lifestyle. If you can control everything [claps]. If you can't, then the prescription pad comes out. It's a long discussion with that patient too. You just don't-- "Here's a script. Take it and I'll see you."
Cynthia Thurlow: [00:09:33] I think now medicine is evolving. I think now there are a lot more clinicians that are sitting down, or whether they're sitting down and then having the patient come back with a health coach helping them really fine-tune this lifestyle. Because if lifestyle alone is going to address your lipid abnormalities, why not try it? It makes so much more sense. Why does LDL cholesterol often rise after menopause even if lifestyle doesn't change? I know we've kind of touched on this, but specifically what's happening physiologically?
Dr. Thomas Dayspring: [00:10:07] The bigger thing is as you're going through the menopause transition, most women tend to become a little bit insulin resistant more so than they were. Your trigs, which might have been 70 are now 110 or 115. Your ApoB is going up just due to underlying insulin resistance. Estrogen is an excellent insulin sensitizer. When estrogen goes bye-bye, your insulin resistance is happy to take over. This is very common, and this is even in men insulin resistance is part of the aging process. It's not only hormonal. There are other factors at play. That's certainly one.
[00:10:47] I got into it a little bit last time. It's very interesting. We now know estrogen is really a PCSK9 inhibitor. For those who don't know, PCSK9 is a protein that controls how long the LDL receptors that your liver makes and they are basically proteins that stick into plasma, grab the ApoB particles, and pull them into the liver where they can be destroyed. Then the LDL receptor is supposed to break loose and return to the surface and do it again and do it again, multiple times over a couple of days.
[00:11:22] But PCSK9 is a protein that catabolizes or pushes LDL receptors to where they're going to be catabolized. This is why PCSK9 inhibitors are a very potent ApoB lowering tool because it sort of assassinates your PCSK9 and your LDL receptors can keep recycling and clearing, clearing, clearing your ApoB particles. Estrogen is basically a PCSK9 inhibitor. Not to the degree of the monoclonal antibodies we inject, but you lose something that's suppressing PCSK9. Then PCSK9 starts killing your LDL receptors. You stop clearing your LDL particles. Remember, there's one ApoB on every LDL particle. So, ApoB goes up. Those particles carry cholesterol, so your LDL cholesterol goes up. That's a very intriguing action and also one--
[00:12:22] Should you be using hormonal therapy for lipid management or so, that's another whole discussion. But if you start prescribing estrogen for other reasons, you're restoring insulin sensitivity and you're back suppressing PCSK9 a little bit. Very interesting. Not everybody knows that. It's been around for a while. I believe that's a big factor with the trigs, the insulin sensitivity, and the PCSK9. We also know at menopause-- Lipoprotein(a) is an LDL particle that has another protein attached to it, apoprotein(a). Estrogen seems to have the ability to stop the production of apoprotein(a).
[00:13:09] This is why at menopause women who do have at least elevated Lp(a) it's going to get a little higher. If a woman's in a borderline Lp(a) range, which probably is not a big worry, but it's going to go a bit higher after menopause. Does it become a worry? If your Lp(a) is totally physiologic, yes, it's going to go up a little bit at menopause, but it's not endangering you. It's another lipid or lipoprotein change that occurs with menopause. Those are the big reasons, I think, that are in there, dealing strictly with lipids and the effect of estrogen. The triglycerides go up and that starts changing the composition of some of your particles. When you put triglycerides in various particles, especially LDLs, you decrease their clearance, ApoB goes up. It's another bad association with the escalation of trigs.
Cynthia Thurlow: [00:14:09] Of course, in the back of my mind, I keep thinking there needs to be a study that demonstrates at what threshold do our estrogen levels need to be maintained at in menopause to confer those benefits. I'm sure we don't know yet.
Dr. Thomas Dayspring: [00:14:21] I don't know of a great trial. There might be very variable among different women or so too. Yourself, especially if you're talking about going on hormonal therapy, is it-- are you just using an estrogen alone? Are you combining it with some progestogen? If so, which one? What method of estrogen are you using? Patch, cream, tablet, vaginal? complex.
Cynthia Thurlow: [00:14:53] It definitely is. It's interesting because we know what levels our estradiol needs to be intrinsically to protect bone. That we know. But we don't yet know, and to your point, bio-individuality certainly plays a role. From my perspective, I'm always thinking at some point someone will probably do a study to look at this.
Dr. Thomas Dayspring: [00:15:12] It would be nice.
Cynthia Thurlow: [00:15:14] It would be helpful because I think there are a lot of people out there. Maybe they're using transdermal applications of Estradiol. Maybe they have a patch. Maybe someone's taking oral Estradiol. I would probably guess that oral Estradiol probably has the largest net impact, but-
Dr. Thomas Dayspring: [00:15:29] Yeah.
Cynthia Thurlow: [00:15:29] -not everyone tolerates that.
Dr. Thomas Dayspring: [00:15:32] We still have to realize I've been trying to practice menopausal lipidology since the 90s. At a time when we knew nothing, you were making it up with what literature existed. Now we're far down the road, but there's so much more data we need to know. It's still well understudied.
Cynthia Thurlow: [00:15:55] It's interesting because only 5% of women right now are reported to be taking hormone replacement therapy. I think that's probably not inclusive of those on compounded hormones, but it's still a fairly small subset of the population.
Dr. Thomas Dayspring: [00:16:10] It's like how many are getting their Lp(a) checked? It's about the same percentage.
Cynthia Thurlow: [00:16:15] Right.
Dr. Thomas Dayspring: [00:16:15] Tragic.
Cynthia Thurlow: [00:16:16] Yeah, absolutely. We're going to round out the conversation around triglycerides. Can you explain why triglycerides often rise in midlife women? We've kind of been dancing around this and how concerning is that compared to LDL changes? We've been dancing around this topic, but for may be for those individuals who don't yet know, we definitely want to see those triglyceride levels lower than what conventional allopathic medicine is suggesting.
