Hypertension 101

Brent: You just published on CRISPR to gene edit to permanently bring down LDL levels.

Luke: Yep. This was early study, phase one, first-in-human. It was safe, but at the top dose, patients on average got a 50% reduction in LDL cholesterol and about a 55% reduction in serum triglycerides.

Brent: Welcome to Death Clock. I'm your host, Brent Franson. Today we speak with Dr. Luke Laffin about hypertension, which is chronic high blood pressure. He's the co-director for the Center for Blood Pressure Disorders at the Cleveland Clinic. He specializes in hypertension, cardiovascular risk reduction, and preventive cardiology. He's published in JAMA, Hypertension, and the American Journal of Cardiology.

Brent: This is Hypertension 101. We talk about what it is and what causes it. How we should think about blood pressure readings, medications, and supplements. We really try to go through everything. He's a wonderful guest. I hope you enjoy.

Brent: Dr. Luke, welcome to the show.

Luke: Thanks for having me.

Brent: So today we're going to talk about hypertension. I'm looking forward to this conversation because I've got high blood pressure myself. We can talk about whether or not it's high or whether or not I should be concerned about it. But it's an issue that affects so many of us.

Brent: And as I've thought about treating it, I've realized how little I really know about what's actually happening and how to think about it. Before we get into that, can you give us a sense of your background?

Luke: Yeah, sure. I'm a preventive cardiologist and a hypertension specialist at the Cleveland Clinic. I'm co-director of our Center for Blood Pressure Disorders here, and I deal with a lot of patients who have difficult-to-treat hypertension.

Brent: Wonderful. I have to start by mentioning my recent experience at the Cleveland Clinic. I'm in Colorado, and as part of my preventative health process, I did a CT scan to look at plaque in my heart and identified an anomalous right coronary artery. So my right coronary artery originates on the left side.

Brent: And I exercise a lot. I was told, "Well, you might die suddenly while you're exercising." So I got referred to Cleveland, and two months ago I did a cath. They went through the femoral artery and stuck a wire through the anomalous RCA. I don't need open-heart surgery, so I'm feeling pretty good.

Brent: And I'm grateful to the team at Cleveland. It's an incredible place.

Luke: Well, that's very nice of you to say. There are a lot of stories like that nationally and internationally. You're a perfect case of someone getting an incidental finding, but needing to dig a little bit deeper. I'm glad they didn't need to do anything. That's great.

Brent: It's such an impressive facility. I hadn't spent much time in Cleveland, so I didn't really know what to think. What an incredible place Cleveland Clinic is, and it must be an incredible place to work. I did some research on the fellows who were tending to me before going in, and I realized these are really competitive...

Brent: ...cardiothoracic surgery fellows in the world.

Luke: Yeah. We like to think of our fellows as the best in the country. They actually just had their Match Day where they go through that process, so we have another great class coming in next year as well. We're very proud of that group.

Brent: All right. Before we get into what hypertension is, how did you come to focus on the heart and hypertension? What's the quick version of your path to this work?

Luke: Well, for the heart, I always knew that I wanted to do cardiology, but it happened a little bit by happenstance. I met my wife at the University of Chicago; we were interns together. She's a dermatologist, so that's an extra year of training compared to internal medicine, which you have to do as a residency before moving on to cardiology.

Luke: So I had a gap year. The question was, when I matched for my cardiology fellowship elsewhere, would I stay or do an extra year? The world's expert in hypertension clinical trials at that time, George Bakris—who passed away about a year and a half ago—was running a one-year fellowship that he had done for about 20 to 25 years prior.

Luke: So I did a dedicated one-year hypertension fellowship with him, and then my cardiology fellowship, and it became a passion of mine.

Brent: Wonderful. We should clarify: medicine is not very good at naming things. Hypertension is just a fancy word for high blood pressure, or should you correct me if that's wrong?

Luke: There's a little bit of nuance to that. We use them synonymously, and most of the time when people talk about them, they mean the same thing. But we can all have an episode of high blood pressure. When we exercise, our blood pressure goes up and it's high. What hypertension is, is chronically elevated blood pressure that increases our risk for end-organ damage.

