AMA #2: Why a 'Perfect' LDL Won't Save You--Plaque, Statins & Metabolic Health

A live, unfiltered Ask Me Anything on preventive cardiology and metabolic health — recorded on about three hours of sleep after a night in the OR, which tends to make me a little more candid than usual.

We cover the questions you actually ask: how plaque forms and how to stabilize it, what the "best" diet for cardiovascular health really is (spoiler: it depends on you), statins from every angle, Lp(a) and ApoB, the lean mass hyper-responder phenotype, GLP-1s and dementia risk, coronary CT angiograms and the AI tools reading them, carotid disease and how I think about stenting vs. surgery, and a few honest detours into supplements, what I eat, and why medicine is so much better at rescue than prevention.

No oracles here — just an informed guide working the front lines, thinking out loud with a curious, generous audience. Use the chapters below to jump to whatever you came for.

⚠️ Educational content only. This is general information, not personal medical advice. Talk to your own clinician before changing any medication, supplement, or treatment plan.

Chapters
0:00 — Welcome + how this AMA works
0:58 — High CAC score but a clean carotid duplex: how can both be true?
3:45 — Cleerly vs. HeartFlow: which AI coronary CT analysis is better?
6:26 — The "best" diet for cardiovascular health (there isn't just one)
10:59 — How to actually find a preventive / metabolic cardiologist
13:08 — Amlodipine, dizziness, and tachycardia after weight loss
14:41 — Do you need an ApoB test if LDL is already low on a PCSK9 inhibitor?
16:26 — The fibrous cap: can you thicken it and stabilize plaque?
18:59 — How does arterial plaque actually form? (Atherosclerosis 101)
23:47 — Beta blockers, AFib, and valve repair: a medication for life?
28:09 — When statins raise Lp(a) but lower ApoB
30:10 — How is familial hypercholesterolemia (FH) diagnosed?
32:20 — Erectile dysfunction and vascular health
33:46 — Statins, the full picture: benefits, side effects, and monitoring
45:23 — Lean Mass Hyper-Responders (LMHR), high LDL, and a clean CT
51:59 — Gene therapy for high cholesterol: promise and unknowns
56:04 — Rosuvastatin every other day vs. daily
57:20 — Best statin for ApoE4 carriers + the obicetrapib (CETP) story
1:00:57 — Easing statin muscle pain: CoQ10, vitamin D, gentler statins
1:02:15 — Is high cholesterol a sign of a liver problem?
1:04:24 — GLP-1s and dementia risk: what the data show
1:09:20 — Can your LDL be too low?
1:12:02 — Longevity influencers and GLP-1s
1:13:23 — Saturated fat and LDL cholesterol
1:15:22 — How often to order coronary CT angiograms — and why AI overlays worry me
1:23:19 — What tests prove your heart is healthy? (Why stress tests miss plaque)
1:28:24 — Citrus bergamot with statins or PCSK9 inhibitors
1:29:55 — Bypass conduits: mammary artery, leg vein, and radial artery
1:30:47 — What supplements I personally take
1:34:13 — What I personally eat
1:37:17 — Weak, rolling veins and difficult blood draws
1:38:12 — Why there's still no screening program for the #1 killer
1:44:42 — Is there a CIMT-style test for the heart?
1:45:43 — Post-COVID and post-vaccine vascular problems
1:48:13 — Can surgeons operate from a CTA, or is an angiogram needed?
1:51:25 — Do we use robots in vascular surgery?
1:54:29 — Carotid stenting vs. endarterectomy (and the CREST-2 results)
2:02:19 — Lp(a) of 295, Repatha, and when new Lp(a) drugs may arrive
2:04:17 — At what degree of carotid narrowing do you intervene?
2:07:01 — Book recommendations (and a preview of "Disconnected")
2:13:46 — Bonus: how much do I trust the gut microbiome science?


Resources mentioned
Bale-Doneen Method provider directory: https://baledoneen.com/find-a-provider/
"Healthy Heart, Healthy Brain" by Dr. Brad Bale & Amy Doneen: https://amzn.to/4o3GvGv
My Lp(a) video series — start with the first explainer on how Lp(a) is measured (mg/dL vs. nmol/L) and the "Lp(a) — what now?" follow-up:
https://youtu.be/i761M_-zjJQ?si=7yjVJ46GC60Mk85a
https://youtu.be/ZdUxECOqd1o?si=i8DhYKF55lKLSafy
My two videos on the lab tests I recommend beyond a standard annual physical (Lp(a), hs-CRP, fasting insulin, HOMA-IR, and more):
https://youtu.be/vPw38B9QzjM?si=E1HJqn-bKwOW10Xb
https://youtu.be/vwORTxzeEMg?si=CpFnD3-MRJjbw39p

Let's keep going
If you'd like this to become a monthly feature, say so in the comments — and tell me which questions you want answered next time. Got a bike-tour recommendation? Drop it in the comments!

High Quality 3rd-party tested supplements at Fullscript (10% discount): https://us.fullscript.com/welcome/ljohnstonmd/store-start

___________________________
🧬 About Dr. Lily Johnston
  
Dr. Johnston is a double board-certified vascular and general surgeon in San Diego, specializing in metabolic and cardiovascular prevention. She’s the founder of CorSight Health and a passionate advocate for reimagining how medicine approaches chronic disease.

Transcript

SPEAKER_00 0:06

Hey guys, happy Saturday. Welcome to the next Ask Me Anything. We are here live today, and I am so excited for you to have an opportunity to chat together and ask me the questions that you have. You are gonna get the benefit of uh my least filtered perspectives. I was up most of the night operating, and usually that leaves me a little bit chatty and uh unreserved the next day. So hopefully we will have a great time. I know you guys have come with amazing questions. So let's get into it. If you want to put those questions in the chat, please do so. If you are concerned about your privacy, there is also a link for a Google form where you can ask anonymously, and I will be monitoring those responses as they come in. So I see Tron is here. Hey Tron, I remember that you had asked a question leading up to our Ask Me Anything because you were so excited and I'm so happy that you're here. Thank you for coming. Uh, you were asking about whether it was possible to have a positive calcium score in like 500 range, but a negative carotid duplex with not even a smidgen of soft plaque there. And how did that make sense? So it is absolutely possible. It is not terribly common, but the overall concordance, meaning the um agreement between coronary imaging and ultrasound of the carotids and the femorals when put together is about 90%. So you might be in that 10% of people who do not have uh imaging that is concordant, and I have seen a few of those patients, but plaque one spot is plaque, and we manage that accordingly. You know, the evaluation of plaque on a duplex, some techs are better at looking at that than others, and some people don't spend as much time going hunting for those little areas of plaque as I might. So, you know, I don't totally take that on face value that they didn't see anything. The other thing I would say is I have patients who don't have imaging in the carotids, but I do look at their femorals as well. We do see plaque tend to form a little bit earlier in the femoral arteries than in the carotid arteries. So if we're suspicious or if we're really on a hunt and concerned that there may be disease present that we haven't seen yet, actually going to image the femoral arteries with ultrasound as well as the carotid arteries can be a way to help improve the diagnostic accuracy of that test. And uh putting in some spa days, we'll see. I'll I'll maybe think about that. I'll get there. All right, we have Lisa Rs Art. Hey, how are you? Thanks for being here. Terry is here. So good to see you, Terry. Thanks for coming. All right. What do you guys want to know about? What are we gonna talk about today? Okay, good. You're gonna get that. While we're thinking about that, I will go ahead and mention somebody had asked me in a comment recently if there were um if we knew something about whether clearly or heart flow were better as the two kind of main companies that are doing AI analysis of CT and geography. And um, there is not necessarily a clear winner. I will say if you have been monitoring any of the keto CTA trial, then you may be aware that there has been some issue with the quality control of Clearly's research data set. I don't know to what extent those issues might also be represented in their clinical data, meaning the scans that they're doing for individual practices, physicians, and patients. Uh so I'm a little more hesitant about clearly than I used to be, just based on the experience of that trial team. Um, heart flow is a little less polished in terms of the report that they deliver, but they are validated against a more invasive technique. And so um I think some people are sort of shifting towards heart flow, but it's hard to know exactly what the true baseline truth is when we're trying to decide how accurate the AI tools are because they're doing so much more than their average radiologist. And that's not anybody's fault. It just happens to be the amount of quantitative data that's available uh through these overlay tools versus what is usually available in the normal radiology report. So, short answer, we don't know. I think either of them are completely valid as a step one, do I have plaque or don't I? An evaluation. If we're thinking about using these sequentially over time to monitor progression, regression of disease, then I would say stick with the same company you had done the first time. And we're gonna need to pay attention moving forward with the validation data that these companies deliver in terms of how reproducible, reliable are their results, and what is the minimum detectable change that represents true change rather than just statistical noise in their data set. And we don't really have a good sense for that just yet. So if we're looking to use these to monitor over time, stay tuned for how that's gonna go. But I would say whichever company did your first analysis, I would stick with that one going forward, and time will tell how sensitive these really are to small changes in plaque volume. Okay, we're now the now the questions are rolling in. So Lisa asks, I wonder what you think about the diet for a good cardiovascular health. Um, I hear so many recommendations. I love Greek yogurt and make it myself. Should I go more towards plants? So, this is a question about what is the best nutritional strategy for just cardiovascular health versus what is the best nutritional strategy for your life? And I'm not sure that these are uniformly the same because yes, absolutely cardiovascular disease is the number one killer of men and women worldwide. And we are here in this channel and many others doing our best to use, especially lifestyle as this key part of our foundation to help mitigate, reverse, and prevent that disease. The diet I know will lower your LDL is maybe not the diet that is going to minimize your insulin sensitive or minimize your insulin resistance is maybe not the diet that's going to manage a couple of other conditions you might have that are not terribly well treated with conventional medical therapies. And also these may not be things that are conducive to your family life or your home life. All of these things come into play. So the diet that has a randomized controlled clinical trial for cardiovascular events is the so-called Mediterranean diet or the PEDIMED study, is how this was uh studied. And it used, you know, mostly fish, lean meats. They did use a lot of whole grains, fruits and vegetables and nuts and olive oil as the predominant food groups within that nutritional strategy. And they did show over time a reduction in cardiovascular events. Um, you can do a low glycemic, even a low carbohydrate, or even a ketogenic Mediterranean style diet. You don't have to. Mediterranean is a catchphrase that people in the nutrition space kind of roll their eyes at because everybody has a sense for what it means. But if you truly study Mediterranean diet across all the cultures in the Mediterranean, it's highly variable. Some eat much more red meat, some eat very little and much more fish. Um, nuts seeds and legumes are different across those cultures. So it's a it's a catch-all phrase. And I tell patients that, you know, if you are emphasizing whole foods, I think that's the best place to start. But I want for any individual person, if you're asking, how do I change my nutrition to support my cardiovascular health, then we need to understand what are the things in your health profile that are concerning risks? So for you, is it insulin resistance? In which case, I might not recommend a, you know, diet with a lot of grain in it, um, depending on how you tolerate carbohydrates. If your main issue is inflammation, then perhaps we need to think about what in your diet is pro-inflammatory and consider limiting that. And that may not be the same for everyone. We might have to do an elimination trial and figure that out. And if your main issue is food addiction, then we may have to figure out how to, you know, construct your nutritional plan around a series of foods that does not trigger your food addiction so that you can modulate your energy intake appropriately and achieve, you know, a healthy body composition. If your main issue is that you're not fit and active enough, then we need to construct a way of eating that is going to support your exercise and movement goals. That's really frustrating because there's not one diet, there's not one easy answer for any person. And I never want to pretend like there is. And in a, you know, quick fix social media world, that is a very unpopular thing, right? Everybody wants one meal to clear out arteries, and um, you know, this one food is gonna melt your visceral fat. And, you know, it it gets clicks, it gets headlines, and there are population studies, but for any individual person, it may or may not be the right thing. So, all that to say, nutritional choices are challenging. And if you want to talk about which diet I recommend for any particular biomarker or issue, then that's um something we can also get into. But if you want the textbook answer for what is the optimal diet for cardiovascular health based on the trial data we have, which are imperfect, it would be the Mediterranean style diet. All right, questions are rolling in. I'm coming back up here. Tron asks, how do I actually find a prevention metabolic cardiologist to help out with these extra concerns? Neat question. Um, we are few and far between. Most of us are picking different names. So there are people who specialize in integrative cardiology, preventive cardiology. Uh, I don't know how how many vascular surgeons are out there doing this besides me. I don't think I've met one yet. And there are folks who do something called the Bale Dunineen method, which you may have seen me reference in videos and comments before. That is by Dr. Brad Bale and uh nurse practitioner Amy Dunine. They have kind of a holistic approach to reducing risk for cardiovascular disease that I have uh learned from and incorporated some of their tools and techniques into my practice as well. So if you want to go to baeldonin.com, there is a provider directory there. You may be able to find somebody who is Bale Danine certified. Uh, please note they will also have some dentists listed. So make sure you're checking for a non-oral health clinician. You might be looking for a nurse practitioner physician and uh go use their provider directory, and that might be another place to start. But it's not straightforward. There are many of us, and we don't all take the same approach, right? Everybody is doing the best they know how with the data they have. I know a number of preventive cardiologists who are very bullish about a whole food plant-based approach for everyone and think that that is absolutely required for optimal cardiovascular health. Uh, if you have been here for any length of time, you know that I don't completely agree with that. I also won't fight it for some patients, but uh I'm not convinced that it's the best for everyone. So you should be able to find yourself an integrative preventive cardiac specialist somewhere, but I don't know what their philosophy is going