Blood pressure: how to measure, manage, and treat high blood pressure (AMA #48 rebroadcast)

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Welcome to a special episode of The Drive. This week, we're rebroadcasting a previous AMA, which focuses on blood pressure. Blood pressure is one of the most important and sadly overlooked risk factors for chronic disease. It's a topic that affects nearly everyone, yet many people either do not know their numbers or don't appreciate how profoundly blood pressure influences long-term health. While this AMA was originally released to subscribers, we felt it was important enough to make it available to everyone, while also giving those of you who aren't subscribers a chance to experience what our AMA episodes are all about. In this AMA, we talk about what blood pressure actually measures and why it matters for longevity, how to accurately measure blood pressure at home and why office readings can often be misleading, the relationship between blood pressure, cardiovascular disease, dementia, kidney disease, and overall mortality. The latest evidence says about optimal blood pressure targets, the lifestyle interventions including weight loss, exercise, nutrition, and sleep that have the biggest impact on lowering blood pressure, when medications become necessary, how they work, and how to think about the different treatment class options, and practical strategies for monitoring and managing blood pressure over the long term. So without further delay, I hope you enjoy this special rebroadcast of our AMA on blood pressure. Peter, welcome to another AMA. How are you doing? Very well, thank you. Awesome. You know, before we get started on this one, some of the people who listened to one or two AMAs ago when we were going over your DEXA results, we were talking and telling the story about Reese's Pieces and how you had never heard of them. And we did a call out to say, hey, if anyone else has never heard of them, please reach out and you will be pleased to know we probably had about 30 to 40 people who had never heard of Reese's Pieces or people who are in the same boat as you and had no idea what Reese's Pieces are. So you are not the only one. Not the only one on this planet. Not the only one. I mean, again, 30 to 40 compared to our listenership is not a good percentage. So you're definitely in the minority. But yeah, shout out to everyone who reached out and the person who was the first to reach out. We have something special going in the mail for them. And ironically, they reached out to us before we even sent the email saying, the podcast was live. So to say they are an active listener would be an understatement. So shout out to that person. They know who they are. Today's AMA is going to be on one subject, but one important subject, which is blood pressure and all things blood pressure. And people who have listened to the podcast will have heard us talk about blood pressure before. Most recently, the episode we released with you and Ethan Weiss, Ethan coming back for the second time, you both spoke a lot about, about blood pressure. And as you said in that one, if you look at cardiovascular disease, three main risk factors for cardiovascular disease are going to be smoking, which we don't necessarily talk a lot about because as you've said before, we're kind of under the impression if you listen to this podcast and you still smoke, you probably should know you shouldn't. So that's nothing really we need to say there. The second is APOB, which clearly is a topic that we cover a lot and has been covered. And then the third is blood pressure. And we kind of realized we hadn't, we hadn't done as much of a deep dive on blood pressure and we get a lot of questions. So we compiled all those. And in today's AMA, we're kind of really going to talk about a few different sections, multiple questions in each section, which is what is high blood pressure, low blood pressure? Why should someone care? You know, what does it affect? Cause it goes beyond just the risk of cardiovascular disease as well as, you know, how do you know where you're at? This is one where, you know, unlike APOB, you can't give yourself an at-home blood test, but you can check your blood pressure and you can understand how it changes throughout the day, what the different definitions mean. And then we'll end with the really the main focus, which is, okay, what can you do to control your blood pressure? You know, what are the lifestyle factors that you can do to lower it? How well do those work? If you have to look to use medications, what are the most common drugs? What do we know about them? Are there factors that would make one quarter quote better than the other? So that's really going to be. We are focused for this AMA and just given the importance of the topic and how many questions that we get on it and what we compiled, we figured we would just focus the entire thing on it. So before we start rolling on it, is there anything else that you want to add to set the stage? No, I think that's a good way to land. I think presumably most people who listen to this podcast have had their blood pressure measured at least some point in their life. Obviously when you go to a doctor's office, even if you're going for anything. Anything random, they'll typically check it. A lot of people will have at home cuffs that they may be checking. So I think a lot of people have had their blood pressure measured, but I think it might be helpful to know like, what does a blood pressure measurement actually mean? Like what is it actually doing and measuring? To understand that you have to sort of think about what the heart is doing. So the heart is pumping. Obviously that's what you feel if you put your hand on your chest and what you're feeling is kind of the pulsatile sensation of the pressure difference in the arteries as the heart contracts. So just remember there's two phases of the cardiac contraction. The first is called systole. And systole is when the ventricles are contracting. The ventricles are the larger chambers, the left one being the muscular one, because it has to pump the blood against the systemic resistance of the whole body. And it's the one that's responsible for getting blood out to the body. We're going to talk about that pressure today. So we're going to talk about the systemic circulation. What we're not going to talk about today is a different blood pressure, which is pulmonary blood pressure. It turns out that when people hear like 120 over 80 is my blood pressure, that is talking about the blood pressure in their circulatory system of the periphery. But if you wanted to know the blood pressure in your lungs, which is controlled by the right ventricle, those would be pulmonary pressures. And those would be significantly lower. Again, we won't talk about those. Just park that over the side. So when your left ventricle contracts, you're in systole, blood is leaving the heart through the aortic valve, goes out the aorta, the ascending part of the aorta, and then it immediately just starts moving to the rest of the body. So at the arch of the aorta, it jumps off three little freeways, if you will. So you have the common carotid, subclavian, and inominate arteries. And then it kind of goes over the aorta, and then it goes over the subclavian, and then it goes over the arch, comes down, and then it goes out to the rest of the body. And this is happening really quickly. Even if your heart is beating as slow as one beat per second or 60 beats per minute, you know, think about the rate at which that happens. I think everybody kind of understands that part. So there's a pressure in the artery that is experienced by literally the blood pushing against the walls of the artery during that phase. And that's obviously the bigger number. But it's important to remember that there is a second equally important phase of the heart, which is the relaxation of the ventricle. And that's how they fill. So that's called diastole. So after the heart squeezes and blood leaves the heart, the heart has to relax to have blood come back into the ventricles through the atria. By the way, it's also important to know that this is when the heart itself receives its blood supply. So the heart receives its blood supply during diastole, whereas all the other organs are receiving their blood supply during systole. And even though the pressure in the arteries is lower during diastole, which I think would be intuitive given what I just described, it's still more than zero. There is still a tonic amount of pressure within the artery wall. So when you have your blood pressure checked and it spits out two numbers, let's just say it's 125 over 79. What that means is when your heart is doing the squeeze and there's a greater force as blood is leaving the aorta, the left ventricle via the aorta, it's whatever number I said, I've already forgotten. I think 124 millimeters of mercury is the pressure. And when that ventricle relaxes and begins to fill through the left atrium, the pressure drops to whatever else I said. I forget. I think I said 79 millimeters per mercury. So millimeters of mercury is, I'm not going to get into what those numbers mean and how you do that. But you know, if anybody thinks back to like a chemistry class, you can have a manometer that basically determines pressure by how many millimeters, it can raise mercury. So the higher that number, the higher the pressure. Sure. Does it ever blow your mind when you think about what the human body does on a daily basis that we don't even think about or see? Like as you were