Dr. Christian W. Mende discusses the correlation between hypertension and cardiovascular disease while reviewing clinical practice guidelines for disease management.
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Good morning everyone. Uh We are delighted to have you all attend our eighth annual um clinical heart failure and arrhythmias conference. Um You know this uh this conference of course typically occurs in uh sunny southern California in the hotel by the beach. Um and of course this year were unable to do that. You know, last year around this time when when things were just picking up the pandemic was starting. We were hoping that by this year we'd we'd be back to normal, but not quite yet. So hopefully our ninth annual conference will be uh back back to normal. Um But we look forward to our sessions today and tomorrow, focusing on heart failure updates and heart failure. And and um and the reason is um we do have some slight adjustments to the agenda. Dr Heywood um needed to make a change to his schedule and so he'll be presenting tomorrow. Um But you know, we look forward again to to some great talks and to start things off. We have Dr Mindy who is a clinical professor at the University of San Diego University California in san Diego. He is a member of the Scientific advisory board at Eilat Sciences, He is a fellow of the American College of Physicians and the American Society for Hypertension. Um He's a renowned expert in the world of hypertension um and we've had the pleasure of having him speak at numerous of our heart failure conferences in the past. I always learn something new every time um hear a lecture from dr Mindy. Um He trained initially in Heidelberg Germany and completed his Internal medicine residency in the University of sorry, in Tucson Arizona followed by postgraduate training at the NIH as well as Brigham Hospital and Harvard Medical School. Um so he'll be giving us an update on hypertension in in 2021. Okay, good morning, thank you very much. Doctor Wuhan for the kind introduction. And uh again what I think that the organizing committee to again inviting me to participate. So um if you look at my uh faculty disclosure that nothing will interfere with my presentation first to look at the U. S. Picture, we have about 100 million americans who have hypertension and almost half of them are controlled. And this would be at 1 30/80 or better. Um And you see the categories which really hasn't changed that normal is less than 1 20/80 and you have elevated blood pressure in between 1 21 29 less than 80. And now we only have two stages of hypertension to make things much easier. It's the 1 31 39 of 80 to 89. As you can see which is stage one and everything from 1 42 9 Ohio is now labeled the stage two. Um, if you look at other classification is hypertension is you know, the sustained and controlled. It's pretty much clear that if it's if it's controlled inside and outside the clinic that this is the ideal situation. But we have people who are having elevated blood pressure only in the clinic and normal outside. If you're not on medications, it's called white coat hypertension and it's called white coat effect. That's a technical thing if you are being treated so there really is the only difference between that very important one will have a second slide is the masked hypertension which is whatever reason people are normal intensive in the office but hypertensive at home. So that is uh not diagnosable unless you take pressure readings outside the clinic and importantly uh if you are traded for that but you may still be uncontrolled outside the clinic. So this is called much M. U. C. H. And also we're paying more attention to something which is called non depressed because you and I normally should have a decline of 10% or more of the blood pressure in the early morning hours. And if you don't do that you're non deeper and just three information. Any secondary cause of hypertension. Cpt pregnancy. Toxemia really interesting. There was a certain any secondary costs. Obesity is always associated with non dipping. So if you have a really pure or hypertension um you may be dipping. But everybody else with a with a co morbidity or secondary association of hypertension usually does not dip. So What about a mask? Hypertension is actually said to be as common as 10-20%. And one should be suspicious as a clinician if you have somebody who's normal density for the office but suddenly has Alban ouya. If as little as 3 30 mg program on the on the U. N. Human credit screen. Or is it a high risk of your A. C. C. Calculator or L. V. H. Or each of us below 60. So you have to have a high index of suspicion uh to to really make that diagnosis. And it's very important to make the diagnosis because otherwise your cardiovascular events are pretty much at least double versus somebody who is controlled. A couple of months ago we saw that data which I think is interesting that if you have, let's see a blood pressure of 1 25/80 versus 1 25/90. There was really no increased cardiovascular events seen in that range. On the other hand, pretty much we have this unwritten rule that if you're 60 or older, don't lower the diastolic below 60. So that's sort of easy to remember. And I think the same would actually be true for diabetics with significant cardiovascular on risk factors that you don't want to go below 60. Because as you know, about 85 of the um circulate a coronary circulation is throwing diastolic. And if you look at mechanism hypertension, we really have learned anything new in the last decade or so. We still have multiple postulated mechanisms from the rest system. Do sympathetic system. Uh, the Aldo Austrian levels are becoming more into play because there is now a linear relationship between al dust alone levels and production. Some of it released by the adult decides in obesity. So the higher ups my actually, the higher normal or slightly elevated cholesterol levels you have, Then we'll talk about, you know, nitric oxide deficiency essentially. You talk about the end of your dysfunction And also saw sensitivity, particular in