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Dr. Gellner: We usually think of high blood pressure as an adult problem. But did you know that kids can get it too?

Announcer: Keep your kids healthy and happy. You are now entering the Healthy Kid Zone with Dr. Cindy Kellner on The Scope.

Dr. Gellner: High blood pressure or hypertension is something adults deal with all the time. However, an estimated 3.5% of all kids in the U.S. have it too. It often goes undetected and thus untreated. Sometimes it goes undiagnosed for years and can lead to problems like coronary artery disease in adulthood. To try to identify more about blood pressure issues in children, the American Academy of Pediatrics recently came up with a report to give pediatricians a simple screening table to follow to figure out when a child's blood pressure needs further evaluation.

First, let me explain what blood pressure is. It's actually two separate measurements. The systolic blood pressure is the highest pressure reached in the arteries as the heart pumps blood out to the body. And the diastolic blood pressure is the lower pressure from the arteries when the heart relaxes between beats, so it can take in blood coming back from the body. If either or both measurements are high, that's hypertension.

In kids, it's tricky to diagnose hypertension because the ranges change based on height, age, and if they're a boy or a girl. Also, if a child is in pain or has a fever, it might be high. But we are more concerned about what their blood pressure is when they are healthy. That gives us our best measurement.

We start doing blood pressures when a child is three, usually at their three-year-old well-child visit. If your child's blood pressure is indeed high, we have you come back for a recheck in about a week. If they have high readings for three consecutive visits, that's when red flags start popping up for us pediatricians, and we need to evaluate further.

Most kids don't have any symptoms when their blood pressure is high. For most kids, especially after age seven, more than 50% of hypertension in kids is due to obesity. That rises to 85% to 95% in teens. The treatment for hypertension due to obesity is the same for kids and adults --healthier eating, lower salt diets, and plenty of physical activity.

Usually, if hypertension in child is due to another cause, such as kidney disease or hormone problem, your child will have other symptoms that your pediatrician will be able to pick up on quickly with blood or urine tests. In these cases, your pediatrician will refer your child to a specialist who can manage the underlying cause and that will help manage the hypertension. So, if you have a family history of high blood pressure, or your child is over three and your child's blood pressure isn't taken at the well-child visit, speak up and ask your pediatrician to check it. This isn't something you want to miss.

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Dr. Jones: Most women who were trying to become pregnant and had a miscarriage are eager to try to get pregnant again. What have we learned about how women might prepare for the next try? This is Dr. Kirtly Jones from Obstetrics and Gynecology at University of Utah Health, and this is "The Seven Domains of Women's Health" on The Scope.

Announcer: Covering all aspects of women's health, this is "The Seven Domains of Women's Health" with Dr. Kirtly Jones on The Scope.

Dr. Jones: Early pregnancy loss, miscarriage, is pretty common. Rates vary from 15% to 30% depending on the age of the woman and how early a pregnancy is detected. Certainly, we know that some things are associated with higher rates of early miscarriage, such as age of the mom, especially after 40, and poorly controlled diabetes, for example. However, for young women who had one or two miscarriages, are there any new clues about causes or things women can do to increase the chance that the next pregnancy would be healthy and go to term?

Now, early miscarriage has been the focus of a lot of research in the past 15 years as well as the focus of a lot of cultural myths for thousands of years. We hear from our mothers, sisters, and aunties that we should eat this, don't eat that, do this, don't do that. One recommendation that had been around for about 15 years is that low-dose aspirin, a baby aspirin of 81 milligrams, would increase the chances of pregnancy and decrease the risk of miscarriage.

Several years ago, a large randomized trial done here at the University of Utah and in three other centers around the country looked at over 1,000 young women under 40 who are healthy and had a history of 1 or 2 early miscarriages. These women are randomized with baby aspirin and folic acid, or just folic acid, and their next pregnancies were studied very carefully. Overall, they found that the majority of women had successful pregnancies, about 58%, with the next try whether they took the aspirin or not, and aspirin didn't decrease the chance of miscarriage.

Now, this work was reported in 2014, but there have been some other interesting findings from this study and one that was reported recently. Women in this study were mostly white, often overweight, and the average was 29. The average blood pressure was 111/72. Now, that's a nice average blood pressure for young women. But here's what's new.

For every 10 points increase in the diastolic blood pressure, that's the lower number, there was an increase of 18% in the risk of miscarriage. This means that young women with slightly elevated blood pressure but not a diagnosis of hypertension were increased risk of miscarriage. The study in the journal "Hypertension" found no association of blood pressure with the ability to get pregnant or the rate to get pregnant. They controlled for smoking, body mass index, marital status, education, and other factors that are known to be independently related to miscarriage. And that means that the blood pressure alone or with other factors that they couldn't measure is associated with an increased risk of miscarriage.

Now, we know that hypertension before pregnancy is associated with a number of various very serious problems in pregnancy including still birth, pre-eclampsia, pre-term birth, and placental abruption where the placenta prematurely separates from the uterus before the birth of the baby. This finding that even what we might call pre-hypertension, just a medium elevation of blood pressure in young women, is associated with miscarriage is important. So what's the takeaway from this?