Luke: And what I mean by that is strokes, heart attacks, kidney disease, heart failure, etc.

Brent: Okay. So blood pressure fluctuates, and it can fluctuate in ways that are totally normal—like when exercising. We would not call that hypertension. But if our blood pressure is chronically high, particularly during periods where it shouldn't be high, then we would call that hypertension.

Luke: That's correct, exactly. I mean, if I was to reach through here and punch you in the shoulder, pain causes high blood pressure, too. It doesn't mean you have hypertension. That's an important distinction.

Brent: Okay. What actually is happening when my blood pressure is chronically high?

Luke: Well, it's a measurement of the force exerted on the arteries. Remember, arteries are the conduits for oxygenated blood to all our organs: our heart, brain, and kidneys. It's the pressure exerted every time the heart muscle squeezes—that's the top number, the systolic blood pressure. Diastole, or diastolic blood pressure, is the bottom number.

Luke: That's the pressure when the heart is relaxed and accepting blood again.

Brent: So when the heart is actually beating, that's the top, higher number (systolic). Between beats, that's the bottom number (diastolic).

Luke: The relaxation phase, yeah.

Brent: We can think about blood pressure itself as similar to a hose. If I run just a little bit of water through it, the water isn't exerting a lot of pressure on the inside of the hose. If I run a lot of water through that hose, it exerts a lot of pressure.

Brent: And the hose wouldn't last as long with more pressure. That's basically what we're describing in our body.

Luke: Yeah, I think that's a good analogy. It's important to note that the body can tolerate high and low blood pressures for short periods of time—particularly high blood pressure. It's that chronic, sustained elevation that really increases our risk.

Brent: What percentage of adults have hypertension? There are multiple types and severity levels, right?

Luke: An off-the-cuff stat is that about 45% to 50% of adults in the US have hypertension. It depends on where you cut it in terms of systolic blood pressure threshold, because those thresholds have gone down over the past decade based on emerging evidence.

Luke: When we think about different stages of hypertension: stage 1, based on current American guidelines, is between 130 and 140 systolic (top number) and between 80 and 90 diastolic. Stage 2 is above that: 140 systolic or over 90 diastolic.

Brent: Stage 2 is 140 over 90 or above. Stage 1 is 130 over 80 to 140 over 90. It seems 130 over 80 used to be considered healthy, but it's not anymore.

Brent: Are these numbers coming down?

Luke: These numbers are coming down. The biggest driver was something called the SPRINT blood pressure trial. It's about ten years old now. It grouped patients at high cardiovascular risk into two categories: one treated to standard blood pressure targets (less than 140 systolic), and one to intensive targets (less than 120 systolic).

Luke: They didn't reach under 120 for that group—they got to about 121—but those patients did much better: lower mortality, less risk of adverse cardiovascular events. They actually stopped the study early. That's been replicated in Asian populations, expanded populations including patients with diabetes, and expanded endpoints like preventing dementia with more aggressive blood pressure control.

Brent: So the optimal blood pressure now would be sub-120 over 80?

Luke: We try to get people right around 120. If someone is doing well on a couple of medicines and they're in the mid-120s, often we'll leave them alone. But if we can get you right around 120, that's best. That's what's endorsed in the most recent guidelines.

Brent: Okay. What is the bottom threshold? This isn't like a calcium score where we want to get to zero. At what point is blood pressure too low and out of this Goldilocks zone?

Luke: It's dependent on whether we're treating you with medicines or not. Typically, if we have patients on blood pressure medicines and they're getting below 110, that's probably a bit too aggressive.

Luke: We'll start peeling medicines away in those scenarios. But lots of people not taking medicines walk around with 90 over 60. Plenty of young people are there, and we don't do anything about that—we don't need to raise their blood pressure.

Brent: Okay. So if it were too low, you'd be symptomatic—passing out or something. But if you just run at 90 over 60 naturally, that's fine, even though you wouldn't treat someone down to 90 over 60 in middle age.

Luke: Yeah, that's a good way to describe it. We're definitely not going to treat you that low or aggressively because then we end up with risk for side effects, but younger people definitely walk around with those lower blood pressures.