African Americans who basically almost three out of four are, you can assume for them to be so sensitive to the rest of the population is closer to 5050 and you've seen this slide before. But over and over again, I think it is really important to have both feet on the floor and have your back supported and not sit on an examining table. Uh if you sit without that back on lake support, you actually may have 8 to 10 millimeters more systolic blood pressure elevation because you're engaging muscles. And also very important is to do multiple reading even if you do them within a minute or so to discard the first one and average the 2nd and 3rd 1 out. And then again, most importantly, we do you only see a hypertensive individuals um you know three times or twice a year and they are on medication. It really is worthwhile for them at least, let's say once a week or so to take their own blood pressure re reading. And now with the gadgets uh becoming very accurate. And we all like to use a silly metric measurements in the clinic which would be automatic blood pressure, the machines or gadgets. And the same for at home because our systematic methods are far superior in their accuracy from any other way to measure your blood pressure. And we know that if you take your pressure at home you are better control because you usually take your medications, their studies showing that you also are showing up for your appointments. And again, the key thing is you do make the diagnosis of masked hypertension, which is very important. So what do you do after you get the pressure of 1 35 in an individual let's say over 85 you not automatically start treatment fortunately uh in two out of three year year on a. C. C. Risk calculator is less than 10%. So for that population it is non pharmacological, will show you the list which also hasn't changed what you do with that and you try this for 56 months. And these are the official guidelines. If on the other hand, your HCC risk is 10% or higher, which is about a third of the patients in the studies, you immediately start treatment because the data show that this will if it continues. If you go up let's say a decade with 1 35/85 or so, you actually have doubled the risk of my card in function. This is why this was instituted. And of course no question if you want 40/90 of a higher you initiate drug therapy. So if you look at this from a different standpoint um uh to say okay what about the old primary versus secondary prevention? Well if you have established cardiovascular disease or you have a 10% or more is uh a. C. C. Risk. Uh It is secondary prevention. So that's why you treat from 1 30/80. On on the other hand, if you have a negative cardiovascular history and it's a is a c score of less than 10, uh you only initiate treatment if you get to 1 40/90. So the goals have not changed from the sec and the 80 as of this year they're less than 1 30/80. And the key Diego, the International Society of NEphrology now about six weeks ago, irrespective of your cause of CKD, meaning that you either have an issue of all of less than 60 which is one definition of COPD Or you have Alban urea. And importantly, even if you're seeking your, each of ours is 90. But you have 35 mg of albumin program of create then on your urine albumin creatinine ratio. You have COPD. So so C. P. D. Is not just the low each of our it is also isolated albino and of course C. B. D. S if if you have both. Its it's definitely also CKD. So there's three ways to look at C. G. D. So this new guideline states that you should shoot for less than 1 20/80. However, there are caveats and stated that not everybody really will would benefit were not so certain that you should drive a diabetic below 1 20 unless they're type one and 18 years old. And also if you have a baseline between 1 21 1 29 it's probably not a good idea to to adjust If you each of us down the 15 or 20 with advanced CKD, you meet that do anybody any good. And of course you have these age groups here over 90, less than 50. But importantly it's from an apology standpoint. Let me tell you that if you go below 1 30 you will have no additional benefits to slow down progression of C. P. D. So if you go below 1 32 let's say close to 1 20 you are actually gunning so to speak up for reduction of cardiovascular events. Which we have seen from the from the Sprint trial. Uh something a couple of weeks ago I saw from the U. C. L. A. And uh also from an clinic up in the northwest that they looked at actually almost 28,000 women or patients. But half of them were women who are followed up to 28 years. And they found something interesting that there seems to be a lower risk threshold from hypertensive standpoint in women than in men. It was surprising for me to see this. Uh It was a research letter from a very very good clinic at U. C. L. A. And it's the first time I've seen these huge disparities between the blood pressure and they try to correct for lipids and and for A. One C. S. And and other confounding and BMS and other confounding um uh parameters. But I think it raises an interesting aspect saying that maybe the cardiovascular risk in women at least you should be aware of. It may be lower than the males. Uh, and we may need a law blood pressure definition for them. Again, there's a big question like this is just I brought this up to you on to to show you uh most recent data. The switch quickly because covid and hypertension got a lot of press initially. People the chinese and the italian said that if you have hypertension that your risk for mortality actually from studies was twofold by having hypertension subsequent. Very good looks at these data showed that the nobody paid attention to the confound ear's age, hypertension, diabetes, et cetera. So then we looked at additional data. It was found interesting left as you already know by now that we have the angiotensin converting inside too. Which is completely different from from is which is is one which you and I are trade with an ace inhibitor but this is too, is found on the surface of most cells, particularly in the lung. This is why you have so much