saying, even if it's 60 beats per minute, which is one beat per second, like it's just constantly doing it. You've seen bodies cut open from your time in surgery before. So it's like you see that more, but does it ever just kind of blow your mind how we're able to function and we just don't even think about those little things every day? It still does. And it's been, I think back to my very first time in the anatomy lab or my very, very first time being in surgery. And it's no less amazing to me today than it was then. I simply can't believe it. The next question then naturally is, what does it mean to have high blood pressure? Because I think this is something that it seems like in the past five or 10 years, the definitions may be changed and there's a few different types of definitions. So I think it'd be helpful to set the stage early of, you know, when we say high blood pressure, what are the two numbers that we're referring to? So people can kind of, as they look back at their own blood pressure results, can kind of know where they fit. Well, as you said, this has changed a little bit. So prior to 2017, we had a little bit more leeway in the system, but the current updates, which have been in place for about six years and which were updated after the sprint trial in 2015, a trial that I'll explain in a moment, leave us where we are today. And where we are today is normal blood pressure is defined as having a systolic blood pressure. And that's where we are today. A systolic blood pressure at or below 120 or technically below 120 millimeters of mercury over something less than 80 millimeters of mercury. So if blood pressure is both less systolically than 120 and diastolically 80, that's considered normal. So 119 over 79 normal, 121 over 79, technically not normal. Elevated is when the systolic, is between 120 and 129, but the diastolic pressure remains less than 80. So we talk about elevated blood pressure as a slight elevation in the systolic, but not the diastolic pressure. And then we get into two stages of hypertension. The first stage is when systolic blood pressure is 130, sort of between 130 and 139, or diastolic blood pressure is between 130 between 80 and 89. So does that make sense? Because you'll notice there's a bit of a gap in there, right? So you could be 120 over 83, and now you're at stage one, even though your systolic is normal. And then stage two hypertension is when either systolic exceeds 140 or diastolic exceeds 90. So again, in summary, normal blood pressure is less than 120 and less than 80. Elevated is 120 to 129 over less than 80. Stage one hypertension is 130 to 139 or 80 to 89. Stage two is greater than 140 or greater than 90. Okay. So where do these numbers come from? Because these aren't just arbitrary, right? These are sort of based on something important. And that something important is called the SPRINT trial. So this is a trial, I think it was published in 2015. I think it was like about a year or two before these guidelines were shifted. And the purpose of this trial was really to ask the question, what is the benefit of, for lack of a better word, aggressive blood pressure control? So the study looked at just under 10,000 people who had a systolic blood pressure of 130 or greater, who were also at advanced cardiovascular risk, but who did not have type two diabetes. And the reason for that patient selection is you wanted a group of people who were at INF risk for ASCVD that you could start events in a relatively confined period of time. You have to remember, this is always the goal of clinical trials. Even when you're doing large double-blinded trials, you want to be able to have enough events in the trial that you don't have to run the trial for 10 years. So you've got a high risk population, though it's worth noting they don't have type two diabetes, and they have to have a systolic blood pressure over 130. So they were randomized into two groups. The first group, which we'll call the intensive treatment, was treated to a systolic blood pressure of less than 120. And the standard treatment were treated to a blood pressure of less than 140. Make sense? So one group is kind of being treated to not be over 140. The other group was really being pushed down to 120. So at coming in, the average blood pressure of all comers was about 140 over 78. Now, Ethan and I talked about this a little bit, but just in case, folks didn't hear that podcast, or just in case people need a little bit of a refresher, is this study did a pretty rigorous job of assessing blood pressure. So they used an office visit where blood pressure was measured three times using the following protocol. So the patient would sit down for five minutes doing nothing, not talking, not doing anything. Their back is supported. Their legs aren't crossed. After five minutes, blood pressure was taken with an automated blood pressure. So they did a pretty rigorous job of assessing blood pressure. This was sized properly and used in perfect, correct way, which we'll talk about in a little while later in this podcast. They would take that reading. Five minutes later, they would repeat that. And five minutes later, they would repeat that. So the blood pressure for that visit was deemed as the average of all three of those readings. And this is a lengthy procedure, right? It took 15 minutes to get those three readings and to determine their blood pressure. But that number served as your blood pressure. So if you were on day one, you were 137 over 81, and you had that reading, well, if you were in the business as usual group or the placebo group, or not the placebo group, but the standard treatment group, they would make no adjustment to your medication. If you were already on medication, if you were not on medication, they wouldn't add medication. But if you were on the intensive group, they would treat you. So at one year, after one year of this, the average systolic blood pressure in the intervention group, high intensity group was 121.4 millimeters of mercury. In the standard group, it was 136.2. This intervention was stopped early. I forget how long they wanted to run this study for. I think they were looking to do this for five years. I could be mistaken on that. But regardless, at just a little over three years in median follow-up, the study was halted. And this is not uncommon in hard outcome studies. We see this quite often where the benefits in one of the arms is so much greater that it becomes unethical to continue the study. And that was the case here. So the primary outcome, which was a composite outcome of reduction in cardiovascular mortality, was significant. It was about a 25% relative reduction. So the hazard ratio was 0.075. And the absolute risk difference was about 0.54%. Over the course of one year. That's actually pretty significant, by the way. It doesn't sound like a lot, right? 25% reduction, a little over half a percent absolute risk reduction. But you have to remember, that's a single year reduction in risk. That's quite significant when you consider that blood pressure, just like lipids, are compounding risk factors. At the three-year mark, the total event rate was, I believe, in an unadjusted way, I want to say 1.7% lower in the intensive group. And again, this was for this primary outcome, which is a composite outcome. It was kind of a mace-like output. So it was myocardial infarction, non-myocardial infarction, acute coronary syndrome stroke, acute heart failure, and cardiovascular death. What I found pretty interesting about this study was that it also saw a benefit in all-cause mortality. I would not have necessarily expected this. So I don't think it's that surprising that they said that. I don't think it's that surprising that they said that. I don't think it's that surprising that they saw a benefit in the primary composite outcome, which really all pertained to heart attacks and strokes. It's maybe a little surprising how big the benefit was in such a short period of time. But what I think really caught people off guard in a pleasant way was that all-cause mortality was also reduced 27%. And it was like a 1.2% absolute risk reduction. This is pretty interesting. It's not that you wouldn't expect the death rate to be from a cardiovascular disease standpoint, which it was, right? It was a 2x reduction in cardiovascular disease death specifically. But it's that you would see also a reduction in all sorts of other types of death. And this was seen in, not surprisingly, perhaps kidney disease. Amazingly, accidental death, suicide, homicide was significantly less. So again, it's possible that maybe a larger study, that wouldn't pan out. Maybe 100,000 people, you wouldn't have seen that. But nevertheless, it's a 2x reduction in cardiovascular disease. So I think it's this was about as dispositive a study as you're going to see demonstrating the efficacy of aggressive blood pressure lowering. And again, the takeaway is even over a relatively short period of time, aggressive blood pressure management to a systolic pressure less than 120 compared to standard of care, which we used to think was kind of 130 to 140 is tolerable, left very little ambiguity about the importance of that kind of recommendation. To double click on something you said, because I think it is important. And we've talked a little bit about it when you've talked about statin therapy before, which is the percentage we saw in this trial over the one, two, and three year mark, you kind of mentioned that that can compound over a lifetime. And so if you saw that much of a difference in a short period of time, it only gives you more