Dr. Thomas Dayspring: [00:16:40] Again, there is individual responses, but you just have to basically realize as triglycerides goes up, you're going to through a variety of reasons, delay those LDL receptors from binding to and clearing those ApoB particles. So, ApoB is going to go up. Whatever worry you might have about trigs, concomitantly you have to look at the ApoB hand in hand with the triglycerides because it tells you how worrisome that triglyceride level is.
[00:17:11] If you want to-- because ApoB is high or because of insulin resistance, you want to lower the triglycerides, starting with lifestyle whatever. Everybody must realize there is no triglyceride goal of therapy in any guideline right now. The guidelines basically suggest for people with high triglycerides, where you're treating them, non-HDL cholesterol becomes your goal of therapy. As I've just talked, that's fine, but there's still discordance with ApoB. They should say ApoB is your goal of therapy, guidelines know ApoB, not everybody knows what it is, so they create a lot of confusion by recommending that. Trigs are just distorting--
[00:17:56] An LDL is an interesting particle. It's basically a collection of cholesterol surrounded by phospholipids, one ApoB wrapping it all. But there is x amount of triglycerides in an LDL particle. It's not a VLDL, which is full of trigs, which is why it's so big and fat VLDL or the chylomicron even more. An LDL normally can pose-- has about 25%-- 20% triglycerides and 80% cholesterol. It's like a 4:1 ratio or greater.
[00:18:28] If an LDL becomes triglyceride-rich and that's what happens in people as triglycerides go up because trigs get moved from the VLDL to the LDL, which enriches the LDL. So, transiently becomes a big LDL, but now that ratio of 4:1 cholesterol to triglycerides is way out of whack. The ratio has got way too much triglycerides compared to cholesterol.
[00:18:54] So, what happens is a triglyceride-rich LDL is a substrate. LDLs are cruising by the liver, and at the surface of the liver with the bladders, there are lipase enzymes called hepatic lipase. Hepatic lipase hydrolyzes, removes those triglycerides, changes them into fatty acids which enter the liver or bind to albumin. When you remove those triglycerides from this LDL, it was full of triglycerides, it becomes a very small LDL.
[00:19:27] Here's the bad news with that. When you change the shape of an LDL from normal size to small, the ApoB on the surface changes its shape also. That's unfortunate because the LDL receptor is looking for ApoB that's contorted in a specific configuration. If the ApoB is on the surface of the LDL shaped like it should be, binds it and pulls it into the liver. But here comes a small LDL with a distorted ApoB. The LDL receptor doesn't even know it's an LDL particle, so it gets to live for another day. That's why the plasma resonance time of small LDLs is up to five days. If you let LDLs hang around hang around, your ApoB, your LDL particle count, is going through the roof. That's really how triglycerides raise LDL particle count or ApoB.
[00:20:22] They're distorting the LDL particle, making it less amenable to clearance by the LDL receptors in the liver. You don't want to do that. You want to enhance clearance, obviously. The trigs are going to likely do-- Just as an aside, those HDLs are floating around. Your HDL should carry almost no triglycerides. But again, when the VLDL or the chylo is packed full of too many triglycerides, even VLDL, we have a lipid transfer protein and the triglycerides leave those ApoB particles and go over to the HDL. It accepts the trigs and sends cholesterol back to the ApoB particles because the HDL can only take so many lipids. Now you have something that mother nature never wanted, a triglyceride-rich HDL. That same enzyme, hepatic lipase "Uh-oh, HDL, you're full of my supper."
[00:21:18] Triglycerides grabs it, pulls the trigs out, the HDL becomes so small, and there's another enzyme, endothelial lipase does the same thing that it breaks apart-- ApoA1 floats over to the kidney which can catabolize it. There's a receptor that grabs and that's why as you become insulin resistant, your HDL particle count goes down, your HDL cholesterol goes down if you are catabolizing HDL part-- That's how tubby triglycerides create so many distorted lipoproteins and they're not functioning well anymore with the ApoB particles, the number is going through the roof.
[00:21:59] Last thing of that story, when an HDL loses its cholesterol and sends it to a VLDL and the VLDL is going to lose its triglycerides to muscle or fat cells, but now it becomes a cholesterol-rich VLDL. It's smaller because the trigs are gone. They're called remnants-- remnant particles meaning VLDLs or chylos are incredibly atherogenic. I call it tubby triglycerides. A friend of mine coined that term 20 years ago. I think he wrote a book, Tubby Triglycerides, but triglycerides are the root of all evil with lipids and lipoproteins if you're one whose trigs go up.
Cynthia Thurlow: [00:22:37] I think you really have to be cognizant of this. That's the most beautiful explanation I've ever heard talking about the pathophysiology of degradation of triglycerides. I think for listeners, helping them understand that when those triglycerides start to climb, it is creating a cascade of negative impact across this lipoprotein.
Dr. Thomas Dayspring: [00:22:58] Remember, it's cholesterol deposition in the artery wall that really causes atherogenesis. Now, triglycerides by causing these small LDL particles that drives your ApoB through the roof, are crashing the artery wall over time, and that's one of the big reasons triglycerides generate plaque. There are nice studies. If you analyze plaques or cholesterol, there's very little triglycerides in them, but triglycerides have driven the particles carrying cholesterol into your artery wall.
[00:23:29] By the time the trigs create the small LDL, the trigs are gone and it's a cholesterol-rich small LDL, but there is way way more of them. Particle number is what drives it into the artery wall. Trigs is like the driver in a getaway car who gets away, and the criminal who jumped out of the car in your artery wall, that's the culprit, but you can’t blame the driver and the darn particle that brought the cholesterols there.
Cynthia Thurlow: [00:23:56] Absolutely. Everyone needs to be aware and cognizant of where your triglyceride levels are. I would actually argue and we've talked about this privately, I have a family member and every time this individual tells me what their triglycerides are, I'm like, "They're not low enough. You've got to do more."