to be and if it will match with yours. But this is an evolving, a very interesting space, and we are all here trying to help and all trying to do the best we can with our own interpretation of what these sometimes messy data tell us. All right, LPD 688. Can emlodipine cause dizziness and tachycardia with significant weight loss? And should I be worried? Does that mean that if you're losing weight, will the emlodipine cause these issues? Um, it what I suspect is if you are losing weight, your blood pressure may have come down by itself. And the mlodipine, which is a blood pressure medicine, can be actually dropping you too low. So often, if I am working with patients through a fat loss or a weight loss journey, uh, we are monitoring their blood pressure because oftentimes, especially if they're using a low carbohydrate approach, uh, fasting insulin will drop. They will urinate out more sodium, and then blood pressure control is suddenly a lot different and a lot better. So all of the medicines they were on to manage blood pressure are suddenly not as necessary or certainly not in the same dose. So if you have lost some weight, I would encourage you to get a blood pressure monitor and check your pressures when you are feeling that way, especially if it is as you're standing from a sitting position or as you're sitting up from a lying down position. That is something called orthostasis or orthostatic hypotension. So it means your body's just not accommodating to the change in position quickly enough and you get a little lightheaded or dizzy because your brain is fighting gravity and not quite getting enough oxygen. So check your blood pressure and see if you're actually reading too low once you're finding those symptoms and you may need to talk with your clinical team about reducing your dose or eliminating your dose. Okay. Is it necessary to test APOB if your LDL is already low on a PCS canine inhibitor approximately? LDLC, I'm guessing, of 50 milligrams per deciliter. So thanks, Terry. The answer is it probably isn't going to change your management. You are already aware that you've got some risk, and this is why I'm sure you're on a PCS canine inhibitor to lower your APOB and your LDLC. If you know your triglycerides and your triglycerides are under 100, I would say the odds of you doing something different based on an APOB level is unlikely because you're probably pretty what we would consider concordant, meaning your APOB is going to track pretty well with your LDLC. Um, if you have significantly elevated LP little A, if you have significantly elevated triglycerides, either from lifestyle or from a family history, um, you know, dyslipidemia inherited issue, then you might find that your APOB is discordantly high and you might have a more aggressive target for treatment and you might add on other agents besides just the Rapatha or the PCS canine inhibitor to get your APOB down to the correct goal. So if you think that there's something missing in your prevention strategy or there's maybe something going on that's a little atypical for you, it wouldn't hurt to check an APOB. It's not an expensive test. And as long as your APOB is also at goal with your LDLC, then that's probably all that you need. And I certainly wouldn't follow it over time. You can just use the regular lipid panel for that and make sure that your strategies are still working for you. But if there's some concern, then you could get it checked once and see where you land. Tron, why did God make the covering over the plaque only one cell thick? And what can we do to thicken that, if anything, at all? So the fibrous cap that sits over top of this plaque, right? This lipid-rich sort of magma inside the volcano is um contained by this fibrous cap and uh it can be thickened. We we certainly know that the thickness of the fibrous cap is related to risk of rupture, even risk of erosion, which are two slightly related um but separate things that both cause heart attack. And stabilization of the plaque in part refers to thickening of the fibrous cap. So the things that will do that are ultimately like exercise, blood pressure control, lipid management therapy, uh management of your insulin resistance and your hyperinsulinemia, if that's a problem for you. All of those things, I think we have good evidence, at least indirectly, will help stabilize that plaque and help that cap thicken over time, which I think is sort of the body's natural inclination, is it would like to thicken that cap. It's a question of how much ongoing inflammation is there. Are there enzymes or active compounds like matrix metalloprotenase 9 or MMP9 that are actively chewing away at that fibrous cap as your body is trying to build it and stabilize it? And if those are present, then of course we're in this, you know, sort of battle of the cap and we need to figure out how to come out on the side of stabilization. But it's all the same boring stuff we usually talk about. I don't think there's anything unique or special, but this is the this is what we need when we're talking about plaque stabilization. All right, Gerard Webster, hey, how you doing? The heart flow results helped get me going ASAP to get fixed up. Awesome. I'm so glad to hear that. Thank you for sharing that. All right, who else we got? Hawkins, 60-year-old female on CIMT results, mild hypercholesteremia 57 LP little A. So for if you're gonna give me LP little A numbers, we have to have the units with them because um 57 milligrams per deciliter is actually a much different answer than 57 nanomoles per liter. If that is confusing, please go check out the first of our LP little A video series where I go through how it is measured and uh what the reference ranges are for the two different ways that we measure LP little A at present. Tom Smith, fatty red meat, one meal that covers all your needs. Yeah, um I am familiar with your approach to that. That works really well for some people. I will say it does not work for everybody. If it's working for you, by all means, you do you, and that's awesome. Um, if it for whatever reason is not working for you, that's okay too. We'll find another option. But uh I encourage everybody to listen to their body, get data, and keep keep track of things. That is that is how I tend to practice. As a general question, says Tron, how does the plaque get there? Is it because inflammation somehow, the foods we eat that cause inflammation? So this is a how does plaque form sort of one-on-one situation? And the question becomes how do particles get retained in the subendothelial space? So we talked about when we talk about CIMT, there are three layers to the vessel wall, the artery wall, and the there's the endothelium, which is the single cell layer that's on the inside of that flow lumen. Then we have the intima, the media, and the adventitia. The subendothelial space is beneath that endothelial cell layer and lipoproteins, which carry, for example, your LTL cholesterol, your very low density cholesterol, all of those are carried on proteins. And so these are called lipoproteins or lipid particles. They travel in and out of that subendothelial space with some regularity. They can also get stuck there. And what causes them to get stuck are some increase in proteoglycans and things that make it more like velcro and less like WD40. So what you'd like is a nice slippery subendothelial space so stuff comes in, comes out, doesn't stick around. But if it gets all gummy in there and it gets sticky, then those particles stick, they accumulate, and eventually the immune system tries to manage them by oxidizing them or incorporating them into macrophages. The uh immune cells will eat those lipid particles, they become foam cells. This sets off another cascade that ends up transforming our vascular smooth muscle cells in the lining wall of the artery into other types of cells that proliferate and cause thickening of the wall. And then here we have a plaque. What starts that process of the subendothelial space becoming sticky is a number of different things. It could be hyperglycemia, too much sugar in the blood. It can be too much insulin, which produces nitric oxide and creates stiffened artery walls that don't relax or dilate normally. And then they get little injuries because the blood pressure pushes up against the wall and we can't relax. And so that creates a stress force on the wall of the artery, and that is enough to start this process. It could be a toxic exposure, like nicotine, for example, is damaging to our endothelium. And that also will cause particles to be retained and for this whole process. To move forward. Autoimmune diseases, rheumatoid arthritis and lupus are particular ones of concern that have a significant elevation in risk for cardiovascular disease. Loss of estrogen seems to be related to cardiovascular risk and poor vascular health. So all different kinds of things can start off this process that lead to the common endpoint of plaque. And I consider it my job to help my patients dig and figure out what are the one or several root causes that might be resulting in plaque formation in them, right? Because not everybody is a smoker, not everybody is a type 2 diabetic, not everybody has LP little A, but if we think about this like big broad list of things that could cause plaque, we can run down that checklist and figure out which one or several you might have. And then we tailor our approach accordingly, because my approach will be different if you have an autoimmune disease than if you have familial hypercholesterolemia, right? Those are very different pathologies. Yeah, they sure end up with plaque and heart attacks, but like I wouldn't treat them necessarily the exact same way. So the mechanism by which plaque forms and starts is a little different for everybody, I think. And I hope that by understanding more about that, I am helping people really manage that risk in a much more informed and useful way than just here's your aspirin, here's your statin, and uh let's hope for the best, which is kind of what we used to have. All right. Hi Rena. If someone has a leaky heart valve repaired and aphib in the past, is beta blocker a drug they would have to take for life? What would be the determinant of having to take or able to get off? Um, so the question is about an abnormal heart rhythm called atrial fibrillation that can happen after any kind of heart surgery. So it sounds like there was a heart valve that was replaced. And after that, uh this person developed this abnormal heart rhythm called atrial fibrillation. And the issue with atrial fibrillation is that the top chambers of the heart, the atria, are now doing their own thing. We what we want is a nice steady rhythm dance between the top chambers of the heart, the atria, and the bottom chambers of the heart, the ventricles. They should pump in coordination. The idea is that the electrical system in the heart is supposed to trigger a sequential contraction of the atria and then the ventricle. And this gives us the most efficient pumping mechanism to move the blood through the different chambers of the heart and out into circulation where it needs to be. In atrial fibrillation, there is a mix-up in that electrical signal and the atria or the top chambers are doing their own dance. And they're typically pumping faster than the ventricles. This creates an inefficient uh pumping mechanism, which most patients tolerate okay, although not everybody feels good. It can generate an elevated heart rate. And the job of this beta blocker medicine that you're referencing is to lower the heart rate. So this is a rate control strategy that your team has uh decided on for you. There are other medicines that try to use uh different, you know, uh calcium channel blockers or like other ions that um are going to help change the rhythm of the heart itself, actually reset that electrical system so that the top and bottom chambers beat together. So that is a rhythm control strategy. Those drugs are uh a little bit more nuanced in terms of which ones people take and why and how to monitor for side effects and complications from those medications. Then we get into questions about anticoagulation or thinning of the blood, because when those top chambers pump inefficiently, blood can pool there and form clots, and that can be responsible for stroke or blood clots going to other parts of the body, which is highly undesirable. And as a vascular surgeon, I will go fish those out from time to time. Um so, and also the last thing would be: are there any recommendations for procedures to try to restore a normal rhythm? Uh, so that would be like an ablation procedure or a cardioversion procedure to see if there's some way to reset that system in the heart to get you back out of atrial fibrillation. Um despite what I have just been going on and on about for a couple of minutes, I am not an expert in heart rhythm issues. I would not be a great person to tell you whether you can ever get off your beta blocker. What I will say is if you are having side effects from your beta blocker, please talk to your cardiologist about this and see if there are any other alternatives for you to help manage your situation. Um, and if you are not happy with that answer, go get a second opinion. Uh, this is, you know, medicine is a wonderful, wonderful tool. And not everybody tolerates every strategy or approach. And we have to sometimes get creative about how to allow patients to live their best life while managing chronic conditions like atrial fibrillation. So that is a total non-answer to the question, because I don't know is really the answer. But I hope that if you are having trouble with it, then you can talk to your clinician and try to find a strategy that's going to work better for you in the long run. And perhaps if there's any sign that your atrial fibrillation goes away in the long run, then maybe we can be off of medications completely at that point. Um, if you are lucky enough to have that as your outcome. All right. Hi, Stephen B. Nice to see you here. All right. Just going through some more questions here. Peter Smith, how are you? Strong family history, APOB in mid-60s on 10 milligrams of Zedia. When taken with Resuvastatin, APOB was 42, but LPA was 101 animals per liter. Off statin, it dropped to 62 nanomals per liter. Take the statin every other day. So this is the question about statins occasionally raising LP little A, but dropping APOB. The general consensus is that lowering APOB outweighs the increase in LP Little A. That is the sort of lipidology bottom line. Um there are other agents like PCSK9 inhibitors that will actually reduce your LP little A as well. Uh you may also choose to lean heavily into some of the data suggesting that waste-to-hip ratio and metabolic markers may mitigate the risks of LP little A. Um, I think for me it would depend a little on what the plaque burden is, if any, and what the sort of desire to maximally reduce risk is versus the convenience of pills versus the inconvenience and cost of the injectable medications, any side effects that you might be having with your meds. Um, but the the textbook answer to your question is you can stick with your resuvastatin and drop your APOB down, and hopefully that is uh overall producing more risk reduction than your that that's by far and away offsetting the small increase in the LP little a that comes from that. Um we do discuss this in part two of the LP little a series, and it that's the LP little a what now video for anybody who is curious for a deeper dive on that. Uh Terry asks, how is familial hypercholesterolemia determined? So there are a number of different ways that this is addressed. The most common clinical criteria used now that I use in my practice is two or more measures of LDLC greater than 190 milligrams per deciliter and an immediate family member with the same. So if you had a sister who also had an LDL measured of 190, then that is essentially a clinical diagnosis of familial hypercholesteremia. There are a number of genetic tests that can be