confidence because the reality is if someone goes with high blood pressure for most of their life untreated, you're not looking at only three years. You could be looking at from 35 to 75. You could be looking at 40 years and obviously you can't run a 40 year trial. And I know you've talked about this before with statins when I can't remember which study came out. And I remember you saying the stock went down because people thought the result would have been even more positive. But you were kind of talking about if you look at how short that period was and how long people live with high ApoB or high blood pressure, even though this was a short period, it still gives you even more confidence that this is something that people should take seriously, even at a young age, even if it's not going to be a long period. Yeah. Compounding is insanely powerful when it comes to this type of biology, whether it be smoking, ApoB, or blood pressure. When we're dealing with endothelial exposure, again, let's just take a step back and talk about why these things pose such a risk. ASCVD, cerebrovascular disease, you can think of them as blood vessel diseases. And elevated blood pressure, hypertension is a mechanical disruption to the endothelium. Smoking is a chemical disruption. To the endothelium. And of course, ApoB is the concentration of the lipoprotein that itself goes through that disrupted endothelium and then causes the pathologic sequence of events that we're very familiar with. So it's not surprising that these are all area under the curve problems. When talking about normal blood pressure, elevated blood pressure, high blood pressure, in the past when we've talked about HbA1c, you've kind of mentioned before, you know, pre-diabetes is about 5%. I think diabetes is about 6.5%. And you've said like, hey, if you're at 6.4%, and so you're not technically at having the diabetes level, does that mean like you should celebrate? It's like, no. The difference between those is so small that you want to take care of it earlier. And so you've always kind of talked about, one, that's kind of why you don't like the A1c metric and you look at other things. But two, you always kind of want lower is better. When it comes to blood pressure, if someone has, let's say, 119 over 78, so they're in the normal category, but they're maybe kind of creeping to the elevated category, if that was your patient, would you be worried about that? Or are you happy with any blood pressure in the normal category? No, we would be very happy with a blood pressure of 119 over 78. I mean, I think what's more complicated with blood pressure is, and we'll talk about this, I'm assuming, is the complexity associated with measurement and really making sure you're measuring it correctly. Which is kind of an obsession of mine. In other words, there's far more heterogeneity in how you measure blood pressure than how you measure ApoB. I mean, once you have a lab that has a validated assay for measuring ApoB, you can have much more confidence in the little bit of variability you see in that. And I think when it comes to blood pressure, there can be enormous swings in blood pressure based on erroneous measurement. The other thing you have to think about is with ApoB, you can't go too low. With blood pressure, you can go too low. I mean, truthfully, in practice, if we're a little bit on the fence, if somebody some days is like 124, first of all, we never make decisions on the basis of one day. We don't even entertain looking at your blood pressure unless we've seen two weeks of checking it two to three times a day under perfect conditions. Only at that level would we even begin to entertain what is high or what is low. But let's assume you've done that. We've got kind of two weeks of twice daily average recordings and you come out at 123, over 79. I would be very hesitant to go straight to medication because as I said, with ApoB, you can't go too low. It's a one-way street provided the symptoms don't kick in from the medications. But with blood pressure, you run a much greater risk of symptoms if you over-medicate somebody, especially if that's where you're starting. You can get orthostasis, which means lightheadedness when you stand, and that can lead to a whole cascade of problems as well. So I don't know if that answers your question. But this is also a little bit of an art. We did get a lot of questions on those things, so we'll dive deeper into those coming up here. But before we do, in looking at, okay, we know now the definitions of high blood pressure, how common is it? Do we know what percent of the population is walking around with high blood pressure, whether they know it or don't? It's actually staggering. The overall prevalence in the United States for both stage one and stage two hypertension is about 46%. Based on those new categories that I just rattled off earlier. And this is based on surveys that collect blood pressure measurements or self-reported antihypertensive medications. So you could argue that's not entirely accurate because that's also including people who are medicated, because if you're just looking at the med scripts. But clearly this is high. And I think the bigger issue is how much of this is hidden epidemic. In other words, how many people walking around haven't been to the doctor in five years, don't know their blood pressure, because presumably they're not checking it on their own, obviously aren't taking any medications. I think that's a harder number for us to come to grips with. But I think it's safe to say that this is a silent epidemic. It clearly goes up with age. So if you look at young people, sort of in the 20 to 44 age range, men might have as high as a 30% incidence or rather prevalence of hypertension, while women would be just below 20%. Once you get more squarely into middle-aged, 45%, to 55, half of men would at that point present with hypertension, 44% of women. And it just goes up and up and up. And by the time you're 75 years of age and older, it's north of 80% effectively for both sexes, men and women. We also see this slightly playing out differently in race. So for both men and women, African-American has the highest prevalence of hypertension. In men, it's about 59% in women, 56%. That's followed by in non-Hispanic white, it's 47% and 41% respectively for men and women. For non-Hispanic Asian, 45% and 36% for men and women. And for Hispanic, 44% and 42% for men and women respectively. So again, the takeaway there is African-Americans are at higher risk. And as you age, you're at higher risk. Men in the younger age seem to be more prevalent than women, but as they get older, those tend to converge. Translation, there's nobody who's not at risk. That's what I was going to say is not only is it such high percentages, but going back to the conversation we had a few minutes ago of the importance of compounding, when you look at 20 to 44, those people have a lifespan that could easily be another 40 to 60 years. And if 30% of men and roughly 20% of women, women from 20 to 44 are walking around with high blood pressure, the longer you don't know what it is and the longer it compounds can create kind of staggering amounts of issues. It is really interesting to see how high all those numbers are, no matter if you're young or old. So I think the next place that I think makes sense to go is we've talked about this a little bit already, but maybe just kind of rounding out the conversation, which is what are those consequences? High blood pressure. How does it relate to cardiovascular disease? How does it relate to everything else? And ultimately this leads to why someone listening to this, if they don't know their blood pressure should really start to figure it out. And if they do know and it's high and they've been ignoring it, should probably stop ignoring it. You know, we've known about a lot of these consequences since the 1960s from the, literally the first iteration of the Framingham heart study. So back then we were kind of using a higher definition. So we were, you know, we were, you know, we were, you know, we were, we were defining hypertension as greater than 140 over 90, but even reducing people to just below that from above that was associated with effectively a call it 35 to 40% reduction in stroke, about a 50% reduction in cardiovascular disease, all told 64% of that in heart failure, 15 to 25% in myocardial infarction. You know, more recent meta-analyses suggest that if you consider people ages about 40 to 70, each 20 millimeter of mercury increase in systolic blood pressure and each 10 millimeter of mercury increase in diastolic blood pressure are associated with a doubling in the risk of death from stroke, heart disease, or other vascular disease. I mean, to me, that's kind of the data that I would want to be keeping in the back of my mind. If your blood pressure is 140 over 90, as opposed to 120 over 80, you've doubled your risk of death, not incidents, death from stroke, heart disease, or vascular disease. So again, you can also then think about this on a yearly basis using the data that I talked about earlier in the sprint trial, where you're talking about 25 to 30% year on year reduction in relative risk. And that includes, of course, the benefits we saw in all cause mortality. If you look at the 2021 step trial, which basically, we repeated the sprint trial, but in a different patient population. This was in Chinese adults, age 60 to 80. very similar size trial, about 8,500 patients randomized to a slightly higher window. So this was a systolic blood pressure target of 110 to 130 was the