Dr. Thomas Dayspring: [00:24:12] To me, that's the only real reason to do a lipid profile, is to look at triglycerides, because I'm doing ApoB with it. I don't have to know LDL cholesterol, non-HDL cholesterol, total cholesterol. I need a trig and I need an ApoB, and then of course Lp(a). “Oh, you said you’d like to repeat.” [laughs]
Cynthia Thurlow: [00:24:30] Yes, absolutely. Just to continue reinforcing this. Okay, we're moving on to inflammation, hormones and vascular health. This is a topic near and dear to my interests. How does the loss of estrogen affect endothelial function and its interplay with lipid metabolism? For listeners, I love to talk about nitric oxide. So, they all this-- [crosstalk]
Dr. Thomas Dayspring: [00:24:53] Like the most important thing [Cynthia laughs] your endothelia introduces, we've already talked about estrogen, modulating lipids, and lipoproteins. Now we're looking at other attributes of estrogen that may or may not be so lipid related. So, estrogen is an anti-inflammatory molecule also. So, again, as the ovaries decide to stop making less estrogen, it should be no shock that if somebody starts doing sophisticated inflammatory markers, they're going to subtly start to go up.
[00:25:24] Your CRP is not going to go from 0.5 to 6, but it might go from 0.5 to 1, 1.2. People say “Well, that's a normal CRP.” Well, not really. CRP is like ApoB. It's a straight line to heaven as it goes up, goes up. [Cynthia laughs] You don't really want it to go up because now inflammation is just so critical to proper endothelial health.
[00:25:51] If your endothelium starts to get irritated or destroyed, then your nitric oxide production goes down. That is a critical molecule to make your arteries function. Arteries are not just tubes that carry blood here, there, and everywhere. They're very functional. They dilate, they contract. They are a barrier to certain things getting in the arterial wall, and they let certain things out of the arterial wall if the endothelium is functioning as it should.
[00:26:20] Part of the inflammation we pumped a little bit back to lipids and lipoproteins. Once those ApoB particles start invading the artery wall, a lot of transformation occurs, but at a certain point, the macrophages that come from monocytes that enter the artery wall start engulfing the cholesterol-laden particles and that generates foam cells, which generates a plaque or so. Estrogen is very much involved with that too.
[00:26:49] If the endothelial barrier is reduced for pro-inflammatory, ApoB particles can get in. Look, ApoB particles can pass through a normal endothelium, but even if that's the case, and it probably is in most people, once those ApoB particles create the foam cells, those macrophages become pro-inflammatory little machines that secrete any number of chemokines and cytokines that enter the artery wall. That's called maladaptive inflammation caused by the ApoB particle and that starts to irritate the endothelium. So, everything's related, but estrogen has effects on the inflammasome, Nuclear Factor-kappa B, all of which regulates the immune responses to everything. It's just another downside to menopause. I wish I didn't have to go through it, but evolution has decided you do because they don't want you reproducing after age 50 anymore. They've taken away that ability. That's probably an evolutionary reason why.
[00:27:53] Now women are not dropping dead at age 50 as maybe they did many many many years ago. Women can live easily into their 80s, 90s, even the century mark nowadays. After menopause, if you want to reach the longevity status, lipoprotein management--. You can almost relate the endothelium to blood pressure. Blood pressure management becomes so crucial.
[00:28:19] Half of the things you're going to do to lower blood pressure are going to help restore nitric oxide or endothelial function a little bit. So, it's very complex. There are pro-inflammatory proteins that are produced. Estrogen affects the type of white blood cells and how they're functioning, even in your plasmin, and certainly after they enter the artery wall. here are book chapters and even textbooks written about this that can take you deep into the whole information on its relationship to estrogen.
Cynthia Thurlow: [00:28:51] I think It's really important for us to understand because we get a lot of messages from women saying, "I've either chosen not to take hormone replacement therapy or I'm not able to take hormone replacement therapy." When I think about the impact of endothelial dysfunction and the progression of atherosclerotic cardiovascular disease, and we know that that is the number one killer of women heart diseases, I start to think we need to be as proactive as possible about helping women understand that bone protection is important, brain protection is important, but the heart is so critically important, and how instrumental Estradiol therapy can be in helping to protect not just the entire heart structures and reduction in arrhythmias and things like that, but also this endothelial piece that is so important.
Dr. Thomas Dayspring: [00:29:42] Look, the biggest way to attain longevity is number one, take out the number one cause that will not let you go to longevity, and that is atherosclerotic heart disease. I get assaulted all the time, "You just think everything is ApoB and everything is lipids." No. Arterial health has a multitude of factors that go into it. ApoB is the causal risk factor because it is invading the arterial wall and doing that illegal dumb job of cholesterol, but that sets off the inflammatory process.
[00:30:19] I don't ignore inflammation just because I'm an ApoB and lipoprotein guy. I concentrate on that. I think if you would really concentrate on making ApoB physiologic, which means your trigs have to be physiologic, a lot of things have to be, there'd be a lot less inflammation going on, at least after menopause, where atherosclerosis is part of the thing that's generating the inflammation. Likewise, if we did all the great lifestyle and we diminished insulin resistance, which is another big contributor to this inflammatory cascade that starts to occur at menopause, we'd be in good shape.
[00:30:58] Inflammation starts not only in the arteries, but your darn brain gets inflamed and even tissues get inflamed. This is why people who have longstanding inflammation, especially due to insulin resistance and diabetes, get so much degenerative arthritis, spinal disease. Osteoporosis is one thing that can eat away your spine, but you don't want degenerative arthritis on top of your osteoporosis. Everything is tied together and nobody is saying “Make your ApoB perfect, that's it. Don't worry about any other aspect of your health.”
[00:31:30] You have to worry about everything, but inflammation is part of the thing. I measure CRP in our patients. We look at it and we treat ApoB aggressively. In large part, that's step one in reducing, but there is many other modalities that you might have to use. I do think for the right woman where estrogen is indicated, it's all part of the equation to help that also. Whether you should or not, the guidelines will tell you shouldn't be modulating lipids with estrogen and stuff.
