Dr. George Bakris offers goals and guidelines for managing blood pressure in diabetes patients.
let me tell you just a little bit about George backers. He is here for a repeat appearance. He had joined us probably four or five years ago at one of our previous annual updates. Um and it was a pleasure to have him. George is um really an amazing a force, especially around the world of hypertension and management in kid in diabetes in particular. He's really written the guidelines a year after year around this. So I'm really happy to have him back and to have him talk to us about this. He's a professor of medicine um and director for the american Heart Association. He's in Chicago and specializes in the diagnosis and reduction of high blood pressure, particularly and complicated and refractory cases. He's skilled in the treatment of kidney disease with a special expertise and diabetes related kidney disease and slowing its progression. So very happy to have you with us George, please take it away and let us know what should all of us now be doing because these guidelines have gone back and forth a little bit, you know, I know and well, thank you first of all for inviting me and let me get into um discussing this, those are my dualities of interest now, you're correct. But I want to give you kind of a history. So this is going back to 1997. So if you look at what are the blood pressure goals From 1997 to today, have they really changed? And the answer is no, not really. Everybody's still hanging on to 1:30. And Anybody that's talking about 120 is hallucinating and we can, I'll show you some data about that. But absolutely nobody should be talking about 1.40. You know, if somebody's got diabetes and their pressures, you know, in the office 1 38 1 40 you're like wringing your hands should you treat them? There's no question they need to be treated. Don't think about it. Now. I just wanted to give you the most recent Uh, documentation that was 2013. But look at 2020 hasn't changed. Really hasn't changed. Now there is one thing and I want to get back to what we were going to talk what we were talking about. Why is it important to measure album in your area? Because it turns out that the more albumin here you have the lower the blood pressure you should get and not down to the 1 10, but you clearly should be well below 1 30 approaching 1 20 if you have a gram or more of procuring. So that's an important concept that you need to be aware of. There it is. So there are three randomized trials to give us information about blood pressure and to allegedly defend less than 1 30 or brady bad news. They're all in non diabetic patients. So really other than a chord we really don't have a prospective trial and I'm going to get to that in a minute. But the trials that we do have are all in kidney disease and they're all non diabetic. And guess what? None of them, none of them. Could you make a definitive argument that if you were below 1, 30 there's no question you're protected because the bad news is that was not true. There was a trend. But it was not true. If you had a line of road in your rear end is I'll show you in a minute. Yeah, it was more true. But really and I can tell you my colleagues when I announced us at the American Society of nephrology back in 2013, the data was overwhelming for less than 1 40 but less than 1 30. The data was very weak from trials I about got killed. But nevertheless, this is where we are now. Everybody wants to talk about Sprint. Look guess what any. Nothing special about Sprint, another non diabetic steady and it was underpowered for anything in kidney wise. And there's no diabetes in it. So, who cares now, this is something that you need to be aware of. I've looked at the different trials and I put together for you, how many blood pressure medications does it take to get the blood pressure to goal? And most of these are between 130 and 140 And you can see in the diabetes field in the middle. It takes an average of about 2.6 months. In fact, there it is. Overall in all these trials, it takes about 2.6 men. So for the clinician that's going to start with five of life center bro. Because they're really worried. No, no, you need real doses of real medications. The trials that you just heard about Grinnell identity. They were using 100 a blow start and they were using 300 of urban garden. Nobody was there on a tincture of aloes are in the 25. They would get no benefit whatsoever. So you've got to use these doses in these drugs and the doses they were used in the trials. This is critical. All right. So the argument to start with combination therapy has been in the guidelines Since 2003 and the wording has not changed. So what is the wording? The wording is if you're 20/10 above the goal and it's your first visit you need to start with a fix those combinations. Now it can be a single pill, make it good for the patient. I know the insurance companies have issues So you can go with two bills. And the beauty of that is you don't have to use high doses you can get by with low doses. This study is a brilliant study but was back in 2009 and it makes the point that if you're on a drug, drug a do you double the dose or do you add another drug to get the blood pressure control? And they took different classes of drugs as you can see here and they either doubled it or they added another complementary mechanistic agent to see what the blood pressure and the purple across the board is what happened when they added a starting ghosts of another complementary agent. So there's no question You want to go with Combo and not push single drug therapy. That concept was out in the 90s. It's a very important point now if you want to get really into the woods weeds about this, We published back in 2011 when the American Society of Hypertension was still alive and well, a document that goes through this in great detail. It's it's almost a guideline. It's definitely a