intensive or 130, but no more than 150 in the standard. This was a median follow-up of about the same amount of time, a little over three years. These people had isolated systolic hypertension. So diastolically, these people had, I think, a mean hypertension of 76.4 in the intensive group and 79.2 in the standard group. Coming in, these people had a mean baseline of 146 over about 83, and they were done using a similar protocol of rigorous blood pressure measurement. Actually, I'm not even going to get into the differences. There was a slight difference in it, but this was also done rigorously. Anyway, I think the point here is the primary reason why we're doing this is because we're not going to get into the differences. We're not going to get into the differences. The primary outcome, which was similar, found a 26% reduction in cardiovascular outcomes on a relative basis, and the death from cardiovascular disease specifically was a 28% reduction in risk. This study did not find a difference in all-cause mortality between the two. Of course, the absolute risk reductions were comparable, about 1% per year, which again, when you start to think about how many years you would undergo this treatment, that's a pretty big deal. The step trial did not include people with diabetes, so that's actually another important consideration. Again, I think all of this is to say the evidence is pretty consistent that the consequences of high blood pressure, if nothing else, just on cardiovascular disease and cerebrovascular disease, are significant. Therefore, if you're serious about the business of living longer, you definitely want to make sure your blood pressure is being managed. That was kind of a good touching on the D side. What do we know about high blood pressure and its effect on other organs? Well, we kind of touched on part of them, which is the brain. There are very few exceptions of things that are good for the heart that are not good for the brain and vice versa. The way to think about high blood pressure is because it's a mechanical force, anything with small vessels is going to be troubled by it. Really, the way you want to think about this is there are three organs that are most susceptible to high blood pressure. We've just talked at length about one, which is the heart. Talked a little bit about one, which is the brain. The one we haven't talked about is the kidney. There's a very high incidence and prevalence of end-stage renal disease in patients with hypertension. Again, you have to kind of go back a little bit to renal physiology to understand how the kidney works and how delicate its vascular system is. I think I've mentioned this on a previous podcast several times. The kidneys are tiny little things. They weigh 1% to 2% of your total body. Yet, they're receiving 20% to 25% of your cardiac output with each pump of the heart. Think about what must be true of the vascular network of that organ to accommodate such perfusion. Therefore, it's highly susceptible to elevated pressures there. People with hypertension have faster rates of decline in their renal perfusion than age-adjusted people with normal blood pressure. This results in a stark decrease in glomerular filtration rate. It's of course not the only thing that can destroy the kidneys. Unfortunately, diabetes is also an enormous insult to the kidneys, though for a different reason, which we're not going to get into today. Then when you consider the fact that oftentimes high blood pressure and elevated glucose go hand in hand, in fact, they are two of the five metrics that define the metabolic syndrome and therefore are proxies for insulin resistance, you realize that I just think it's an epidemic that's not getting enough attention, which is inappropriately or overly aggressive decline in glomerular filtration rate as a result of the double whammy of high glucose, high blood pressure. In our patients, we're very aggressive about checking a biomarker called Cystatin C, which we think is far superior to creatinine as a way to keep tabs on their kidney function. It's very common for us to see people that have quote-unquote normal kidney function, but it's far too low for their age. They might have a GFR of 60, so 60 milliliters per minute of glomerular filtration, which technically gets considered normal. It's not normal until it's below 60. We think normal is 100 for someone who's 50, and 60 might be normal if you're 75 years old, but we don't think it's normal for someone who's 50 or 55. A lot of times, that immediately hints to us that they've got hypertension even before you put a cuff on them to just see those numbers. The last thing I'll say is there's another trial that's similar to the SPRINT trial. It's called the SPRINT MIND trial. It's basically a subset of the other trial, but it's looking at the impact of intensive blood pressure lowering and the state of dementia. It's the same cohort, a little over 9,000 subjects. The absolute risk reduction of dementia was 0.6%. That's pretty significant, the relative risk reduction about 16%, which again, this is consistent with the observational data and the other long-term prospective studies we've seen. Data that speak in the opposite direction. If you care about your brain, if you care about your heart, and if you care about your kidneys, you need low blood pressure. I think we can say that as confidently as we can say almost anything in medicine. That leads to the next question, which is the last one of this section. We need low blood pressure, but you mentioned it before, you don't want too low. Even though low blood pressure doesn't seem like it has its own category, like elevated or high or normal, what do we know about the consequences of having low blood pressure? People who listen to the podcast might be familiar with a guy, we don't have to name him, who was on a trip, maybe had some low blood pressure, maybe was dehydrated from a flight, woke up, face planted into a nightstand, picked up some stitches on his head. Again, no need to name him, but I think you may know some people who have been affected by low blood pressure. What do we know about that? Well, what we know is that there is no numerical diagnosis for this. I think most observers would feel that if you truly measured accurately a blood pressure below 90 over 60, we would argue that that would be probably low, but the truth of it is low blood pressure is defined by symptoms more than it is by numbers. There are people who walk around with a blood pressure of 100 over 70 and they never experience orthostasis, the thing that your friend experienced when he face planted into a table. There are people who walk around with a blood pressure of 100 over 60. There's no issues whatsoever, yet there are other people, if you medicated them to that level, they'd be syncopal all day long. Again, I think this speaks to a little bit of the art of it. One of the reasons that you should need to be careful when you're using medications for blood pressure, especially when other variables are changing. We see this with our patients where if they're on blood pressure medication when they come to us, but then they lose weight and they're exercising, well, their blood pressure is going to start to come down. There has to be a really good medication for them. If they're on a blood pressure medication, they're going to lose weight and they're going to lose weight. If they're on a clear manner in which you safely begin to reduce the dose of their blood pressure medication, or else you could indeed induce some of the symptoms such as dizziness or lightheadedness, fainting, as we've talked about, lack of concentration, blurred vision. Again, these things tend to be far more extreme, but you want to be mindful of all these things. This leads to the next section, which is how do people know where they're at? One of the questions that we got, which is an interesting question, is are there any symptoms that might indicate a person has high blood pressure? Unfortunately, just like is the case with elevated ApoB, there are no symptoms generally. High blood pressure is often referred to as a silent killer because it really doesn't have a warning sign. Someone might say, well, gosh, I've never had headaches or anything like that. Therefore, I must be fine. But the reality of it is unless you're accurately measuring your blood pressure, there's truly no way to know if you have hypertension. That gets to a question that I think is worth covering a little bit because I know you mentioned earlier, you take your blood pressure throughout the day a few times. You have all your patients when they come on, take it for two or three weeks, multiple times a day. If people are listening to this and they maybe don't have a doctor's appointment or obviously when you go to the doctor, they're not going to let you typically sit there for five minutes, not do anything, take it, wait five minutes while not doing anything. Take it again, wait five minutes, take it a third time. The doctor's office, it's not optimized for the proper blood pressure testing like they were doing in those trials. I think the reality is a lot of people are going to have to do this at home. What type of advice do you give patients where it's like, hey, we want you to do your blood pressure? How should they think about that? Well, I think as you said, this is definitely an area where you as the patient need to be in charge. I couldn't care less what my blood pressure is in the doctor's office because of the same reasons you've stated. I'm probably running up the stairs to get there and I'm certainly not