[00:32:08] You're going to use estrogen for a lot of reasons, but I think arterial health in the right woman, or early in the perimenopause or early menopause, those are the times to get really the greatest benefits from that. Not to start an 85-year-old woman per se on estrogen who's full of heart disease and think you're going to do too much. You better be careful doing it to that person.
[00:32:3] There's just a lot of questions and there's a million answers to them, but they're all connected. Inflammation, lipids, and lipoproteins go hand in hand. You go to an NLA meeting, you're getting X number of lectures on inflammation and stuff.
Cynthia Thurlow: [00:32:45] If someone's listening and they're curious, obviously pain, joint pain, and things like that can show up as a sign of inflammation. What are some of the other common symptoms when patients come to you that clue you into thinking “Okay, there's some degree of inflammatory response that's ongoing in this female patient”?
Dr. Thomas Dayspring: [00:33:10] Other than the neurotypical menopausal symptoms in that age group, I don't know that there's a specific symptom. Fatigue would be one I would want to look through or so. A multitude of other crazy--. Women for years are told to go see a psychiatrist because they would have this symptom or that symptom and there are so many autoimmune diseases going on nowadays, that would come into play.
[00:33:35] Again a woman who comes in with a list of six or seven symptoms, before I tell her, "Here's some Valium for you or something,” no, no, no. You have got to do a thorough workup and inflammatory markers are a certain part of that workup. I don't even know that you need a dozen inflammatory markers. I think starting with hs-CRP is probably the wisest, but you also have to understand CRP levels. It's not, "Hey, 4 and above, you're in big trouble." Even the guidelines, probably at least for cardiovascular disease, will tell you 2 mg/L is too much, but it's really much lower than that. It should be under 0.5 in my mind.
[00:34:15] Then you start looking “Why this is out of whack?. All right, I don't see any lipoprotein abnormalities.” We will then start searching for a multitude of other stuff. Are you euthyroid or not? Before you tell somebody they're crazy, maybe do a few more cognitive tests. Is something going on here? What is your ApoE genotype? Speaking of genetic things other than Lp(a), something I think is very useful baseline information.
Cynthia Thurlow: [00:34:47] I kind of put you on the spot, but I was curious what you were going to say about this inflammatory piece, which, I think to your point that most of the symptoms that women come to us for in perimenopause and menopause are a sign of some degree of latent or provoked inflammation. The autoimmune piece is really discounted. I think that many clinicians are downplaying what's happening for women as they're navigating this perimenopause to menopause transition and understanding some of the immunologic changes. We are at greater risk for developing autoimmune conditions just by nature of our gender. That just escalates as we are transitioning. There's thymus involution. Our thymus gland really shrinks, that's what involution means, it’s a fancy way.
[00:35:38] But understanding the differentiators between different types of thymus gland hormones that are impacting our ability to fight off infections. It's no wonder that we just become much more likely to develop autoimmune conditions as we get older.
Dr. Thomas Dayspring: [00:35:53] There's not an absolute test that you have an autoimmune disease. You have got to look at a lot of things and even still be suspicious if you don't suddenly diagnose it with certain biomarkers. There's a lot of biomarkers, nobody can check every one, but I think the hormonal milieu is certainly at that age group, unless you're dealing with a younger woman who's obviously got some hormonal issues which would translate with other symptoms, gynecological perhaps but-- it’s in with the brain.
[00:36:26] If you are going through-- The big advocate is as you go through the transition, some degree of hormonal therapy, unless there's a reason not to use it, is why not give it a try and see. I do get into it pre-menopausally.
[00:36:44] Technically, you should be using some sort of low-dose birth control or so because the doses of hormones used in menopausal hormone replacement, you could still wind up pregnant on it if you're a sexually active woman, and obviously many women still are at that age. You don't want that surprise to happen because you thought because you're on menopausal hormone therapy, maybe a little earlier than you should be. You better make sure a woman's using proper contraception if you're going to go with some of the hormone therapies in that perimenopause area.
[00:37:19] As you know, the estrogen levels and other hormone levels can tell you when somebody is absolutely menopausal and not peri--. Maybe this week she is and maybe next week she's not, and that can go on for a long time, these fluctuations. It's very tough to know. You know, classic-- no period in a year. What do you do for that year while you're waiting for the period to—they are gone for 12 months in a row before maybe somebody can declare menopause?
Cynthia Thurlow: [00:37:51] Yeah, It's interesting. I interviewed Dr. Felice Gersh, she's a GYN, and she was saying “So many of her women in the last two or three years, they're in perimenopause, they are anovulatory, they're just having dysfunctional uterine bleeding. Because they continue to bleed episodically, they're not yet fully menopausal.” She was like, "They're not ovulating anymore.” They're ovulating so sporadically that what's happening for them is really just this dysfunctional uterine bleeding."
[00:38:19] On the other side, I was talking to a woman who was 48 years old, and she said to me, "It would be devastating if I got pregnant right now. I'm not willing to come off oral contraception--." The conversation wasn't about encouraging her to come off. It was more like, "Is this working for you? Are you happy?" She said “It would be devastating for me at 48 to get pregnant, so I am staying on birth control until I go into menopause because I'm just not willing to get pregnant.”
Dr. Thomas Dayspring: [00:38:42] Another issue, though, if you're on those, are you ever going to know when menopause occurs? Because some of the hormone levels--
Cynthia Thurlow: [00:38:49] Right.
Dr. Thomas Dayspring: [00:38:52] Your FSH and LH are not going to tell you. Sooner or later, you are going to have to stop it and transition. Nobody said menopausal health care is easy.