consensus report. And we looked at all the different combinations and looked at outcome studies and looked at all kinds of different things in the bottom line is if you want to use a rasp blocker with a diuretic diuretic or a wrasse blocker with the CCB, that's where the bulk of the data are. That will get you where you need to be. And if you're 20/10 above the goal. So the patient comes in and they're 1 50/95 you start them on a single pill combination if you can because that will get them to go and it will be very important to do that. And people give excuses for not doing this about side effects and all that. Pick an A R. B. There was a huge study. two million plus people looked at for efficacy and safety comparing aces and the Arby's no difference in the cuisine. Airbnb's clearly we're much safer, much fewer side effects. Much better tolerated, publishing hypertension last month. Now, in case you didn't believe me, here's the guideline, the most recent guideline from H. A. C. C. 2017 and you can see 20/10 above the goal. This is what we said in 2000 and three in the J. N. C. Seven. So it's alive and well 10 years later here important point, the brits beat us to it. They mandated, Did you start with the two pill Combo? You can use a single pill if you want. But they knew they wanted to go combo combo out of the box. Why? Very simple people are going to take their meds. They're not adherent this there that if you do this, boom, at least if they take the pill, if you can get it as a single pill, they've got a shot because there's two drugs on board. Now we're back to the heat map. I apologize. But I think the concept I want you to get is albumin urea is a very important point. If you're not measuring spot albumin creatinine ratio. You literally literally are doing a half as job of taking care of somebody's kidneys. So it's important that you integrate that. And just to make the point that I think I was talking about earlier. If you have g. fr of 65, you're not going to tell the patient got kidney disease why would you? And the patient feels pretty good. But it didn't measure albumin urea But it was measured and it's 500. Now look at the color where they are. They're not all of a sudden green, they're orange. They're in deep trouble. And that's what you miss by not measuring album and your. I wanted to make that point because it's relevant and hypertension as much as it is in diabetes. Now this is something you need to know the level of kidney disease that somebody has directly affects their cardiovascular risk. They're not independent. They're intimately linked. You need to think about the heart and the kidney is a married couple. So if you're going to screw one, the other one's gonna get screwed. Whether you like it or not, that is the way it is. This is a classic study from your friends up north at the Kaiser Ellen. Go look at this. Look at all cause mortality on the left. All cause mortality. G fr of 44. It's almost five times that of somebody with a G fr at 60 or higher. So no question if you want to go for cardiovascular events. Well cardiovascular events are dramatically increased at this level. There are 11 times higher. So very important that you understand that the level of G. F. R. Is not just indicative of the kidney. It's indicative of your cardiovascular patients cardiovascular risk? I want to talk about the accord steady. I mean corn steady. You know the blood pressure stuff was that was negated because somebody got a little too zealous with the insulin and we had some people die from hypoglycemia. So this is a very nice analysis. This is done by pharm D's. But they went into the database and they looked at the Sprint criteria which by the way, we're not too different than the according criteria for cardiovascular risk. And they pull all that data and did an analysis for blood pressure. And what you see here is everybody this is important. Everybody had greater than a 15 10 year risk for cardiovascular events. That was true in Sprint. That was true in the court. So the guidelines say 10 because the epidemiologists went to push it. But the clinical trial data Supports greater than 50. Now here's the baseline data and I'm not going to get into this. I just want to make the point that this is nine years of follow up and there's no differences here between the intensive group in the standard and you can see their blood pressures. I don't know if you can see it there. But the blood pressure is starting with around 1 39 1 40 systolic here is the outcome and the outcome clearly shows that intensive blood pressure control reduced cardiovascular events. This particular mason points. So does this mean you need to be less than 1 20? Absolutely not. Because the blood pressure is that they're talking about here. We're around 1 24. 1 25. Less than 1 30. Now, I want to show you some some epidemiology analyses here. This looks at outcome and it compares people above and below 1:30. And what you can see here Is if you were below 1:30, you're doing better than if you were above 1/3. That's an important point. If you look at stroke, heart failure and renal failure, If you're below 1, 30, guess what? There's no interaction here. So, it doesn't matter. That's the interesting thing. There's not that many studies that look at these issues at blood versions below 1:30. But clearly for stroke, There's no difference. But that's because if you're above 1:30 and below, there's no interaction. I think the point here to be made is that the the if you're to the left the light of identity, it favors lowering of blood pressure. So, for kidney disease, if you're above 1 30 it clearly favors lowering it. For heart failure. If you're above 1:30, it clearly favors lowering it. If you have a stroke, it doesn't really matter based on this. But again, the point is That you want to be below 1:30 for the cardiovascular point. So, that's that's the issue. Do you need two people at 1:30 for the kidney? Well, it's not gonna hurt you, but it's not gonna help you that much. But the cardiovascular risk that goes along with this, you need to be below 1/3. Okay. Now, there's another analysis that was done by a friend of mine in Greece. And this was a tour de force men analysis. You can see here. How many randomized trials are there? 