First of all, all pregnancy should be started with women in their best emotional, physical, social, and financial health. If you're thinking about getting pregnant, stopping smoking and maintaining a healthy weight are important because both of these conditions are associated with miscarriage, smoking, and being overweight. And if you can get your blood pressure checked before you get pregnant and if the lower number is between 70 and 80, you might consider increasing your exercise, being mindful to manage your stress, and consider a diet lower in salt and higher in vegetables and healthy fats, kind of that Mediterranean diet thing that we've talked a lot on The Scope a lot.

No matter what happens in your pregnancy, these changes are good for your current and long-term health. Of course, if you are hypertensive, with the lower number over 80, you should get your blood pressure under control before pregnancy with diet and exercise, or with medication. This is really important not just for you, but for the new person you hope to grow. And thanks for joining us on The Scope.

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Interviewer: Lowering blood pressure below current guidelines can have a big impact on the health of people with high-risk hypertension. I'm talking with Dr. Brandon Bellows and Dr. Natalia Ruiz-Negron, from the College of Pharmacy at University of Utah Health. What is the problem with high blood pressure?

Dr. Bellows: Yeah, so high blood pressure is a major risk factor for cardiovascular diseases, and as blood pressure increases, there's a strong increased risk for having cardiovascular disease events, so things like heart attacks and strokes.

Interviewer: Over the past few years there has been a milestone study that suggests that tweaking that a little bit can have a high impact.

Dr. Bellows: Yes. So in the last, I guess this is about two years ago, the SPRINT study, the systolic blood pressure intervention trial, came out and it was looking at different systolic pressure goals. So historically guidelines have recommended that most adults target a systolic blood pressure of less than 140. So when you get your blood pressure taken, that's the top number. This study was looking at inpatients who were at higher risk for heart attacks and strokes, targeting a lower blood pressure goal of less than 120. And they found that there was a significant reduction in the risk of cardiovascular disease events as well as mortality with the more intensive goal.

Interviewer: They have results from the short-term study that lasted, what, two and a half years?

Dr. Ruiz-Negron: It was meant to be extended out till five years, but because they did see such a favorable outcome, then they stopped it about halfway through.

Interviewer: But what wasn't known is the long-term effects?

Dr. Ruiz-Negron: Yes. That is correct. So that's where kind of modeling studies can come in. Using the short-term effects that we see, we can try and incorporate that into a model that will try to evaluate what that long-term effect may be out till really whatever time frame we want to look at, say 10 years, or in the case of an older adult, the lifetime just because of their age.

Interviewer: When you looked at these longer-term outcomes through your computer modeling, I mean, what were some of the things that you found?

Dr. Bellows: Because of the extrapolating, three to five year data out for a lifetime has a lot of uncertainty around it. We looked at different scenarios of what may happen to patients. Do they continue taking their medication, do they stop taking their medications, and so on. But what we found is regardless of whether or not patients continued to be adherent after the five year period that SPRINT looked at, that intensive blood pressure control, the less than 120 goal, cost more but it increased survival of these patients and it did so at a value that society is generally willing to pay to increase life.

Interviewer: So Natalia, help me understand what some of these different scenarios can look like. I mean, what are some of the things that might happen to somebody if they take their medication or if they don't?

Dr. Ruiz-Negron: To give you an example, say after five years this person may stop taking their medication and one of the big things that we say in pharmacy is if we don't take the medication, then you don't achieve the blood pressures. So that's really important, and so if you don't achieve that less than 120 blood pressure, then the benefits of the systolic blood pressure target would go away.

So then during the first five years, the person had really good chances of lowering their risk of experiencing these complications, but then after the five years, because they stopped taking their medications, then that lowered risk would go away. So the lower risk could be just lower risk of experiencing a heart attack or a lower risk of experiencing a stroke event in the long run.

Interviewer: Yeah. I mean, one thing I wanted to mention is that there were incredible number of variables that went into your different models because there's a lot of variability to real life. Right? So I mean, what were some of these other things that were factored into your modeling, and how did you go about figuring out what you should put in there and what you leave out?

Dr. Bellows: Yeah, that is a great question. So we had lots of different variables. So there are lots of things that contribute to cardiovascular disease risk and so we tried to capture the most important ones. So some of them in terms of the population characteristics were derived from the SPRINT trial. So we modeled a population of patients that looked like those in the SPRINT trial. So we got their cholesterol values, their kidney function, their blood pressures, all of that came from SPRINT.

The other thing that we do with modeling is that we grab variables from lots of different sources, so published literature, large med analyses that are synthesis of lots of different randomized controlled trials. So we pulled together all of these variables from one source or another, and what we did is we consulted with physicians who treat patients with hypertension to figure out what are the most important things to include in this model to try and predict their cardiovascular disease risk. And so after doing that, we constructed a model that we felt like it's not completely accurate. It's a simplification of reality, but it covers the major complications and major risk factors that patients might have.

Interviewer: What can we do with this information? Now that you know that it looks like the benefits outweigh the risks, what's next?

