 Well, good evening everybody, I hope you can all hear me okay. I'd like to welcome everybody to the last talk in what has just been our 220th session of lectures. And I'm extremely pleased to introduce tonight's speaker. As you know this talk tonight is only on zoom. And that's because our speaker is not with us in Scotland she's in Montreal in Canada, which is one of the advantages of zoom that we can have a speaker from a distant part of the world. This evening now this evening's speaker is an extremely talented scientist, Professor Reang Toyos. She is a clinician and a scientist. And she has dedicated her scientific career to unraveling the mechanisms behind hypertension and what damage it does and how it occurs. So as a clinician she works with patients and as a scientist she tries to find out the cause of disease and the best treatments. Now Rihanna trained in medicine at the University of West Waterland in Johannesburg. And then she did her research training in Montreal. She was in Glasgow for 10 years at the where she was director of the Institute of cardiovascular and medical sciences and she was also held the British Heart Foundation chair. She's now moved to a very prestigious position where she's running a large research Institute at McGill University Health Center in Montreal, where she also holds the Dr Phil Goldchair in medicine and she's professor also of family medicine. Rihanna is a very well known scientist. She's editor of very important journals in her field. She's received numerous prestigious awards, for example, the research excellence award, the premier international award for research in hypertension. She's from the council on hypertension. She's played many leadership roles also she's been president of the International Society for hypertension and president of the European cardiovascular research organization. And she also has an interest in the careers of women in science, and she was founder and chair of the women in hypertension research network. So we're extremely fortunate to have Rihanna join us this evening and tell us about high blood pressure, the number, the world's number one killer. Now, I just like to remind the audience first that the format is Rihanna will give her talk. And then we'll have a short five minute break when questions can be entered. Please enter your questions into the Q&A and not into the chat. If you have any issues, you can put them into the chat if you're having difficulty hearing or joining the meeting, but questions please in the Q&A. So I'll now hand over to Rihanna to give us a talk and I can just remind you to switch your video to presenter mode and I'll switch off my video for the time being. Thank you very much, Rihanna. Perfect. Well, well, good evening everybody and I really would like to thank Leonard Izakovitz and Pat and the council for inviting me this evening to share with you some of my thoughts related to hypertension or high blood pressure. And indeed, Pat is absolutely correct. I am absolutely passionate about this field. And I hope you'll appreciate why during the course of my presentation. Before we actually start, we need to understand what blood pressure really is all about. Blood pressure is a physiological phenomenon. It is very, very important, obviously, because it is the pressure within blood vessels that is responsible for maintaining and regulating blood flow from the heart through the vascular system to all parts of the body. And the pressure that occurs within the lumen of the blood vessel, the amount of force that is created by blood on the walls of the arteries as the blood circulates around the body is what we term blood pressure. And the function of large arteries, primarily the carotid arteries, the aorta, these are what we call large arteries and are responsible in large part for the transport of the blood from the heart to the rest of the circulation. So again, the pressure that is exerted within the lumen or the inner part of a blood vessel, the pressure that is exerted onto the walls of that vessel is what we refer to as the blood pressure. And the pressure is very, very important because as I said, it is responsible for the blood flow that is ultimately responsible for driving the circulation to all parts of the body. So indeed blood pressure drives blood flow from the heart to all the vessels in the body, and particularly I want to highlight what we call the small arteries. These are the arteries that occur within all organs and tissues and are responsible for providing every cell, every tissue and every organ in the body with blood and oxygen. And the small blood vessels actually play a very, very important role, not only from a functional point of view with respect to what blood pressure is responsible for, but also these vessels contribute to high blood pressure itself. So just to highlight, we have the heart that is responsible for pumping the blood to the large vessels that ultimately get through to the smaller vessels and eventually to the very, very small vessels that supply the brain, the heart, the kidneys, and as I said, every organ, every tissue in the body. When we talk about blood pressure, blood pressure is measured in a unit called millimeters of mercury. And this was based on the original studies that were done many centuries ago. And the amount of pressure that was exerted in a blood vessel was measured as the change in a column of mercury. We talk about blood pressure as having two values, an upper value and a lower value. And the upper value or the upper number is what we refer to as the systolic blood pressure. And the lower value or the lower number is what we refer to as the diastolic blood pressure. So whenever you go to your doctor, your physician and your blood pressure is measured, you will be told that your blood pressure is comprises two numbers, the systolic and the diastolic. So what do these numbers actually mean? Well, as I said, using a sphic momentometer and today we don't use mercury sphic momentometers, we use automated methods by and large. But the upper number or the systolic blood pressure is that pressure that occurs when the heart is contracted during what we say systolic. And the lower number or the diastolic blood pressure is the blood pressure that occurs in the blood vessels when the heart is relaxed or when the heart is in the phase of diasterein. So these numbers, and you'll hear a lot of numbers that are referred to in your doctor's clinic, but the ideal blood pressure that we would consider in adults would be a blood pressure of less than 120 over 80 millimeters of mercury. Because it is at this blood pressure that the heart can function efficiently and where all organs tissues and cells can be properly perfused with blood that is generated through each cycle of the cardiac function. So understanding what blood pressure is and what we would consider as being an ideal or normal blood pressure of less than 120 over 80 millimeters of mercury, how then do we define high blood pressure or in clinical terms called hypertension. And I would just like to spend a minute in terms of this definition, hypertension, because very often when the word hypertension is mentioned, people think that this refers to high anxiety, high stress, but actually all hypertension means within the blood pressure setting is that it means high blood pressure and high blood pressure by definition today in most guidelines is considered as a pressure