1000 plus people? Major? Uh tour de force that was published back in 2017. And when you look at this, what you can see just I'm not going to go through this with you because it's gonna drive you insane. Which contrary to past recommendations and diabetes, diabetes, There's little to no further benefit from lowering the systolic blood pressure below 1:30. Whereas if you don't have diabetes, very important, if you don't have diabetes, you do get a benefit going below. So, all of these trials that are non diabetics, well, of course they want them lower because there's nothing stopping you. You get a pretty good benefit. Now, There's another analysis here. This is a 19,000 patients going out 16.2 years. I want to make the point between diabetes and no diabetes. So this is in Haines data. And it's also data pool with the diabetes heart study. And I put the arrow there is where you get your maximum benefit. And if you look at that, it looks like it's around 1 28. 1 25. Once you get above 1 20. Once you get above 1 20 guess what the hazard ratio skyrockets in diabetes. What about without diabetes? Well, guess what? It's very different. And The point estimate is at or below 120. So important to know there are differences between those with diabetes and those without and no lower is not better in diabetes. You're going to increase the risk. All right. I want to show you this study. It's a very interesting study was done in china And it's a very large study. As you can imagine. You can look at the numerator is here we've got 25 27,000 people plus. But here's the point they randomize people to less than 1 20. Less than 1 30. Less than 1 40. And these are people with diabetes and they wanted to see was there a difference in cardiovascular outcome? And when you look at this, you're the curbs. So if you were less than 1 40 in this group here, 1 30. 1 39 or less than 1 30 there was no difference. But if you're a less than 128 you're dying faster. That's a good thing. So that's an important observation to keep in mind when you're thinking about level of blood pressure. Now there's another study that you may not be aware of called the J. Do it three. I thought this was a new music group. When they saw this. This is a study in Japan and it's a randomized trial also in patients with type two diabetes. And you can see it's properly powered. But what they did is they randomize people to two different levels of blood pressure control and you can see they were pretty well controlled to begin with. So the intensive group was down around 1 22 and but the regular group was around 1 29 1 30. So there wasn't a huge difference. But they went out nine years. And what was the result didn't make a difference when the band there is no It didn't the primary outcome at AP value of .9 and the main secondary outcome was closed but it didn't make it .055 so lower is not necessarily better in diabetes. So the take home message is about blood pressure. You want to be less than 130 over 80 if you have a lot of albumin urea. Another reason to check blood virtues. There need to be really in the mid one twenties If you really want to slow things down combo therapy for blood pressure's 20/10 above the goal and Do not stop Asian emitters if the creatinine goes up but is less than 30 because the data is overwhelming that you're protecting the kidney there. So stop it and I want to show you some data before I finish as to where this all came from. This is very early data From the 80s where I actually looked at people where we listen to really just come out looking at people with diabetic no property and looking at G. F. R. And blood pressure. And what we wanted to see is is this harmful? This increase in serum granting? You can see here we actually measured the G. D. F. R. And we measured blood pressure so blood pressure came down very nicely with the center bro Talking about 20-30 mg and G Fr dropped substantially in the first month. But then look what happened after that. It didn't fall as much fell a little bit more blood pressure remain in control. And after about 5.5 years we stopped the ace inhibitor and substituted our friend cloNIDine because it's really neutral and we just wanted to do it for a month and see what happened to G. F. R. So you can see G fr went back up and blood pressure stayed down. Now you're going to say wait a minute. It didn't go back up to normal. But let me remind you, the average rate of decline in G fr is about one ml per minute per year. And this is six years later. So that's about what the G. F. R. Should be anyway. So just keep that in mind now. Okay, so in the absence of hyper Kaleem ium On a brass blocker. You can tolerate up to a 30% increase in creatinine. It will stabilize as long as the patient is hydrated. That's key. Now, according BP looked at this, they went back our friends, a different group now from the Netherlands, looked at the database in accord and wanted to see what happened with creatinine and who was intensive and who was regular. And what did they find? Well, here you go. You can have up to a 30% increase in the creatinine and in the intensive group or whatever, it didn't matter in terms of outcome, the outcomes were similar. So this does not affect renal outcomes. It doesn't affect cardiovascular sprint. You already know. And they made a big deal out of this. But the reality is with Sprint. It was underpowered. There were changes though. And everybody thought it was a K. I. They were looking at this. Nothing. None of this was significant because again, they were underpowered. What in case you think it's