done. Most people with familial hypercholesterolemia have a defect in the LDL receptor, but there are a number of other variants that can generate this phenotype. By the way, mostly what we're talking about are heterozygous FH. Most people who have homozygous FH, meaning two different alleles that are causing severe, severe elevations in their LDL cholesterol, are typically diagnosed in childhood because their cholesterol levels are so high and they have a strong family history because they're generally getting one allele from each parent. So by and large, we're catching cases of homozygous FH early in life. But for people who are showing up and presenting to their primary who've never had labs before, who were showing up in their 30s or 40s with an LDLC of, you know, 250, that is somebody that we're going to screen for FH. If you have that diagnosis, then we're going to also recommend that your immediate family members, siblings, and children in particular, also be screened just with a lipid panel to see whether they might also meet criteria and warrant further investigation. All right. Oh gosh, there is such a great cat here. I'm having trouble keeping track of it. I'm gonna go to some of the anonymous questions. Let's see. We have to. Can some type of erectile dysfunction be reversed, improved through statins, PCS-K9 inhibitors, and or vascular surgery? Um there is not a vascular surgical intervention that is commonplace for this. Uh, it is, I think, possible that stabilizing plaque might help, but that is not a super common therapeutic indication for these medications. Um, certainly we have good evidence for the phosphodiesterase 5 inhibitors that as the Viagra cialis group of medications. The other thing I would uh encourage you to look into would be um shockwave or ultrasound-based treatments that can create more small capillary blood vessels in the corpus of the penis itself. And uh I have had a colleague who's had very good results with uh shockwave in his practice, using that for men with ED, and in combination with improving the vascular health on the inside, meaning all the things we're talking about, like stabilizing plaque, improving your insulin sensitivity, getting your own nitric oxide pathway functioning better with more exercise, all of that combined can lead to very successful management of erectile dysfunction if it is vascular in origin for you. All right. Another anonymous question Can you please talk about what to look for when taking statins and how to objectively measure each? Good, bad, and ugly of statins. Okay, so statins are a medication that is taken to lower LDL cholesterol or APOB, and it functions in the synthetic pathway. It blocks an enzyme called HMG CoA reductase. And this is a fairly high, meaning top-level enzyme in the whole cholesterol synthesis pathway. And the statins, when they are taken orally, are absorbed, and that is active through many different tissues in the body. It is predominantly active in the liver, but we certainly know that it is also active in the muscle tissues, for example. And it does a pretty decent job of producing LDL cholesterol, especially through this synthetic pathway. The bottom line is even though it's a synthesis inhibitor, that has the ultimate downstream impact of increasing the LDL receptors on the surface of the liver and pulling more LDL particles out of circulation. So it's not so much that we're just decreasing synthesis overall. Ultimately, it's that we're actually increasing the flux of cholesterol through the liver through the LDL receptors that get upregulated as synthesis goes down. All that to say, statins don't block synthesis in all tissues everywhere uniformly. For example, the synthetic pathway in the brain is quite different. And there are lots of concerns that the use of even low-dose statin therapy will completely stop your brain from making any cholesterol. Um, that does not seem to be true for many people. There are some people with you know desmosterol issues, and that may be a separate small subset. Um, we're not going to talk about that in detail because I think that that's a little bit of an esoteric rabbit hole. But generally speaking, the things that are most concerning about statin therapy are the side effect profile. And this is a fraught topic. Lots of people have reported very bad side effects from statins. I tend to believe all my patients who tell me that they feel terrible, right? Um, I why would I not believe you? That said, uh, in especially in low doses, I also have many patients who tolerate them and don't feel any differently on them. Your mileage may vary. So you are your own unicorn, you will decide and figure out how your body feels. And I hope that your clinician will listen to you, whatever your experience is. Muscle soreness, myalgia is the most common thing that I hear about. And it tends to be in the big muscle groups, so thighs, shoulders, and general sort of achiness malaise. And if people are experiencing side effects, my usual protocol is to stop the drug for a week or two, make sure that they go away, and then briefly rechallenge and see if the side effect comes back, because sometimes it's coincident with a flu or some kind of bug. Uh and if the symptoms don't come back, then maybe it was something else going on, or maybe your body adapted. Um, but if it comes back when you rechallenge, then I consider that a failure of statin therapy or that particular statin, and we are intolerant and we move on to either a different statin because there's a fair amount of cross-tolerability, meaning just because you don't do well on one drug in the class does not mean that you won't tolerate any of them. We have lots of them that some people tolerate and others don't. So we potentially would challenge another medication in the same class, or if we failed multiple medications in the whole statin class, then we escalate or move beyond statins and use other medications, such as bempadoic acid, such as azetamide, such as PCS canine inhibitors. Um, you know, the toolbox is large. So we have lots of other options. Um impaired glycemic control is another problem with statins that I have seen in my practice rarely, but when it happens, it's noticeable and it tends to happen in my patients who have difficult to manage type 2 diabetes or type 1 diabetes. And uh probably this has to do with the impact in the muscle of the statin medications. Um, so if you are concerned about this, I would encourage you to wear a glucose monitor and again, you know, monitor your sugars on the medication for a week, monitor off, and then rechallenge and see what happens if you're noticing a significant change in your glycemic control. I don't consider that acceptable. Um so now that assumes that you're on an optimal insulin-sensitizing nutritional plan. If not, then I think that that's a place to start. But uh in general, I would not be excited for any of my patients to have worsening glycemic control or problems with insulin resistance related to medication. In my experience, this is fairly dose-dependent for patients who are not brittle. Uh, if you are a brittle diabetic for whatever reason, your pancreas is shot. I mean, this is uh a bigger challenge. But for many of my patients who are eating a sort of um nutritional strategy that minimizes any insulin resistance problems, I find that low doses of statins are very well tolerated and do not seem to change hemoglobin A1C, fasting glucose, or fasting insulin. And I feel comfortable using them. And, you know, the good news is we get about 80% of the benefit at the lowest dose of these medications. So I tend to start at the lowest or even very low dosage, which is, you know, the lowest dose every other day in some patients. And uh I find that with that, typically in combination with a zetomy, I am able to get pretty nice lipid lowering results for patients who need it and um a pretty reasonable side effect profile. And of course, the benefits are um well espoused in the in the main cardiology literature, especially in patients with plaque. We do see reduction in inflammation as measured by high sensitivity C-reactive protein uh reductions in APOB or LDLC, and with that an associated reduction in heart attack, stroke, limb loss, which is a big deal for my PAD patients, and all of that. Now, we don't see as much of that as you would want, and this is because there's what we call residual risk. So statins drop the risk of all these events, but they don't drop it enough. And this is why lipid lowering therapy has not cured heart disease, right? And we can, you know, this is why people who are anti-lipid lowering therapy will tell you that it's totally useless. I don't believe that, but I also don't think that it's the only thing. And if all I ever did was prescribe lipid lowering therapy, I would still have an enormous number of patients who had recurrent progressive heart disease or vascular disease. So we are not helping anybody by saying this is the only thing. And I saw a really interesting case report the other day. I think I'm gonna make a video about this because there are two interesting case reports that have just come out. And this one I'm thinking of was a patient who had had genetically very low APOB and LDL cholesterol his whole life, somewhere in the like 40 milligram per deciliter range for an LDLC. And this was a genetic thing. This patient also became diabetic and had poor metabolic health and developed plaque. So this idea that you cannot form plaque if your LDL is less than 55 milligrams per deciliter is just not true, at least at an individual level. So if your metabolic health is poor enough, again, we have all these particles roaming in and out of this sub-endothelial space on a very regular basis. The more particles you have, the more transit there is, and the more chance there is for stuff to get stuck and below 55 milligrams or 60 or 50 or whatever you want that number to be, somewhere in that general range, yeah, your risks of getting particles stuck goes down dramatically, but it's not zero. And if you have enough insul, either from smoking or high blood pressure or metabolic syndrome and insulin resistance and hyperglycemia and diabetes, you are probably still at risk for forming plaque. So, all this to say lipids are part of this equation, and especially if you've already got plaque forming, but they are far from the whole story here. And I always want to be really honest and clear that taking this all in a big picture perspective is really, really important. So there are some, you know, certainly other side effects that people talk about with statins. Um, there is potentially some impact on the native GLP1 system. We have no idea what the clinical relevance to that is. Um, but that has been discussed recently. Issues with actual muscle loss. That was also an associational study that I didn't think was particularly compelling. But again, statins do seem to be active in the muscle and probably at higher doses, they could be problematic. So I don't know what to make of that, but I am concerned that uh long-term use at very high doses and people who are not doing a lot of resistance training may have an impact. But again, is that because they're just not doing enough resistance training and they were going to get frail and sarcopenic anyway? I don't know. This is a tough area to study and follow, but I would say, you know, get your own data, get your body composition measured, get your labs done, assess your plaque, assess yourself for side effects and symptoms, and uh feel free to readdress, right, as things in your health change and evolve and as as new agents come available and have cleaner side effect profiles. Somebody was asking me recently on a podcast about, you know, are statins the best drug? And they're probably not. The clinical reality is for most of my patients who do not have a huge amount of disposable income to spend on cash paid drugs, the statins are a very necessary step in stepwise treatment that I have to rule out if there's any prayer of getting the newer medications that are still on patent covered by insurance. Even with insurance coverage, they can still be very expensive. So when people are like, well, why do you use statins at all? Why don't you just get rid of them and completely go to these newer medications with a cleaner side effect profile like bempadoic acid or like PCS canine inhibitors? I don't think those are great drugs. I would love to use them more. The truth for most of my patients is that they're doing okay on statins, and that's what they can afford. They're cheap, they're generic, and they are tolerating them okay. If I thought they weren't, of course we would do something different. And if they tell me they're not, of course we're gonna do something different. But the corporate practice of medicine, the insurance regulations have made it very difficult to get around that. Even for patients who are truly needing these extra medications, there are a lot of obstacles, and I can spend an inordinate amount of time on paperwork and providing notes and doing, you know, um peer-to-peer calls to like try to get these tests and these medications approved for my patients who need them. So unfortunately, it is not as simple as like the doctor decides what they want and uh everybody gets what they what the doctor says. Um there is there is some corporate practice of medicine going on that is making that a little harder for us than I would wish. Okay, I think that's probably enough on the statins just for now. Let's keep going. All right. Wayne Oakley, what is your opinion of LMHR people and their high LDL? I have all the markers, but CAC0, CT, and Geoclear. 