Cynthia Thurlow: [00:09:02] No. No. I think that’s for many people, that is their bugaboo is whatever they've been doing is working, and they're like, "I'm not willing to make a change." It's also important to identify that oral contraceptive therapy is very different than menopausal hormone therapies dosage wise and there are a lot of women who will write into the podcast and say, "Oh, I finally got prescribed HRT." Then they tell us what they're taking, and I'm like, "That's oral contraceptives." I'm curious, have you see some of that in your clinical experience where a patient comes to you and is like, "Hey, I'm on HRT," and they're not actually on HRT?
Dr. Thomas Dayspring: [00:39:42] Meaning they're on contraceptive.
Cynthia Thurlow: [00:39:46] But they don't know that it's actually not.
Dr. Thomas Dayspring: [00:39:49] Oh, sure. This is why, again, perimenopausal and menopausal healthcare, you to have seriously involved discussions with the woman because there's a lot of things to address. We're just talking about that now. Then you got to start going through every organ system. This is perhaps one of the reasons in the real world because nobody's paid to spend hours with women counseling them on this stuff.
[00:40:16] I was able to do it because I was really making enough income from doing educational teaching where I didn't have to see 42 patients a day. I could spend an hour, an hour and a half, and that may be our first meeting. We'll do it again in another month. I was blessed that way. Not every practitioner is.
[00:40:35] Short-shifting is going to occur. This is where it comes back to, you have to be your own advocate. Start reading about this and go in with at least a few questions prepared. You can maybe get into a discussion. But again, the clinician you're talking to has to understand some of the things you just threw at me there. I'll bet there's a ton of clinicians who don't know the difference between low-dose oral contraceptives or whatever oral contraceptive a woman might be using. What is menopausal hormone therapy? The same? Different? Obviously, it's very different.
Cynthia Thurlow: [00:41:12] Absolutely different doses.
Dr. Thomas Dayspring: [00:41:13] How many truly understand, apart from even the methods of administration, when you get into the menopausal hormone therapy?
Cynthia Thurlow: [00:41:20] It really goes back to education and advocacy so that women, the more they can go to their provider and ask for the things that they want. I have a wonderful Gyn locally. She's young, she trained at Duke, she's probably 32. She said, "I love middle-aged women." She's like, "You guys know exactly what you want. You're very clear. Most of you are not talking about birth control. You're very clear about what you want, very intentional." She's like, "I find it is incredibly gratifying because everyone is so grateful for receiving good care." I said, "I wish that's what every woman had." Unfortunately, that's not always the case.
Dr. Thomas Dayspring: [00:41:57] Let me throw a question at you. You probably know the words more or maybe even a gynecological question, but if a woman comes in with an IUD as far as her birth control, then I guess you could jump right to menopausal hormone therapy. Why would you have to use a low-dose contraceptive?
Cynthia Thurlow: [00:42:13] Absolutely. For some of those women who are using, let's say they're using a progestin IUD. They're happy with what-- that's working for them, they are happy with it. More often than not, sometimes you're adding in some estrogen, sometimes they actually need some progesterone. We talk openly on the podcast about how progestins are different than bioidentical progesterone. Sometimes controversial because some clinicians feel differently about that and I’m like-- in some of these women, as they are navigating that perimenopause to menopause transition, what they really need is progesterone. They have anxiety, they're depressed, they're not sleeping well. Sometimes adding in some low-dose progesterone can be very very helpful.
Dr. Thomas Dayspring: [00:42:54] This is one of the changes that even occurred since I jumped out of this field. That's why I'm asking you questions-
Cynthia Thurlow: [00:43:00] Yeah, yeah, no, no.
Dr. Thomas Dayspring: [00:43:00] -taking over the podcast because you obviously have to know this stuff. You're going to venture into that world again.
Cynthia Thurlow: [00:43:06] It goes back to bio-individuality. What works for five women may not work for five others. Certainly, getting back to some of the changes that are happening in women's bodies as they are navigating middle age, obviously changes in subcutaneous versus visceral fat accumulation. We know that abdominal fat can be very pathologic. I think about how visceral fat accumulation impacts our triglycerides and our cardiovascular risk.
[00:43:37] I always say that visceral fat around our abdominal organs, our visceral organs, is very different than pesky subcutaneous fat, which I think everyone dislikes but is much more benign in terms of its composition and how it impacts our health.
Dr. Thomas Dayspring: [00:43:54] It basically comes down to the portal vein, what drains the viscera. If the adipocytes around all your viscera in your abdomen decide to hydrolyze their triglycerides and release fatty acids into the bloodstream, they go through the liver first before they go anywhere else. Now they're in the hepatocytes. What does a hepatocyte do with extra fatty acids that it suddenly is getting continually drowned with?
[00:44:20] Triglyceride synthesis occurs. Lipoprotein synthesis occurs. The wrong type of lipoprotein synthesis occurs. That's a real easy answer on visceral adipocytes. We already discussed in pretty good depth how triglycerides are going to screw up all your lipoproteins. Why did the liver suddenly decide to become a fatty liver and start making the wrong type of lipoproteins? It's the visceral fat.
Cynthia Thurlow: [00:44:49] It's something that people really-- whether it's by ultrasound, whether it’s by CAT scan, if you've been told you have fatty liver and you have significant amounts of visceral fat, that should be one of the first things that you're working on.
Dr. Thomas Dayspring: [00:45:05] By the way, for your listeners, I threw out the word portal circulation. The portal circulation is the veins that bring things to the liver. What you eat goes through the portal--. But your subcutaneous fat, if they are released and it’s in your systemics. It goes right to the right side of your heart or the left side. It's not influencing the liver so much.
Cynthia Thurlow: [00:45:25] It makes a big difference. I always say that the subcutaneous fat that all my patients complain about, it's pesky, it's bothersome, very, very different than visceral fat for sure. A lot of questions came in around testing, and I know we were talking about this before we started recording. How would you rank the different lipid markers and tests in terms of predicting atherosclerotic cardiovascular disease?
