Managing Difficult Blood Pressure

We're so lucky to have Mel Lobo who has focused directly on blood pressure control as his whole working life. And he'll tell us about the strategies that we're looking at now and potentially in the future for patients with difficult blood pressure issues. Thanks Sandip. Thank you ladies and gentlemen. So it's a privilege to speak here today on the management of difficult blood pressure in the context of aortic dissection. And rather And rather than spending a lot of time on outlining the drug-based approach to controlling blood pressure rigorously, I think we need to think about why blood pressure can be difficult to control in some patients. And then Sandip was particularly clear that we should highlight some of the work that we do in BARTs in novel approaches to treating blood pressure that perhaps take us away from the use of conventional tablets. And a very dense and busy slide, the specialist is thinking about many, many different causes of blood pressure when he sees his patients. But in reality, there are very, very few that are common. And most of these on this list here are exceedingly rare. And so we have to work out who and when to screen without overusing precious NHS resource by committing everyone to an enormous array of tests. And the list here sort of outlines quite clearly that on the left-hand side, table two, we are looking for certain features in some of our patients that point towards an increased likelihood that we may find an underlying cause of high blood pressure. And on the right-hand side, we have a panel which indicates a sort of process to go through by which we can eliminate different secondary causes. And a secondary cause of hypertension just means something that we can identify as an underlying factor that could be either treated, targeted, or reversed, which may make the blood pressure either easier to manage or even cure it altogether. And one example could be, for instance, high salt intake or alcohol overuse. And if we identify those and there are ways of doing so, we can work on the patients from a lifestyle perspective. And I've had a lot of patients whose blood pressure comes under control with just a salt restriction program without the need necessarily for fancy drugs. So what do we do to determine that the blood pressure is high in the first instance? Well, we use something called ABPM, which is short for ambulatory blood pressure monitoring. And some of you in the room may have had this. It's not necessarily pleasant for patients to have it. It's a cuff on the arm attached to a box around the waist measuring blood pressure periodically throughout the day and night. And some of our patients complain that it keeps them up at night. And some of our patients complain that they can't put up with it during the daytime because it interferes with their activities. Maybe they're in meetings. Maybe they're in situations where they don't want to have a cuff being inflated. But the thing is, it's very important. Because you can see on the slide that the OBP, the office blood pressure, was 156 over 88. And that indicates that the blood pressure was high in the doctor's office. Now, if we didn't do 24-hour monitoring, we'd be treating this patient for hypertension. But the daytime mean you can see there was 128 over 68, which is normal blood pressure. So this is a classic example of what we call the white coat effect. And that doesn't need treatment with drugs, but it may need some form of surveillance. So the idea is that the 24-hour monitor gives us some useful data. And then there's a lot more added data that it gives us listed on this slide here, which includes looking at the blood pressure profile during the nighttime, looking at the heart rate as well, and looking at the blood pressure drop between day and night. So there's a ton of useful information that comes from ambulatory blood pressure monitoring, which in the UK now is mandated as a standard of care. So NICE has said that all patients who are being diagnosed with hypertension require ambulatory BP monitoring as part of the diagnostic process. But it's not that straightforward. And in specialist hands, we've come to realize a number of pitfalls from this simple screening technique. It is obtrusive for the patient and high readings when the cuff has to inflate to a very high level. If the patient's blood pressure is 180 over 110, the cuff is going up to in excess of 200, which can cause pain and discomfort. Also, the frequency of recordings in some of the protocols that we use for clinical trials, the blood pressure is being measured every 15 minutes during the day and every 30 minutes at nighttime, and you can imagine that that isn't necessarily convenient or acceptable for a lot of people. And then also, what about night workers? If the device is applied during the daytime and the patient's about to go to sleep and then go to work for the night, have the parameters been set correctly? So there's quite a few little tricks that we have to think about, and they're not always at the forefront of the clinician's mind. So we've learned to be a little bit careful with cuff-based ambulatory BP monitoring. And there are newer technologies on the horizon that may offer us non-cuff-based approaches, but they require further validation. I can't stress that despite the number of fancy techniques and technologies we have available to us, simple things like sodium are very important. And we all consume far too much. In the UK, the average intake is probably about eight grams a day of salt. The physiological requirement for humans is less than a gram a day. There are tribes of primitive peoples in the Amazonian