Brent: With roughly 50% of the population affected, is this a disease of modernity? If we looked at cavemen thousands of years ago, would we see 50%, or is it our sedentary lifestyles and diet that drive the rate so high?

Luke: We wouldn't see numbers nearly as high as today. It's driven by sedentary lifestyles, dietary choices, obesity, and highly processed food rich in sodium. Historically, run-of-the-mill hypertension was deemed "essential hypertension."

Luke: We don't use that term anymore because people used to think as you age, you needed higher blood pressure to better perfuse your brain. We know that's not the case. Actuaries found that out before doctors—they knew a person would die earlier if their blood pressure was higher.

Luke: We were just a little bit later to realize that in the 1900s.

Brent: So if you're 75, really healthy, on meds, and at 110 over 70, that's fine and not bad for you.

Luke: No, that's really good. Hypertension is a disease of aging: we get stiffening of our blood vessels, which can be related to medical problems like diabetes or kidney disease.

Luke: There's also a genetic component. Up to 75% of individuals over the age of 70 have hypertension. You could do everything completely right and still develop hypertension as you get older.

Brent: How do we measure blood pressure? Do we trust a $30 cuff on Amazon? Is there a best time of day? Is arm better than wrist? What's the best at-home way of measuring?

Luke: It's recommended that everyone with hypertension or at risk for it measure at home, because home measurements give a different picture than in-office readings and are often better predictors of future events. There's a noncommercial site called Validate BP, a joint project by the AMA and AHA.

Luke: It lists up to 40 validated blood pressure machines in the US. The cheapest is about $30 to $35. We generally recommend an upper arm cuff. The most instructive time to measure is in the morning before taking medicines, and occasionally at night.

Brent: I have both a wrist cuff and an arm cuff, and I see different measurements in the same setting. Is that common? Should I trust the arm more than the wrist?

Luke: Generally, I trust the arm more than the wrist. Over the age of 50, we typically don't trust wrist monitors due to arterial stiffness. Upper arm cuffs are recommended. Younger people can sometimes get away with wrist monitors, as they are close enough.

Most validated monitors on Validate BP are upper arm cuffs. That's where all the outcome data comes from, not wrist monitors.

Brent: Why are health outcomes worse at 140 over 90 than at 120 over 80?

Luke: Every time the heart beats, organs receive that pressure. The heart squeezes and shoots blood forward to supply organs with oxygenated blood. Certain organs handle stress or pressure differently. The brain, for example, doesn't like very high blood pressure.

Luke: It can adapt for short periods by vasodilating, but repeated stress and high pressure cause damage. It's like a punching bag. Your brain and kidneys prefer the 120s—nice and soft.

Luke: And that high pressure is hitting them 60 to 90 times per minute.

Brent: So the punching bag is the entire cardiovascular system, and every heartbeat hits it harder than ideal for long-term function. It affects everything.

Brent: If I have high blood pressure, am I at increased risk for other types of heart disease, diabetes, Alzheimer's, dementia, or cancer?

Luke: Not so much cancer. I don't necessarily think of hypertension as heart disease itself, but as a precursor to it. It increases your risk for five main things: strokes, heart attacks, heart failure, kidney disease, and dementia.

Brent: So hypertension isn't diagnosed as heart disease itself, but as a condition?

Luke: It's a comorbidity that increases risk for heart disease. "Heart disease" is a catch-all term. Most of the time we mean atherosclerotic cardiovascular disease (plaque buildup), but it could refer to valve problems or arrhythmias.

Luke: Hypertension can increase those risks, but unto itself, I wouldn't call it heart disease.

Brent: Does hypertension increase the odds of atherosclerotic disease and plaque buildup in the heart?

Luke: Yes. It damages the vessel wall, which increases plaque buildup.

Brent: So it changes the vessel wall in a way that makes it more likely to accumulate plaque.

Luke: Exactly. It causes plaque accumulation, plaque instability, and rupture.

Brent: If someone is at 135 over 90 or 140 over 90, what lowerings can they expect from changes to sleep, diet, and exercise without medication?

Luke: Hypertension management is roughly 70% lifestyle and 30% medication. Most patients I see ultimately need medicines, but without that 70% lifestyle effort, you'll keep accruing medicine after medicine as you age. Lifestyle makes a huge difference.