Dr. Ruiz-Negron: That's a great question. So what we can do with this now, now that we know that intensive blood pressure is a cost-effective alternative for a specific subset of patients, we can try to figure out how to best implement it in different settings. So there's outpatient settings that we can try and evaluate. There's also within the hospital systems what something like that might look like. And so those are things that we're trying to work on next. Potentially developing some sort of tool to identify those patients that would benefit the most from this intervention and then kind of moving forward with that tool in order to implement it in these settings so that we can deliver the best care possible.

Dr. Bellows: Other things that we're doing are looking at how do we actually implement this in health care systems as they exist now. Do we need to hire more pharmacists and nurses, or do we need to buy more blood pressure monitoring devices? Do we need to send home blood pressure devices with patients? So we're looking also at the cost effectiveness of implementing this in health care delivery systems, both here locally as well as nationally.

Announcer: Interesting, informative and all in the name of better health. This is The Scope Health Sciences Radio.

Announcer: Is it bad enough to go to the Emergency Room, or isn't it? You're listening to "ER or Not?" on The Scope.

Interviewer: All right. Here, you get to play along with "ER or Not?" Today's scenario that we're going to run by Dr. Troy Madsen, who's an Emergency Room physician at University of Utah Health, is higher than normal blood pressure. So here's what happened. It's an individual, has one of those blood pressure cuffs at home, for whatever reason, routinely monitors their blood pressure, and one day gets a reading of about 160 over 100. ER or not?

Dr. Madsen: So, first, let me clarify this by saying, high blood pressure, absolutely, go see your doctor. But in this kind of scenario, if you're not having any other symptoms, and again, emphasizing that, no other symptoms, you don't need to go to the ER. We very often will see people in the ER who come in with exactly this sort of thing that happens. They have a blood pressure cuff at home, or they go to the grocery store and check their blood pressure, and it's, say, 160 over 100, or 180 over 110.

Interviewer: And, as a reminder, what's normal?

Dr. Madsen: So, you know, a normal blood pressure would be, say, 120 over 80.

Interviewer: All right.

Dr. Madsen: Or something within that range. You know, most people, healthy people, are going to have something around there.

Dr. Madsen: So, you know, they'll rush right into the ER, thinking, "Wow, if I don't get in right now, I'm going to have a stroke, or something really bad is going to happen." Oftentimes, you know, we'll check some tests on them, make sure things are okay, but quite honestly, a lot of those tests we're doing, primarily, because they're in the ER and we want to say, "Hey, we're offering something. We're going to make sure this stuff's okay."

But unless you're having some symptoms with that, let's say:

• chest pain
• confusion
• stroke-like symptoms (arm weakness, numbness, trouble speaking)

Interviewer: All right. And what would you do then, at that point, because that still can be very concerning to people.

Dr. Madsen: Absolutely, and it can be, you know, often, in those scenarios, when someone gets that high blood pressure, what I'll do is just let them relax in the room, turn the lights down, come back in 30 minutes, we'll recheck their blood pressure, and it's, let's say, it went from 180 down to 150 or 140, I'd say 90% of the time, that's what happens. So if this happens to you and you don't have any other symptoms with it, it's just, it's really not a reason to have to rush into the ER where you're going to have to wait in the waiting room forever, sit in a room, maybe get some tests done, sit around for several hours, and then, at the end of it all, we say, "Go follow up with your doctor."

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updated: September 7, 2018
originally published: August 28, 2017

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Interviewer: The current medical guidelines for systolic blood pressure are between 140 to 150 but new research indicates that reducing that to 120 can drastically reduce the chance of heart disease and death for adults 75 or older even if they are considered frail elderly. Dr. Mark Supiano is a geriatrician and the executive director of the University of Utah Center on Aging. This study, is this a new revelation that lower could be better with systolic blood pressure especially for elderly adults?

Dr. Supiano: Yes, Scott. This is exciting new information that came out of the systolic blood pressure intervention trial otherwise known as SPRINT. The trial ended late in 2015, earlier than anticipated because of these very dramatic benefits.

Interviewer: When it initially ended early, a lot of people speculated that that meant bad news but it actually meant quite the opposite.

Dr. Supiano: Yes and particularly for the 28% of the SPRINT subjects who are over the age of 75 there were some concerns, myself and other geriatricians, that the very intensive systolic blood pressure target of 120 might not be safe for older people. When we first got news of the trial ending early I first thought that it was possible that older people had more side effects or more injurious falls or other complications of the very low blood pressure and that was why the data safety monitoring board might have ended the study early. In fact, the results were just the opposite.

Interviewer: Like a revelation almost it seems like.

Dr. Supiano: It really was a surprise to be honest. Not so much as a surprise that the benefit but the surprise that the benefit was of this magnitude and that this occurred this early on on the trial.

Interviewer: So the current guidelines are between 140-150. This study points out that 120 can drastically reduce the chance of heart disease and death. How drastic are we talking?

Dr. Supiano: I'll focus on the population 75 and older as I said, this is 28% of the SPRINT cohort and in that group there was a 33% reduction in the cardiovascular outcomes. This is primarily a myocardial infarction or heart attack or congestive heart failure and stroke and then in addition overall reduction of 32% in mortality.

Interviewer: That's pretty substantial.