66, and doctor wants me to try Rapatha. All other markers, good, not diabetic or in blood pressure meds. So, Wayne, this is of course an area of evolving research and interest. Um I can, so I have a number of LMHR patients in my practice. For those of you who are here for the discussion of familial hypercholesterolemia and diagnosis earlier, this is not the case for LMHRs, even though they will have two sequential measurements of LDL greater than 190, because the minute they re reintroduce carbohydrates, they should be able to drop their LDL back down into a more normal range, uh, hopefully under 190. So the LMHR phenotype is distinct from familial hypercholesterolemia in that it is essentially inducible with a very low carbohydrate diet. For those of you who are actually not familiar with an LMHR, I'm sorry, I just assumed that everybody here might know that, but I shouldn't. Um, this is lean mass hyperresponders. And these are a group of people who tend to have a low to normal body mass index, who, when they begin a very low carbohydrate style of eating or a ketogenic diet, end up with significant elevation in their LDL cholesterol, but they will have low normal triglycerides, high to normal HDL cholesterol, and this LDLC that was normal before they had a low carbohydrate diet that shoots up in the very elevated range once they begin a high-fat, low carbohydrate way of eating. So this is an inducible phenotype. It's not something people are born with. It is something that comes on as they have this strategy. And I think that's an important distinction. Um, and it again does not apply if your triglycerides are high, it does not apply if your HDL is low, it does not even really apply if you are not able to easily manipulate this with your nutritional interventions. So there's a number of nuances about this phenotype, but there are a large number of people who meet or mostly meet this phenotype. Some people in that have plaque, some don't. And what I'll say about the data we have so far from KEDA CTA is I don't know what to make of this. There are a lot of people who read that study and thought there's rapid plaque progression, this is a death sentence. Um, that is sort of an aggregate overview, and now we know that those clearly based data were spurious, uh, and we don't think that they're accurate. So I have a hard time making any conclusions based on the keto CTA trial so far. Um, I have talked to Dave recently, and I know that we are working on you know the reanalysis and the paper's been retracted because of this issue with the clearly uh AI data set, the data from Heartflow and from QAnGio show not a lot of change. They show some progression, some regression, and so it's kind of a wash. Um, what this means to me is if you are an LMHR who has no plaque and you have absolutely done your due diligence, you can go either way. Um I I don't have a recommendation, right? This is about personal philosophy. This is, you know, do you think that it is appropriate to have not appropriate, that's the wrong word. Um do you think there's a benefit to having that level of LDL cholesterol or APOB particles circulating in your in your bloodstream? Um, do you think there would be a harm in reducing it? And how do you feel about that? And what do you want to do? If you have strong family history, if you have anything that tips you in favor of being more aggressive with your management, then I don't think that's the wrong approach. And I understand why every cardiologist and, you know, person who's um looking at your lab tests wants you to be in this range. And also I can completely get behind somebody who says, look, I don't have any black. My blood pressure is normal, my inflammation is normal, my glycemic control is optimal. This is just a number and does not reflect my physiology. I would say it is also very reasonable to consider serial monitoring. You can use CIMT, we can do serial CCTAs spaced out, you know, your 10-year event risk is low, right? You have no plaque, no soft plaque, no hard plaque. Like we have some time. The most aggressive prevention people would say, that's dumb. Why would you just leave this risk factor circulating around and wait for a disease to emerge? Um, just manage the risk factor. Well, because it's not entirely clear that in this particular population of people with this particular set of circumstances, meaning zero plaque, that it's a meaningful risk reduction. I just don't know that. So again, I there is no, like, I know what the lipidology community says, which is sure, beyond a path and get it down. Um, and I know what the, you know, people in the low carb space would say, which is it's all bullshit, like don't do anything, you're fine. Um, and I think that the right answer is probably somewhere in the middle, and you will pick based on what makes the most sense for you and your own philosophy about your health. And are you sort of risk tolerant? Are you a little risk averse? Which risks are the most important to you? And, you know, I everybody will come up with a different answer and you might try stuff for a while and see. I have one LMHR in my practice who's on Zedia monotherapy because she does have a little bit of plaque, but not a lot. And she is an LMHR, she feels great on her low carbohydrate diet. It has managed something for her that nothing else in, you know, conventional medicine could do. So she's feeling great about that. And she's not wanting that plaque to progress. And so we're trying Zedia monotherapy for a while. We'll see what happens. We'll follow with CIMTs. It's certainly not getting her LDL down to a normal range, but it's better than it was. So that I think does represent some risk reduction. Is it absolutely necessary? I don't know. We don't know. So that's where I am with the LMHR story. Let me know what you guys think about that. Um Tron, need to throw in an easy question to give me a break. How many donuts can you eat a day and still be healthy? Um, I have settled on zero and I miss apple fritters dearly. So um sorry about that. All right. Jared Webster, thoughts on gene therapy, ongoing trial started by University of Penns uh cardiologists for two, yeah. So I think for people who have homozygous FH who are developing plaque in their childhood years and having heart attacks in their teenage and 20 years, um, gene therapy for these patients is going to be game-changing, right? They are having um, you know, plasmaphrasis, they're getting their blood cleaned to like get these lipoproteins out of circulation several times a month, you know, throughout their whole childhood. They're afraid of getting pregnant because they have to be off of their meds and all of this while they're, you know, bringing new life into the world. And it's this huge medical burden for these patients. So I think gene therapy for those people is probably definitely on the horizon and going to be life-changing in a in a positive way. What does it mean for the rest of us with moderately elevated LDLC or APOB? I don't know yet. Um, I think there is absolutely now the prevailing wisdom of the lower the better for longer, right? That this APOB story is an accumulation of risk over time. And just like we talk about smoking in pack years, right? The number of packs per day that somebody smoked times the number of years that they smoked, and we integrate this whole thing and come up with this total volume that, you know, APO B burden is the same. So you might have had slightly elevated APOB your whole life, or you may have had wildly elevated APOB for a few short years, and perhaps those risks are a little bit equivalent just because that is the same integral under the curve. But that is hypothesis right now, mostly. Um it's a it's a popular one, and I think there are data that support it, but I don't know that we know what the unintended consequences of gene therapy will be. Certainly our Mendelian randomization trials or investigations and other genetic patients who are historically low LDLC for a lifetime do not seem to have a particularly increased risk of cancer or autoimmune disease or infectious risk. Uh, however, that is something that might be different if we are doing the gene editing. You know, we don't know what the unintended consequences might be in the long run. So I think that certainly initially this will be used in a very small subset of the population. Uh, I don't know if the Brian Johnsons of the world will uh try to use this for themselves and see what happens. It would be an interesting natural history experiment, but I think it's gonna be decades before we really understand whether this is as clean as we hope it is and whether it is something that is going to be game-changing for cardiovascular disease and all cause mortality, right? If it reduces heart attack and stroke but increases cancer death, is that a win? I'm not, I don't think so. Um, certainly that was what we saw with one of the autoimmune drugs, uh, or so the immune modulator cannokinomab that was studied for heart disease. This was an interleukin-6 inhibitor, and that's one of the inflammatory molecules in our bloodstream that uh sets off our immune system. And if you block it, you absolutely reduce major adverse cardiac events. Like it's 15% reduction in major adverse cardiac events. The problem was that all-cause mortality was totally the same because there was an increase in fatal infections. So the drug never came to market. It was never approved because it was an expensive way to die at the same time of something different. So gene therapy for elevated cholesterol might turn out to be that way for people who don't have homozygous FH. So I don't know. Uh I don't think I will be first in line for that. I think I'll wait a few years and see how that goes before I would throw my hat in the ring. But it's a fascinating question, isn't it? All right. Um, so this is the point about low-dose statin therapy being pretty effective. I don't think it's the same every other day as it is daily, but it is pretty close. Again, you're getting a fair amount of I there are reports from people who actually were doing the initial trials on Rasuvastatin that even one milligram of Rasuvastatin had almost uh about 50% of the effect of the five milligram dose. So um, even very low doses can be dramatically useful for people, especially if you don't have that much LDLC to go, like meaning you're not that far above goal. You might be able to do that with five every other day. I have some patients who are on that as an approach. Um it won't be quite the same, but it'll be most of the benefit. And so the nice part about Resuvastatin is we can use pretty low doses, probably lower than even the the studied and published lowest dose, which is five milligrams daily. Yes, Dr. Ford talks about very low dose crest, or yeah, he and I are buddies. Uh all right, you guys are having the time of your lives with each other. This is awesome. I'm excited. All right. Which statin has been shown to be best for ApoE4 carriers? Don't know. Um there is some idea that the lipophilic, meaning um, you know, fat dissolvable statins are more likely to cross the blood brain barrier than the water-soluble statins or the um hydrophilic statins. Ultimately, my impression is that all of the statins, when taken for long periods of time, show some penetration through the blood brain barrier and into the central nervous system. So if you're an ApoE4 carrier and you want a little bit of statin help in your central nervous system because your ApoE4 creates a lipid trafficking problem in your brain, and you need to sort of unload that system a bit, then I would say our evidence would suggest that all of the statins will probably get us there to some extent. Again, um, Crestor is my personal first statin of choice. Uh, there's some evidence that it might be worse for the insulin resistance component. Again, at low doses, that has not been a real problem for my patients, but I respect the fact that that has been documented in other places. Um, certainly if you are an ApoE4 carrier, we want to do everything possible to keep you as insulin sensitive as possible because it is also potentially a brain energy problem. And uh your brain may be a little bit more insulin resistant than the rest of you. So making sure that we are not compromising any insulin sensitivity and giving you, you know, the best chance to beat your ApoE4 physiology on all possible fronts is really important. Unfortunately, I don't have data uh at my disposal that would tell me that one versus the other is better. The interesting newcomer, new kid on the block will be obacetropib. This is the CTEP inhibitor that is currently in clinical trials. And this is uh an interesting story. They actually looked at very disease-specific markers for Alzheimer's. So they looked at P tau217, they looked at amyloid beta 4240, they also looked at GFAP and uh neurofibrillary light, all of these are different serum biomarkers for Alzheimer's disease. And in the patients who were APOE4 who took obacetrapib, they showed a significant decrease in Pau217 and amyloid beta 4240. All of these markers really decreased in the ApoE4. Uh, and it was preferentially like it worked better in patients who were APOE4 carriers than in those who were not. And I don't know whether that will ever translate into clinical outcomes. We have a lot of drugs that have been shown to modulate amyloid plaque in the brain and reduce amyloid levels that have not been very clinically satisfying, right? They have not moved the needle very much for people with Alzheimer's dementia in terms of improving significantly their cognitive function or quality of life. At least that's my understanding based on my review of the literature. But um, and we don't know whether obacetropib will have any cognitive impact. We know it moves these biomarkers and that the biomarkers are associated with changes in cognition and the development of Alzheimer's dementia down the road, but stay tuned. Uh, this will be a very interesting molecule to see if there is some APOE4 specific benefit for obacetrip, but I know that folks in the uh lipid space are are pretty intrigued by this initial data. All right. So there are some people talking about things that we can do to help mitigate effects of um muscle pain and statins. The uh patavostatin and pravostatin are both less likely to cause muscle issues. They are also much less effective at lowering LDLC, but if it's the statin you can tolerate, great, we'll keep that as part of your regimen. Um I typically find that trying to get patients optimized for vitamin D prior to starting statin therapy and optimized for CoQ10 levels, which most people don't require supplementation for that, but um it's always a possibility. I think there's very little harm in 100 milligrams of CoQ10 twice a day. Uh I have not found it moves the needle a lot for my patients, but there are a few reports in the literature where optimal vitamin D and CoQ10 levels prior to starting statin therapy might reduce chances for statin associated muscle soreness or myalgia. All right. Change California, your ED may be cured by a younger sexy woman. Uh, let me know how that works for you. That sounds like a good plan. All right. Alpha lipoic acid. Yes, I've had uh somebody who had some improvement in neuropathy with ALA. Good. Is hypercholesterolemia an indicator that there is something wrong with your liver? I take 20 milligrams of Resuvastatin, but I wonder if I'm ignoring something. No, it's usually not a sign of liver issues, although the same lifestyle that brought you elevated LDLC may also be causing what we would now call metabolic associated steatotic liver disease, MASLD, which is essentially fatty liver. Um, and it used to be called non-alcoholic fatty liver disease. And this is essentially what happens when your liver becomes especially insulin resistant. It starts to accumulate fat in the liver as a way to try to store the excess energy that is circulating in the body, and that fat impairs our function of our liver. Um excess energy may also be converted into energy in the form of triglycerides and circulating lipoproteins. So uh there are certainly folks who end up with elevation in LDLC from an excess of nutritional energy that is problematic. And certainly that can be reflected in both the liver and our lipid panel. So, no, elevated LDL by itself is not per se something that is a problem with your liver, but I would wonder if the reason you also have LDLC might also be a reason that your liver is unhappy. Um, you can check AST and ALT, those are on a standard liver function panel. GGT or gamma glutamil transferase is also a nice test that will reflect your liver's function pretty well. Uh, platelet count to some extent is reflective of liver function. If your platelets are too low, that might be a problem with your liver. Uh AST and ALT would love to see those in the 20s or less in an optimal metabolically well person. They will start to creep up, sometimes with medications or supplements. Um, but also if we are starting to see fatty liver or this um statohepatitis metabolic. Okay. GLP1 are showing crazy results in dementia risk reduction. Yeah, thanks, AV. This is a fun, interesting space. The um kind of wrench that was thrown in this earlier was a study that just showed no improvement in patients who already have dementia, who are treated with GLP1s. So here we're now stuck between, well, they might be good in a prevention setting, but they're not helpful once you already have the disease. And I don't, I could, I could have some thoughts because that was done mostly in diabetic patients who are on GLP ones who had a diagnosis of dementia. And I wonder if the energy system in the brain is just so demolished at that point that the GLP ones can't rescue it, even though we're improving insulin sensitivity and even though we're improving, you know, the the energy milieu of our bodies. I wonder if, you know, if you've been diabetic and already developed dementia, that we just don't have enough impact with the GLP ones. But I do think that this is a fascinating class of medications and they are showing benefits basically in every organ system, particularly if we are using them, me like prophylactically or in the prevention early disease modification situation. So they seem to be helpful for kidney function. They seem to be helpful for inflammation, they are certainly helpful for