above 130 over 80 millimeters of mercury. We know that blood pressure is not static. We know that it changes minute to minute depending on activities. We also know that blood pressure changes with aging. And we can see very clearly here that the prevalence or the cumulative incidence of hypertension as indicated by the y-axis and the x-axis being increasing age. We can see that with aging the prevalence or the cumulative incidence of hypertension increases. It's also very clear from many, many, many studies that the incidence of hypertension with aging is different between men and women and between blacks and whites. If we look at this red graph over here, we can see that black men have the worst incidence of increasing hypertension with respect to age compared to white men. We can also see that men have higher blood pressures by and large compared to women. And this actually is very important. In fact, with respect to women, it's actually at the level of about 40 to 45 years of age that blood pressure starts to increase linearly the period of the pre or the post menopausal phases of the aging of women. So the question with respect to these changes in these differences, we still don't know the exact causes, but it seems that at least the differences between men and women are related to changes in the sex hormones that occur with aging. If we just look again at this graph with the x-axis over here being increasing age from 20 years to over 75 years and over here being on the y-axis, the number of individuals with hypertension. Again, we can see with aging blood pressure increases. Also, as I said, we can see that in women as indicated by the light gray bars, the proportion of those with hypertension starts to get higher after the menopause. And we can see at least in women that this is associated very closely with a reduction in the circulating concentrations of sex hormones such as estrogen. So we know that sex hormones do play a role not only in the regulation of blood pressure, but also in the increasing prevalence or incidence of hypertension with aging and after the menopausal period. So if we consider the heart to be a tap and the blood vessels to be, for example, a hose pipe, and we equate this to what happens in a pipe and a pump situation, if we have the situation where the amount of pressure at the level of the pump is altered, or the lumen diameter of the pipe is altered with a change in the pressure that is exerted, for example, by different devices, we can appreciate then that this would result in an alteration of the pressure in these pipes equated to blood vessels leading to damage to these pipes or to the blood vessels. And it is this process that is so dangerous in the context of a clinical medicine. So blood pressure is a very complex process in terms of its regulation, because there are many organs and many systems that actually contribute to the regulation physiologically with respect to blood pressure. But because blood pressure is so closely linked to blood vessels, as I said, the exact organs and systems that are responsible for regulating blood pressure are themselves what we call targets of high blood pressure. So we know that the heart, very importantly, can regulate blood pressure as we saw with respect to the tap and the amount of water or blood that could come out of the tap, if you change the pressure in the tap. So too, if there is an increase in blood pressure at the level of those small blood vessels, this can have an effect on the function and the structure of the heart and can lead to, for example, heart disease. Now the concept of hypertension is not new. And this relationship between hypertension and consequences at the level of tissues or organs is also not new. In fact, in 2600 BC, already the Chinese Yellow Emperor's doctor suggested that the impact of hypertension related to salt and blood vessels was very clear. And it was already stated at that time that too much salt in the blood can cause hardening of the pulse and that treatment of a heart pulse or a stiff blood vessel was targeted with respect to acupuncture, veneer section and bleeding by leeches. So already 2600 BC, there was this relationship between the blood vessels, the stiffness of blood vessels, and interestingly salt and the impact on the pulse or by definition on blood pressure. In 1550 BC, this relationship was further evidenced, and it was ready by the Egyptian physicians to the very famous herbus papyrus, where it was discovered that the relationship between the palpated pulse and the development of heart and brain afflictions was closely linked. In 1628, there was the first description of the circulation of the blood by William Harvey in this book entitled on the motion of the heart and the blood. And in the 1700s, there was the first publication of the measurement of blood pressure and this was done in Hosses. In the 1890s, for the first time, what we now know as a mercury sphigma manometer was developed. And at that time, there was the recognition that hypertension was a very important clinical entity. In 1896, as I said, the Riba Roki invented the cuff based mercury sphigma manometer, which is what we base our current devices on to measure blood pressure. And Karatkov, a very famous Russian physician, actually further went on to describe the sounds that we use as physicians when we listen to the heart sounds, when we measure blood pressure, this was attributed to him as a Karatkov sounds. And in the 1920s, we started to understand more about contemporary hypertension. At that time, the only treatments that were available were very aggressive types of surgical treatments. And it was only in the 1940s, 1950s, that we started to get the development of drugs that effectively lowered blood pressure. But the drugs that were used in those times were very harsh and had terrible side effects. Now the impact of hypertension has really been huge in terms of world affairs and world politics. And in this very famous conference, the Yalta Conference of 1945, where we know it played such an important, it was so pivotal in defining the end of World War II, the three very famous leaders, as we can see here sitting very comfortably together, in Ireland, Russafelt and Churchill, besides having the common interests in terms of getting to the end of the terrible World War II, they had some other common features, and that was that they all had hypertension, and all of them died. And especially with respect to Russafelt, they died prematurely due to hemorrhagic stroke. And these are recordings of the blood pressures of these individuals at this time. And the blood pressure that was recorded for Russafelt at this conference was about 260 over 150 millimeters of mercury. A few months after this meeting, Russafelt had a portrait that was being painted for him, and it was at this portrait sitting where he said to the artist, I have a terrible headache, he then collapsed and he died very soon thereafter. His blood pressure as measured by his physician at this time was as high as 300 over 190 millimeters of mercury. So one can appreciate if we are talking about blood pressures being normal of 120 over 80. Russafelt at this time had blood pressures double more than double of what we consider to be normal. So the reasons for the devastations as we've just seen for Russafelt are related very closely to what high blood pressure does to the target organs at the level of the brain, causing