behaving according to protocol when I'm there. Sometimes the person checking my blood pressure doesn't put my arm in the right position, so that doesn't really matter. What matters to me is the type of blood pressure measurement that we've talked about. In the show notes, we have found some really good videos on this and it took a while because I really want to make sure people understand the different ways to measure blood pressure. I do both a manual cuff where you're using a blood pressure cuff and a stethoscope. and then I use a couple of different automated cuffs. And I want people to kind of understand how to use both of them. I think this type of stuff is better learned kind of watching illustrative videos. So we're going to link to the best versions of these that we've found, and we've got several videos on them. But I do want to, again, before I explain just how blood pressure is measured, because I think that is worth kind of understanding, I want to just talk about some of the common things that can really screw up a blood pressure reading. So having a cuff that's the wrong size, it's very important to make sure the cuff fits your arm correctly. And you'll pay attention to this when you're buying a cuff, you make sure it's fit to your arm. You want to make sure the cuff fits over your skin directly. Don't be lazy and check your blood pressure over your clothing. If you can't roll your sleeves all the way up, take your shirt off and put a different shirt on. But if you're trying to do it over your clothing, the variance in blood pressure can be very, very high. So if you're trying to do it over your clothing, it can be significant. You want to make sure your back is supported. Sounds silly, but the variance here can be somewhere between five and 10 millimeters of mercury if your back and feet are not supported. So if you're just hanging off a chair, you don't have your feet on the ground. You don't want your legs to be crossed. When you cross your legs, you can see anywhere from a five to eight millimeter per mercury increase, not doing the five minute rest. At a minimum, I tell patients three minutes, but I think five is the right way to go. And that can easily account for 10 to 20 millimeters of mercury. Now it doesn't always do it. So a lot of times I'll just sit down and take my blood pressure right away and it's totally fine. But sometimes it's actually quite high on an initial blood pressure reading if I've been running around or just whatever's going on. But usually if I wait that five minutes doing nothing, which means I'm not checking my phone or talking to somebody, it'll come down 10 points easily. Believe it or not, not talking, just talking during or right before your blood pressure will easily be 10 to 15 points. Being in pain can have a significant impact on this. So it could be anywhere from 10 to 30 millimeters per mercury. Another one that people take for granted, and I think about this a lot when I do my heart rate variability checks in the morning, is having a full bladder. So having a full bladder can raise your heart rate and raise your blood pressure by 10 to 15 points. So all of these things need to be kind of optimized to make sure you're getting a good reading. When you start to then look at arm positioning for every inch that your arm is below your heart, you'll see about an average of nearly two millimeters of mercury per inch. And similarly, it's about two millimeters of mercury per inch for every inch your arm is above your heart. And if you don't believe this, it's pretty amazing to do. Put a cuff on and have your blood pressure measured with your heart way above your head and dangling way down beneath you. So again, all of these things matter, which is why I think it's very important for people to be their own blood pressure checker. Because it's very difficult to have all of these things optimized in the doctor's office. I'll just say a word on what the heck blood pressure actually, like how you're measuring it with a manual cuff. If you choose to do this, you'll need a stethoscope, of course. This is something everybody learns in medical school and nursing school. But basically, let's just assume your blood pressure is 120 over 80. You're putting a cuff over on your arm, and you have a stethoscope over the brachial artery, which is a little bit on the medial side of your arm. And then you have the antecubital fossa, which I realized as I say that, that means nothing to anybody. But if you think about like where your arm bends, that little area is called the antecubital fossa. If you have your palm up and you put your hand in that little area and move in towards your body, so to medial, you'll feel a pulse. That's your brachial artery. So you want the stethoscope sitting there. You want the cuff about an inch above the crease in your arm. And while the stethoscope is there, you insufflate the cuff. Insufflate until you feel the loss of that pulse. Presumably, that's approximately your systolic level. You continue to inflate the cuff to about 30 millimeters of mercury beyond that. So let's just assume that's about 120. You take it up to now 150. Okay. Now you start to slowly release the valve of the cuff. And you're going to hear nothing. You're going to hear nothing. And then you're going to hear your first tapping, thudding sound. And that is the stethoscope. So you're going to hear nothing. You're going to feel the systolic reading. That is the first bit of blood that is now going through the artery because you've now lowered the cuff pressure just enough so that blood can travel through. Let's just say in this hypothetical patient, that occurs at 117. And that would make sense because you approximately heard it vanish at about 120. So that becomes your systolic. You're going to continue to hear as you slowly continue to release pressure. You're going to hear these sounds change. They kind of change from like a murmur maybe into kind of more of a swooshing sound. By the way, as the patient, you will feel this. It has a very weird feeling in your arm. In fact, I can usually tell my blood pressure just by the sensation from the onset of that sensation at systole and the reduction of that sensation at diastole. You'll keep kind of going down this line until at some point the sound becomes a little muffled and then it decreases and stops. And when it stops, that's your diastolic reading because by definition the pressure is below that minimum pressure in the artery where the artery is feeling the expansion of the blood during the total relaxation phase of the heart. And then you note that number. That number might be 75. You'll see that on the cuff, on the manometer. So that's how you measure a blood pressure manually. Automated cuffs have their own algorithms. On average, they're pretty good, but the gold standard, of course, is measuring manually. But if you do measure with an ultrasound, you'll see that the blood pressure is a little bit lower. So just make sure you're doing everything correctly. You know, it was really interesting when you went through that list of things that can raise or lower if you do it properly or not. And some people, I'm sure some patients too, might be turned off when it's like, okay, you want me to dedicate 10 to 15 minutes of my day twice a day to do this over three weeks? It can sound like a lot of time, but I think hopefully based on what we talked about earlier, the importance of it kind of gets people to do it there. There's no point in thinking you know your blood pressure if you're not doing it the correct way and you just have a false reading and it leads to either wrong treatment or no treatment. And I will just say that I find the manual readings more accurate. I find that automated readings can be easily 10 to 15 millimeters of mercury off for me, especially systolically. You know, I've had multiple different people check manually and those readings are always consistent. The automated cuffs tend to overestimate. I don't know why that is. I've suspected that varies from person to person. And so yours are often the automated is higher. The automated tend to run higher in me. Yeah. Interesting. And I've even had my doctor check this on three separate occasions. It's unambiguously higher. And that's using literally two of the most expensive automated cuffs that you can buy. No idea if this is accurate. I would just be curious if the algorithm tends to run slightly higher solely for the fact that they would rather tell people they are higher when they're normal than they're not. Yeah. Tell people they are normal when they're higher and they miss readings, but I don't know. That's a bit of a conspiracy theory there. I'm going to go with more of an Occam's razor. Like I think there's just the automated cuffs are not directly measuring systole and diastole, right? They tend to be measuring sort of mean arterial pressure and then using some algorithm to try to impute the others, but regardless. And do you encourage, because the manual version is obviously more intimidating for people who have never done it before than an automated which is much easier. So even with that said that the manual is better, are you fine if your patients use an automated cuff at the beginning just to understand? Yeah, for sure. The next follow-up question we received kind of fits well right here, which is, you know, we talked about all the little things that can affect your blood pressure when you read it, such as crossing your legs, full bladder, feet dangling, whatever it may be. What do we know about the blood pressure variation throughout the