rainforest that consume less than a quarter gram a day of salt. And they have no issues with stroke, heart attack, dementia, aortic dissection. But they may get eaten by a wild animal or be killed in tribal warfare or in climate change. So it's not all easy for them. So we do have to think about what population norms are and look at the epidemiology. But when we study our own patients with high blood pressure, we find a number of them are exceedingly high salt consumers. And there are certain ethnicities that seem more prone to this. For instance, a lot of our Caribbean patients and patients from the African nations will consume up to 15, 20 grams of salt today. I've even had a patient who loves salt so much, he put it in his coffee. And so we see all sorts of extremes of behavior. We have to take those into account and measure 24-hour urine collections to look at salt ingestion. And there are, again, pitfalls to that that I've listed there. Just doing a spot urine collection in the clinic isn't enough. The patient has to commit to doing a 24-hour collection. And then probably the most important issue in blood pressure control that will resonate with many of the patients in the room is, by and large, you end up being treated for high blood pressure and possibly an aortic dissection with more and more and more tablets, because you have tablets to control your blood pressure, you have tablets to control your cholesterol, you may be diabetic, you may have some arthritis, and by and large you could end up on anything between five and 25 tablets a day. And actually the medical world hasn't been very considerate about this because we just keep writing prescriptions and chucking more tablets into our patients. But what we've come to realize in the hypertension universe is that non-compliance with drug therapy is now one of the major causes with us failing to get to blood pressure targets, and that we need to find out from our patients what their attitudes are. Do they believe in taking tablets? Do they understand the need for this? As well as, are they actually finding the tablets acceptable? Because if you're a chap who gets erectile dysfunction from your medication, or if you're a woman whose hair is falling out with a calcium channel blocker, I think it's quite reasonable not to want to take that medicine on a long-term, lifelong basis. So as physicians, we've probably been neglectful of our patients' perspective. As patients, it's probably true to say that a lot of them will come to the clinic stating that they take their medication and in truth, they may not be. And there may be a variety of reasons for that. But what we've come to realize is if you formally measure these things, you can see that blood pressure medicines compliance in the specialist setting is very poor. And up to a quarter of patients are completely non-adherent with their tablets when they come to clinic. That means there's nothing that they're taking when we measure the urine sample for drug adherence. There's no drugs found at all. But they're coming to the clinic. Their blood pressure is 160 over 100. They've had a stroke. They've had a heart attack. They've got a list of their blood pressure recordings with them, and they're on time for their appointment. And then they sit there saying, yes, doctor, I'm getting on fine with my tablets, and here's my blood pressures. The blood pressure is not controlled. We do an objective test with the urine collection, and there's no drugs in urine. So what's going on there? This is about a clinician-patient interface that, frankly, there's very little time for in a standard clinic consultation. You go to see the GP, you've got seven minutes in a standard GP consultation for anything. In my clinics, we spend a bit longer with specialized care, but still, there's not a lot of time to explore attitudes to medication. And the problem is that we have a very substantial amount of non-adherence. There are ways of addressing this listed on this slide here that include all sorts of fancy technologies, up to and including the most expensive approach, which is measurement of drug levels in urine using chromatographic techniques. That's not cheap, but it's increasingly available in the UK. But again, pitfalls arise whereby this isn't necessarily the strategy by which we get patients to take medication. Because assessment of drug adherence is costly and time consuming. We don't actually know whether or not patients can game the system by taking their medicine the day they come to clinic and then not taking them on other occasions. And then also, we haven't proven that by demonstrating patients adhere or don't adhere that we can improve adherence in the long term. And the very telling thing is in high stakes scenarios, for instance, the transplant clinics where you have people whose organs may be rejected because of non-adherence to drugs, we have non-adherence being documented there, and people running that risk of rejection and losing a very vital organ that's been precious to harvest, precious to transplant into them. And so the world of medication and medication adherence remains full of challenges for us. And as a result of this, we have moved into looking for non-medication approaches to treat hypertension in the Bart's Blood Pressure Clinic that involve patients with MDIS, which is Multiple Drug Intolerance Syndrome, for patients who do not adhere for any reason to their lifelong drug therapy for hypertension. Also, it allows us to interrogate the pathophysiology of hypertension, because by studying the devices, we can work out what's going on from a more kind of pathophysiological focus basis. And there's no issues with adherence