Dr. Thomas Dayspring: [00:45:51] First thing is my definition. A lipid marker is your serum triglyceride level or your various cholesterol levels, total cholesterol, HDL cholesterol, LDL cholesterol, or calculated non-HDL cholesterol. Those are lipid metrics, and that's what the overwhelming vast majority of people get checked when they go see a clinician. They get the lipid profile, the lipid panel.
[00:46:13] Lipoprotein concentrations are very different. Lipids are what's inside the lipoproteins. Lipoprotein concentrations, you have to have a methodology that counts the number of the various and the many different types of lipoproteins that circulate. Using the knowledge of both, you'll be well more equipped to understand if there is atherosclerotic cardiovascular disease related to this.
[00:46:40] The traditional ones, which everybody looks at, whether it's LDL cholesterol or you're actually calculating non-HDL cholesterol, some labs report that calculation now, but it's easy. You take your total cholesterol level, you subtract from it the HDL cholesterol. Total cholesterol is the cholesterol that's in everything, VLDLs, IDLs, LDLs, and HDLs. So, if I subtract HDL cholesterol from total cholesterol, the only particles left are VLDLs, IDLs, and LDLs, your ApoB particles. So, non-HDL cholesterol is basically your ApoB cholesterol.
[00:47:18] If ApoB is the best blood test, the best guesstimate of ApoB is ApoB cholesterol or non-HDL cholesterol. There are endless studies showing that as LDL cholesterol goes up, non-HDL cholesterol goes up, even triglycerides goes up, your risk of atherosclerotic heart disease goes up. But the real reason is escalation of those markers are generally just reflections of too many ApoB particles and maybe too few HDL particles, because I've told you, the HDL sort of makes your kidney--
[00:47:50] After the HDL explodes, the components of it get excreted in your urine. That's the difference between lipid and lipoprotein concentrations. The lipoprotein concentrations of interest are LDL particle concentration total, which you can get by doing the NMR, nuclear magnetic resonance spectroscopic assay. Many labs offer that. There's another one, Quest is the big favorite. They count LDL particles using a technology called ion mobility transfer, very different from NMR.
[00:48:26] Each are going to give you lipoprotein concentrations, but there are different techniques of how they're coming to what your total LDL particle or your HDL particle count is. NMR has been around a lot longer. There's a lot more literature for it. If you want LDL particle counts, I would prefer NMRs to ion mobility. The guy who invented ion mobility is a real genius and he knows a heck a lot more about that.
[00:48:55] By the way, just as an aside to show, back in the 30s, they first separated lipoproteins in an electrophoretic field, a gel, an anode and cathode. You put serum in the middle of it, you turn on the current, positive, the negative, and every lipoprotein has a different charge, so it starts to migrate, and different lipoproteins migrated in different directions. They noticed that the HDL particles went in a very different direction than the ApoB particles. They didn't even know what these particles were. So, they wound up calling them beta proteins and alpha proteins, or alpha lipoproteins and beta lipoproteins.
[00:49:36] Fifteen years later when centrifugation came along, then came very low density, low density, and high density. We use that terminology for years. NMR takes urine and its subjects it to magnetic waves. The magnetic waves-- lipoproteins are full of lipids, triglycerides, cholesterol, free cholesterol, [00:50:00] cholesteryl phospholipids. The magnetic waves oscillate the hydrogen molecules on these lipids and a spectral signal comes back. This really smart computer changes the spectral signals into, "Here's your LDLP, here's your HDLP." That is highly a lot of calculus and physical chemistry to understand how that works. I don't have it. Jim Otvos, the inventor, does.
[00:50:28] The ion mobility-- I described electrophoresis to you because it's aerosolized electrophoresis. They take your serum and they aerosolize it and they shoot your lipoproteins into a chamber. Then, they turn on the current. So, the lipoproteins that are floating around go in different directions and they get trapped and they’re [unintelligible 00:50:45]. It's sort of aerosolized electrophoresis.
[00:50:50] Your people don't have to know that but I like-- Look, if you’re running a test, you ought to know a little bit about it. At the end of the day, you'll have your LDL particle count, NMR, ion mobility, or you can do an ApoB, which is typically done by immunoassay, well-standardized, been around a long time. That's how most labs will report your ApoB concentration to you. Remember, because of plasma residence time, 95% of your ApoB particles are LDLs. In essence, ApoB is an LDL particle count.
[00:51:24] Those are your lipoprotein tests, ApoB, total LDLP, total HDLP. Maybe we can get into that a little bit, whether that matters or not. You have your lipid metrics because we started off this conversation saying sometimes the lipid metrics, LDL cholesterol, and non-HDL cholesterol are discordant from the ApoB or LDLP, please always have an LDLP or ApoB on board.
[00:51:50] Don't bet your life solely on LDL cholesterol because if you're one of those discordant folks, you're going to likely be overtreated or not treated when you should be treated. That's the difference between the two. ApoB and LDLP have just as many studies showing high correlation with atherosclerotic coronary disease. You're silly if you get a high LDLP or ApoB. Even for those who say, "Oh, my LDLC is through the roof, non-HDL too, but I'm not worried about it," that's called Russian roulette to me. Some people do get away with that, the overwhelming majority do not. So, don't do that please. If your metrics do come back high, please respect them. Again, have a nice discussion with your clinician as to what they mean.
[00:52:42] But, boy before somebody tells you to ignore high ApoB or LDLP, if somebody actually says that to you, you better have a lot of questions. What study would suggest that's a wise thing to do?
Cynthia Thurlow: [00:52:54] What I see often and this is reported by people on social media, people that send in questions, there are clinicians just looking at that LDL and they're not actually looking at some of these other markers. It begs the question of, if we're going to treat this with medical therapy, we need more information.