stroke, also causing vascular dementia. We know today that hypertension is a major risk factor for vascular dementia and the consequences from a personal familial social point of view with respect to dementia are enormous and they are getting more challenging in terms of managing. We know that high blood pressure is responsible for heart disease for heart failure for ischemic heart disease for kidney failure for aortic aneurysms for changes in the vessels of the of the of the eye causing changes in vision, and also causing peripheral vascular disease because hypertension is also closely linked to narrowing of arteries due to atherosclerosis, which leads to not only ischemic heart disease at the level of the heart, but also to block vessels and the small vessels in the periphery that causes very severe. What we call peripheral vascular disease where patients suffer from enormous ischemic type pain in their legs. So, you can see already that there are very bad consequences linked to uncontrolled hypertension. To talk about the good and the bad of hypertension. Some people would say well the good is that they are no symptoms, unless the blood pressure is very high as we saw with respect to Rousseff felt where his blood pressure was 300 over 190 by and large patients will have no symptoms related specifically to high blood pressure. And so therefore patients feel very well. The bad is that they are no symptoms, and therefore patients do not know that they've got high blood pressure. And sometimes the first time that a patient may become aware of the fact that they have high blood pressure is when it may be too late because they may present at the emergency with a stroke heart disease kidney failure or other. And so it is for this reason that hypertension has been described actually very effectively as the silent killer. One of the statistics that may be of interest to you is that about seven or every 10 people 70% will have their first heart attack. Those patients have got high blood pressure. So every 10 people having their first stroke have got high blood pressure, and about seven of every 10 people with chronic and long lasting and debilitating heart failure have got high blood pressure. And so you can appreciate that the consequences of high blood pressure are enormous. What does this mean in terms of global disease, not only in our developed westernized environment, but also in low and middle income countries. Well, this was a graph that was actually drawn up in 2013, but actually has not changed even until current times. The global burden of disease across the world is that of high blood pressure. And many people don't appreciate this. Many people think that it's cancer infection, a trauma, but we seem to have lost the presentation. Can you see the slides. You can still see the global burden of disease slide. Okay, from my side, everything has disappeared. Oh, this is very bad. I wonder whether I should. Okay, is that okay now. Can you see the slide. Other people are saying they can also see. Good or it disappeared from my screen, but it seems to have reappeared. So anyway, just to say that globally, high blood pressure is the real burden of disease. And in Scotland or the UK, it's particularly important in this statistic that comes out from the British Heart Foundation, actually, the premature cause of cardiovascular disease across the UK as we can see by the red color, and particularly by the dark red color indicates the areas where there are very, very high incidences of cardiovascular disease, and particularly linked to hypertension. I mentioned to you that high blood pressure. Many years ago was thought to be a disease of the affluent, a disease that occurred primarily in developed countries, and a disease that was linked to westernized type lifestyle. However, it has become extremely clear as we can see by this graph over here, very recent data indicating that high blood pressure or hypertension is increasing in low and middle countries as well. And the darker the red or the brown color, this indicates the countries that have got very high prevalences, as we can see up to 50% in some countries of hypertension. So hypertension is no longer considered to be a disorder or a disease of the developed world, but also that of the low middle income countries. And because of this, it really has a massive impact in terms of non communicable causes of morbidity and mortality. So in terms of Scotland, just again to highlight to you that it is very common in the adult population that one in three adults and that might even be more these days have got high blood pressure. So for those of you who are at this presentation, if you were in the auditorium, I would say look to the right of you and look to the left of you, one of the three of you would have hypertension that would require treatment. So the prediction over the next three years by 2025 is that the number of patients with hypertension is going to increase to almost one and a half billion, and one can appreciate that because of this morbidity and mortality associated with hypertension, the impact is very, very large. So why does it really matter? Do we have evidence that it does matter at a global sense? Well, I do want to share with you this very important study that was published in the New England Journal of Medicine. And it was a study that actually modeled the cardiovascular risk. In other words, the risk of having a cardiovascular event linked to systolic and to diastolic blood pressure. And you can see based on this modeling that as blood pressure increases, both the systolic and the diastolic, the percentage of individuals who are going to have a cardiovascular event is going to increase. So we know that there is this association and very, very importantly that both systolic and diastolic blood pressure are independently linked to cardiovascular risk. And this study that was a modeling study defined this to be independent of how you actually defined hypertension, whether you defined hypertension as 130 over 80 or 140 over 90. In other words, the higher the blood pressure, the greater the risk of a cardiovascular event. So again, getting back to the impact of this at the level of morbidity or quality of life. And again, I want to emphasize to you that the impact of hypertension and the impact of cardiovascular disease occurs across the age spectrum. In a study that was published a few years ago, we can see that the years of life lost to cardiovascular disease associated with hypertension, as you can see here is huge in young and adults, middle aged adults, as well as in the elderly. So the impact is very, very significant from a quality of life point of view, as well as to that of premature death. Again, just highlighting why this is so important. So if we look at this very nice and very important study that has had a huge impact in the world of clinical medicine, again, looking at systolic blood pressure, and the incidence of both ischemic heart disease and stroke, again, almost a linear association between increasing blood pressure, stroke and ischemic heart disease. So we know now that high blood pressure is not good, that it is associated to cardiovascular events and that cardiovascular events are driving this morbidity and mortality worldwide. So what then is the optimal blood pressure to target to prevent these cardiovascular events? This has been a very difficult question to answer, because to answer that