cardiovascular health. Now, caveat, this is all in patients who are either diabetic or overweight. So the cardiology data in uh semaglutide, so that's Ozempic and Wagovie, was done in patients with BMI 27.5 or more. So this was not necessarily the classic definition of obesity, which is BMI 30 or higher. We could go a little lower, but definitely still in the category of overweight. And so we don't know whether this will work for patients who are BMI of 26, right? That would still be considered probably excess adiposity. And especially if we have an elevated waist to hip ratio, meaning a lot of that fat is in the abdominal region, probably visceral fat around our organs, which is much more inflammatory than just the stuff under the skin that we pinch. Then I think these may be just game-changing for all kinds of things. And again, dementia is the accumulation of, or it's the umbrella term for a number of different pathologies in the brain, but many of them seem to have key risk factors, right? Most of the vascular risk factors risk increase risks for dementia, including high blood pressure, including uh hypercholesterolemia, including overweight obesity, including diabetes. So anything we do that will help manage that situation, I think will absolutely reduce our risk of dementia going forward as well. Probably also reduces our risks for cancers. So anything that is going to meaningfully drive metabolic health in the right direction, I think is a rising tide that will lift all ships. I know that there is a lot of emotion around the use of GLP1s, and there's a lot of people on both sides of this. I spend um probably too much time, you know, in and around GLP1 subreddits and listening to the experiences of people on these medications and people prescribing these medications. And, you know, there's there's just a lot of emotion around obesity in general and a lot of stigma. And yes, there are people who are able to manage their weight and their metabolic health with nutrition alone. And there are a lot of people who have not been successful despite years and years of trying. And I feel as though continuing to flog those people and force them to keep trying things that aren't working while their health suffers for years and years and years ongoing is probably not in anybody's best interest. So I am um happy to be able to offer these medications to patients who are willing to help themselves. And I've worked with a lot of patients with obesity. Um, very few of them are hoping that a shot by itself without any change to nutrition or any change in their exercise is going to do something. Most of these people want to be more active, they want to be more engaged, they want to eat better, they want to be well. Um and I have seen some pretty remarkable transformations as people have used these medications as a springboard into a new and better life. So uh do I have thoughts about how we use them responsibly? Do I have thoughts about mitigating muscle loss, about how we use this along with a critical foundation of movement and nutrition and sleep and stress reduction? Of course I do. But um overall, I've been I've been happy to have this in my practice as a tool for the right patient. Hello, Rena. Is there an LDL level that's is it true that an LDL level that's too low can be dangerous as well? Uh there have been a lot of concerns about this in the recent cardiology trials using PCSK9 inhibitors. This was not really substantiated. They have a whole cohort of people who have an LDL less than 20, and they don't really have any major adverse events to report. Not an increase in hemorrhagic stroke, not an increase in any cognitive impairment. They actually did cognitive testing for them. Uh, and so I think there are probably some people who have adverse impacts at low circulating LDLC levels, but not everybody. What I think is important to remember conceptually is that the circulating level of these lipoproteins in your blood is not necessarily reflective of what is happening in your tissues. So, for example, sex hormone production happens at the level of the gonads, right? The testes and the ovaries, and your circulating LDLC level doesn't have a big impact on your actual sex hormone production, even though, of course, cholesterol is a foundational component in the synthesis of testosterone, of estrogen. And so, while, yes, of course, cholesterol is required, dropping it with these medications does not seem to be causing any impairment because each tissue creates its own cholesterol. Every cell membrane, every cell in a body with a nucleus can make its own cholesterol if it needs it for the membrane or for other functions. So just because our circulating levels in the plasma are low does not mean that at the tissue level in the brain, in the ovaries, uh in the kidneys for whatever, like wherever you're looking, the adrenal glands, that the levels would be low there too. So there's there's always this mismatch between what we see versus what might be going on in any other tissues in the body. But people who have genetically low levels seem to be okay. And people who have now pharmacologically reduced levels also seem to be doing okay. And there is not a clear ad, you know, like if your LDL is this level, it's too low and we should back off. There's there's no guidance for that at this time. Certainly, there are people who have reported their own experiences. And again, if people tell me that this is how they feel, I believe them. That is my job. So uh I respect that what is published and what is documented in our scientific literature may not be anybody's personal experience, but to the best of my knowledge, we are thinking that like we can be safe at very low levels. I think uh Avi says, well, I think we'll see all of these longevity gurus taking GLP1 soon. Yeah, I just saw uh a video on by Brad Stanfield where he's uh taking low-dose trzepatide. I haven't watched the whole thing yet, but um certainly the there are some people who've made their entire social media presence. I'm thinking of Dr. Tina based on uh GLP1 use. And uh there are a large number of folks in the space. And there are also a large number of folks in longevity space who are against them because of the risk of frailty, low muscle mass, or sarcopenia, muscle loss. And um, I think that that's a reasonable concern. However, I also am certain that it is possible to use these medicines without having that problem, as long as people are actively doing resistance training and prioritizing enough protein in their diet to support muscle protein synthesis. I have absolutely seen people put on muscle and lose fat while on these medications because I ask people to track it in my practice if they can. So the longevity space is probably a little divided on this right now, but I agree that there is certainly a signal for um lots of people going forward. All right, Tron, go get that ice cream, see how that goes for you. Um Gerard Webster, is it true saturated fat locks those liver receptors? Um, I don't know what you mean by locks. There is absolutely an association between dietary saturated fat intake and LDL cholesterol levels, and a diet where you reduce saturated fats, especially if you replace them with polyunsaturated fatty acids or monounsaturated fatty acids, uh, will lower LDLC. The question is what else is it doing? Um, and the cardiology community is is pretty set on reducing saturated fat, is the right answer. Certainly the historical data from Ansel Keys onward for a number of years was very confounded and or falsified, uh, as the case may be. So, you know, there's some tension here. And this is where I come back to are you trying to lower your LDLC only using nutrition? If that is your goal, then yes, I would support reducing your saturated fat and increasing your soluble fiber intake. That will reduce your LDLC using a nutritional approach, and it will um probably get you 20 to 30 percent reduction in your LDLC, depending on how aggressive you are with reduction of your saturated fats, maybe total fats. And also, uh, I have people who do that who develop insulin resistance or who worsen insulin resistance because that tends to result not only in replacement with other fats, but also with carbohydrates as an energy source. And some people tolerate that really, really well and actually improve insulin resistance on that way of eating. Um, other people don't. So just because it's the optimal diet to reduce your LDL cholesterol level doesn't actually mean it's the optimal diet for your cardiovascular health or for your overall health. And this is where it gets complicated and really needs to be personalized, in my opinion. All right. Let's see. Another anonymous question: How frequently do you order coronary CT angiograms for your patients? And if risks were zero, would you order one for every patient? Um We don't know what the right answer is because of the radiation, because of the dye, I would probably not order one more commonly or more frequently than every couple of years. And I would probably do it, you know, a time zero, one to three years. And then depending on what the trajectory of disease was over that time frame, we would potentially space it out or use CIMT or another tool to try to measure things going forward just so we don't have the ongoing radiation. The question that I really have about CCTA right now is this issue with the AI overlays. Because again, when people were getting CCTAs because they were having symptoms and chest pain, we had a pretty good mechanism where the radiologist or the cardiologist would read that CT angiogram and say, oh, there's a 70 to 80 percent blockage in the LAD, the left interior descending artery. Great, this is the culprit for their chest pain. Now you can go on and get your stent. Or no, there's no plaque anywhere. Chest pain is a non-cardiac cause. Okay, great. Now we have a lot of people getting CTAs for asymptomatic disease. They're not having symptoms, they're not having shortness of breath, they're not having chest pain, but they want to know do they have soft plaque? And the, you know, radiology cardiology evaluation of CCTA depends a lot on how they're reconstructed. Uh, meaning, are they doing a 3D rendering of all the coronary arteries? Are they straightening them out? Are they making sure that they're looking extraluminally, including intraluminally for the plaque? But they're not quantitative in a way that a calcium score is if they're just being read by a radiologist. They are semi-quantitative. So you'll get, you know, there are multiple lesions, one in the RCA, one in the LAD, and you know, two in the circumflex. Okay, so that's multiple vessels involved. Got it. And uh this one is moderately stenosed, 40 to 60 percent, and this one here is mild, less than 50%, and those two were severe, 70% or greater. Okay, so that's also semi-quantitative, but it doesn't give you a number like your total plaque burden. It doesn't give you calcified versus non-calcified plaque. To get those numbers, now we're looking at these AI overlay tools. We're looking at clearly, we're looking at heart flow. Those are the two that are most commonly commercially available. And what I don't know is if I give my scan to clearly today and I get another one in three years, is the algorithm, the AI tool that is analyzing that scan, the same one that analyzed my first scan at year zero, or is it a totally separate algorithm with different risk tolerance, different reproducibility and reliability? And it's actually not really fair and valid to compare my year zero scan to my year zero or my year three scan? Or does the year three algorithm now have to go back and analyze my year zero scan itself first and then the new one again and come up with that comparison? I don't know if that's clear, but to me, as we are using tools that are constantly evolving and we don't have a lot of visibility into how often are they updating the algorithm? How often are the metrics for the test changing, right? When we get a new lab test, right? A new blood test to measure, you know, whatever your pixie fairy dust in your blood, that lab test has to undergo a comparison with some other gold standard like microscopy or immunossays or spectroscopy or something else, right? We have to compare the blood test to some other way that we measure this and then determine how reliable and valid is this test based on the other measurements that we have. And then once it's done, we think that that's kind of true forever. Now, accredited labs are required to like repeat these tests and to make sure that their instruments are calibrated and that they're generating kind of the same results over and over again. And this is part of the administrative side of lab accreditation and lab testing. Um, but generally speaking, you know, when there's a blood-based test, it's the same test and it's the same test we run today as we run next year, as we run in three years. But the imaging stuff is different. The imaging stuff is software that is constantly being updated. And I don't know what is changing between our clearly scan at year zero and our clearly scan at year two or three. And to me, it means that I'm less excited about using these technologies right now to follow progression over time or to evaluate the effectiveness of my therapies over time, because I'm not sure how to interpret the changes. And conversely, you know, CIMT for me with my lab, I know pretty clearly that it's two hundredths of a millimeter is the minimal detectable change threshold. So if we see that the IMT has changed by five tenths of a millimeter, like that's real change because I know that in this test, our detection limit is this, and this is what our statistical uh power is for this test. So the AI stuff is very interesting. I think it's very important for people to get probably a one-time soft plaque imaging of some kind. If you have specific concerns about the heart in particular and you really want the heart vessels imaged, then I think CCTA is a good thing. Um and if cost were not an issue, would I get one for everybody? I'd be tempted, but I'm actually not sure it's the right thing. So we get so excited about the data, we get so excited and so nerdy about all the numbers and like the NMR lipid panels and how big and fluffy are, how small and dense are the particles, and how many of these, and how many of those. It's important to take a step back and say, is it gonna change my management? Is it really important that I understand this to change how I treat this patient? Uh and for many patients, the answer will be yes. And I think for many patients, the answer is actually no, because we're gonna do the same thing anyway. And I would have similar recommendations based on my understanding of the whole clinical picture and the additional radiation and dye exposure doesn't help us move the needle that much. Where I think it's really helpful is younger patients with a lot of risk factors who would be missed by a calcium score, or um, people who are in a high-risk phenotype like LMHRs, who are trying to monitor for progression of disease without having to necessarily manage the biomarker that may not be as informative in their particular case as it is at a population level. So um would I do it for everybody? No, I would definitely do it for more patients if cost were not an option. And I would definitely be more excited about it if I had more confidence in the AI tools that are uh available. I'm just not quite sure they're totally ready for us to be prime time with them, especially in a prevention setting where this is um really an evolving, an evolving space. All right. Terry says low dose fast food once in a blue moon. Uh blue moon is coming tomorrow. So if uh if you're waiting for a blue moon for Tron, your donuts, or uh Terry, your uh occasional fast food, I think tomorrow is your magic day. Oh, Paul, uh, where can you get the Pixie Fairy Dust serum test? Insurance will not cover this, but I highly recommend that you get that done. You can see me after we can talk about