day? Earlier, we kind of talked about as you age, the percentages get higher and higher, but I think also throughout the day, your blood pressure can vary quite a bit. And so what do we know about that? Well, it can. I mean, the most important observation is that blood pressure should really be dropping to somewhere between 10 and 20% at night relative to daytime, just based on the fact that you're horizontal. So the heart shouldn't have to work as hard to get blood to your head. And also we should see reduction in sympathetic tone overnight and an increase in parasympathetic or vagal tone. So, you know, when people do continuous blood pressure monitoring tests, which are pretty cumbersome, where you have a cuff around your arm hooked up to a device and it just goes off every 15 to 30 minutes and you wear this for a couple of days, that's one of the things you'd be looking for is kind of that reduction of at least 10% in blood pressure while you're sleeping. The other thing, of course, is stress. So we'll talk about exercise, I guess, as well, but just transient stress can also raise blood pressure significantly. I certainly notice when I'm wound up, my blood pressure is going up. I don't know if it's because I'm in a coma or not, but my blood pressure is routinely over 140 systolicly if I'm even just slightly irritable, which I think really speaks to the old adage that stress can kill you. You know, you think of like, oh, how can stress kill you? Well, I mean, I think hypercortisolemia, if left unchecked, is harmful and so is hypertension. So if you're constantly kind of in a sympathetic tone, there's both mechanical and chemical reasons why that's problematic. You mentioned exercise just now, which is a question we received because you've talked about it on a few podcasts, you know, what blood pressure is going to increase with exercise. I think the one I'm thinking of is Lane Norton in particular. You all kind of talked about that. What do we know about blood pressure and exercise. Does it go up? Why does it go up? Ultimately, too, is if for some reason someone's testing their blood pressure during exercise and it is going up, is that something they even need to worry about or is that just natural? No. An increase in systolic blood pressure during exercise is completely normal. We do this on our patients when they're getting a VO2 max test. We also have their blood pressure checked. What we're really looking for is a rise in diastolic pressure. The normal physiology should be that systole goes up, diastole stays about the same. Sometimes it even goes down. The reason for that is that the vasodilation of the arterioles, which is there to provide more oxygen to muscles during exercise, actually causes a reduction in systemic vascular resistance. Again, we tend to see the rise in systolic blood pressure, but typically no change, or potentially no change in systolic blood pressure. Even a decrease in diastolic blood pressure. I actually haven't checked my blood pressure in a while during exercise, but it could easily be 180 to 200 millimeters of mercury. Frankly, it would be very interesting for me to know what my peak blood pressure is doing a heavy deadlifter squat. I'm sure at that moment it gets insanely high, which is probably why in patients that have very dilated aortas, we would say, hey, maybe doing very heavy Valsalva type maneuvers might not be in your best interest. For those of us who maybe just got a little lost on the end of the day, can you explain what a Valsalva, the word you use, the type of movement? Valsalva is just any time you're increasing intra-abdominal pressure so much. If you think about when you're really bearing down, which you would be doing, obviously, if you were trying to pick something very heavy off the ground or do a very heavy squat, that type of pressure is associated with pretty significant increase in, obviously, blood pressure. Peter, the last question that we got in this section on helping people understand where they're at and what this all means before we get to the next piece, which is how to lower is, some people have heard or their doctors have told them they have primary hypertension versus secondary hypertension. Some other terminology that people have maybe heard from doctors, can you just walk through what each of those mean? Secondary hypertension is blood pressure or high blood pressure that's caused by a correctable other medical condition. About 10% of people diagnosed with hypertension, actually have a secondary cause, a driver. That's why it's important to make sure that if somebody shows up with high blood pressure, you don't automatically assume that it's what we would just call primary or what used to be called, quote unquote, essential hypertension back when I was in medical school. There are a couple of clues to consider that somebody might have secondary hypertension. If a person's already being treated for high blood pressure and it's not having any effect, so it's not responding to medications, we'd call that medication resistance. That's a bit of a clue. If they no longer respond to medications that they previously responded to similarly, if their blood pressure is incredibly high, north of 180 millimeters of mercury systolic, if the onset occurs really suddenly or increases really suddenly, again, that's all cause for alarm. If it's high and you're really young, 30 year old people that otherwise have no risk factors, such as family history for high blood pressure and they're not obese, and yet they show up with high blood pressure, all of these things make you start to think of something else going on. I'll just share a brief story of an example of this. I had a friend who, God, this was probably back in 2013, maybe 2014. I don't know. Somehow we were talking and he mentioned his blood pressure was really high. This guy was a really serious athlete. He would mention he wakes up every morning and his blood pressure is through the roof and again, through the roof was like 180 or 190 over 120, insanely high. He would exercise and it would go down a bit, but it was generally pretty high. His doctors were putting him on all sorts of medications and it wasn't really having an effect. Every medical student will know the story of what's called the pheochromocytoma, which is a tumor of the adrenal glands that secretes catecholamines. These are not that common, but he sounded like the perfect case. I said, look, I'd want to rule out this type of tumor in you. Have your doctor check your urine for the metabolites of epinephrine and norepinephrine. He goes and asks his doctor. His doctor says, no, that's a dumb test. We're not going to do that. Then I remembered that he had had an MRI earlier. He had surgery six months before that and they had done an MRI of his chest. I said, it's possible that that MRI also captured your adrenal glands, which sit on top of the kidneys, which can often be seen in a chest MRI. I said, can you send me that MRI? He did. Sure enough, there was an adrenal nodule on that MRI, but it didn't get called by the radiologist. They sort of missed it. Again, that's not that uncommon because they weren't really looking at the adrenals. I said, take this to your doctor and say, look, you've got an adrenal nodule and high blood pressure. They really need to check for these metabolites. His doctor still didn't want to do it. He said, okay, one, you need a new doctor. This guy's an idiot, but two, let's go get it done somewhere else. We did. To make a long story short, he ended up having a rheumocytoma, which meant he just needed to go to surgery. They removed that adrenal gland and his blood pressure completely normalized. Again, that's pretty uncommon. It's an extreme example of what you don't want to miss. What are some other things you don't want to miss? Well, you don't want to miss kidney disease. You don't want to miss any stenosis of the renal artery. You don't want to miss thyroid conditions. You don't want to miss hyperaldosteronism, which can be idiopathic, meaning it can be caused by steroids that you're taking. So people that are on continuous doses of corticosteroids, but can also be caused by the adrenal gland itself undergoing hypoplasia. There are a lot of secondary causes of hypertension. When you consider that in total, they amount to probably 10% of cases of hypertension. When you consider how many people have hypertension, it's important that these things be run to ground before we just immediately assume that somebody has primary hypertension, which again is just code speak for we don't really know what the cause is. In that conversation, you kind of mentioned family history there, which is something we haven't talked about. We've talked in the past a lot about how family history is really important to know your family history because that can really help understand the different causes of death and what you may need to look out for. Does hypertension, is that something that runs in families? And if your parents, grandparents had a history of hypertension, that should even make you more aware of this potential issue? Dr. Justin Marchegiani Absolutely. And it's the main reason that I think so much about this. Both my parents have hypertension and therefore I understand that despite all of the things that I do to have low blood pressure, it won't be surprising to me at some point if my genes overcome my lifestyle and at some point I'll need to take medication. My goal in checking my blood pressure so frequently is to make sure that I don't spend a couple of years or even a year not recognizing if that condition has