Henry R. Black, MD; William B. White, MD

Disclosures

May 18, 2010

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Henry R. Black, MD: Hi, I'm Dr. Henry Black. I am immediate past President of the American Society of Hypertension. I'm a Clinical Professor of Medicine at the New York University School of Medicine and a member of the Center for the Prevention of Cardiovascular Disease.

We're talking to you today from the 25th Annual Meeting of the American Society of Hypertension (ASH) in New York City. I'm here with my former colleague, friend, and President-Elect of the American Society of Hypertension, Dr. William White, who is a Professor of Medicine and Head of Clinical Pharmacology and Hypertension at the UConn [University of Connecticut] Medical School.

Bill has been one of the innovators in ambulatory blood pressure monitoring and even edits a journal called Blood Pressure Monitoring, which has been present for about 15 years now.

William B. White, MD: Yes.

Dr. Black: And an excellent resource for those of us interested in this, and I want to ask him a few things. What do you think the place of ABPM [ambulatory blood pressure monitoring] is now?

Dr. White: Well, for hypertension specialists it's a very important tool. I think that somebody asked me just yesterday here at the meeting, Henry, "How often do we use it? When do we use it?" I find myself monitoring somebody probably in 50%-60% of our patient practice and not over and over again --probably once every few years depending on what the problem is. For the primary care physician who might be listening, ambulatory monitoring is a very useful tool in probably 1 out of 10 of their patients with hypertension -- when they can't figure out what the real control is based on other modalities to measure pressure.

Dr. Black: What about the patient or the doctor that says, "My pressure is always okay somewhere else, but it's always high in your office -- white-coat hypertension?"

Dr. White: Well, that's one of the subtypes for which this test often is useful. Of course, first, we have to make sure that our measurements as doctors are okay, so it should be done systematically and in many numbers -- not just 1 or2. We also have to make certain that the patients' blood pressures are believable, not just 3 or 4 random blood pressures on the back of an envelope, but usually some kind of log where they've measured their blood pressures in duplicate each morning for 7 or 10 days in a row before they took their drug. So, we can at least do an average and see where they are. If those values are distinctly lower than what we've been getting in the office under standardized conditions, then, yes, I think that ambulatory monitoring helps to differentiate whether they're at high or low risk.

Dr. Black: How about the use of ambulatory blood pressure monitoring to evaluate a drug or a device?

Dr. White: For routine evaluation of a drug in practice, no, but for evaluation of a drug or device in clinical research, absolutely. There are several reasons for that, and one is that if you're looking at a new chemical entity or even an old one added to another one -- some kind of combination drug -- it's very valuable to understand whether or not the drug does, in fact, have its 24-hour duration as it's supposed to be, whether or not there's any excessive blood pressure reduction, and then to characterize it vs other drugs. So it's unbiased. It's the most pure way to assess the dynamics of a drug and for blood pressure.

Dr. Black: Now you mentioned taking blood pressures, and I think recently there was some attempt to look at home monitoring, which we'll talk about shortly, and how many times you had to measure it in order to get a reliable home average. What do you think about this "take 16 in 2 weeks and that's good enough"? Should it be more than that, less than that?

Dr. White: Well, there have been a lot of studies on that. I mean, you look at is 1 week enough, 2 weeks enough, and so forth, and usually what it's doing is evaluating its relationship with 24-hour mean blood pressure, because that's a gold standard, as it predicts harm to a greater extent than clinical measurement. So, let's say your goal is to try and regress data from a bunch of home readings vs a 24-hour mean. It looks like about a week's worth of readings is, in fact, adequate. Whether it's 16 or 18 or 28, that's something that I don't think matters as much, but the AHA [American Heart Association] came up with, I thought, a very reasonable approach a couple of years ago. This is when Tom Pickering was alive, and he actually characterized this as the standard way in a quarterly basis to monitor patients. You do 2 readings seated and relaxed prior to dosing of your morning medicines, and, if you're taking an evening medication so you're on a twice-daily regimen, do that again at night, and you average the 14 readings in the morning so you have some workdays, some not workdays, and you just do the same thing in the evening. And if those blood pressure values, in fact, are less than 125 over 76, and that number comes from a receiver operating curve piece of information, then you're controlled. You don't need to do much else. If it's not well controlled, then you go for the monitor or adjust drugs.