to a device. You put one in, and it's there. And we've actually improved our clinical trials as a result of doing clinical trials in devices of hypertension because we've learned new approaches to assessing hypertension. And we reviewed this in an article, and the reference is there on the bottom. And Sandip will make the slides available to you all at the end. But there are a variety of different approaches going around the body that involve targeting the neck with the carotid sinus and the carotid body. We can target the kidneys and the kidney arteries specifically, and we can also use approaches in the groin to join up arteries and veins to provide a pressure outlet for the circulation. And I'll just run through those briefly with you to give you a flavor of what we're up to in BARTs. This technology of renal nerve ablation was first described in 2009-10. And we got involved in it fairly soon afterwards. It involves putting a catheter in the groin, passing it up to the kidney arteries, and applying energy across the wall of the artery to burn the nerves that supply the kidneys on either side. And these nerves are thought to be important in blood pressure control. Several years on from the first studies, we're now working with a way of doing this treatment using ultrasound energy. And this is a lovely, colorful slide to distract you a little bit. But the premise of this is that we're putting now a catheter, again, through the groin into the kidney arteries. At the end of the catheter is a balloon with water-cooled ultrasound probe, which emits ultrasound energy to destroy in nerves that supply the kidneys without causing collateral damage, such as to the wall of the renal artery. And we've just published a nice study in a group of patients with mild to moderate hypertension, showing that the renal denervation technology on the left in green was significantly better than a sham procedure in lowering blood pressure. And that's going to lead to further studies in this area. Another technology that we're using With the help of my vascular surgical colleagues, Paul and Sandip is a baroreflex activation therapy, which targets the carotid sinus to lower blood pressure by tricking the sinus into reducing nervous system activity. And on this slide here is a beautiful example of a reduction in heart rate with the technology and concomitant reduction in blood pressure from a very high starting level to a much more acceptable lower level of 144 over 96. And you have a live display of what's going on as you're using the technology, which has now been miniaturized, as shown on the bottom there. And so we have a very exciting, different approach to renal denervation that we can use. And I've won a grant with a colleague of mine to study this in more detail in BARTs, harnessing the talents of the vascular surgical colleagues who will be implementing the devices for us in a national registry. And BARTs will actually be the only center in the whole of the UK to be doing this treatment, because nobody else has actually moved on this. And we'll be studying patients who haven't been treated before with this particular technology to try and understand it a little better and perhaps create a national registry where we can involve colleagues from other centers. Another couple of technologies include the central iliac arteriovenous anastomosis, which is in the groin. And this involves putting in this little butterfly-type clip in the groin and joining up the artery and the vein, external iliac artery and vein and the purpose of this is to basically provide a pressure outlet for the high blood pressure system in the arteries into the venous system and what the slide shows very nicely is that when we put the coupler in and blow it up to make it functional we drop blood pressure from 182 to 158 and if we close it off again to test its use the blood pressure goes up again so we've got a very effective way of lowering blood pressure, which is more mechanical than the other two that I showed you. And we published this in the last two or three years, showing sustained blood pressure reduction using both office blood pressure and 24-hour blood pressure. And so there's a lot of excitement about this technology. And then another technology that I'll be studying in conjunction, again, with Paul and Sandeep is the endovascular bariflex amplification, which puts a stent in the carotid artery to deform the geometry of the carotid sinus and trick it into lowering blood pressure that way. And that's something that we're about to embark upon. We've done a couple of test cases already with some interesting early results. And this is a busy slide, but you should just read the headline, which says that we're going to be doing a rigorous, randomized, controlled clinical trial, which will be sham-controlled and double-blind. So we'll be testing the treatment under the most rigorous of conditions. And I'll just leave this slide up here as a kind of final summary of the things that we get up to in the Bart's Blood Pressure Clinic, where we've been globally leading recruiters in the clinical trials with high impacts. And that's brought a lot of patients to us. And what that means is that we can study in patients for whom there are no other alternatives ways of targeting blood pressure control that are actually not available to anyone else in the UK. And this is, obviously, patients are going to be guinea pigs in this setting, but it's only where there are no other options. And believe you me, if you're 40 years old, had a stroke already on eight pills for your high blood pressure, you might be very interested in some of these trials. Thank you very much. Thank you. you