Luke: If you have stage 1 hypertension, guidelines recommend at least 3 to 6 months of lifestyle therapy first to see if you can bring it down. If someone is already doing all of that, they might not see a huge change, but most of us have room to improve.

Luke: But most of us are.

Brent: If someone at 135 over 90 went to extreme lifestyle changes—running 15 miles a morning, eating a vegan/low-salt diet, no alcohol, early sleep—how low could they get?

Brent: So for somebody I'm at 135 over 90. If I were to just say, all right, starting tomorrow I'm going to run 15 miles every morning and I'm going to eat a vegan diet. And, I'm never going to have any alcohol and I'm going to go to bed early or whatever, and I'm never going to have any salt.

Brent: Could they get down to 105 or 110 over 70, or at age 43 is that unlikely without medication?

Luke: You're probably not going to get down to 110, to be honest. But could you get into the low 120s and avoid medicine? Definitely. Lowering dietary sodium is worth about 1 to 1.5 blood pressure medications—a 5 to 10 mmHg drop just from that. Losing weight and exercising also make a huge difference.

Luke: Similar things. They're sitting on the couch all the time and start exercising. You can make some really important changes, and drastically lower blood pressure.

Brent: So if you're at 140 systolic, you can probably get into the 125 zone through lifestyle, but going below that usually requires medication?

Luke: Above 140 over 90, guidelines recommend starting lifestyle therapy plus medicine together because most people will need both. Below 140 over 90, we give people as much opportunity as possible to try avoiding medicines first.

Brent: How often do lifestyle changes actually work long-term? Sustainable behavior change is difficult. Do you see people stick with it?

Brent: Or do you see people struggle?

Luke: It comes in waves. Many patients are really motivated at first and do well for six months to a year. Then 18 months later, life happens and things creep back up. That's okay.

Luke: We reinforce that we can get numbers back down, perhaps adding a bit of medicine temporarily. I'm not wedded to any specific doses long-term.

Luke: Nothing gives me more satisfaction than when a patient says, "Doc, I'm feeling a bit tired, and my blood pressure is 111." Great, let's cut that pill in half or come off it. Sustainable changes are hard. A low-sodium diet is a good actionable step—you see a difference in blood pressure within 4 to 5 days.

Luke: Losing weight and building exercise habits take time, but low sodium yields quick feedback. Sustaining it during holidays or social gatherings is where it gets harder.

Luke: And and so but to actually sustain that when, you know, around the Christmas time or a holiday season. Right, you know, you've gone out to parties or you're having meals with friends, it's just more difficult to do that.

Brent: Your body adjusts to low sodium in a nice way. We switched to low-sodium soy sauce at home, and now regular soy sauce tastes far too salty. If someone wants to use diet to lower blood pressure, what is best?

Brent: Is it a DASH diet, vegan, carnivore, keto?

Brent: What is the best diet for lowering blood pressure?

Luke: The DASH diet (Dietary Approaches to Stop Hypertension) has the best data. The original DASH diet wasn't strictly low sodium, but the DASH Low Sodium iteration is the gold standard.

Luke: You can get well over a 10 mmHg reduction in blood pressure with the combination of a DASH diet and low sodium.

Brent: What about people on social media claiming carnivore or keto diets lowered their blood pressure and allowed them to get off meds?

Brent: Is there truth to that, or is it mostly short-form nonsense?

Luke: In individual cases, it may have worked for them—perhaps by reducing refined carbohydrates, losing weight, and feeling healthier, which lowers blood pressure. I would want them to check their cholesterol to make sure that isn't moving in the wrong direction.

Luke: On an individual basis, some people can adjust their diet to lower blood pressure, but broad trial data isn't there for those diets.

Brent: Is the lack of clinical trials for keto or carnivore because those trials haven't been done, or because results are inconclusive?

Luke: They haven't been done to a high-quality extent. Dietary and blood pressure trials are both difficult to conduct. If someone wants to try keto for a couple of weeks to see if it helps, I'm not opposed to that, but there's no high-quality data supporting keto specifically for blood pressure lowering.