Dr. Thomas Dayspring: [00:53:16] A quick aside to that, it gets into the particle sizes of the ApoB particles, especially LDLs, which are your predominant ApoB particle. Particle for particle, it can take up to 70% more small LDLs to traffic a given mass of cholesterol than it does big LDLs. That's why almost always people who have small LDL particles have a very high ApoB or LDL particle count, if they're not on therapy, of course, which would address that. Those are the people where your LDL cholesterol might not-- looking back because remember, small LDLs carry very little cholesterol per particle. Even when there's a bunch of them, your LDL cholesterol concentration is not in the stratosphere and you might have a false sense of security.
[00:54:01] But if you did the ApoB or LDLP, you would say, "Oh my God, despite my pretty good-looking LDLC, I'm in big trouble because of discordantly high ApoB." But just the opposite, say you have large LDL particles, but you don't have too many of them. Why is an LDL particle large? Because it's carrying more cholesterol molecules than a normal LDL particle. It takes less of them to traffic a given mass of cholesterol, but there's a lot of cholesterol in those particles.
[00:54:33] Your LDL cholesterol might be high, but your LDL particle count is not. Or it’s just the opposite, your LDL cholesterol is high, no that’s good. Your LDL particle count would be low because you just don't have a lot of them. They're cholesterol-enriched. But there's a certain point where you can have too many big LDL particles too and that's basically FH. That’s when your LDL cholesterol is 160, 170, 190, virtually none of those have a normal ApoB.
[00:55:03] You might have an LDL cholesterol of 100, 110, or 90, which might be a little worrisome, but your ApoB there would be okay because you just have big LDL particles, but you don't have too many. Never believe big LDL particles can't hurt you. If like small LDLs, when they are present in excess numbers, they'll crash your [unintelligible 00:55:22] wall just as easily. The VLDLs, which are three times the size of LDLs, even the biggest LDL, have no problem crashing your artery wall. The mantra of big LDLs per se are protective is nonsense. This explains it's the cholesterol composition within the particles.
[00:55:47] One last thing, the volume of a sphere is a third power of the radius. It's four-thirds pi radius cubed. That's how you calculate the volume of a balloon. I always used to show a nice graphic on this. How many people know it takes 16 marbles to fill the volume of one ping pong ball? You would never guess that. That's because the marbles, which are much smaller, the ping pong ball is much bigger, but the volume is a third power of the radius.
[00:56:18] When you do third powers of anything, your numbers jump up real quick and I heard. Even a few nanometer increases in particle sizes, HDLs or LDLs, translates into the ability to carry a whole different amount of lipids in there. Typically, the LDLs and HDLs are carrying cholesterol, not so much trigs under normal circumstances. There's a little bit of geometry involved with lipoproteins also.
Cynthia Thurlow: [00:56:46] I'm dusting off cobwebs in my brain. But I think for people listening, when I was still functioning in Cardiology, we did a lot of these particle sizes and we would say to patients, right or wrong, "You've got light, fluffy, buoyant particles versus these small, dense which are the ones that we think are more atherogenic." And I think that, correct me if I'm wrong, things have evolved over the last nine years. That just gives a piece of information, that is not the sole information. You definitely don't want to solely focus on particle size to determine relative risk or concerns.
Dr. Thomas Dayspring: [00:57:27] I hate the term fluffy because fluffy--
Cynthia Thurlow: [00:57:29] That's what we used to call it, fluffy, it's benign, it’s benign. Exactly.
Dr. Thomas Dayspring: [00:57:33] If you have too many fluffy LDLs, hello CCU in the future. That term was first used, I believe, by Bill Castelli from Framingham. He started talking--
Cynthia Thurlow: [00:57:42] Yep.
Dr. Thomas Dayspring: [00:57:43] And those were the days when even they didn't know what the heck these meant because they were just the first discoverers of these things. There were certain generalities that they applied for and they had to come up with a cool term. So, fluffy LDL. We now know, because I just told you, VLDLs which are immensely bigger can crash your artery wall. Fluffy LDLs, if there's too many of them, have the ability to go in your artery wall too.
[00:58:07] Where particle sizes can really help you, and this is probably one of the things you wanted to discuss, because when people order the NMR, they're probably not just going to get back an LDL particle count or an HDL particle count. Oftentimes, you get what's called their LPIR score. This is where knowing the sizes of various lipoproteins can help us diagnose insulin resistance without [unintelligible 00:58:34]. Of course, nobody does for your listeners. That's putting an IV in somebody, infusing glucose, and see how much insulin does it take to keep your glucose level normal. It's the best way of determining in a metabolic ward is this patient insulin resistant or not.
[00:58:52] They did these studies and they brought people into these metabolic wards, made them insulin resistant, but then they analyzed what happened to their lipoproteins as insulin resistance was occurring. So, the lipoprotein changes that occur. And by the way, these changes occur way earlier in life than do raises in your serum insulin level and decades before your glucose starts to escalate into a pre-diabetic or a diabetic range.
[00:59:20] It basically all comes down to triglycerides. Insulin-resistant people have too many triglycerides. That means because of your visceral adipose tissue and your liver, all of a sudden got a lot of fatty acids which changes to trigs. What does the liver do? The liver wants to get rid of the triglycerides to prevent fatty liver from developing. Its first line of defense is to export the trigs. How does it do that? It decided to-- making VLDL particles. If you're not insulin resistant, you make normal size or even small VLDL particles. You absolutely do not make big VLDL particles. When your liver is full of trigs, the liver starts making your VLDLs that it's going to excrete big, big, big. They're triglyceride-rich.
[01:00:08] Two things happen in the bloodstream. If you measure it, VLDL diameter increases, but large VLDL particle concentration goes up. The first two markers you're going to see on the LPIR score, lipoprotein insulin resistance score using NMR is, “Wow, the concentration of large VLDL particles is going up and your VL diameter is going up.” You'll see on the result, it's going to be in the red zone, the yellow zone or the green zone.
[01:00:42] Those are the first two metrics they look at. I've already told you, when a VLDL comes out and is full of trigs, it starts transferring those trigs over to HDLs and LDLs. What happens to the LDL? It becomes triglyceride-rich and very quickly becomes a small LDL and the particle number goes up because you can't clear small LDL particles so readily.