lung disease with covid. And the question was raised is hypertension uh, risk factor for for covid infection. And what is interesting is if you look at uh is the is to is to has two components, one is circulating and what is on the surface of cells and what does is to do. And I'll show you as a diagram a moment that actually is our mother nature's counter acting um, enzyme to break down entry attention to faster. So with other words, is to Converts Angiotensin two into Angiotensin 1-7 and Angiotensin 1 7 is actually a counterpart to Angiotensin two. So if you now have is um to being occupied by uh, covid and you have very low circulating is two levels you actually do not metabolize and she tends to do as much and so interesting enough. As sick as the people with Covid are very little hypertension. Initially on admission has been noted because they have relatively high levels off out and she attention to. And the next one just to remind you that the is in the center is the one which converts extensive 12 extension two. That's the one which is inhibitors work but is too which is not affected by Air B. C. Or by its inhibitor is the one mainly uh converting angiotensin two in the angiotensin 17 which by the way has its own cellular receptor which is called Moss Mes. So to summarize how does the covid get into ourselves? It actually circulates of course in the bloodstream then gets attached to the ace two receptors on the surface of the cell. Then you have the underside poses so the whole complex is internalized, gets to your D. N. Your nucleus and high checks the D. N. A. And then multiplies intracellular early to A. Level where you get cell death. And then of course all these viruses burst into circulation and repeat the process with new cells. So this is the mechanism one more time or angiotensin. 17 There are actually experimental drugs beings are evaluated which increased angiotensin 17 as a potential further downstream. And the hypertensive because H. 17 is you know the mother nature's counter um um uh component to enter attention to and it is a visa dilator if it's and if I properly it is anti inflammatory and so it is an important component. Now if you look at conditions where our age is low with diseases and this is a hard day of meeting. I like to point out to you that the higher your N. G. Appropriate beers or the higher your heart failure classes to actually the lower your plasma levels of these two are and again old agent and diabetes and and C. G. D. All of the factors. So we have conditions were were is to is low and that may be one reason that you are uh susceptible to more of covid because you then attach us to to the cells that actually therapy suggested to infuse is two in the plasma to neutralize covid before it attaches to the is to undersell. So this is why if you see this list here of the low circulating is two levels. You can see that's a list of people who are at higher risk of covid. So I thought this was interesting to show you. So how do we uh stand now with the with the stopping is an ambition. Initial people that stop it. But right now, basically the data show that in retrospect you may actually be better off to be on an ace inhibitor or an Air B. So don't stop them. Uh in the official recommendations now for multiple societies or is we should not discontinue is a therapy or Air B drawing an infection. Actually there are study on going to start it in china. I wouldn't necessarily advise that. But definitely you have lower its european levels, You have lower signs of information. So, so at this point is an AIR B should not be discontinued unless you have somebody with significant hypertension or secondary bacterial uh infections. The list of non pharmacological therapy is really unchanged. We are now at the 56g of sodium restriction for everybody, which you know the sodium chloride divided by 2.5 gives you the sodium that's 1004 100 mg. But something we are increasingly aware of is that if you look at the dash diet, what is so unique about it? It is very high in magnesium, very high in potassium. And both of them are visit dilator. In particular, potassium actually has a significant uh effect by counter acting people who are taking a large amount of sodium in and we also now have data that actually potassium uh in jake causes the natural races in the fireside like effect. So they have some effect on the same transporter which you blocked by giving somebody a thigh side. So it lowers your soul sensitivity. Is visibility very um to go you know above 50 60 Mq. Today the average american diet by the way is under 50 M. Make U. K. And the dash diet is somewhere around 80 to 90 Mq. Just to give you a ballpark figure. And nephrology wise we now have good data to show that the best potassium if you have CKD is between 4 to 4.5 and it's actually better than down in the mid threes because it may indeed uh slow the progression of CKD. So what are your choices of medications? So we drive no more step there it is all up to you to look at your individual patient and look at comorbidities. So you got, you know the major groups listed here. We also know that stage one. You should start one drug and then if you're not controlled a month or so later at the second truck, if you're above 1 40 or 90 the statistics show if you want to get down to the lower mid twenties, uh you really need to drugs people are still somewhat reluctant because of potential side effects giving your combo. However, you can start with one at the second and then write the prescription for the combo because uh combinations you, you know the fewer pills you take, the better the compliance is. So what about racial choices? Um The thigh sites and council channel blockers actually are more effective effective in african americans because they are a source sensitive or be these movies are constricted to the thigh sides of the salt sensitivity and the CCPS for the S. A. Visibility very Uh and that is true unless you have diabetes for me, I like to start the East Air B. S. with your own argument. Confederation of 30 or higher. But officially here is is uh 300. There