Dr. Supiano: It is. To be honest there are very few treatments I can recommend for people over the age 75 that can have this dramatic impact on those outcomes.

Interviewer: So if you're going to do one thing, according to the study so far, it would be try to get that blood pressure down to 120. Now, does that mean taking medication? Does that mean lifestyle changes?

Dr. Supiano: All of the above. On average, the people in the intensive group who are managed to a blood pressure of 120 or taking one additional anti-hyperintensive medication relative to people on the standard arm.

Interviewer: Of course your eyes looking at the risk benefits and something like this. So the benefits are tremendous. Are there risks?

Dr. Supiano: Absolutely. The good news was, and again focusing on those 75 and older population, our major concern would have been there were higher rates of injurious falls or what's called orthostatic blood pressure - a reduction of blood pressure when the people first stand up and get light headed or dizzy. First, there was no increase in serious adverse events between the intensive and the standard arm. Second, and again very reassuring, there was no high rate injurious falls in the intensive group, nor were there serious rates in the intensive group. The intensive group did have higher rates of low blood pressure, of electrolyte abnormalities, largely low sodium levels which was to be expected because of the medications that were used and some other adverse events. But when we weigh though over the benefit of preventing heart attack, stroke, heart failure and death, most believe that those benefits outweigh those risks.

Interviewer: That number of 120, can you go lower than that and get more benefits or is there a point where no?

Dr. Supiano: That would be another study. And it's important to point out the one on average for 75 and older group achieve of systolic blood pressure of just under 122. That meant that half the people had a systolic blood pressure above 122. So 120 maybe recommended as a target blood pressure. That doesn't mean everyone is going to get there. Nor does it mean that the benefit won't accrue if you don't get exactly to that target. I think the take home message is, it seems to be that the lower, the better.

Interviewer: So is this something that if somebody does fall under this group or somebody has a grandparent or parent that's in this group that you would recommend that they go to their doctor and say, "I would like to try for a blood pressure of 120"? Because this isn't the guideline yet.

Dr. Supiano: So important point, the guidelines are being written down or likely incorporate this new information but those guidelines won't be out until later this summer. Even with that guideline, like everything we do in medicine and particularly in geriatric medicine we have to be patient-centric. So we need to weigh someone's benefits and risk of their elevated blood pressure and incorporate that those at greater risk are likely to have greater benefit. So it needs to be an informed decision with patient who discussed the pros and cons and determine their level of interest in trying to achieve this lower target and recognize those benefits.

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Interviewer: What are the symptoms of HHT and what should you do about it? We'll talk about that next on The Scope.

Announcer: Health tips, medical news, research and more for a happier, healthier life. From University of Utah Health Sciences, this is The Scope.

Interviewer: Nine out of 10 people with the genetic disorder HHT are still undiagnosed. What makes it so difficult is it can have multiple and seemingly unrelated symptoms. If not treated properly, it can have dire consequences. Jamie McDonald is a licensed genetic counselor and Co-Director of the HHT Center of Excellence at University Utah Health Care. I'm not going to attempt to say it. I'd like you to say it and maybe I'll try afterward. What does HHT stand for?

Jamie: It stands for hereditary hemorrhagic telangiectasia. Hereditary, of course, means it runs in families. Hemorrhagic means that it is associated with bleeding. And the word "telangiectasia" that indeed, one has to hear about 50 times to be able to say, refers to a very specific type of blood vessel abnormality. It is, in particular, a blood vessel that is abnormal because an artery is directly connected to a vein rather than connected via a capillary network, which is the normal thing.

Interviewer: And different places, different people have it in different places and different quantities of them? Some people might have a few, some people might have a lot?

Jamie: Exactly. That is the case that there is huge variability and surprising to even many physicians that don't see a lot of this disorder, it's variable even within the same family. So it would be reasonable to expect that if a parent had certain manifestations of this disorder or a certain severity of different manifestations, then maybe it would be likely that their child would as well. It's absolutely not the case. It's very variable from person to person, even within the same family.

Interviewer: And it is a genetic issue, as we've established before so it's hereditary. Why are we just now hearing about it?

Jamie: The fact that 1 in 5000 people are affected rather than the frequency with which people have diabetes or congestive heart failure has decreased the chance that people are going to become aware of it.

Interviewer: So it's something that affects even 1 in 5000 doesn't sound like a lot, it can turn out to be quite a few.

Jamie: Absolutely. And those of us that see many HHT families and sort of collect them, if you will, because we focus on this disorder, feel that 1 in 5000 probably is a significant underrepresentation. When I see families and take a three to four generation family history, as I do, all of a sudden, after having asked the right questions about those family members, I have in front of me on my family tree a pedigree of five people in my patient's family that clearly have HHT but haven't been diagnosed because the pieces of the puzzle haven't been put together.

Interviewer: Let's talk about some of those pieces. What are some of the symptoms that people might have? I've heard nosebleeds commonly referred to. Is that one of the main ones?