Luke: You know, to try it and see. Right. I'm never opposed to someone doing it for a couple weeks and seeing if it works, but there's no high quality data to support blood pressure lowering with keto onto itself.

Brent: Are you skeptical, or hopeful that it gets studied in the future?

Luke: I hope someone studies it. There are no absolutes in medicine, and everyone is a bit different. Guidelines exist to help, but the physician-patient relationship is key so you can adjust based on evidence and individual response.

Luke: But that's why the individual physician patient relationship is so important. Right. We can adjust and we can say, okay, if this isn't working, let's try this. Or you want to try that, that's fine. Let's do that. Let's have that conversation and see how it works. And it's my job to have a conversation with someone and say, this is what the evidence would say.

Luke: This is where I think we should go. What do you think about that? And then, you know, bring that back and forth.

Brent: What type and amount of exercise do you recommend? Is cardio better for lowering blood pressure than strength training or yoga?

Luke: Cardio is best. We aim for at least 150 minutes a week of moderate-intensity aerobic activity (where you can carry on a conversation, like a brisk walk or light jog). 150 minutes is a baseline.

Luke: Light resistance training helps too. For uncontrolled hypertension, avoid heavy weightlifting initially because straining can spike blood pressure. Bring the baseline down first, then reintroduce heavier weights. Resistance bands and light weights work well.

Luke: And then we can add that back in. Right. But lightweights like bands are also pretty helpful as well.

Brent: "Uncontrolled" in this context means very high blood pressure overall?

Luke: Yes, when baseline numbers are very high (e.g., 160s systolic), hold off on heavy bench pressing until pressure is under better control.

Brent: Is stroke the main concern with those acute spikes?

Luke: We worry about acute elevations. Most people are fine, but why take the risk? During stress tests, we stop if blood pressure exceeds 220 systolic for men or 200 for women.

Luke: We want to get things under control first. It doesn't mean you can never lift heavy again, just that you need a lower baseline starting point.

Brent: The 150 minutes a week recommendation is common. Is more exercise strictly better for hypertension, or do you reach diminishing returns?

Brent: If someone is running 70 miles a week training for an ultra, is more better, or does it eventually cause harm?

Brent: Strictly from the perspective of hypertension is just more better or at some point does, you know, I don't know, I get diminishing returns or I get the opposite effect. It starts to harm me in some way.

Luke: Extremely high endurance training (like marathon running or long-distance cycling) shows a slightly higher incidence of atrial fibrillation, thought to be due to scarring/fibrosis in the upper heart chambers. But I wouldn't discourage long-distance training.

Luke: There are diminishing returns for blood pressure once you hit a certain threshold. You get most of the benefit by 150 minutes. Pushing to 250–300 minutes might give a couple more mmHg drop.

Luke: If you feel better doing more, do it, but don't do extreme volume solely for blood pressure points.

Brent: I'm surprised going from 30 minutes 5 days a week to 60 minutes 5 days a week wouldn't yield a big incremental gain for blood pressure.

Brent: And you're you're saying as it relates to blood pressure, not necessarily.

Luke: Once you reach 150 minutes of cardio, use additional time for strength and resistance training rather than doing double the cardio and neglecting strength. A balanced approach works best.

Brent: How important are sleep quality and sleep duration for blood pressure?

Luke: Exceedingly important and under-recognized. You need 6 to 8 hours of uninterrupted sleep per night. Lack of sleep disrupts the sympathetic nervous system ("fight or flight"), driving up heart rate and blood pressure.

Luke: In older individuals, poor sleep causes extreme blood pressure lability (ups and downs), mimicking adrenaline-secreting tumors (pheochromocytomas)—a phenomenon called pseudo-pheochromocytoma.

Luke: I see this frequently. Aim for at least six hours of uninterrupted sleep—not waking up to use the bathroom twice, but sleeping straight through.

Brent: How does chronic stress impact blood pressure?

Luke: Acute stressors don't have a huge long-term impact, but chronic stress degrades lifestyle factors (70% of the equation). When stressed, people eat poorly, skip exercise, lose sleep, and drink or smoke more.