a K. I take a deep breath and remember this slide. This is data from Sprint Where they looked at people that had elevations and creatinine up to 30%. These are markers of acute kidney injury. They are all negative. They are all negative. That's the whole point of this paper. So stop talking yourself into stuff that isn't true just because the creating of the kidney is a regulatory organ. It's going to just and it will adjust again, independent of what you're trying to do. I want to finish with this study. This is a classic steady. You should go read it. This is from our friends at the guys in the room and what they did is they took people g frs below 30 average was 23 and they randomized people, Aces and Arbs or continue doing what you were doing. And they looked at all cause mortality. They looked at Mason, they look to kidney disease progression. This is all cause mortality going out five years. If you were in an eastern ARB, you had lower all cause mortality, what about mason? And I endpoints same thing and you can say, wait a minute, what if the creatinine went up? What happened? We'll look at the bottom That G fr went up 40% there. They continue to follow these people, they didn't stop. I'm sorry, the G fr decrease was 40%, but they continue to follow them. And you can see even in propensity matched analysis, which is in the bottom right, you can see very clear benefit from the Aces and the arms. And then lastly, and as far as I'm concerned, most importantly, the kidney, if you looked at in stage kidney disease across the board, Aces and herbs still protected you when you're on Stage four. So I've asked the question philosophically, are we denying patients with Stage four CKD therapy that's going to save their kidneys because of fear that the creatinine went up or task team changed, or oh my God, so just think about that so quickly predictors of hyperglycemia. So you have some weapons. If you're GFR is below 45, that's a risk factor. If you serve the tasks him on an appropriate diuretic For GFR is greater than 4.5 and you're gonna add now um, spiral or something that's going to affect the potassium uh then these people are at risk. That doesn't mean they're going to get it there, just at higher risk. And if you modify the diet you'd be amazed how much protection you'll give the pastry, You do have the bikers. The binders are alive and well, they're out there, they're they're being used, I use them all the time. Material mary calcium binder, sodium zirconium silicate, which is a sodium biter major side effect with patera mirror constipation major side effect with the zirconium silicate is Oedema because it's sodium based and that's it. And I'll answer any questions and comments that you have. That was great. Thank you so much George quite uh there has been a back and forth, but really, I think you summarized it well with the medications that are now available which we should be using? There was a question that came up at the end of the last talk that kind of touched on what you were talking about with that decline in G Fr but with SGL T two inhibitors and people were worried just like you made the point with ace and ARB, how much should we worry about that? They wanted to know what the Splc two inhibitor drop. How much should we worry about that? Okay, first of all stop worrying. Okay, all of the S G. L. D. Two s will cause a drop in G fr acutely and it's about three mls 3.5. If you're on the diuretic it would be 4.5. And that's why Reza told you to stop the diuretic before you started a good piece of advice. And if you need to bring it back you can now, Yeah, it turns out that the magnitude of that initial drop, there's two papers that have been published recently. The magnitude of that initial drop correlates with better renal outcomes as you go down the road. So you want a little bit of a drop by the way, the lower your g fr the less of a drop you're going to get because it's glucose dependent. So you know, if you've got somebody with a G. F. R. 40 or 30 who you should be using these drugs in, you're not gonna get a big drop. But if the gr 70 you're going to get a nice drop. God that's interesting because there was a follow up question, what concerns do you have for us guilty to Fergie far less than 30. Um and you kind of touched just touched on that. We're we're actually pushing To get s guilty to is used down to 20 and there is a steady going on in dialysis patient. So I think and don't get mad and I'm surrounded here my endocrinologist but G. L. T. To our cardio renal risk reducing agents. They just happen to lower glucose. That's by the way. And I think that's really how you have to think about it. Yeah, interesting. Okay let's see. Um One more question came in. Should we check urine micro albumin and hype in patients with hypertensive in two? Yeah. So here's the thing in diabetes. Rizzo was very clear and I want to just reinforce it. You need to check it once a year and he's correct if you've got a higher level probably twice a year just to make sure that you're moving in the right direction. So can't overemphasized that in hypertension. They've done an analysis and it's not cost effective to check in every year. So the recommendation there Is to check it minimally every 2-3 years and I think that's reasonable. You're gonna be treating them anyway, in other words. So, yeah. Okay. Um I there was one question this was unrelated maybe the hypertensive but I don't know if you you are able to address this one are DPP four inhibitors protective against kidney disease. And all those studies that were done with the DPP four inhibitors? Well I don't want people to start crying hell no, They were not protected at all. They were not predicted at all. Leonard Lipton has the best data, and even that couldn't beat. So funny, Yuria forgot to text so. No. Yeah. Good. All right, George. Thank you so much. It was a pleasure having you with us once again. Um.