question you need to do very, very large studies. But I want to highlight a very important study that was published in 2015, where the authors asked that question, what is the optimal blood pressure to target to get patients who've got hypertension to treat it to treatment so that they are prevented from having a cardiovascular event. I don't want to worry you too much with the details of this study, but I will explain it to you, because it is such a brilliant study. It was called the Sprint study. And this was the systolic blood pressure intervention trial. What these investigators did is that they approached a whole lot of family physicians, and they said, please, would you treat these a group of your patients with normal blood pressure medication, but we want you to treat these patients such that their blood pressure is controlled to about 120 over 80 millimeters of mercury. And then they said we want you to treat another group of patients, just as you would ordinarily. Don't worry about trying to get the blood pressure to the target of 120 over 80. And this was a very successful study. There were about nine and a half thousand patients in this study. And what we can see is that indeed the family physicians, the GPs did a wonderful job, and they did treat the patients very effectively in getting them down the blood pressure to about 120 over 80. And they called this the intensive blood pressure arm of the study. And the other patients, their blood pressure was controlled at about 136 millimeters of mercury. And what these investigators did is they followed these patients or they intended to follow these patients for five years, and they were going to track what happened to cardiovascular events such as heart attacks or stroke. So what did these investigators found? The results were absolutely astounding. They found that in the patients who were treated with the same types of antihypertensive drugs, but that their blood pressure was targeted to 120 over 80 millimeters of mercury. There was almost a 30% reduction in death due to cardiovascular events. This was extremely important in the terms of clinical medicine, because for the first time, it was very clear to us that as physicians, we need to be very aggressive in treating patients' blood pressures to that of 120 over 80. And that study, the SPRIN study, had a huge impact in the definition of hypertension, and actually many international guidelines changed the guidelines with respect to when patients should be treated. And blood pressure was not defined as being normal, as I said, at about 120 over 80, but elevated blood pressure now was defined as somebody having a blood pressure of 120 to 129 over 80. So if you're sitting in the audience and you've got a blood pressure of 128 over 83, by definition, you have got high blood pressure. We define patients as having hypertension as having a blood pressure of 130 to 139, and various stages of hypertension as having higher blood pressures thereafter, with very high pressures being defined as a hypertensive crisis, which is exactly as we know what happened to Roosevelt. So, of course, then we know there's no question about it, we need to reduce blood pressure, but actually, it's not that easy. We have to use a number of different approaches, a public health approach, we have to use a patient approach with a patient himself or herself has to take responsibility, and also, there needs to be better health care and self management across the board. So how can we help patients to control blood pressure to ensure that they are not at risk of those terrible sequelae complications of elevated blood pressure. Well, there are a number of different modalities that can be used lifestyle modifications. In other words, how do you change your lifestyle such that you can have a positive impact on your blood pressure. And there are many, many different types of lifestyle modifications that we know are effective in reducing blood pressure. Also, of course, you know, in modern medicine, we are very lucky to have very effective antihypertensive drugs, and there are many different types of pharmacological approaches that can be used to reduce blood pressure. So in terms of the lifestyle modifications, which are those that have been shown to be most effective. Well, diet is very important, eating a healthy diet, controlling the amount of salt that is taken in is very important, exercise, weight loss, alcohol, reduction, smoking cessation. And there's now a huge amount of research to show that environmental pollution can contribute to elevated blood pressure. So therefore, improving the air quality, reducing the number of these micro particles and nanoparticles that are found in our environment can also positively impact blood pressure control. In fact, at a population level, even a very small reduction in blood pressure, as little as two millimeters of mercury can have a very significant effect in reduction of mortality at the population level. We can see here that by simply reducing blood pressure by two millimeters of mercury, we could reduce the risk of ischemic heart disease by as much as 7% and as much as 10% of stroke. So therefore, making every effort to reduce blood pressure is what we should be striving for, both at the level of public health and of course at the level of the individual patient. What about salt? You may hear a lot about salt and the controversies associated between salt and blood pressure and hypertension. Well, there have been many studies, some that were done many, many years ago, where individuals were given different amounts of salt and blood pressure was measured. And this is just one example where the relationship between sodium intake or salt intake was associated with blood pressure. And you can see very clearly a linear relationship, at least in this population that was studied, was that as salt intake was increased, as measured by the amount of salt that was excreted in the urine, so too was there an increase in systolic blood pressure. Now the relationship or trying to explain why there's this very close relationship between salt and blood pressure remains a huge area of research. But what we do know is that there are some individuals who are very, very salt sensitive. So even a small amount of an increase in salt intake can have a very big effect on blood pressure. And this seems to be especially evident in African Americans in blacks in Africa, they tend to be very, very salt sensitive. So if sodium or salt is so important with respect to how it is driving this increase in blood pressure, what can we do about it in terms of lifestyle modifications. Now I want to highlight to you how much salt we take into our diet so without even knowing that. It is very clear that processed foods are the major source of salt. Processed foods contain about 70% of sodium that is taken in on a daily basis. And actually, when one does the analysis, very little of the sodium that is taken in on a daily basis is actually taken in by added salt in the kitchen or during preparation. The amount of salt that is in processed foods is huge. And I would just like to highlight to you that the salty six that have been identified as having the most. The highest concentrations of sodium are breads and especially cereals, you know, processed cereals, cold cuts, pizzas, processed foods, processed chicken that you get at the delicatessen. Any tinned food, you know, tinned tomatoes, tinned