Jamie: Absolutely. It is the main one. About 95% of people with HHT will have recurring nosebleeds by the time they're adults, say, 40 years of age. But recurring may mean one every two weeks or it may mean two an hour. So it's extremely variable and you can imagine that if somebody has one nosebleed every two weeks that stops in a minute's time, they may not have even reported that to their physician. So it's the cardinal, most common feature, but not the feature we're most worried about.
The features we're most worried about are the larger, abnormal blood vessels we call AVMs or arterial venous malformations, that can occur in the lung and the brain and liver and lay hidden unless you go looking for the because you've been tipped off that they might be there based on the person's history and family history of nosebleeds. And then, the second thing that can actually be seen on the outside of the body, before we start doing fancy imaging tests to look inside the body, are little tiny telangiectasias or what show up as red spots on the hands, mouth, face of the body.

Interviewer: And are those red spots there all the time?

Jamie: They're there all the time. They don't come and go like a rash would, for example. They're there all the time. Although, people tend to develop more of then with age. At birth, a baby that's born with HHT, for example, because, after all, it's hereditary, a baby gets HHT by inheriting it from a mom or dad. So it's there at birth in some fashion or another. But, usually, the telangiectasias on the skin don't show up until adulthood.

So one of our key concerns as we work our way through families where many people aren't diagnosed yet is people will develop an AVM in their brain in this disorder, usually, years before they actually develop the nosebleeds and red spots on the outside. So the underlying features of HHT that we're most concerned about don't jump out at doctors when they see these patients in their clinics.

Interviewer: The symptoms might not show up so what are some of the damages of this?

Jamie: The significant damage is the baby that has a brain bleed or brain hemorrhage from a ruptured AVM at three years of age before they've had a chance to develop the nosebleeds that begin at average age 11, 12 or red spots on the outside on the skin, which develop average age 20s or 30s. The brain bleed can occur in a young child from an AVM in the brain or a 30-year-old can have a stroke or a brain abscess due to a lung AVM. The blood isn't being filtered out of clots each time it circulates the body and passes through the lungs.

If blood goes through an AVM in the lung and the clot isn't filtered out and that blood then goes to the brain, it's a stroke. So strokes, both of hemorrhagic nature and of a clot blocking off a blood vessel nature, are both risk factors for people with HHT that haven't ben appropriately diagnosed and screened.

Interviewer: So what do you do? How do you find out if you have it if you're not showing the symptoms of the nosebleeds? I guess, first of all, if you have fairly consistent nosebleeds, you probably should go do a little bit more research on that and see if you have HHT.

Jamie: Absolutely.

Interviewer: I could have it and not know it, right?

Jamie: Absolutely. The key there is once HHT is identified in a family in someone old enough to have the nosebleeds and the red spots on the skin and/or brain hemorrhage that leads to the diagnosis, to not let the evaluation stop there. When we have a patient come to our clinic and say it's a 50-year-old mother and grandmother, and we make the diagnosis of HHT, there's an evaluation we're going to do for her to make sure she doesn't have one of these hidden time bomb AVMs inside an internal organ. But, from our perspective, the whole family has become our patient. We're going to talk to her about her kids, her grandkids and what they should have in the way of testing.

At this point, thankfully, genetic testing for HHT is available. I can draw a blood sample on that 50-year-old mother/grandmother we just diagnosed with HHT and prove in her down at the genetic level what's causing her HHT, exactly which gene and which mutation in which gene is causing her HHT. Because it's different in each family with this disorder. But once I've pinpointed that in one member of the family, I know that anybody in that family that inherited the HHT will have that exact same mutation. So I can now test her kids and grandkids.

Interviewer: So the key is to think, "Huh, did Uncle Al have regular nosebleeds all the time? He did and he always complained about them. Hmm."

Jamie: Exactly. Exactly.

Interviewer: All right.

Jamie: But again, these are pieces of the puzzle that had to be put together in order to come up with a diagnosis. Often times, it requires looking at the whole family, not jus the individual in front of you.

Interviewer: Most of your patients, do they figure this out on their own or they have a doctor help them?

Jamie: It's a combination. Oftentimes, an astute physician suspects it originally, oftentimes in a member of the gamily that has a particular number of manifestations and then after having had that diagnosis floated to the patient by a primary care doc, the patient gets on the Internet, finds out that there actually are specialty centers and specialty clinics for this rare disorder and makes their way to either us or one of the other specialty centers.

Interviewer: That sounds like if you think you might have it, the next step for most people is to find the specialty center, like here at University of Utah Health Care. If somebody's looking for more information about HHT, do you have a resource that you recommend to somebody?

Jamie: Absolutely. There's a national group called CureHHT, formerly known as the HHT Foundation, that is a resource for patients and physicians alike, including a list of HHT centers of excellence nationally.

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Jamie:

Interviewer:

Interviewer: A new drug to combat viral infections may have been hidden in plain sight. Up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs, The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Sankar Swaminathan, Chief of Infectious Disease at University of Utah Health Care. Dr. Swaminathan, you just published some interesting findings in the proceedings of the National Academies of Sciences. What did you find? How did that get started?

Dr. Swaminathan: Most people are familiar with mononucleosis or mono that Epstein-Barr virus causes. Epstein-Barr virus is also referred to as EBV. Not only this EBV caused mono, but it also in a small number of people can lead to various types of malignancies or cancers.