Dr. Black: Now, you and Tom also talked about masked hypertension, and I thought that was a somewhat new idea until I found some very old slides from you which discuss that. What is masked hypertension?

Dr. White: Well, there are 2 concepts for masked hypertension. One is that you've got just a normal healthy population, not treated with drugs, and what's the likelihood that they really have high blood pressure when they're outside of the medical care environment? Surveys suggest it's about 4%-7% of people, most likely because, number one, when they come to the doctor they actually like us.

Dr. Black: There are a few people that do like us.

Dr. White: Yeah, there are a few people like that. They relax; they sit down; their blood pressure is lower. They go to work; they get stressed; and it's the opposite. Other people go out of the office and start smoking cigarettes, eating a lot of salt, maybe taking a decongestant, or they're just hyperadrenergic, and so they get higher blood pressures. They're at risk and they don't know it, and it's very problematic right down to screening for them. There's no good way to do that unless it's found out fortuitously when somebody is getting a stress test, their blood pressure is going up, or they happen to get a reading outside of the doctor's office.

Dr. Black: Are you recommending that every home have a home blood pressure monitor?

Dr. White: Well, it's not a bad idea for somebody to get blood pressure measurements done when they're in their younger years. We have this typical situation: You finish college; you don't have to get your sports physicals anymore; and if you're a guy you don't ever get a blood pressure again until you get life insurance 20 years later, so you have this huge gap where nobody knows what your pressure is. In that instance, it might be a reasonable thing to do. They're not that expensive and that's where you find it out.

But there's another kind of masked hypertension that I actually want to mention, and that is a person who is treated. We know they're hypertensive; we think they're well controlled in the office based on all of our parameters, but they're not. Now, I think that's very common. I think, unfortunately, about 1 out of 3 treated hypertensives whom we believe have good control are actually masked hypertensives.

Dr. Black: I always have a little trouble with this idea of white-coat hypertension in someone who is being treated.

Dr. White: Yeah.

Dr. Black: That's not what it is. It's got to be -- It's office resistance.

Dr. White: Exactly.

Dr. Black: In my case and this is masked hypertension. So, on treatment it's just -- I think -- we need another term.

Dr. White: And there's another term.

Dr. Black: Yeah.

Dr. White: But they're poorly controlled, yet we do not know this. They're undefined, undiagnosed, closet hypertensives out there, and the best study to define what happens to these people is the Office Versus Ambulatory study, or OVA. They had 2000 treated hypertensives. They measured ambulatory blood pressure. They measured clinic pressure. In the group who was normotensive by all guidelines in the office -- that is, less than 140 systolic -- about a third of them had an ambulatory blood pressure greater than 135, which is about the usual reference difference. They had more events over a 10-year follow-up, and a lot more events. So I think that in that population -- high-risk -- you're not really sure. One ambulatory monitoring can go a long way in preventing harm.

Dr. Black: This may explain some of the people who have events when we think they're well controlled.

Dr. White: Yeah.

Dr. Black: Or some of the people who have strokes or a left ventricular hypertrophy that we can't blame on the office blood pressures.

Dr. White: That's right.

Dr. Black: Because we're not really getting a full view of what's going on. Now, you recently wrote an editorial about the morning surge and the increase in blood pressures as you wake up. We both are very interested in this, having done the CONVINCE [Controlled Onset Verapamil Investigation of Cardiovascular End Points] study together, where we looked at a nighttime drug designed to be taken at night to dampen and prevent the morning surge -- something which, unfortunately, never got properly completed. Now, what do you think about the suggestion that you can quantify how much the morning surge ought to be and whether it's normal or abnormal?