soup and sandwiches, especially with the, you know, if they contain processed cheeses and meats, these foods have a very, very high sodium content. And in fact, we now advocate that the amount of salt that should be taken should be less than six grams, which is equivalent to about 2.5 grams of sodium per day, and that equates to less than a teaspoon. Now, if you remember that 70% of the sodium that is taken in on a day to day basis is primarily from processed foods. You can appreciate that it's actually quite difficult unless you're very cognizant of the content of sodium in foods, it's very easy to see how high sodium intake can occur without one even knowing. This is the evidence that, you know, lifestyle modifications can impact blood pressure. Well, these are the numbers that have been well validated from a number of different studies by reducing the amount of sodium that is taken in. So blood pressure by as much as five millimeters of mercury weight loss associated with exercise is very important. As much as five millimeters of mercury as well by increasing exercise, a regular exercise program, reducing alcohol. So this is the evidence when we have a healthy diet or the dietary approach to stop hypertension or the dash diet, which is a diet, very rich in fresh fruits, vegetables, grains, and fresh meat and fish by assuming a healthy diet, a low salt diet without blood pressure in hypertensive patients can be reduced as much as 11 mercury millimeters of mercury. So indeed lifestyle modifications can have a huge impact on on blood pressure control. But we do need drugs to help us. And as I said, we are very fortunate with modern medicine that we've got many different types of antihypertensive drugs. You'll remember when I mentioned the history of hypertension in the 1950s, the first antihypertensive drugs were used. And today we've got many, many different classes of antihypertensive drugs that can be used to effectively lower blood pressure. So how are we doing with all of this knowledge, you know, we know lifestyle modifications can influence blood pressure positively. We know that we've got all these antihypertensive drugs. But can we actually treat patients to blood pressures that are recommended in the guidelines. And today, as I said, the guideline recommendations are 130 over 80. But this study looked at how effectively patients were treated from many different countries to a level of 140 over 19. And what is very, very clear as indicated from these graphs, where the green indicates effective blood pressure to a level that is recommended in the guidelines, you can see that we do very, very badly. And if we look at England, for example, only 10% of patients who are treated who are hypertensive are treated effectively. We've got many, many challenges, based on what I've just told you with respect to why treating hypertension is so important. So where are we today in 2022. Well, treatment of hypertension should be by definition, one of medicine's major successes of the past 50 years, because the advances in therapy provide the capacity to lower blood pressure in almost every patient. However, uncontrolled disease remains despite improved therapy, and Avram Chabanian in this very famous Shattuck lecture defined this as the hypertension paradox. And this hypertension paradox is actually getting worse. I want to just highlight to you some statistics that have come out of North America. If we look at the success rate of treatment from 1990 to about 2010, looking at the number of patients that were treated with antihypertensive drugs. And we can see that blood pressure control was slowly increasing over the years, as we can see here. But look what has happened more recently, since about 2013, the number of patients that are being treated and more importantly treated to the targets that I've just mentioned is actually declining. And if we consider in the UK where about 30% of individuals are hypertensive, or in North America, where as many as 45% of adults have hypertension, huge challenges await us. And so it is understandable why the surgeon general in the US has called to action and actions that we need to address the control of hypertension. So why do we have this hypertension paradox? Why do we have these challenges? Well, as I mentioned when I started this presentation, hypertension is a very complicated disease. There are many factors that contribute to high blood pressure. We know that there are many environmental factors that can play a role predisposing somebody to the risk of hypertension. Perhaps we don't have the right therapies. Patients may not take their medication. But at the end of the day, I want to highlight to you that despite all the research over these years, the pathogenesis, the mechanisms of hypertension still remain unclear. And that means we cannot, to date, cure 95% of patients who've got high blood pressure. Now this complexity in terms of what contributes to high blood pressure was actually defined in the 1960s by Irvine Page. And he was very astute because he actually said that hypertension is the result of many factors that interact to raise blood pressure and cause, target or end organ damage. He said hypertension is not a single disease, but that several different diseases with different origins and development contribute to hypertension. And he started to draw up what we now define as the page mosaic theory of hypertension, where it was emphasized that genetics, physiological processes, hormones, environmental factors all network together to influence blood pressure. And that is what Irvine Page developed in the 1960s. But since then, with modern research, we know that this is even more complicated than what Page originally described. And this is what we are now looking at in terms of understanding the mechanisms that underlie hypertension. Through a lot of genetic studies, and other sophisticated types of research protocols, you can appreciate just how complex the mechanistic understanding of hypertension really is. So putting together a number of the recent discoveries, and we have now defined what we have termed a new look at the mosaic theory of hypertension. Because it seems that processes linked to inflammation, processes linked to the gut microbiome, the immune system may also be playing a very important role in the processes that contribute to high blood pressure. But all that being said, I want to emphasize that 95% of patients who've got high blood pressure, we don't know the cause. It is only in about 5% of individuals who've got hypertension, where the cause is defined, and where if we address the cause whether it's a hormone problem, a kidney problem, we can cure the hypertension. So as researchers, we've got a huge amount of work still to do. But because of this multi-disciplinarity with respect to hypertension, when we assess the risk of patients in our clinics, we consider not only blood pressure, but very importantly the importance of age of whether an individual has diabetes or smoking. So we now use what we call a risk score, which enables the physician to have an idea as to just how prone the patient may be to developing a severe cardiovascular event. And actually the world of hypertension and cardiovascular research has been incredibly exciting. In the past we relied primarily on blood pressure and some blood tests. Today we've got many sophisticated technologies that allow us to look at the blood vessels, the