it. All right. Canadian, I am worried about my heart health due to previous lifestyle factors. I have had an echocardiogram in the past. What else can I have done to make sure my heart is healthy? Okay, so heart health. Um, in terms of testing and diagnostics, right, we need to think about lab tests, we need to think about imaging. An echocardiogram is an ultrasound-based test and it looks at the function of your heart. How well does the muscle itself pump and contract? And are the valves all working? But it does not look for plaque. If it is a stress echocardiogram, that means either medically with uh drugs or with a treadmill, you exercised and your heart had to work harder, and then they would look to see if the heart pump function changed with stress. That can be a sign that there is ischemia or poor circulation to the heart muscle. That means there's probably a narrowing in one of the arteries supplying that heart muscle. That would you know prompt or provoke an angiogram typically. Um, I am not as excited about stress tests as some of my cardiology partners just because I've had so many patients who've had negative stress tests and subsequently, shortly thereafter, had a heart attack. Um and that's because these plaques that we've talked about can rupture at less than 70% narrowing. So a stress test will provoke this ischemia or poor circulation response. To do that, the narrowing in the artery has to be about 70% narrowed. So that means 30% of your normal flow channel is open, but plaques can rupture at 50% or 40%. So you won't see that on a stress test because it's not narrowed enough to change the blood flow to the heart. But if that thin fibrous cap that we talked about earlier ruptures and all of, you know, that volcano erupts, the pimple pops, you spill all that really inflammatory, yucky, gooey lipid stuff into your circulation and the platelets go attack it and plug everything up. Yeah, I mean, that's how you get an event with a negative stress test. Those patients would be potentially detected with CT angiogram, and we would be able to find plaque, soft plaque that way. We still don't know if or when it's going to rupture. So there are, again, AI tools that have looked at exactly how soft is the soft plaque. The very softest plaques are more likely to rupture. Um, and those tend to be, you know, hopefully low volume for most patients. But um right now there is no standard that says, oh, you have like a bunch of really soft low plaque. We should go in and put a stint across that so it doesn't rupture. No, I mean it drives more medical therapy, uh, more medications typically, but it does not necessarily mean we're gonna stop that or prevent that. So, circling back to your question, I think you should have a, you know, make sure you're checking your blood pressure, make sure you're exercising like it's a drug because it is. Make sure you're getting a complete lab evaluation. If you want to know what labs I recommend, I have some early videos on that. There's two of them that talk about the lab tests that I generally recommend for my patients above and beyond what you're gonna get for your annual physical. So make sure that you've had your LPA checked, LP little A checked once in a lifetime. Make sure your high sensitivity C-reactive protein, make sure a fasting insulin is in there somewhere. Um, Homo IR you can get from your fasting insulin and your fasting glucose, all kinds of things in here, and then some kind of plaque-based imaging. So that's gonna be a calcium score at the bare minimum. It could be also a CCTA, this CT angiogram that we've been talking about, where there's dye and we can image soft plaque, or an ultrasound-based test like a CIMT, or also an FIMT, femoral intomedial thickness, so that we're trying to detect soft plaque in the leg and neck vessels instead of imaging the heart directly, but some kind of plaque-based imaging technique to help put all those labs in context and see what are the chances that there is some kind of ongoing smoldering forest fire of plaque in there somewhere that needs to be aggressively managed. Doctors are not oracles either. No, we are not. We are doing our best out here, uh, but it's messy and it is the front lines. So I am absolutely not an oracle. I um want to be here as uh maybe a slightly more informed guide, uh, but we are kind of in this together, and I am so grateful for your contributions and your information that you guys share here with me, for my patients who allow me to be on this journey with them and who allow us to you know proceed in some. Of these things with just some curiosity and humility, right? My LMHR who's on Zedia monotherapy because that's what we decided was the best synthesis of her philosophy and goals and the clinical scenario in front of us. And we're figuring it out as we go. So um thank you guys for being here and uh helping teach me. Matthew, is citrus bergamot a supplement that is synergistic with statins or PCS canine inhibitors? Can they be taken together or are there any sort of issues? Um I think if you are already taking statins and PCS canines, I'm not sure you're gonna get a lot of additional benefit from citrus bergamot. Uh it's my impression that it's generally used in lieu of instead of in addition to. I'm I don't have an extensive experience with citrus bergamot. I don't think that there's a safety risk or interaction. And if you wanted to try it, see what it does for you. But I would be curious and I would run it as an experiment. I would uh check a lab panel without it and then uh add it to your regimen and then check another panel. And if it's not doing anything for you, I would probably just get rid of it. Um, but I do know some integrative cardiologists who are enthusiastic about citrus bergamot, especially in patients who are unable or um do not want to take any conventional lipid lowering therapies. All right. AI aliens from space will visit us soon. How soon do you think? Uh Tron, yeah, you fired a number of doctors. I get that. Um oracles in science. Yeah, amen to that. It is pretty much the antithesis of good science. Jared, my surgeon took a vein out of my leg and decided to use my mammary arteries once they got inside. Visual inspection for the win. Yeah, so um the mammary is always the preferred conduit. And the only question is, is it enough to get to all your targets if you're having a coronary bypass operation? So vein is the secondary conduit, but they'll usually try to plug your mammary into your best uh left-sided target. And then if they have something else they need to do, then they'll use that vein. There was a period of time actually where they were using radial artery from the arm as conduit that has fallen out of favor. Um, but my dad, who's a retired heart surgeon, uh used to harvest radial arteries for that. So uh good news is you have the other ulnar artery in your arm. So you can almost always live without that radial artery without too much, too much issue. But I find uh you'll find every so often a patient who has an absent radial pulse and you'll see a scar there, and they're like, oh yeah, they harvested that for my coronary bypass a couple of years ago. William Donahue, what supplements am I personally taking? Okay, I take about five grams of creatine a day, unless uh it's a day like today where I have gotten three hours of sleep, in which case I take 10 to 15 grams, which might totally be placebo, but I think I function a little bit better with a little extra creatine on days where I am sleep deprived. So I don't know, your mileage may vary. There's some evidence for that in the literature, it's not overwhelming, but creatine is super safe, in my opinion. So uh I don't see why not. I also take magnesium at night for uh sleep support. I use a combination of glycinate and threonate, which also I'm not sure that I can personally tell the difference between them. I've heard different things and different sources about uh, you know, brain penetration and and the conjugates and all of these things. Glycine in general is also something that supports sleep. There are people who will take like five grams of glycine a night to support sleep. The magnesium glycinate may actually be helpful because partially the magnesium, but also partially the glycine that comes as that uh is metabolized in your system and the glycine is separated from the magnesium. So uh I like magnesium glycinate in general. The three and eight, I don't know if it makes any difference or not, but it makes me feel better. So I I uh also incorporate some of that. And uh I personally take some vitamin D3 with K2 because my levels were suboptimal even in Southern California, um, mostly because I spent too much time inside and not enough time in the sunshine. So um, so much for that plan as I embark on creating a YouTube channel to do more recordings outside. Um and I also I go back and forth on a general multivitamin. I'm not convinced that this is a great idea for everybody all the time. There is one paper that looked at Centrum Silver as a or Centrum daily multivitamin and showed some decrease in long-term risk for dementia in older adults who were taking a multivitamin versus those who were not. Uh, and I do think that even if you're eating a whole food-based diet, whether that is carnivore, omnivore, uh, herbivore, however you get there, our food ecosystem is not what it used to be. Our soil quality is not what it used to be. And um so I I don't know if a little bit of trace mineral and and other support is helpful. It's probably not harmful. So sometimes I will take a half a dose of a multivitamin, sometimes I don't. Again, really loose evidence for that. I don't think it's harmful, but it may not be doing anything. And uh also if there are periods of time where my diet is a light in fish, then I will add omega-3 fatty acids. I don't, again, do that all the time for no good reason. Uh I try to get that from fish, but again, my meal prep situation, my lifestyle does not always lend itself to um fish. So I will supplement with omega-3s if I don't think that I am getting sufficient amounts through my diet or if my omega balance labs are out of whack, which I haven't checked in a while. It's probably time to do that again. If you would uh like to see my lab panels, uh let me know below and I'll get those done and we can uh we can go through that. I think that might be fun. All right. Wondering about my own diet because my skin is lovely and healthy. Thank you. Uh I am grateful for that, especially uh sleep-deprived. My own diet is a um Mediterranean-influenced low carbohydrate approach. So these days I am I was ketogenic for a while, then I was low carb for a while, and now I have evolved my low carb from a little more red meat heavy and ketovore now into leaner meats as I am just changing how I play around with things and how I evolve. I may go back to red meat at some point. I don't think that I personally have a big issue with that, but uh I would stay leaner. I just feel better with leaner cuts right now. Um, the really fatty cuts just don't settle with me. So right now I'm doing predominantly um chicken as my protein and eggs um with like I'm reintroducing some soy just for giggles because I find roasted at a mommy to be a very satisfying snack. Um, my best friend really likes tofu and she's asked me to play around with it. So like I roasted some tofu last week. I don't know. Uh it's not really anything I thought I was gonna be excited about, but it goes really well in curry. So um that's fun. It goes well with my roasted vegetables. I saw I'm doing salads, I'm doing roasted vegetables, uh, not starchy vegetables, mostly still squash and um cruciferous veggies to some extent. I do better with those if they're cooked. I do whole fat dairy. I don't do a lot of it. I don't do yogurt every day, um, but I will put a splash of cream in a coffee occasionally. Mostly I drink my coffee black, but every so often as a treat, I'll put a little cream in there. Sometimes I get on a Greek yogurt kick and we'll do uh whole fat Greek yogurt for a while. Um I am starting to bring more seeds into my diet, so I'm adding some chia seeds and a little bit of pumpkin seed to my salads. And yeah, I think again, I I go in phases where I'll do the same thing for a long time and then I get tired of it all of a sudden and I'll switch. So this is kind of what I'm doing now. Um, what I had today after I worked out was a um some berries, some eggs, and some protein, and threw that together with my chia seeds and had a had a little snack before we started recording here. Uh all right. Oh, almond butter is also uh almond butter and dark chocolate are my cheats. It would not be fair to pretend that I am a saint with my nutrition. I am absolutely not. I have largely given up alcohol, and instead I will occasionally reward myself, not with a donut, Tron, um, but with a little bit of dark chocolate or sometimes some almond butter. Those are uh those are my vices. Snickers have trace amounts of vitamin B3, B5, and B6. See, I knew I kept you around for a reason, Tron. Thank you for that. That's very helpful. All right. Terry, my veins are weak and collapse to the point that it is, oh, sorry, it jumped around on me. Impossible to give blood and even blood draws on IVs are problematic. Uh, is this an issue? No, this so um this is usually an issue of getting um a better phlebotomist and having and trying to be as particularly well hydrated. Uh, in general, unless you have a diagnosed connective tissue disorder, something like ailers-danlos, vascular ailer-danlow's or Marfan syndrome, um things like that, then I don't suspect it's likely to be a problem anywhere else. There are just people who are tough sticks and who have veins that roll, but that's not a pathology, that's just you. Uh, and it does make getting blood draws kind of painful. Sorry. William Donahue. So we do periodic screening with colonoscopy. Uh seems to me CTA is cost effective to screen for number one killer. So this is an interesting point about screening. And I have given this talk publicly before, and I have a master's in public health. And from a public health standpoint, the issue about screening is that we actually have to prove that detecting the disease earlier allows us to make an effective change in the trajectory of the outcome. So there is a phenomenon where if you, you know, detect something earlier, you don't actually live longer. It just seems like you live longer because you've now lived with the disease for longer because we detected it earlier, but we actually didn't change your outcome. And the same issue has been with screening for cardiovascular disease. As a whole, in medicine, we have done such a poor job of helping prevent cardiovascular disease that the screening is ineffective. And this is why there is no recommended imaging screening for cardiac disease, even though it's a number one killer, right? It's so prevalent. You are flabbergasted, as am I, that there is no screening test for this when we know we can detect disease, right? We've just been talking about this for like an hour and a half. Of course we can detect the disease. Uh, the issue is at the public health perspective, is it cost effective enough? And are we sure have we shown that as doctors, clinicians, we can change people's outcomes? And again, this goes back to this idea that if changing your cholesterol or your LDL was the only thing relevant to cardiac disease, we would have cured cardiac disease 30 years ago. Throwing an aspirin and statin at somebody with a CAC of 300 isn't really moving the needle enough. There is too much residual risk because we have not understood why people have plaque in the first place and actually gone after these root causes. We have not addressed all of the metabolic dysfunction that persists or might even get worse as we just manage this with aspirin and statin and a prayer. So the problem with screening from a cardiovascular disease standpoint in the population is we have done a crap job of helping people when we've detected this