So the most common malignancies that are associated with EBV are Burkitt lymphoma, which is a type of malignancy at the lymphocytes. And there's also a tumor that occurs mostly in Southern China and other parts of the world called nasopharyngeal carcinoma, which is a cancer of the nose and throat. And these had been associated with EBV.

So we're very interested in studying EVB and its association with cancer. Almost all of us are infected with EBV and it's asymptomatic that is without any known symptoms. But yet in a small percentage of people, it can cause disease that's quite serious in later life.

When we started working on this project to look at compounds that could inhibit EBV replication, we didn't originally start out to look for pharmaceutical antivirals really. What we set out initially to do was to see if we could find compounds that would inhibit one particular protein that's made by EBV and this protein is called SM protein. And we've been interested in the mechanism of action, the basic research and to the function of this protein for many years.

And one of the reasons that we've been interested in this protein is that all herpes viruses whether it's herpes simplex virus or chicken pox virus, they all express a similar protein and this family of proteins is critical for virus replication. We're very interested in this essential protein and learning how it works. And so we devised an assay to look for small molecules that can inhibit the function of this protein.

Interviewer: What did you find when you did that assay?

Dr. Swaminathan: When we first started doing this assay, we had only screened a few hundred compounds. When one particular compound, in this so-called library of compounds, very clearly showed up as inhibiting the function of the SM protein. And then we tried it on cells that were actually infected with the virus and we were very gratified to find that as one might predict, those viruses could no longer replicate because they really need that SM protein to replicate.

Interviewer: So you found a drug that could work to reduce infection by Epstein-Barr virus. And what was surprising about this compound? What was it?

Dr. Swaminathan: And I'm still surprised, by in a way, because this is a drug that's been in used for 50 years and it's primarily used to increase loss of water. So it's a diuretic really and it also has effects on the heart. So it's used on people with heart failure and who have liver failure, who have abnormal fluid retention, and it causes to increase loss of free water from the body.

During all this time, nobody had ever thought to that it might have other functions like this instance, really serendipitous that we made this finding. And I think we have preliminary evidence that not only does it work on SM protein of EBV, but that it may work on other herpes viruses. So we're now actively trying to see, in fact, it's working on those similar proteins and those other viruses.

Interviewer: And what is this drug called?

Dr. Swaminathan: It's called spironolactone.

Interviewer: And so you wouldn't want to use spironolactone right now as an antiviral?

Dr. Swaminathan: No, because it is a potent diuretic and heart failure drug and has hormonal effect. So and those hormonal effects are somewhat of an undesirable side effect for use in heart failure patients, for example.

The interesting thing is that there are other very similar compounds, one of which is also used in patients. Those very similar compounds that have this diuretic function do not have the antiviral function at all from what we can tell. So that really makes us think that we can separate those two functions. We're actively working with chemists here at the University of Utah to try to make some of those derivatives and test them to see if we can separate the antiviral effect from the known effects of spironolactone.

Interviewer: So your hope is to modify this existing drug so that it only works as an antiviral and hopefully one that works against that entire class of herpes viruses. Is that right?

Dr. Swaminathan: That's exactly right. And this target is different from the current target of available drugs. Although available drugs against herpes viruses currently are directed against replication of the DNA or genetic material of these viruses. What that means is that it's one class of drugs. When you get resistance, you often have resistance to many of the drugs in the class. So we're somewhat limited once we get into problems with resistance or toxicity with this class of drugs. And so I think it would be a significant advance particularly for CMV to have another set of tools as far as fighting this virus or virus infections.

Interviewer: Is there a particular reason why doctors or patients might be excited about a new drug like this coming aboard eventually?

Dr. Swaminathan: This is all speculation, any time you have a limited or a moratorium against the particular infection or infections, it's important to try to have additional drugs. And I think another potential exciting possibility to my mind is that there's a possibility of synergy. When you have drugs that are directed against two different targets, you can help prevent the emergence of resistance, you can potentially get synergistic killing. So these are all reasons that it will be good to have additional drugs.

Sometimes you have drug intolerance or allergies. These are again why it's important to have additional tools in suppressing viral's replication.

Interviewer: I have another question that's kind of show my naÔvetÈ. When I think of medications that are used to treat infections, they're usually antibacterial medications. Do we use antiviral medications as often? If someone were to come down with mono, do we typically give them antiviral medication?

Dr. Swaminathan: That's actually not a naÔve questions. It's a very good question. The reason I think that we don't use a lot as many antivirals as antibiotic is number one, we just don't have very many effective antivirals. If I could give you an antiviral drug that would cut your cold symptoms in half or even by a third, most people would jump at the chance to take it. Now we do have some antivirals that are effective against influenza. They're not as superbly effective as perhaps we would like.

The reason that people have actually tried antivirals, available ones, for mono. The problem with mono is by the time you have symptoms, it's actually a couple of weeks after you are infected, and I think it's a dollar short and a day late. And as you know it's transmitted by saliva. It's called the kissing disease and I think it would be very hard to do at trial where you gave teenagers a drug before they kiss someone.