heart, the kidney, and we're getting into the era now where we can actually stratify patients who've got high blood pressure as having different types of hypertension, what we call stratification. Because not all patients will have the same type of hypertension and not all patients will need the same type of treatment. And these are just some of the new technologies that we use in our research-based clinics to allow us to understand what is happening, for example, at the level of blood vessels. Now in this world of genomics, proteomics, we also want to understand from a gene point of view, what is it that is responsible for creating the patient phenotype as having high blood pressure? What is it that is responsible for causing the damage, the injury to the blood vessels, the kidneys, and the heart? And there's now a huge amount of effort in understanding the genomics, the proteomics, the metabolomics in terms of hypertension. And so why is this important? Well, if we look at this very nice example, which explains to us, which really highlights the importance of understanding the what we call the genome or the genetics of a subject. We know, for example, that a caterpillar with time becomes a very beautiful butterfly. The genes are the same. This butterfly has got the same genes as this caterpillar, but we can see that the butterfly doesn't look like the caterpillar. And this is due to the fact that genes become very special proteins and that it is the proteins at the end of the day that will define this phenotype. And similarly, with respect to aging, we know the genes are the same, but the proteins that are the message of the genes actually undergo change. And so today we talk about the world of omics, genomics, epigenomics, transcriptomics, proteomics, and metabolomics that ultimately is going to allow us to define each individual patient so that each patient can be diagnosed treated in a very, very specific way. And we are entering into the world of precision medicine. This is termed the next frontiers in clinical medicine. To just highlight what this means, as I said, not all hypertensive patients are the same. These patients, the pink patients, the red patients, the blue patients may have very different types of regulatory processes that are impacting the development of hypertension. So by stratifying them into very discreet groups, we can treat them in a very disease and mechanisms specific way and ultimately provide the right treatment for the right patient at the right time. And indeed, this is an exciting time for clinical medicine and therapeutics across the board. The impact of RNA biology has had a huge effect, as we know, on vaccines for COVID, but also there are now new trends to use RNA biology and vaccines for the treatment of hypertension. And they are today some very exciting strategies to treat hypertension using what we call an SI RNA approach. Also, there are now huge investments in the development of devices to treat hypertension. Some of these devices, such as the renal denervation, which is a device that is used to actually burn the renal nerves, the nerves that supply the kidney. This seems like a very aggressive approach to treatment, but it seems that doing this treatment can cause blood pressure control for many, many, many years without antihypertensive drugs. So why is hypertension the world's number one killer? I hope you can appreciate what I've shared with you today. Again, it is the number one killer because it causes heart attacks and heart failure. So hypertension is the major cause of stroke, vascular dementia, it causes renal failure, it causes and is very closely associated with atherosclerosis, and therefore associated with aortic aneurysms with ischemic heart disease and also with peripheral vascular disease. I want to highlight something very important before I finish my talk, and that is that when you go to your doctor and your blood pressure is measured, it's very important that blood pressure is measured in the correct way. Because if blood pressure is not measured in the correct way, you may land up with false readings either too high or too low. And the one thing I want to highlight to you is please, if you're in your doctor's clinic and you're having your blood pressure measured, please insist that you are sitting with your back well supported in a chair. Very often, especially in a busy clinic, blood pressure will be measured without good back support. But this can have a very important impact on the true measurement of blood pressure. So I've shared with you why blood pressure hypertension is the number one killer that it behoves us as clinicians to treat patients properly to diagnose patients properly. And of course for the patient him or herself to make sure that they do their part as well by helping in terms of proper lifestyle modifications and adherence to treatment if drugs are prescribed. At the global level, the World Health Organization and many other international associations have as a target. This is the in the US they've come up with the non global targets to be attained by 2025 against a 2010 baseline of blood pressure, such that there will be a relative reduction in premature mortality from cardiovascular disease and reduction in blood pressure elevation. Very importantly, that blood pressure medication and technologies will be made available to the majority of people across the world. And that most people, if not all people should be eligible to receive drug therapy of course in the in in the United Kingdom. This is not a problem. But in some countries, and this is a problem. And, of course, everybody, we would like that they should have access to treatment. So for those of us who are working in the field of hypertension research as clinicians, when we see these patients such as Rousseff felt to present it with his blood pressure 300 over 190 millimeters of mercury have now been enormous efforts for making the world aware of the importance of blood pressure. And in my association with the International Society of hypertension and the World Hypertension League, we now have what we call a World Hypertension Month, which is the month of May, every year. And this is really targeted at making everybody aware of the importance of knowing your blood pressure, if you've got hypertension what to do about it. And of course at the end of the day to try and reduce this terrible global burden associated with hypertension. And with that, I really thank you for your attention. Thank you very much indeed for that very, very clear talk. We'll just have a short break, we and so that people can put their questions in and and then record time for some questions so you can have a short break. Thank you. In 10 minutes, and we'll come back. Hello, Ryan. Thank you. Thanks so much for that talk we have lots of questions. So I'm going to have to lump quite a few of them together. So there's quite a bit of interest in the age effect from different perspectives. Do we see such an increase with age is it a natural phenomenon. The interventions appropriate for people of different ages, you know, for example, exercise in the old might also be in itself damaging. So what do we know about the core that age related increase. Thank you. And thank you for the, those very, very important questions absolutely. So blood pressure normally increases with aging. We know that. We know that the, as I said in women, once women reach menopause, the