early. So that is the reason, in my opinion, that screening for cardiac disease has not become widespread yet. We don't have trial data that support the fact that if we found it early, we would make some meaningful difference because we would change how we manage these patients, or the patients would change how they live their lives to, you know, really embrace the foundations of this lifestyle medicine approach to get everything in order, because it's a disease process with such a long time horizon that there's not a huge sense of urgency in your 30s or 40s to really, you know, get this under control uh in a hurry because it's people don't have symptoms. Even with high blood pressure, high blood sugar, um, plaque, there's no symptoms. So people don't necessarily think that they'll feel better if they go after all of these things, and that's the problem. Um answer questions from bike trips. Yes, that's a fascinating idea. Uh, I have been contemplating an international bike trip for a couple of years now, I'm embarrassed to say. And maybe, maybe this fall will be the year. I'm thinking about maybe uh a bike tour of the volcano regions in Chile. Uh Japan is also on my list. If you have bike tours, uh Backroads is the company that I used the first time. I've also looked at Trek, and there's another company that uh has like month-long tours that I would die to do someday if I ever can get away from the hospital long enough to do that. If you have recommendations, uh leave them for me below. That'd be awesome. Thank you. Oh, William Donahue, if you have problems with getting blood draws, call ahead and arrange for ultrasound for blood draw. I didn't know this was an option. Uh is that Quest Lab Core or your hospital's lab? I think that's a great option if uh if it's available for people. I'm not sure if everybody has that available, but that would be awesome to know. Well, since half of our patients present dead, I think we should start screening. Um yeah. Yeah, I don't think it's quite as high as 50% these days, but um it is it's a lot. And you know, I spent the night last night helping a patient who has end stage heart disease largely from a metabolic origin, I think. Um and in some ways it is both a miracle and a tragedy that we are so good at rescuing severe chronic disease in this country, right? We don't do well with prevention for years and years and years or even management of existing chronic disease, right? We keep escalating medicines for diabetes, we keep escalating medicines for blood pressure, we don't spend the time to talk about what else people should do from a lifestyle perspective to mitigate this disease process. We don't really talk about, you know, how this impacts their day-to-day living. It's just someday in the future this might be a problem. And we're like, yeah, okay, doctor, yes, I'll do better. And we, you know, have the same conversation again in a year. Uh, and so we we really drop the ball on all this chronic disease for years and years, and then somebody shows up in Florid organ failure, and our ICU teams kick into action and our you know, doctors kick into high gear and we all mobilize and we all do these heroic things, and like we can we can revive people from near death and keep them there for a while. Um, and sometimes that works and we recover organ function, and sometimes it doesn't, and it becomes a very prolonged uh last, you know, few weeks to months of life for people. And and it's a source of great moral distress for me to like watch this happen. And I just again want to thank you for being here and for allowing me the opportunity to talk to you all about prevention, because um that is how I get through those cases now, is remembering that there is a group of people who are so invested in their own health that they will show up for uh an hour and 45 minutes on a Saturday afternoon or evening to shoot the breeze with somebody who is doing their best to learn about this and provide some meaningful guidance and information to people in the uh in the big white world. So thank you guys. Tron, is there a CIMT test specifically for the heart instead that we should be doing? Um so C the C and C IMT is carotid. Uh, carotids and femorals are the two things that are done well with ultrasound. The heart is not, the the vessels in the heart are too small and moving too quickly to be seen well with ultrasound and the heart. So um the best test for the vessels in the heart is the CCTA, CT angio angiogram. Uh my life goal is never to present debt. I have some bad news about that for you. Right now, the uh mortality associated with living is currently 100%. And uh I hope that maybe you'll be the first to beat those odds. Uh, if you do, you'll have to let us know and um also let Brian Johnson know how that all went and how that happened for you. But until then, uh we will see how that works out for us. Rena, question post-COVID. Have I seen a lot of vascular heart problems uh after COVID and the VAX? So I personally have not seen an enormous amount of this early in the pandemic. There was uh an early strain of the virus that caused a lot of blood clotting problems. And we had people who were in the ICU who had failing lungs who also had severe blood clots in their legs, in their arms, uh, everywhere in the body. And that was definitely associated with the early rounds of the virus. And then there was one of the vaccines that was also associated with something called vaccine-induced thrombotic thrombocytopenia, Vit syndrome, and also was associated with uh a fair amount of clotting events, and that was unfortunate. That kind of went out of circulation very quickly. I believe it was the Moderna vaccine. And after that, what I hear more about are patients who either have long COVID or persistent autoimmune issues after a COVID infection or andor vaccination. And it's unclear because a lot of people who got vaccinated also had the virus at some point, whether this is related to vaccine, whether this is related to COVID itself, the infection. This is an emerging area, and I am sad to realize that there's a lot of political spin on what gets published in the scientific literature, which should be apolitical, but isn't. And so I am not sure that our best understanding is well reflected in the current journals or in the current research, just because there've been a lot of reports of people who have things to say who've been unable to get published and unable to present their data and present their work because of some, you know, political feelings about what this might mean and how that's re being represented. So this is a complicated story that I don't fully understand. I absolutely know of people who are have not been the same, like their health has not been the same since vaccination and or infection or both. Uh, how we are managing that is again, there are people who are specializing in this now. I believe that the you know best strategies are largely sort of autoimmune support, but not my area of expertise. And I fortunately have not seen a lot of um vascular issues specifically related to this in my surgical practice. William, can surgeons operate on the basis of a CTA or do they need an angiogram? Uh-huh. Um I'm laughing because this will depend a little bit on the surgeon and which vascular bed we're talking about and how the process evolves. So if you're thinking about the heart, um what I want to say about that is the CT scan will go to a cardiologist, and the cardiologist is the one who makes the next decision about how things are going to be managed. They will likely try to do an angiogram and get a better idea of exactly how narrow things are. And that's also their opportunity to potentially treat you in a minimally invasive way with a stent or atherectomy or something else, usually stents. If they decide that you are too high risk for stents based on the location of your lesions, then they will refer you to a surgeon. A surgeon, a heart surgeon, is used to this general referral pattern where they always come with an angiogram from cardiology because all of their referrals come from cardiology, right? So cardiology is a medical doctor who treat heart disease, and they have interventional cardiologists who will do the minimally invasive approaches to the coronary blood vessels and to the valves in and around the heart. So all wires and catheters, either from a poke in the wrist artery or a poke in the groin artery. Then there are the heart surgeons who are generally speaking the ones cracking your chest open with a saw and going in and harvesting your mammary artery or your leg vein to go around the areas that are blocked in your heart circulation. So the way that that whole referral process works is that patients almost always come with an angiogram first because they came through cardiology. And cardiology wants that opportunity to treat you minimally invasively. So even though I think a surgeon in the cardiac surgery world would probably be willing to operate on just the basis of a CTA, that almost never happens. In vascular surgery, where we are not beholden to another specialty who does angiograms first, I will absolutely operate just based on a CTA and not do an angiogram first unless I think there's value in an angiogram either for diagnosis to plan a bypass, for example, or because I think there's a chance that I could treat it minimally invasively without having to get out the knife. So usually the imaging is sufficient from a CT to make a clinical decision to go to the operating room. Angiograms are for some additional diagnostic information. The smaller the blood vessel, the less reliable a CTA is. So for me, if I'm looking at arteries below the knee, the tibial arteries, those are pretty small. And if there's any calcium whatsoever, then a CTA can be very difficult for me to tell whether those tibial arteries are open. And I will want an angiogram before I'll take somebody to the operating room for a bypass, uh, just to make sure that those arteries are really open and healthy enough to make it worth a long operation, high-risk operation to restore circulation. But uh I and other under other circumstances, I'm happy to go to the OR without a CTA. Uh do I use robots in the in my surgery? So there are some people who have done um robotic assisted vascular surgical procedures. It is really uncommon. So the robot is a tool that is replacing a lot of the laparoscopic techniques in surgery, and most of that is done in general surgery, in pelvic surgery, so urology, OBGYN, um, and even, you know, like the thyroid and some breast surgery I've seen. I know a couple of people who have used robotics in vascular surgery, but it's far and away the exception. And I think there's it's mostly based on this fear that if you lose control of a blood vessel and you don't have your ability to like just put a hand on it or put a clamp on it quickly, then that can get really hairy really fast. And the robot, you know, there's a little camera that's in there. But if you lose control of a blood vessel and blood starts squirting everywhere and now you can't see, then you can't safely put a clamp on anything because you don't know what you're clamping. You can't see it to put a clamp on it, and all of a sudden you're in a bad situation, and now you have to, you know, get the knife out and open the patient up and do all of this and sort of have this recovery. I'll say that I uh I assisted when I was a general surgery resident. I spent a lot of time on the transplant service, and we had a transplant surgeon there who was very like his whole career at that point was built around robotic kidney transplants. And to do a robotic kidney transplant, you have to connect the kidney artery to an artery in the pelvis and the kidney vein to a vein. So you have to do two vascular connections. That means there is a clamp and you're potentially losing control. I never saw that happen. Now he was a really good robotic surgeon. Um, but it's uh, you know, I was anxious watching him do it, and like I had my hand in there trying to help him uh do these cases, and um, it was it was anxiety provoking for me. Uh, but he did a great job and it's been done safely, and there are some people who are doing it safely. So I think this is mostly a challenge around mindset uh and around thinking outside the box in terms of how do we create a safe way to do this and how are we going to troubleshoot uh because, you know, right now my brain has a set of ways that I get out of trouble in the operating room. That would be really different robotically. It doesn't mean it's not possible. My best friend is a colorectal surgeon and she uses the robot all day, every day. She would take it home with her if she could. Um, and I think, you know, if I went out and operated with her for like a couple of weeks, I could probably figure out how to be safe using a robot, but it's just so uncommon for us to be doing it minimally invasively that way that most of us have not invested the time and energy to do that for the very few cases that it would apply to. So um long story short, we're not using robots. We do a lot of minimally invasive stuff with our own hands and eyes, uh, but it's not the robot yet. All right. Please talk about the results of carotid stenting versus end arterectomy. Okay, so the carotids are the arteries in the neck that go up to the brain, uh, at least the two in the front that go up to the brain. There are two in the back, also called the vertebral arteries, and those supply the posterior circulation. If you get plaque in the arteries in your neck, the carotids, that can be responsible for stroke. That plaque can break off and go up into usually the middle cerebral artery in the brain and cause a stroke. Also, if the disease is severe enough, usually greater than 80%, there are many people who would recommend treating that prophylactically to help prevent the risk for stroke in the long run. The old way of managing this was to make a big incision along the muscle in the neck called the sternocladomastoid, open up that carotid artery, put clamps above, clamps below, block the circulation, scrape all that plaque out until it's nice and smooth inside, and then close the artery up using a little patch, either of fabric or of uh other material, and then you restore the blood flow to the brain. It's actually a pretty nice operation. It works well. Uh, recovery is not terrible, and um, it's cool, it's fun. There is, of course, a risk of stroke with that. There's also a risk of stroke with stenting. The big downsides are the incision. The other downside is that there are some nerves that run along that artery and in the neck that, if they are damaged, are pretty inconvenient or life-altering. So, your ability to swallow well, the ability to move your tongue and talk normally, the ability to uh use and modulate your voice, these are all things that can get impacted by surgery in the neck. And so, nerve issues are one reason um that surgery is not a great choice. The other issue is time under anesthesia. Stenting uh in experienced hands is faster. And so even if you're using general anesthesia to do it, and we can talk about why we would do that in a second, the um there is an advantage of stenting for the duration. So a stent is a rigid or semi-flexible tube, usually of metal, sometimes with a plastic coating on the outside, sometimes without. The ones that we use for the carotids are not covered, so it's just sort of a metal cage and it starts as a little small tube. We snake it up across the area that is narrowed or blocked, and then it expands and we we blow it up. And that traps that plaque against the wall of the artery and prevents it from going up into the brain. The early data with stenting was better for heart attack risk because it was faster, but it was worse for stroke risk, probably because getting a wire and then the stent across that big plaque shoved plaque up into the brain before the stent was deployed. People have used little baskets to try to catch the plaque so that it doesn't go up