Dr. White: Well, the best data these days are coming from this collaboration among, I think, 5 continents but engineered by the University of Leuven in Belgium, and the PI [principal investigator] is Jan Staessen, in which they have been collecting ambulatory blood pressure data and cardiovascular outcomes for all this time. They've got several thousand people with more than 10 years of follow-up, and they've characterized people according to their morning surge in blood pressure as the difference between the 2 hours post awakening minus the 2 hours right before they awaken. They have pretty good data on that. If looking at quintiles of the blood pressure or even deciles that top 10%-20% of a rise in blood pressure from sleep to wake has an increase in stroke and cardiovascular morbidity... In reviewing that paper, I asked the investigators to tell us: "Is there a value of change at which you really don't see any increase in harm?" There was: It's about 20 mm. So, if you're sleeping and you're 90 and you go up to 110, that is probably normal, and you don't get into trouble. In contrast, if you're sleeping and you're 100 and you go up to 135, so now you've had a rise of 35 mm and your result in pressure is 135, [then] you are, in fact, at increased risk of having a stroke in the near future. So we could target that.

Dr. Black: I'm considering adding this to my reports, but I'm a little curious, though, if you go from 90 to 110 that's 20; if you go from 110 to 130 that's also 20. If you do a percentage would it come out differently?

Dr. White: It would come out --

Dr. Black: Percentage of increase?

Dr. White: It would come out differently, and I think that has to be taken into consideration, so it's not a perfect situation. I think that whoever... When you're making your report for physicians ordering the test, I would agree that I would look at the net change as well as the result in blood pressure and then kind of put into clinical perspective that, although your patient's blood pressure went from 82 to 102, which would be consistent with the borderline increase in surge that we'd consider harmful, 102 is in fact not associated with an increase in harm. So it's something like that.

Dr. Black: I think the same thing happens with us categorizing dippers and nondippers.

Dr. White: Right.

Dr. Black: When you're very low to start with, you can't really go down very much more, and yet we would consider that sort of person a nondipper, someone whose blood pressure doesn't fall more than 10% or 15% at night.

Dr. White: Yeah, I actually object to the whole dipper/nondipper terminology, because it's poorly reproducible. I would rather stick with an absolute definition of nocturnal hypertension, and there's plenty of population data to suggest that if you're 115-120 systolic or lower, [then] you are normotensive at night because nocturnal hypertension in absolute terms is very reproducible, whereas were you a dipper or a nondipper, you're going to lose that status every other time that you get another ambulatory report.

Dr. Black: Yeah, if you do it twice. it's going to be different.

Dr. White: Yeah, right.

Dr. Black: Entirely.

Dr. White: Exactly.

Dr. Black: So, I think we're getting much more sophisticated in evaluating blood pressure in patients, and, as we decide what drugs we should be using, do you see anything in the future?

Dr. White: Well, I think that what we might see in the future is a couple of things. Technology is getting better. Here at our 25th meeting of ASH I saw a device that actually people could wear on their wrist and got readings over 24 hours, and you could download it onto a computer, so very unobtrusive. If that's refinable and validatable, that would be very interesting from the standpoint of office space practice in getting these kinds of out-of-office data in an unbiased way and get sleep readings.

I think that there is going to be a trend in new clinical trials, what's left of them, to perhaps do a substudy where we can look at the impact of using out-of-office reading as the goal vs clinic, because it's usually been the other way around. So we can determine whether intervening, based on an out-of-office measurement whether it's home or ambulatory, will give us different or better outcomes than if we use the clinical measurement. That will change everything if we get that kind of finding.

Dr. Black: Yeah, I would still refuse to make clinical decisions based on what a patient calls up and says my blood pressure was -- whatever it was -- because, most of the time when they think it's too high and I measure it in the office, it's not, and I guess people have some secondary gain about being high or they want more medicine, which so far I've refused to do. Maybe I should change my mind.

Dr. White: No, I've had the same tendency. I mean, I think that when a patient brings in or calls in in fear that their blood pressure is either too high or too low, it warrants an evaluation. It doesn't warrant a change over the phone, though, because you just never know what you're going to get.

Dr. Black: Exactly.

Dr. White: There's erroneous information being obtained -- at least in my practice -- 50% of the time or more, so I'm hesitant to make any decisions without other types of assessment.

Dr. Black: But I agree and I'm certainly willing to consider it now. Anyway, thank you very much, Dr. White.

Dr. White: Sure.

Dr. Black: Thank you very much.

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