blood pressure increase becomes very linear. It reaches that of males whereas during life the blood pressure of younger women and younger men, men have higher blood pressure. So we know that there's this sex difference with aging. With respect to blood pressure targets and older ages for a long time. The thinking was that, you know, don't reduce the blood pressure in the elderly, because they won't cope well with the lower blood pressure. In any event we don't have any evidence that in people over the age of 75 or 80 that lowering blood pressure to levels as low as not only 130 over 80 but even 120 over 80. We had very little evidence for a long time to show that that was beneficial. I can tell you that the evidence today is indeed that in the healthy very elderly. What does that mean. That means for the very elderly. And when we talk about the very elderly we usually talk about people over the age of 80 in in a clinical sense or medical sense. For the very elderly 80 to 85 who are active, who are not frail, who don't have other significant co-morbidities, then indeed blood pressure control should be as aggressive as that for younger individuals. So there's much more of a trend now for being more aggressive in treating the healthy elderly or the non frail elderly to pressures similar to that of adults in their 60s or 70s. Okay, there are also a number of questions related to the geographical differences. Some countries seem to have very low levels, others much higher, they didn't look directly related simply as you said to how developed on develop the countries. Well, can we get more insights from that geographical variation. So as I said, you know a number of years ago 1015 years ago, hypertension was something that was a problem in the higher income countries. So why are we seeing so much hypertension now in some places as much as 50, the prevalence is as high as that of 50%. And we're seeing this in sub Saharan Africa in Asia in India, especially in areas of South America. So the number of individuals with high blood pressure is increasing globally and this is something that we can't emphasize enough. So why is this happening. Well, there are a few reasons. Perhaps we're just measuring more, you know, measuring more people these days than what we were before. So that being said, we do know, as I mentioned to you that there are some risk factors associated with the development of hypertension, sedentary lifestyle, high salt diet, obesity. You know, a lot of these low middle income countries, not only is there an increase in hypertension, but there's also an increase in diabetes and obesity and a trend to eating a more westernized diet. So it's the whole package if you like that is probably contributing to this. So as we said, there are some areas from a geographic point of view, where blood pressure hypertension is much lower. For example, in, in Sicily, in, in the southern part of Italy. So the blood pressure, the problems related to hypertension are much less. And we know that from a longevity point of view, these populations can live well into 110 fairly from a fairly healthy standpoint of view. These are populations that tend not to be obese. They tend not to have a high salt highly processed diet. They are populations that tend to eat lots of salads and olive oil and maybe wine and there's something in that perhaps as well. So again, environmental factors are probably playing a role as well. And then there's quite a bit of interest, obviously, in the fact that you said we still really don't know for most people what the cause of their high blood pressure is. Is there for any danger in treating high blood pressure or treating it with these drugs when we don't actually know the cause. Well, basically we're treating the symptoms and we're treating the symptoms, which is the blood pressure. But of course we do know mechanisms, we do know the mechanisms from a physiology or pathophysiology point of view. We know that if we constrict the blood vessels too much, the pressure will go up. If you relax the blood pressure, the blood pressure will, if we relax the blood vessels, the blood pressure will go down. If we change how the heart beats, if we improve the function of the kidneys, for example, these are physiological processes that can be manipulated with very specific drugs and that is what we do. Many of the drugs we use are drugs that will change hormone levels that regulate the blood vessels, for example, but not all patients will respond the same way to all of these drugs. So that is why, as I say, it's not like we can cure hypertension, that we know that the cause of hypertension is this, and if we do that, we can cure it. We have not got to that point yet, unfortunately. And I often wonder whether we ever will because of the multi-factorial and complex nature of what hypertension is all about. There are questions about monitoring your own blood pressure and how accurate are these numerous devices that are available? Is it something that's worth doing even if you don't have high blood pressure or might you get an inaccurate picture by trying to monitor it yourself? Yeah, an excellent question and I can't stress enough how important it is to do home blood pressure monitoring. That being said, one could be very confused, you know, with all the different monitors, devices that are available through Amazon, through the drug stores or wherever. The one thing that is absolutely critical is that if you are going to buy a blood pressure machine, please make sure that it has been validated by the British, British and Irish hypertension society. So these are devices that have gone through a process of validation using very specific criteria, and by and large these devices are pretty accurate. We tend to find that there might be a slight variation between the home blood pressure reading and the office blood pressure reading. But if one takes regular blood pressure readings, one gets a pretty good idea of what the blood pressure levels are. So today I can tell you that the diagnosis of hypertension is being relied much more upon the blood pressure readings of the patient's home readings than that in the clinic. We know that cardiovascular events, as I've just shared with you, are very tightly linked to the blood pressures that patients have at home. So having a high blood pressure using a home monitor is very significant and should be reported to the doctor. And I advocate absolutely that home blood pressure reading is really important, especially as I said, because it's the silent killer. You don't know if you've got high blood pressure unless you measure it. There's also a question about the difference between the systolic and the dystolic pressure. Is that in itself of any significance? Yes, thank you for that very interesting question. When I was a medical student and a young doctor, it was the diastolic blood pressure that we focused on, because we thought that if the diastolic blood pressure was high, it was the diastolic blood pressure that was determining the risk of stroke and heart attack. It's now very clear that it's the systolic, the upper level, the upper value that is primarily linked to a cardiovascular event. We also talk about the pulse pressure, which is the pressure between a systolic and the diastolic pressure, and we know that that too is very, very closely linked to cardiovascular events. In what way, is it good to have a big difference or a