is this uh idea going around that the blacks do not respond well. two is an air b alone. That is true. However, the minute you add a second drug to an ace or Air B. And an african american, like a thigh side or calcium channel blocker. You sort of supercharged the rest pockets. So then you recapture excellent responsiveness uh to to all races. So, so only monotherapy of an ace of Air B Is less effective than American and the combination fortunately are effective. So your goal and that group is also less than 1:30 over 80. For sure. So if you say, Okay, what are the data showing last year? If you have extensive meta analysis, almost 250,000 patients. And you say, look, is there a really big difference? I think the bottom line is, is the with the number of the blood pressure you achieve. So you do reduce the events on the average by treating somebody above 1 40 down to 1 45 down to the 1 25 or less than 1 30 range. You can see 25% all events cbs 35 in overall mortality by by 20%. And importantly this is a nice number I like to to always tell in my presentation. Is that if you all at 1 40/90 for each 10/5 you reduce you go from 1 50 to 1 40 or 41 40 to 1 30 each time you do that you have a 13% reduction of cardiovascular death. 14% of all cardiovascular events. And that's actually almost a 15 to 20% reduction of heart failure to which in that study was not listed. But I know from the literature that is the case. So what about comorbidities While if you have diabetes and C. G. D. Uh you start at 1 30/80. And again most of us would prefer an is an Air B. As an apologist. And we know that using bedtime you may actually convert 85% of the non diploma in diapers. So we prefer bedtime therapy for a sea or Air B. And their studies to show that. But you can actually if there is no Albany area you can use the CCB or thigh side. Also. Beta blockers are not being used as first light anymore unless you have pulse rates in the high eighties or you have angina or heart failure. Uh particularly we don't like a tender little anymore unless you use it B. I. D. It is inferior because of the short half life. So tender law for hypertension once a day has not a very good cardiovascular track record. So how effective or anti hypertensive. And you can see most monotherapy if you start at 1 41 35 1 45 you get about 10 to 12 millimeters. Uh And then you see the first three weeks. If you go beyond a month there is very little additional uh lowering of blood pressure. And and unfortunately adding any second drug, you lose about half of the potency. So you're down to five millimeters. Just to point out how powerful the M. R. S. Or L. Doctorow there's been elected and then or not they're actually adding 10 to 20. The issue is that if you combine and ace inhibitor on air B. With an M. R. A. Uh you have about the 567 time risk of hypercholesterolemia, meaning that your kid gets to be about five. And very often you get around it by also people with significant, difficult to treat hypertension. You need diuretics on particularly look diabetic or thigh sites and then you have a chance to literally wash down or increase the potassium excretion allowing you to use a CRB council telelombardia, M. R. A. And a diuretic which is very often needed Or refractory hypertension underneath three or 4 drugs. So if we look at the the the discussions over and over again from sprint and other studies about age, I think basically it is very important. Even if you're 95 years old to get your pressure below 1 40, that seems to be a real uh threshold for cardiovascular events. And I think that most of the studies now show that irrespective of your age. I think getting as close or just below 1 30 is really the ideal number for most of us. And I put the heart failure number in there too. Pretty impressive. That you have a 23% reduction if you get down below 1 40 even better if you go below one Um uh 1:30. So this is the association just quickly. Uh Some of us are, you know, if you see an increase in creatine within the first two months by starting an ASR Air B of more than 10% the number one cause is volume the patient. So before you get excited about the increase to make sure that you adjust your diuretics and the patient is dehydrated. So the same is actually true for SQL two inhibitors. If you start in A Air B or escrow to inhibit in a volume depleted patients, you'll get Um increases of creatine of over 10 in each of our drops of more than 10%. However, if you're not volume depleted, we now have mortality data And it looks like there is nothing wrong with the kidney. If you go 15 or 20%, your credit goes from 1 to 1.5. That's a 50 injuries there. This is not an issue of kidney disease. It's an issue that you have a vascular of reactivity and be considered this now. A biomarker. So what is the rule? And our rule stands right now that if you have an increase of over 30% of of your craft and or an increase of over 30 decrease of 30% of each of our S. U. Two inhibitors. That is reason to discontinue on. Hopefully rehydrated if it Rikers that is the reason not to use in its or A. Or B. Or S. So the 30% increase is a good guideline now. So don't discontinue is an AIR B. It will not reduce your end stage kidney disease dialysis risk. However, look at this, you increase mortality in in in in a major cardiac vascular events significantly and said used uh they lower your efficacy of all your drugs and make you salt sensitive. So it's not a good idea to use them together. To summarize one more time. 1 30 to 1 39 U. U. Uh use your calculator if you're less than 10%. It's a lifestyle for 3 to 6 months. If you have over 10% you initiate therapy and uh one more time the treatment goals. So less than 1:30 over 80. And unless you have a the philologist who who looks at all the variables were each a blood pressure of less than 1 20/80 is uh advantage I think probably should try to push the blood pressure closer to 1 20 if you can, if you don't develop metastatic hypertension. And uh, the situation individually is tolerated. So thank you again for listening. It was my pleasure to present the data to you.