[01:01:04] The next thing they look at on the LPIR score is, what is your LDL diameter? If you're small, that's a sign of insulin resistance in most people. If it's not small, you might not have insulin resistance. Then they also look at the small LDL particle count and if that's increased, you are insulin resistant.
[01:01:28] I always like to point out, “Yes, they're going to tell you your small LDL particle goes up”, and everybody panics, "It's a small LDL." But guess-- if your small LDLs go up, guess what else goes up? Totally LDL particle count, ApoB goes through the roof. There is nobody who has excess small LDL particles that doesn't have an increased total LDL particle count or ApoB. Never forget it. Those are two markers that tell me you are insulin resistant.
[01:01:54] The last two, I told you what happens when the VLDLs and even the LDLs send trigs over to the HDL. Hepatic lipase, it becomes a small HDL. A big HDL becomes a small, HDL diameter decreases. You no longer have big HDL particles. What the NMR, LPIR score reports to is large HDL particle concentrations because the more insulin resistant you are, the trigs have destroyed your large HDLs. You no longer have large HDLs.
[01:02:31] By the way, large HDLs carry most of the cholesterol. Of course, your total-- HDL cholesterol is going down also. That's not part of the LPIR score, but that's typically why people with high trigs have low HDL cholesterol. Your last two markers, you don't have big HDLs anymore and your HDL diameter is now decreased.
[01:02:52] They've developed an ingenious algorithm where they score each of those six lipoprotein pathologies that I described. They're weighted and they have this complex algorithm that weighs them. It's published. You can see how much weight they put on the VLDLs versus small LDLs. At the end of the day, they generate an LPIR score. To make it simple, 0 is no insulin resistance, 100 is welcome to the diabetes family, 50 is in the middle, but obviously, you want to be well below 50. You don't want to be above 50 in any direction. That's a very useful test. As I said, nobody's doing insulin. It's better than HOMA-IR, even insulin levels, which are a tricky assay that can jump all over the place and vary day to day, week to week.
[01:03:44] The LPIR score is really a good date, but it's used to diagnose insulin sensitivity. Now, how do we treat insulin sensitivity? It's a whole kitchen sink of therapy, starting with lifestyle primarily. But if the total LDLP is up and the ApoB is up, which invariably it is when your score is above 50, then you are on lipoprotein management along with your insulin resistance management.
[01:04:09] That's why in NCEP ATP III, 2004 I think, they described this new entity called metabolic syndrome. It's basically what I've just described. It’s-- The criteria are of course your glucose, your waist size, triglycerides, and what is not on the metabolic syndrome, blood pressure of course. There's no LDL cholesterol as part of the criteria for metabolic syndrome, but all of those metabolic syndromes have high ApoB.
Cynthia Thurlow: [01:04:39] I think that's important for people to realize that maybe not every clinician is doing an LPIR score, but I think for a lot of individuals it can be a differentiator when they're on the fence. Maybe their A1c is starting to creep, maybe their fasting glucose is not optimal, maybe their fasting insulin looks okay, but as you said, it can vary day to day and depending on what's going on in someone's personal life. I think this is another way that we can evaluate patients in a way that is objective.
Dr. Thomas Dayspring: [01:05:12] Look. There are other things that can raise glucose a little bit that are not related to insulin resistance. The score can make out-- "This is definitely insulin resistance here," because that has a very prescribed therapeutic avenue that you venture down.
[01:05:28] I have got to mention in this though, the criteria for the metabolic syndrome, probably the largest group of metabolic syndromes that are out there are African Americans. But African Americans, through a variety of reasons, do not typically have high triglycerides or low HDL cholesterol. How do they qualify for metabolic syndrome? Hypertension, glucose elevation, and even with their visceral adiposity, they don't manifest the hypertriglyceridemia. That's the one class of folks that, as important as trigs is--
[01:06:01] We've basically been talking about Caucasians and Hispanics and Asian Indians, but African Americans, never write them off because, "Oh, your triglycerides are pretty good, your HDL cholesterol is good. I'm not worried about you." Look at their blood pressure, look at their glucose, look at their waist size, all strict parameters of insulin resistance. Just keep that in mind. This whole spiel about trigs that we've talked about a lot today may not apply to you African Americans. What does apply to them is Lp(a).
Cynthia Thurlow: [01:06:34] I think you said 50% of African Americans have high Lp(a) and again, it goes back to every single person listening needs to know their Lp(a), and it probably needs to be lower than what your clinician is telling you.
Dr. Thomas Dayspring: [01:06:48] It's funny, we had a block party in our neighborhood home owners association last night and a fellow neighbor, he likes to sit next to me at these events. He comes over, he goes, "Tom, you told me last time and I forgot what you told me. When I go see my doctor next, [Cynthia laughs] what are the-- You said there were two blood tests I had to have." He was an African American man, aged 60.
[01:07:12] I said, "Well, there's two. One is called ApoB," and I spelled out what Apo stands for. "And this other one Lp(a)," and I spelled out what that is and made sure he's looking at the lowercase little a. I said, "Now here's the bad story." I said, "Upwards of one out of two African Americans have a really high level of this and it is the number one genetic cause about--." I could see a little bit of sweat. "Oh my God. Then you're going to have to tell me what diet I can go on." He was a little bit overweight. I said, "You probably need a diet for a lot of good reasons for cardiovascular health, but it's not going to help your Lp(a) per se." There are anecdotal reports, the guidelines and people who know about this say-- no, so if that is your issue, I just told him, "Hey, knock on my door, leave behind me, and we'll discuss what else you have to do. Basically, I have to hook you up with a good provider here in the Michigan area who understands Lp(a).
Cynthia Thurlow: [01:08:15] I think that goes without saying, but again, it's just there are those little pearls that you drop throughout our conversation, just reiterating Lp(a) is very important.
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