Interviewer: Yes. So the drug that you would be developing would probably be reserved mostly for these special situations from compromised patients, for example, where it's life threatening or . . .?

Dr. Swaminathan: Well, one of the other areas where it's commonly used actually is in drugs that are active against herpes simplex virus. Valacyclovir is one. It's used every day by people who have frequent recurrences or outbreaks of genital herpes or cold sores on their lip. So these people take Valtrex every day and this helps to decrease the incidence of symptomatic recurrences.

Interviewer: So what are your goals going forward with this project?

Dr. Swaminathan: So we would like, like I said, to make those derivatives that will not have adverse side effects due to spironolactone's known properties, we would like to . . . assuming we do manage to develop these derivatives that are strictly antiviral or preferably antiviral. Excitingly in vitro anyway, in the test tube in the laboratory, we find that spironolactone is as effective as some of the currently available drugs against EBV.

So if we can make a derivative that we think might be clinically useful, then we would hope that we could advance that into preclinical testing with the goal of getting it into a patient's trial.

And while that's not the business that we're in, it really I think is incredibly gratifying when there's some possibility that in your lifetime, you could see something that you've been working on in a laboratory actually make it to patient care.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.

Interviewer: Clinical guidance statements on treatment of blood clots or venous thromboembolism, up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Dan Witt, Clinical Professor of Pharmacotherapy at the University of Utah. He's one of a group of leading experts assembled by the Anticoagulation Forum to generate a series of clinical guidance statements on treatment of blood clots or venous thromboembolism. Doctor Witt, why now?

Dr. Witt: So the Anticoagulation Forum is a professional organization that is comprised mostly of front-lying anticoagulation providers. So these would be pharmacists, nurses, nurse practitioners, physician's assistants and physicians who spend most of their time working with patients who are taking blood-thinning medications or anticoagulants for treatment or prevention of blood clots.

The Anticoagulation Forum was interested in producing this document for a couple of reasons. One is that there have traditionally been guidelines produced by a group called the American College of Chest Physicians. Recently, it was rumored that maybe those weren't going to be coming out on such a regular basis. So one attempt was to try to fill a void that was going to be created by not having the regular release of these guidelines coming out.

The second one was that the evidence-based guidelines, like the American College of Chest Physicians puts out, sometimes don't resonate with frontline providers as much because they are so heavily based on what the evidence says that sometimes they can't make concrete statements about things that providers caring for patients really wonder about. So there has to blend of sort of expert advice that isn't necessarily backed up 100% by the evidence and also relying on evidence as well.

So what the Anticoagulation Forum was trying to do is provide a series of documents that really capitalized on the expertise of the people that were writing the chapters, but at the same time keeping at least one foot in that evidence-based medicine realm.

Interviewer: On the first hearing, it might sound like giving advice that is not based on evidence might sound a little scary. But you gave me an example that illustrates that idea very well.

Dr. Witt: Yeah, so one example of that was that when patients begin taking these blood-thinning medications, they have dramatic effects on their lifestyle. For some of the medicines, even the food that they eat can interact with these medicines and they have to be careful of the activities that they're engaging in. There are just a lot that you have to be aware of.

And so providing a lot of education up front is something that anticoagulation providers just do as a course of business. The evidence-based guidelines went out and tried to find evidence, studies in the literature, that would back that up and say, "Well, education improved outcomes. So reduced the risk of bleed, reduced the risk of blood clots, reduced the risk of death."

And you can imagine that those kinds of studies would be very difficult to do. So there wasn't any "evidence" to substantiate that. And so the guideline committee is then sort of faced with this decision to say either nothing or to accurately say what the evidence says, that there is no evidence to support that this is beneficial. So you really can't make a recommendation and say, "We don't recommend that you educate your patients about that."

And so it's situations like that where it makes sense that a course of action would be warranted, but you can't back it up with "evidence."

Interviewer: Right, and also based on the collective experience of your experts, you can make some of those recommendations.

Dr. Witt: Absolutely.

Interviewer: It seems like these statements, a lot of them are just centered on very practical situations. "This is what I see with my patient. How do I go about evaluating what to do next?"

Dr. Witt: That is right. Each of the panels as they got together, they first came up with a list of about 10 or so questions that they felt like, "Well, here are the common things that we see coming up when we're managing patients." And so then, they worked off of that list of questions to design the guidance statements. So I think it was a real practical, everyday sort of helpful way to approach the recommendations.

Interviewer: And maybe a little different than what's been done before?

Dr. Witt: Yeah, I think it is. We just learned also that the American College of Chest Physicians has published some updated guidelines on venous thromboembolism and those are extremely helpful. But I think the Anticoagulation Forum's documents stand on their own as well because they take a slightly different take on it. And I think that using the two documents complementary together can really provide clinicians with the information that they need to know to take good care of the patients.

Interviewer: You know, it seems like one of the things that are changing in managing venous thromboembolism is the treatment. Is that part of what these guidelines are about?

Dr. Witt: Yeah, that's a great question. And up until 2012, there was really only one option for the long-term treatment of venous thromboembolism, an oral medication, and that was warfarin or Coumadin.