small difference? No, no, it's not good to have a big, I mean, it's bad to have a big difference, even if your diastolic blood pressure is lower, the higher the bigger your pulse pressure, the more the chance of an event. And sometimes, as a clinician, it's very hard to treat patients who've got what we call isolated systolic hypertension, because many of the drugs also reduce the diastolic blood pressure, and this can increase your pulse pressure, and it becomes sometimes quite difficult to manage. Coming back to the age difference, do you see an increase in other primates or other ansropoid apes with age? Yeah, that's a really good question. You know, I think that under natural normal circumstances, animals don't develop hypertension unless we give them a Westernized diet. So it's very, or you make them obese in captivity, of course, in research type environments. So blood pressure will change with aging in animals, but what we would define as being hypertension, I guess one would have to do very, you know, careful studies looking at the relationship between what happens to an animal in terms of an event and the blood pressure, but in the natural normal environment, I don't think primates do develop hypertension, and interestingly, one of the most curious animals with respect to blood pressure regulation is the giraffe. Because they've got such a long neck, they need a very, very high blood pressure to get blood to the brain, and they have blood pressures as high as about 250 over 120 millimeters of mercury at the level of their heart. So they've got all special regulatory processes to prevent them from having strokes, etc. Interesting. There's also a question about pulse rate and blood pressure and how are they related to each other? Yes, yes. So I didn't really go into the physics and the physiology of what determines hypertension, but heart rate can influence blood pressure. Usually a higher heart rate or what we call it tachycardia and can cause an increase in blood pressure and this is usually due to the fact that the sympathetic nervous system is very, very activated. And that's usually what it reflects. And so the heart rate can be linked to high blood pressure. High heart rate itself isn't usually a cause of sustained hypertension though. So some questions about salt and both whether the government should be acting more aggressively to control salt intake, but also in another sense, why do we like salt so much? The whole salt story is a very complicated story, let me tell you. It's amazing because as we saw even BC, in the era of BC, the Yellow Emperor's physician already identified salt as being bad for the pulse and bad for the blood vessels. I mean, I think since then we've still been debating how we understand the influence of salt and what we can do about it at a population level. There's very, very clear evidence that high salt intake above a teaspoon of salt a day is not good for blood pressure. What should we be doing about it? I'm a very strong advocate that we should be reducing the amount of salt that is added to foods that are commercially prepared. That the population needs to be very aware of the salt content of foods and we are doing a much better job in terms of salt content with labelling of foods, but still not enough. For example, in some areas, especially in Asia, for example, in China and in Japan, where they use a lot of sources, for example, soy sauce or whatever, they can have as much as 15 grams of salt a day. I think in the UK, people are consuming up to, you know, six per day. The recommendation is 2.5, as I said. So huge efforts need to be made in terms of reducing the amount of salt that is taken in and some countries have done very well. For example, Portugal, there was, and it was at the government level where the policy was that the bakers needed to reduce the amount of salt added to bread. Bread has got a lot of salt, and this has had a very interesting positive impact in blood pressure control in parts of Portugal. So yes, I think we need to be doing much more. However, as I said, it's very complicated, because unless this is mandated at a government level, it's very difficult to institute because the food industry. The food industry does not want to reduce the amount of salt that is in their food products, because salt is a preservative, salt is very addictive. So it makes you want to eat more of the tinned tomatoes or whatever. So there's a huge commercial interest in terms of this, this debate and it is a very big debate, I can tell you. And do we know much about historic salt intakes? You mentioned there that salt was used as a preservative. In cultures where that's still the case or in the past when we had more salty food because salt was used in that way, do we know anything about that? Well, probably, I mean, we know that the lifespan of an adult was about 30 or 40 years ago and maybe and probably they died from strokes or heart attack, probably linked to just supposing to maybe the salt intake. But there's no doubt epidemiological studies tell us in areas where there's lots of salt intake. For example, in Japan, Japan has a very big problem of strokes. And this is linked directly to the salt intake. So there was also a question about France. Why does it do so much better than the UK? Maybe they take in less salt today? Yeah, so there again, similar to what we see in the south of Italy, the hypertension, the wine paradox seems to be quite evident there. Lifestyle, as I said, environment plays a big role. The French tend to drink maybe especially good red wine and we know that the red wine has got these tannins which may have the protective effect on the blood vessels and the heart. They tend not to be obese. So there are a number of environmental factors that probably contribute to the improved blood pressure status in France. The minute you start adding obesity, diabetes, hypercholesterolemia to the package, hypertension immediately gets amplified. And then I'll just squeeze in. We're running out of time. I'll squeeze in one last question about a question that's being asked is, is the high blood pressure paradox in any way related to increasing obesity? Yes, yes, yes, yes. There's a very close link. We call this comorbidities. And we know that in the presence of obesity plus hypertension, the risks are amplified. When I say the risk, I'm always referring to the risk of a cardiovascular event. Absolutely. And the more morbidities or the more diseases that you have together, including diabetes, high cholesterol, the effects are amplified. And unfortunately, what we see today is that most patients don't just come to the clinic with high blood pressure. They've usually got high cholesterol, maybe some diabetes, and they may be overweight. So it's like a package. And the more of these components you have, the worse it is. Well, it's now nine o'clock, Rian. So apologies to still a lot of people listening and apologies for those questions which we haven't been able to answer. But thank you so much, Rian, for such a clear and interesting talk. There are lots of people saying how much they enjoyed it. And although it's a complex topic, you made it, the message is simple, but also your passion for the subject came across very, very, very clearly. So thank you very much. Thank you. Thank you, Pat. Thank you to everybody. And I hope you all have a good evening and stay well. You go and do that and then go and do some exercises.