taken place. So would I love to say that I'm going to go my whole life without having to take blood pressure medication? Sure. But the second best option would be being on blood pressure medication the second I need to be on it. Dr. Justin Marchegiani That parallel seems very similar to how you talk with patients about ApoB as well, which is check it often and if you can lower it through various lifestyle factors, do it. But the second you find out that you kind of can't, you want to address it with medication. I think that leads to this next section really well, which is a lot of people are asking what are the drivers of primary hypertension and how can people address them with lifestyle factors? I think there's two pieces that are worth talking about there, which is one, what lifestyle factors can lower blood pressure? And two, do we know anything about how much those lifestyle factors can lower blood pressure? Dr. Justin Marchegiani I think there's a really big opportunity here with lifestyle to lower blood pressure. In fact, I want to be clear. I think lifestyle, I hate the word, you know, I hate that word lifestyle so much. I don't know why I hate it, but I know that it's shorthand for whatever we're talking about. But regardless, lifestyle is a far greater hammer on blood pressure than it is on lipids for two reasons. I think the first is why lifestyle is not a great hammer for lipids is that frankly, to get your ApoB to the levels where it's no longer an issue is very difficult to do without a very extreme diet that is so extreme that it comes with a whole bunch of other problems with it. So profound fat reduction and calorie restriction will lower cholesterol levels dramatically. But again, it comes with so many other problems that it's simply not worth it. It's sort of robbing Peter to pay Paul. But with blood pressure, that's not the case. The benefits of weight loss are dramatic. The benefits of exercise, reducing insulin resistance, avoiding type 2 diabetes, and getting good sleep, as we'll discuss here in a moment, are pretty significant. In addition, the electrolyte management thing is kind of interesting, though controversial, and we'll talk about that. But let's start with something that is pretty clear as day, which is the impact of weight loss on blood pressure. We'll link to it in the meta-analysis of this. It says that basically for five kilo reduction in weight, well, let's just put it in per kilos. For every kilo of weight loss, you're going to see a little more than one millimeter of mercury reduction in systolic. And on the other hand, you're going to almost one millimeter reduction in diastolic. So again, we're agnostic as to how one gets there, right? Weight loss is primarily going to be accomplished by reducing intake. Reducing intake can be accomplished by those three things we always talk about, CR, DR, TR, or combinations thereof. Here's where I think things are a little more controversial, and that is what's the role of sodium on this? Now, I think it is safe to say that there is pretty significant heterogeneity in the population here. I think there probably are some people that are more sensitive to sodium, dietary sodium, from a blood pressure perspective than others. And we talked about this at length with Rick Johnson, who's a nephrologist, and his take was that salt plays a role, but the role can be reduced by drinking water with or before a salty meal. He points out that if you're getting thirsty with a salty meal, it means you've already reduced the amount of sodium in your body. So if you're getting thirsty with a salty meal, you raised sodium. And if you have, you're probably also getting the increase in blood pressure. So it's really about pairing water prior to a salty meal. So salt sensitivity is sort of a quantitative trait in which an increase in oral sodium can disproportionately increase blood pressure. So the question then becomes, who are the patients that are probably more sensitive to this? The data might suggest we see this more in African-Americans. We see this more in older people. We see this more in people who already have higher blood pressure and in people who have metabolic syndrome, diabetes, or chronic kidney disease. And we'll probably see it less in people who are not otherwise in those situations. You'll sort of have to pick and choose your battles and see where you are on that spectrum. But again, this is also something that you can be empirical about this and decide, hey, what happens if I kind of reduce my sodium intake? What bearing is that having? Now, I would caution people that going to very extreme levels of sodium restriction, even if it might improve blood pressure, seems to be associated with worse overall health outcomes. So some advocate reducing sodium to as little as 1500 milligrams per day. Keep in mind, the average American is somewhere between three and a half and four and a half grams of sodium per day. To suggest we're going to reduce that to as little as 1.5 grams per day is pretty significant. Now, that will very likely reduce systolic blood pressure by five to six millimeters of mercury in somebody who already has hypertension. But that also, at least according to the most recent meta-analysis I've seen from the Institute of Medicine, also increased all-cause mortality. So we have to be a little bit careful there. There's some evidence that increasing dietary potassium, so eating potassium-rich foods, bananas, potatoes, things like that, and not doing this through supplements, by the way, because you can certainly get into a bit of trouble there, can lower blood pressure based on the relationship that we see between potassium and aldosterone in the kidney. So let's talk about exercise. So this is, again, an area where I think there's very little ambiguity here. So if you look at aerobic exercise, you look at a meta-analysis of RCTs that were at least four weeks in duration, found that endurance exercise was very effective in patients with hypertension. They're looking at reductions of systolic blood pressure in as little as four weeks of aerobic training, reducing it by as much as eight millimeters per mercury and diastolic lowered by at least five millimeters per mercury. So as far as duration and intensity goes, the takeaway of this meta-analysis was that at least 90 to 150 minutes a week at somewhere between 65 and 75% of your maximum heart rate was the sweet spot. And that's actually right in the zone of what we would call zone two. For most people, zone two is about 75% of their maximum heart rate. And we tend to advocate at least three hours a week of that, which would be 180 minutes. So right then and there, you say, look, if you're getting your zone two in at three hours per week at roughly 75% of your maximum heart rate, you're already capturing the benefits of much of the exercise. As far as dynamic resistance training, this is something that I don't think is entirely intuitive. You might think, well, gosh, resistance training would transiently increase blood pressure, which it does. But the interesting thing is it actually reduces blood pressure slightly as well. Not nearly as much as aerobic training, but we're looking at about two millimeters of mercury on systolic, about three millimeters of mercury on diastolic. And this is doing kind of 90 to 150 minutes a week at somewhere between 50 and 100% of one rep max. So this is anywhere from modest weights up to very heavy weights. This could also be done using isometric resistance, so you don't even have to be lifting weights. And that showed even a greater reduction in systolic blood pressure, about six millimeters of mercury, and diastolic of about three millimeters of mercury. So again, let's just talk about insulin resistance and type two diabetes. Why are these things increasing blood pressure is probably the easiest way to think about it. Well, I think insulin resistance does a number of things, but among them is it reduces the bioavailability of nitric oxide. And nitric oxide, of course, acts very locally to increase vasodilation. So therefore with less nitric oxide, we have less vasodilation. There are different ways that this can happen. I think one of the ways that this happens, and we see this also, by the way, in impaired kidney function is the inhibition of one of the important cofactors in nitric oxide synthase, or one of the important variables that allows nitric oxide synthase to make nitric oxide. So there are actually biomarkers you can measure, like one's called SDMA and one is called ADMA. And these are typically things that we see elevated in people with high homocysteine or people with impaired renal function. So again, to think about these as kind of a cascade of things, insulin resistance we proxy by metabolic syndrome. Two of the factors of metabolic syndrome are elevated glucose and elevated waist circumference or obesity. So type 2 diabetes then in some ways just becomes this triple whammy where you have the first insult being the high glucose load, which then has the microvascular damage to all of the organs of interest, heart, brain, kidney. You then have the blood pressure load or the blood pressure damage that comes from that. And then of course you have the ApoB burden that comes from type 2 diabetes. Type 2 diabetes and insulin resistance are associated with hypertriglyceridemia, which is then associated with an increase in ApoB as you now need more low density lipoprotein particles to traffic not just the cholesterol ester, but now the triglycerides as well. The last thing I kind of want to talk about here, and this is an easy