And warfarin is sort of an interesting drug. It got its start as rat poison. And so many people still know it was used as rat poison and as they begin to take it, they'll often ask you, "Well, what is this medicine that I'm taking?"

Well, it's a very effective medicine, but it's a difficult medicine to manage because the dose is different for every patient. And then, Warfarin can be affected by hundreds and hundreds of different drugs. The food that you eat in your diet can affect how the drug works. And so, it really needs to be managed carefully.

And so, in 2012, the first of a series of new drugs called direct oral anticoagulants came out that produce the same effect of warfarin but don't require the same type of intensive monitoring that is required with warfarin therapy.

And so practitioners are now trying to figure out, "Well, how do I incorporate these new treatment options into the management of the patients that I'm seeing with venous thromboembolism?" And that was one of the things that these guideline statements were really intended to address.

Interviewer: And so what is your hope in getting this information out there?

Dr. Witt: My hope, and I think the hope of the people who were behind this project, is to get information that's practical and usable at the bedside into the hands of the people that are taking care of these patients. We tried to make it so that it was easier to read. The information is written in a very straightforward manner. We tried to summarize all the recommendations so that they're easy to find. Our hope is that it just elevates the care that patients that are requiring these medications would receive. And that will, in turn, lead to better outcomes.

Interviewer: Where should someone go to find out more?

Dr. Witt: One of the things that I think is great about these guidelines is they have been published in the Journal of Thrombosis and Thrombolysis and they are open access. So if you go to the journal's web page, you can actually click on the journal edition and any of those articles can be accessed and downloaded for free.

Announcer: Interesting, informative and all in the name of better health. This is The Scope Health Sciences Radio.

Scot: New guidelines are out when to treat high blood pressure. The recommendations may surprise you. We'll explore that next on The Scope. Medical news, and research from University of Utah physicians, and specialists you can use for a happier, and healthier life. You're listening to The Scope.

We're with, Dr. Tom Miller, from the University of Utah Hospital. Dr. Tom, I understand that there are new guidelines for treatment of high blood pressure. What's going on?

Dr. Tom Miller: Hi I'm Dr. Tom Miller, general internal medicine at the University of Utah and today I'm going to tell you about the benefits of measuring your blood pressure and that you don't have to go to the doctor's office every time to get our blood pressure measured. That's coming up today on The Scope.

Announcer: Medical news and research from University of Utah physicians and specialists you can use for a happier and healthier life. You're listening to The Scope.

Dr. Tom Miller: High blood pressure is still the major risk factor for heart attacks, strokes and kidney failure. Sometimes you go to your doctor's office and your blood pressure is elevated, but it doesn't mean that you have high blood pressure. The best way to check that is in a normal environment at home.

You've probably seen home blood pressure monitors available at your stores. By measuring your blood pressure you can find out, one, is your blood pressure elevated. Two, if you've had a measurement of high blood pressure at the doctor's office, you can confirm this by taking home blood pressure measurements, and third, it will help you track your blood pressure if you need treatment.

Basically one needs to learn how to take a blood pressure at home, you don't want to be checking your blood pressure after you exercise or if you've just had a big meal, or if you're running about and you're anxious.

The great news is that these monitors are now easy to use and you don't have to wear a stethoscope like the nurse used to do in the doctor's office, because that's way too difficult. There are digital readouts and from anywhere from $80-$150 you can buy a machine that is accurate and that will measure your blood pressure and either record it for you or you can write the numbers down and then send those back to your doctor is you like.

Once you purchase the cuff, I'm suggesting you go to the website www.hypertension.ca, this is a Canadian site and you can find a video on how to measure you blood pressure accurately. Basically it requires that you sit resting, feet on the floor for 5 minutes and arm at heart level on a table, no talking, take three measurements, you do this twice a day for 3 days.

You average the measurements each time and if your blood pressure is greater on average than 130 systolic and 80 diastolic, you're going to want to talk to your physician about what to do next.

The other part of this is if your physician has told you that your blood pressure is elevated, that doesn't actually mean that you have high blood pressure. It could be that you're just anxious, even though you don't realize it, when you go into the doctors' offices, probably 20% of people are, getting you a falsely elevated pressure.

Best to know if you truly have hypertension and need to take medications by double checking this at home with your new blood pressure monitor, and you can use the monitor on other family members.

You want to purchase an arm blood pressure cuff because wrists and finger blood pressure cuffs are not always accurate, so you stick to the ones that measure the arm. One size fits most people but for people with large arms, greater than 13" in diameter, you will need to ask for and purchase a large blood pressure cuff, and they also make pediatric cuffs for kids, although you may not need to measure blood pressure in children very often.

The other point is that you can check your blood pressure cuff for accuracy at your physician's office, now most of these cuffs, as I've said, have been quality controlled by engineering groups, but the best thing is to take that cuff in and have your physician measure it against his cuff, and then you'll know that yours is reading true and you'll be able to access your blood pressure at home and know that you'll be getting a correct reading.

Hypertension is the silent killer so it's best that you know what your blood pressure is so that you can do something about it. Most people know their own weight; I would say that most people should know their blood pressure.

Announcer: We're your daily dose of science, conversation, medicine. This is The Scope, University of Utah Health Sciences Radio.