Luke: Those behavioral knock-on effects drive up blood pressure.

Brent: So stress itself isn't the main driver, but the cascading impact on sleep, diet, and exercise is what raises blood pressure.

Luke: Exactly. I treat patients worldwide with high-stress jobs who have normal blood pressure because they prioritize sleep, diet, and exercise despite their work demands.

Luke: So eat right, you know, exercise and try and get as much sleep as they can.

Brent: How effective are blood pressure medications? What main classes exist, and what are their side effects?

Luke: We have over ten classes of blood pressure medications, heavily studied with proven track records for reducing cardiovascular events. They are among the most prescribed drugs worldwide.

Luke: Initial treatment focuses on three primary classes ("A, C, D"): A is an ARB (Angiotensin Receptor Blocker) or ACE Inhibitor; C is a Calcium Channel Blocker (dihydropyridine); D is a Diuretic.

Luke: We often start patients on a single-pill combination of low-to-medium doses from two of these classes, as they work synergistically.

Luke: They're amongst the most prescribed well-studied drugs in the United States.

Brent: What are the side-effect profiles? I recently started losartan and it seems fine, though initially I felt a bit lightheaded when standing up quickly.

Brent: I mean, I'm 64, and so when I first started taking it, I get a little lightheaded if I stood up too quickly. But that seems to have gone away. So how do we think about the side effects.

Luke: When lowering blood pressure from 150s/160s down to 120s, patients may feel tired or lightheaded for about two weeks as the body adjusts.

Luke: After that adjustment period, you feel fine. ARBs like losartan have excellent side-effect profiles—comparable to placebo in clinical trials.

Luke: Calcium channel blockers (like amlodipine) are also well tolerated, though higher doses can occasionally cause minor ankle swelling (vasodilation, not fluid retention).

Luke: Diuretics block sodium reabsorption in the kidneys; if someone eats too much salt, they might experience mild cramping, but overall these classes are very well tolerated.

Luke: And it's not a dangerous it's not fluid retention. It's just how the medicine works. It's a vasodilator. But the lower dose is it's less people if it's paired with a drug like losartan tends to be less diuretics. If you overdose on salt. Yeah. You're going to you're going to run into problems with some muscle cramping and everything because that's how the drug works.

Luke: It blocks sodium uptake within the kidneys, but otherwise generally, well tolerated.

Brent: Do people stay on these medications for life once started?

Luke: For the foreseeable future, yes, though we trial weaning off when appropriate. New developments are emerging, like long-acting injectable therapies administered once every six months.

Luke: Gene editing therapies for hypertension are in early development, as well as renal denervation—a one-time procedure to lower blood pressure.

Luke: If a 43-year-old with a strong family history develops hypertension, long-term medication is likely, but we minimize the required regimen as much as possible.

Luke: Well, odds are they're probably going to be on some medicine. But I give them my word that we're going to try and limited as much as possible.

Brent: Are there concerns about long-term side effects after 20 or 30 years on blood pressure meds?

Luke: No long-term adverse effects have been seen. In fact, long-term data shows reduced risk of dementia with sustained blood pressure control. These drugs have been safely prescribed for over 40 years.

Luke: You know, a lot of them been prescribed for 40, 40 years or so.

Brent: An anesthesiologist once half-jokingly told me we should put statins and antihypertensives in the municipal water supply because it would save millions of lives.

Brent: Is there a grain of truth in that?

Luke: There's a kernel of truth. Broad population data shows lowering blood pressure yields widespread benefit. Lower is generally better, down to a reasonable threshold.

Luke: Adherence is the main challenge: many patients stop taking prescribed medications after a year, so ongoing reinforcement is critical.

Luke: GLP-1 receptor agonists are an exception where adherence is higher due to visible weight loss benefits.

Brent: Tell us more about renal denervation. How does that procedure work?

Luke: It's a catheter-based procedure done predominantly by interventional cardiologists. Nerves run on the outside of renal arteries supplying the kidneys. Decades ago, surgeons performed sympathectomies to strip those nerves and drop blood pressure dramatically.

Luke: Today, interventionalists go through the femoral artery using ultrasound or radiofrequency energy to disrupt those renal nerves without leaving any implant behind. It typically reduces pressure equivalent to one medication and was FDA-approved recently.