one to miss, is the role of sleep. So both sleep deprivation and insomnia will also drive hypertension. This is something I notice in myself. You know, I check my blood pressure so often, but I notice that if I have a really lousy night's sleep, all things equal, my blood pressure is definitely higher, just as my blood sugar is, by the way. So I always notice the effect. And anybody who's ever worn a CGM will tell you that if they have a horrible night of sleep, their glucose tolerance goes out the window. And so too does your blood pressure response. So if you look at either very long or very short sleep, you're going to see in all cases an increase in hypertension. And this can be as much as a 40% increase in the risk of hypertension if you're sleeping less than five hours a night or more. You could argue, of course, that sleeping more than 10 hours a night is a proxy for other things that are going on, be it either chronic disease or heavily fragmented sleep. I know you hate the term lifestyle, but it does seem like when it comes to lowering blood pressure, it's really that whole gamut of what you talked about. Everything from nutrition to sleep to exercise is stuff that you have to pay attention to as it relates to blood pressure. You want to make sure you get as far as you can on these. Because I do think that most people, I don't know what the percentage is, but it could easily be that half the people who have hypertension could manage it without the use of pharmacologic. And on that front, we do get a lot of questions on the pharmacologic side, which is what are the most common drugs prescribed for hypertension? If someone has hypertension and they're thinking about taking drugs, how much can they lower blood pressure on average? Just a little overview on that I think would be really helpful. Yeah, look, a detailed overview of this is probably more than people would want, so I'm not going to really get into the mechanisms of how these drugs work. We can link to materials on that in the show notes, but we really today have four, I would call first-line drug categories for hypertension. So the thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors or ACE inhibitors, and angiotensin II receptor blockers, ARBs. Notice I didn't mention beta blockers in there. We're really not using those for first-line agents in high blood pressure. So for primary hypertension, all first-line agents are pretty much good for about 12 to 15 millimeters reduction of systolic blood pressure and about 9 to 11 millimeters reduction in diastolic blood pressure. The blood pressure lowering effects of ACE inhibitors are pretty high. They're at the upper end of that spectrum, and that's typically at about one half the recommended maximum dose. So you don't start somebody at the maximum dose of these things. You typically work your way up. You don't want to overshoot these things. It's not like a cholesterol medication where you could start somebody at a mega dose, and if they get symptoms, it's just like a muscle ache or something. You can take it away. But here, if you overshoot this, you can cause some damage. The ARBs are right there on par. with the ACE inhibitors. In fact, we did an internal whitepaper paper on this very recently. The consensus view is that basically across the board, the ARBs are probably slightly better drugs than the ACE inhibitors. So in every manner that we compare them in terms of efficacy and side effects, the ARB is as good, if not slightly better than the ACE inhibitor. The ACE inhibitors have been around longer. And so one of the things that you have is you have more of them and they're cheaper. So a lot of times people don't necessarily have a choice in them because their insurance company is going to pay for an ACE inhibitor. They're not going to pay for an ARB. But if ACE inhibitors are causing symptoms, such as a cough, which is probably one of the more common symptoms, you want to know that you have other agents there as well. Thiazide diuretics and calcium channel blockers are also highly efficacious. Those are easily in the 15 millimeter of mercury and nine to 10 millimeter of mercury impact on blood pressure, but they do tend to come with more side effects. And I wouldn't consider myself at all an expert in the treatment of hypertension. I wouldn't consider myself an expert in the treatment of hypertension. I wouldn't consider myself an expert in But we typically do not like to rely on those as first line agents and instead rely on those as add on agents. If we've maxed out an ACE inhibitor or an ARB and we still need more reduction. I think it's worth pointing out here, by the way, that these blood pressure lowering medications by themselves are larger than any single lifestyle factor. However, when you consider the sum total of all of these medications, you're going to find that they're not as effective as they used to be. So I think it's worth pointing out here, by the way, that these blood pressure lowering medications by themselves are larger than any single lifestyle factor. All lifestyle factors, it can be at least on par with what we see pharmacologically. And some of the other questions that we received are people saying, hey, I do have to go on a drug for primary hypertension. And you kind of mentioned there's four different ones. And one of the factors could be cost, but are there any other known factors that would make one medication maybe quote unquote better than another for people with specific, like with anything else that would make one medication maybe quote unquote better than another for people with else going on or is there anything else people should be thinking about if they have to take one of these and their doctor's willing to work with them on which one to take? I think there are definitely some rules of thumb on this. So somebody who's got heart failure or reduced ejection fraction, you would want to avoid a calcium channel blocker because obviously calcium channels play an important role in contractility of the heart. So to give a calcium channel blocker to reduce blood pressure would be potentially problematic at reducing cardiac output as well. So that's something you want to keep in the back of your mind. It used to be, I think, the dogma that anybody with diabetes should be on an ACE inhibitor over an ARB if you're going down that path. I would say when we looked at these data, which we did for our internal white paper, we didn't see a strong enough case for that. I thought the data were inconsistent here. So I think I would say this, the textbook answer is for type two diabetes and chronic kidney disease, ACE inhibitors might offer, some benefit, but I think that both of these are probably reasonable. Obviously you want to be careful about somebody with renal artery stenosis. This is kind of one of those reasons you want to rule that out. But in the case of renal artery stenosis, you wouldn't want to be using either of those. Diuretics, we probably want to avoid in people who already have gout or significant hyperlipidemia, type two diabetes, because they can actually increase somewhat insulin resistance. We personally find that those drugs are kind of ones that we want to reserve for when we don't have other factors. Again, ACE inhibitors and ARBs, we tend to avoid certainly in pregnancy or in somebody with a history of angioedema. And race might also play a role here. It would appear that in African-Americans, thiazide diuretics or calcium channel blockers might actually be more effective than ACE inhibitors or ARBs or even beta blockers when it comes to reducing cardiovascular events. Again, I'm not talking much about beta blockers and certainly not about alpha blockers. It's not that these other categories aren't used, but they certainly would not be considered first line today. All right. So Peter, I think that covered the vast majority of questions we received on blood pressure and kind of follow up a little more detail to how people should think about this, why they should care, why they should care early and often, how to monitor what theirs is, how to know what lifestyle factors can affect it. If you have to do medications, how to think about it. So hopefully people found that overview helpful. Helpful. And again, we just thought it would be important to gather all these questions because we've been talking about blood pressure recently, but we've never gone as deep as we just did on that risk factor compared to something like ApoB. So with that said, anything you would want to say to people about blood pressure who are listening and why they should care? No, I mean, not that I haven't already said, I guess if there's one thing in my book that I didn't write enough about just due to space constraints, but I felt as strongly about it as some of the other stuff I wrote about it would be this. This is such an important part of the longevity playbook and it's not sexy, right? It's not like taking rapamycin or taking some little drug that's going to whack your senescent cells or doing anything like that. I mean, it's just bread and butter primary care medicine, but it's so needle moving. I view it as sort of catastrophic when I see people and I see them all the time who are biohacking their way into obscurity all the while ignoring their blood pressure. With that, I think we will wrap this one. So until next time, have a good one. Yep. Thanks, Nick. Thank you for listening to this week's episode of The Drive. Head over to peterottiamd.com/shownotes if you want to dig deeper into this episode. 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