there. What we use now is something called flow reversal. So we actually put a big hose in the carotid artery and we connect the other half to a vein in your leg. And instead of having the blood flow up the carotid into the brain, we actually reverse that flow and we bring blood down from the other carotid from the vertebrals, pushing it down, and we feed it back into the leg. So if any plaque or little bits become dislodged, instead of flying up into the brain where they cause a stroke, they fly down into the tubing, they go into the filter. Worst case, they go into the vein and the leg and end up as a tiny little thing in the lung that is of no clinical consequence. So the flow reversal technique that we are using right now for transcarotid stenting, so that means a small incision down here in the neck. Uh, it's smaller than the endorterectomy incision, but it's still a little incision and it is in the neck, is game-changing for us in terms of making sure that the stenting is as safe as putting a clamp on the artery and preventing embolization that way. The recent data for endorterectomy versus stenting was presented and it was the CREST II trial. The nuance about the trial results are that they didn't compare stenting to surgery head-to-head. They had two arms of the trial. There was one arm that was surgery versus optimal medical management, there was a second arm that was stenting versus optimal medical management. And so everybody's now trying to make an extrapolation to surgery versus stenting. It's not totally fair because of how they designed that trial. What we know is that for asymptomatic patients who have not had a stroke or a mini stroke in the last six months, that's the definition of symptomatic, by the way, that um if you have greater than 80% stenosis, a carotid stent is probably in the long run going to help reduce your risk of stroke above and beyond optimal medical therapy. But it was kind of close. And so we're not totally sure that that's um best for absolutely everyone. But for a good risk patient, probably that will reduce stroke risk in the long run. The surgery arm was equivocal. So the risk for stroke in medical management, best medical management, and the the medical management was pretty aggressive and was the same basically as the risk for future stroke if you had a preventive surgery. All of this is very nice and nerdy. It does not actually answer your question if you are being faced with this clinical decision. So, what would I do if it was my mom or my dad who had this issue? Um, I would say in 2026, if I knew somebody had done 50 to 100 transcarotid stents and uh their outcomes were good, I would probably go for a transcarotid stent in 2026 if they have appropriate anatomy. There are some geometry things about how you put a stent in and how much room you need and what the configuration of the artery is that are required to have a safe and good outcome from a stent. And not everybody has that. So if your anatomy is bad for a stent, don't do it. Um, and the other thing I'll say is if you are in a place where you only have one person, one clinician who's offering this and they recommend certain things, let them do what they are most comfortable with. Because again, I think that the outcomes are very, very similar. There's not one clear winner here. And if somebody who's treating you is very comfortable with the way that they've been doing things, our data in the surgical literature is actually very strong about this. Let people do what they have gotten accustomed to doing, and that's typically how they will have their best outcomes. So if you are with a surgeon and you like them and you trust them and they say, for you, I really recommend this, that's what I would do. Um, if I were shopping around and I just wanted like to pick somebody based on what procedure was on offer, and I thought that it would, you know, if it were me, I would probably prefer the shorter, shorter procedure and the less invasive one. So that's how I'm leaning and and how I and you know the surgery has higher or lower risks depending on a lot of things, right? Um, how high is the lesion? How high in the neck do I have to go? If it's close up to the skull base, that's a big slog, higher risk for nerve injury. That patient in my practice, I will preferentially offer a stent first if I can. Um, patients with a big, very dense like rock of calcium. You can imagine that a tube is not gonna expand very well. It might get crushed by the calcium in there. And if it's very focal and very bulky, I might actually recommend surgery. Again, this is based on imaging. So um I would say they're both very good choices in 2026. All right, let's get back to our questions. Oh, Roxanne, you're here. My LPA is 295. I'm terrified. Oh, I'm so sorry. I start on Rapatha, I am pre-diabetic and on blood pressure medicine. When will the new drugs be available to help us? Good question. I am hoping that we are getting the first phase three trial results late 2026. So uh depending on when those come out and what they find, right? We are all assuming that this will be positive. Um so I think if they are positive findings, uh, the FDA has been pretty rapidly approving new molecules that have shown good safety and efficacy. So my hope would be Q1, Q2, 2027, if we get results late 2026. That's my best guess. If those trial results are delayed and we don't get them until 2027, I would expect another six to 12 months, probably before we start seeing the drugs come to market. And of course, that will all change if the drugs, in fact, are not as successful as we hope that they will be. If I were in your shoes, I would say, you know, Rapatha is absolutely the place that I would start. And think about doing everything in your power, of course, to work on the metabolic side of things because it does seem to be modulated. The risk from LP little A does seem to be modulated at least in one cohort by the metabolic factors associated with metabolic syndrome, insulin resistance, right? High blood pressure, prediabetes, elevated waist to hip ratio, visceral fat. So getting all of that under optimal control, plus the repatha, I think, is a great way to think about it. I would also potentially ask your clinician whether there's a role for aspirin for you. There are some patients with LP little A who do much better with Lidose aspirin, some people who don't, or who are not good candidates for it for other reasons relating to bleeding risk. So uh that's also something to check in with your clinical team. All right. At what percent of carotid obstruction do you start thinking about surgery or stenting the carotids? For patients who do not have stroke or mini stroke related to a carotid in the last six months, so now asymptomatic patients, I would recommend waiting until it is 80% narrowed before I would go in there with uh surgery or stenting. I have a patient right now who has about an 80% narrowing, but she's still actively smoking. And for all kinds of reasons, uh, that's not likely to change anytime soon, and she's not having symptoms, so I'm putting off her surgery, even though technically she would meet criteria, and we've talked about it, right? I didn't say I wouldn't do it, but I sort of said, I don't think I'm necessarily helping you all that much because you're still actively smoking, so we still have a lot of residual risk and risks of surgery are higher. And she also thinks that she's doing fine, and so we are aggressively medically managing her. But um, that is, and I had some partners in my first job who almost never took anybody to the operating room for asymptomatic disease. Uh, we just did really aggressive medical management, and there were some studies that showed that that was also a very reasonable approach. So some of it depends on life expectancy. If you have less than five years life expectancy, so if you're in your early 90s uh and you have an 80% stenosis, I'm not sure that's worth it. Um, if you're in your 60s and you have 80% stenosis, I definitely think that that's worthwhile. So a little bit of nuance there, but the threshold for asymptomatic disease is officially 70%. Most of us in clinical practice are now eking up towards 80% before offering intervention for asymptomatic carotid disease. If you're symptomatic, if you've had a stroke or a mini stroke, um that threshold is lower, it's closer to 50%. And it has to be a stroke or a mini stroke that is obviously associated with the same clinical territory of the carotid artery. So if you had a stroke on the left side of your brain, but a right-sided carotid narrowing, that's not a stroke from that carotid artery. So that's asymptomatic disease. Uh, hopefully that makes sense. All right. Who do I know who has done those 10,000 stints? Um I don't know who's done 10,000. Uh, I have a partner who's done over a hundred, and he's excellent. I operate with him as often as I can. I have not done anywhere near a hundred, I have done about five, and that is uh an ongoing process, and I'm very transparent about that with patients, by the way. I like to um I like to say all of that. Uh what books do I think that everyone should read for health and also in general? This answer has changed a little bit uh based on some people's downfalls and social media recently. Um I was a big fan of Peter Retia and the Drive. I thought he had a lot of really exciting perspective on healthcare. Um, it is a little bit more challenging for me to recommend his content these days after the Epstein files. I don't think he's a bad person, but um anyway, Outlive was a good book that covered a lot of ground about prevention, longevity, and chronic disease. I think um the most recent book by Brad Bale and Amy Denin, I mentioned the Bale Denine method earlier. Um, I think it's healthy heart, healthy brain is I'll link it for you guys in the description, uh, is a great book. It's pretty conversational, but there is some high-level stuff in there. Some of it's about genetics, some of it's about different risk factors for heart disease. Um, but it's definitely accessible to to a public audience that wasn't necessarily written for doctors or clinicians. So I think that's a pretty um eye-opening book if your whole perspective on heart disease up until now has been cholesterol only. Uh, and so that's pretty cool and fun. And I think that a lot of the best health books we can read are actually about mindset and growth and how we increase our capacity for resilience and joy in everyday life because our modern environment is full of a lot of chronic stressors, and that's not changing anytime soon. But how do we stay focused on the things that bring us joy and connection and meaning in the world? And how do we try to move beyond some of the um ennui of like living in a very politicized, contentious, conflict-rich environment? Um, I have a personal stake in this with respect to the health and well-being of clinicians in particular and and high performance individuals. I think that there has been an epidemic of disconnection. And I realized that part of my training as a doctor was actually very intentionally designed to disconnect me from what made me human. And they did that on purpose and nobody talked about it, but it was absolutely part of the culture, the unspoken, unwritten rules of medical training. And it cost me a number of years and some mental health, and it has cost many physicians their lives. This is a problem, and it's been called burnout. Uh, it's been called issues with paperwork and prior authorization and insurance and managed care. That's all a symptom of a much bigger problem that we have in medicine. And um, I hope that in the coming months I will have more information for you on another book that might be coming out uh to a retailer near you called Disconnected. Ask me about it again. All right, no smoking. Yes, I agree. You had the left-sided stroke from the right carotid. Oh no, I'm sorry. So you had left-sided symptoms, but the stroke was probably in the right brain from the right carotid. That's very confusing for a lot of people. Uh, I just wanted to clear that up because if the lesion is on your right brain, that is usually the left side of your body that's impacted, the left arm, left leg, and so forth. Um, but yes, we would absolutely expect that to be from the right side of the brain and the right carotid artery. All right, we have a couple of more anonymous questions here. What do I think of eating a can of unsalted sardines and water a few times a week? Walnuts and pumpkin seeds. Um I think that the uh so the the sardines are rich in omega-3 fatty acids and some vitamin D. The walnuts are rich in omega-3s, which is the plant-based form of omega-3s, which is ALA. ALA is fairly inefficiently converted to the DHA and EPA, which are the two primary omega-3 fatty acids that we really want to see circulating. Uh as a plant-based source, it's it's okay. I just you have to be aware that the conversion from plant-based omega-3s to the DHA and EPA is pretty inefficient. And then there was uh mention of pumpkin seeds with vitamin E to protect the omega-3s. Um, once fatty acids are oxidized, you're not gonna unoxidize them. So if your omega 3s are rancid for whatever reason, whether that's in supplement form or because the oils in the fish went rancid for any reason, adding adding vitamin E to that is not going to undo that or reverse that. Um You know, antioxidants in general, vitamin E in particular, was tested clinically and actually had increased mortality. Now they gave one very specific form of vitamin E. There's actually multiple different um like isoforms or ways that you can give vitamin E. And there's some indication that if you get a good mixed vitamin E supplement rather than just one of the like isolated tecopherols, that perhaps that result would have been different or we would have had um improvement or or at least no worsening of mortality. Uh, I generally don't recommend vitamin E by itself coming from whole food sources. Uh, sure, I have no idea if the pumpkin seeds are good because of the vitamin E or because of some other thing that's in there. Whole food sources of everything are always the priority. And um, in general, I would say this is a great approach, right? Whether we're doing it to target specific nutrients or just because this is um an overall wise strategy, doesn't really matter. I think that's a great approach. All right. Okay. Guys, we have been at this for over two hours. I am so impressed with all of your questions, your enthusiasm, and your participation. Uh, we are kind of running our end of the chat here. I am through all of the anonymous questions. I'm gonna call it for today. I am so grateful that you all took the time to come and hang out and chat with each other, with me. And uh, I had an amazing time. Thank you so much. If you want to do this again, please let me know in the comments. Uh, reach out to me on the channels. We will try to make this a monthly recurring feature if there is enough interest. You guys have been amazing. Oh, wait, one more, one more. How much credence and science do you have on our gut microbiome? Okay, this is a bonus question. If you didn't already sign off, um, I think the microbiome is fascinating and I think it's very important. And I think that our understanding of it is so infantile that we just can't quite get there yet for most people. Stay tuned, give us another 10 or 20 years, and I hope that we will be better informed on how to make meaningful change in the microbiome for people. Right now, it's still very much a uh hit or miss self-experimentation thing. I think the measurements are pretty unreliable, like the GI map tests and all of this. Um I I don't use that in my current clinical practice, but uh I certainly think that it's an enormous part of our health and well being. We just don't understand it very well or know how to move the needle for most people very well yet. So stay tuned and um thank you guys. I hope you have a great rest of your weekend. Stay safe, and until next time, take really good care.