Luke: It's covered by Medicare/CMS via a national coverage determination, so centers nationwide offer it for patients interested in non-medication options.

Brent: It's a quick outpatient procedure done under light sedation with a small groin incision.

Brent: It's that kind of thing.

Luke: Same-day, conscious sedation, well tolerated, no permanent implant, and no need for post-procedure blood thinners. It can be very effective.

Brent: What about supplements for blood pressure?

Luke: There is lack of strong data supporting supplements for blood pressure reduction. Small studies exist for beetroot juice and others, but money is better spent on whole healthy foods rather than processed supplement pills.

Luke: Supplements lack manufacturing consistency across batches, so I do not recommend them for blood pressure lowering.

Brent: Are you anti-supplement generally, or do you view a select few (like vitamin D, fish oil, magnesium) as useful?

Brent: Would you would you agree with that? Or would you be anti the half dozen or dozen that maybe do have some some research?

Luke: Vitamin D supplementation is reasonable, especially in northern regions like Northeast Ohio. However, trials show fish oil does not offer cardiovascular benefit and may increase risk of bleeding or atrial fibrillation.

Luke: We published the SPORT study comparing low-dose statin (5mg rosuvastatin) against six supplements (cinnamon, turmeric, fish oil, etc.) and placebo for cholesterol and inflammation changes.

Luke: None of the supplements performed better than placebo. While individuals may feel subjectively better taking certain supplements, evidence does not show long-term cardiovascular benefit.

Brent: Yeah. And we even heard an anecdote here once that, I think we were talking about oncologist who was saying that cancer patients who take supplements actually have worse outcomes. For some reason. He's very anti supplements for, for people being treated, for cancer. I don't I don't know if that's actually true or not being a smart guy.

Luke: If a supplement truly had proven therapeutic efficacy, a pharmaceutical company would modify it slightly and package it as a prescription drug.

Brent: What research are you currently working on at the Cleveland Clinic that excites you for the future of hypertension treatment?

Brent: So what is that for you or what are you excited about? That's coming down the pipe for hypertension.

Luke: We recently published a study in the New England Journal of Medicine evaluating a one-time CRISPR-Cas9 gene editing therapy targeting the ANGPTL3 gene to permanently lower LDL cholesterol and triglycerides.

Luke: That same platform is now exploring angiotensin targets in the liver for hypertension. We're running high-impact trials through C5Research (Cleveland Clinic's academic research organization) to scale blood pressure control population-wide.

Brent: You published on using CRISPR gene editing to permanently reduce LDL levels?

Luke: Yes. In this Phase 1 first-in-human trial, it proved safe, and patients at the top dose achieved an average 50% reduction in LDL cholesterol and a 55% reduction in serum triglycerides.

Luke: Got a lot of coverage nationally and internationally.

Brent: A 50% reduction is incredible. Is it a low-impact procedure rather than major surgery?

Luke: It was a single IV infusion lasting 1.5 to 4.5 hours with monitoring, and then you're done. Follow-up at 60 days showed durable results, and ongoing long-term monitoring continues.

Luke: There's a lot of interest.

Brent: Did you observe any off-target cuts or unintended genetic consequences?

Luke: No off-target editing was observed. The FDA requires 15-year patient follow-ups for gene therapies, but data from approved CRISPR mechanisms (such as for sickle cell disease) show high precision.

Luke: So we haven't seen any off target editing at this point.

Brent: Where can listeners learn more about your work and resources on hypertension?

Luke: Visit the Preventive Cardiology section at Cleveland Clinic, or explore C5Research (Cleveland Clinic's academic research organization) for our latest clinical trials.

Luke: You know, reach out to us and, you know, we'll see what we can get involved with.

Brent: Thank you for your research and for taking time to speak with us. Dr. Luke Laffin, thank you for joining.

Luke: Great. Thanks very much, Brent.

Brent: Death Clock is recorded in Boulder, Colorado and San Francisco, California. Produced by Patrick Godino, music by Patrick Lee, and hosted by yours truly, Brent Franson, founder and CEO of Death Clock.