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Q&A

William B. White Explains the Changes In the Way We Look at Blood Pressure

Which Numbers Matter Most—and Why Can They Be Deceptive?
Jack McCain

William B. White, MD, FASH, FAHA, FACP

William B. White, MD, FASH, FAHA, FACP, is Professor of Medicine and Chief of the Division of Hypertension and Clinical Pharmacology in the Calhoun Cardiology Center at the University of Connecticut School of Medicine. He is Editor-in-Chief of Blood Pressure Monitoring and Past President (2012–2014) of the American Society of Hypertension. He is known worldwide as an expert in the use of 24-hour ambulatory blood pressure monitoring to make correct diagnoses and guide antihypertensive therapy as well as to evaluate the cardiovascular safety of drugs.

P&T:

During the course of your career, our understanding of blood pressure (BP) as a predictor of risk for cardiovascular disease and other conditions has changed substantially. What’s the current thinking about which particular BP measures deserve the most clinical attention (systolic, diastolic, pulse pressure, etc.) because of their predictive ability?1,2

WBW:

Thirty-five or 40 years ago, the focus was on the diastolic BP. It was thought, just on physiological grounds, that diastolic BP was more important because it is the pressure when the heart is at rest. However, based on epidemiologic studies and clinical trials that occurred primarily in the 1980s, systolic BP became much more of a focus, particularly in people over the age of 60, because it became clear that it is a more prominent risk factor than diastolic BP for predicting stroke and heart failure. We often weren’t even treating systolic hypertension in older people 35 years ago because we thought systolic BP should equal 100 plus the patient’s age, but that notion was clearly erroneous.

The pulse pressure is the difference between the systolic pressure and the diastolic pressure, and it is also an important risk factor for stroke and heart disease in the older population, but it isn’t superior to systolic BP. As a researcher, I like to calculate pulse pressure and correlate it with target organ disease and so forth, but I really don’t use it pragmatically in clinical practice.

There are some concerns that when you lower systolic BP you also may be lowering diastolic BP too much, and that is a reasonable consideration, particularly when the diastolic BP is less than 50 mm Hg in people with heart disease. We don’t purposely treat patients to lower the diastolic BP to less than 60 mm Hg, but sometimes it is unavoidable in order to reach the systolic BP goal.

P&T:

BP measurement is often regarded as the most valuable biometric assessment. Compared with many other commonly measured biological markers, however, BP measurement seems subject to many variables. How should BP be measured in the office or at home? My own experience is that some health care personnel either don’t know or don’t care or lack the time to do it properly.

WBW:

Good blood pressure measurement technique is very important to me; I teach it all the time to our clinical residents and house staff. Sloppy BP measurements are a big disservice to our patients. It’s important for a physician to know whether the patient has had or done anything in the hour or so before the visit that could raise BP, particularly drinking caffeinated beverages or smoking. The physician also should take note of the patient’s emotional status, such as severe anxiety. The patient’s position is critical—patients must be sitting in a chair with their back supported and feet on the floor. Having your BP taken while seated on the edge of an exam table, with your legs dangling and no back support, can create substantial errors, making BP appear higher than it actually is. I also make sure the arm on which the cuff will be applied is free of constrictive clothing. We don’t make BP measurements over sweaters or sweatshirts with elastic constricting the flow of blood in the upper arm, which can increase BP. I am amazed that patients say, “Wow! No one has ever told me about that—sometimes I have to correct the nurse at my doctor’s office.”

P&T:

What is automated office BP (AOBP) measurement, and would its use lead to better diagnoses?

WBW:

AOBP devices are commonly used in research but are not routine in clinical practice. Use of AOBP probably will increase in clinical practice. These devices have become more precise and their measurements now are more reproducible than doctors’ traditional BP measurements. Unfortunately, an AOBP device costs a few hundred dollars, which may make them unaffordable for primary care physicians who wish to have one in each exam room.

In the SPRINT trial that was completed in 2015, BP was measured with digital devices that could take automated readings without a doctor or nurse in the room.3 The clinician pushed a button, left the room, and said, “I’ll be back in about five minutes.” The readings, taken in triplicate, were very stable, allowing researchers to titrate the drug to that level instead of to a level produced in the “white-coat” environment.

The results of SPRINT were so striking that it could influence the way we take BP in the future. This won’t happen overnight, but specialists in hypertension and cardiology should strongly consider using AOBP measurements. At UConn Health, we’re going to start a pilot program in the cardiology division to study how AOBP measurements would work with respect to patient flow. One of the experienced adult cardiology nurse practitioners and I will assess how a patient can sit alone in a room and have three measurements taken and then move into the environment of the doctor, and we might compare the automated readings with those taken in the doctor’s domain. In fact, work done by Dr. Martin Myers in Toronto has demonstrated that BP is about 6 to 8 mm Hg lower when an automated device is used without the presence of a clinician.46

P&T:

Should antihypertensive drugs ever be prescribed on the basis of office BP measurements alone? If so, what would those circumstances be?

WBW:

In the initial evaluation of a patient for hypertension, I will start antihypertensive medications under the following circumstances: If the BP is exceedingly high, for example, 180/110 mm Hg. The chances of such pressures being normal on out-of-office monitoring are exceedingly low. A second scenario is a lower BP of, say, 160/100 mm Hg but in the presence of target organ involvement from hypertension, such as damage to the retinal vessels or kidney or enlargement of the heart. But in a totally asymptomatic hypertensive, I believe we need more data than just a couple of clinical measurements. I would strongly advocate for 24-hour ambulatory BP monitoring (ABPM) in that situation to confirm a diagnosis of hypertension.

P&T:

What is ABPM, and how has it advanced our knowledge of blood pressure?

WBW:

ABPM is taken with a device worn by a person, usually for 24 hours. The device has a BP cuff and bladder attached to a rubber hose cable about 4 to 6 feet long. We program the device to take measurements every 15 to 30 minutes—it can store data on an internal chip. Today’s devices use rotary air compressors, which are quieter than they used to be, making some noise during cuff inflation but little noise during deflation. Using a separate lithium battery, the devices store data for long periods, such that if a patient uses it for 24 hours but doesn’t return the device for two or three weeks, the data will still be available. We can download the data into various software programs to assess BP variations over the day and night, during different activities, when different medications are taken, and so forth.

ABPM has greatly advanced our knowledge of BP behavior in all kinds of situations—in normotensives, hypertensives, people with secondary forms of hypertension, resistant hypertension.7 It has been a critical tool for evaluating new drugs being developed for treatment of hypertension—how long they last, how they compare with other medications, and so forth. In the last 20 years or so, no antihypertensive drug has been developed without the use of ABPM.

P&T:

In clinical practice, when is ABPM desirable?

WBW:

In clinical practice, we like to use ABPM when we’re not comfortable that the clinical measurements are verifiable or valid.710 There might be a white-coat effect; there might be so much variation in one set of measurements during a clinical visit that we don’t feel comfortable making a diagnosis. ABPM also is desirable in other situations outside the medical care environment, such as assessing work-site impact on blood pressure, working a night shift, problems with sleeping, or sleep apnea syndrome.

P&T:

In an update of its evidence-based guideline for management of hypertension, England’s National Institute of Health and Care Excellence (NICE) said a “key priority” is to offer ABPM to patients with clinic BP greater than or equal to 140/90 mm Hg to confirm the diagnosis of hypertension.11 More recently, the Canadian Hypertension Education Program updated its algorithm for the diagnosis of hypertension specifically to call for the use of out-of-office BP measurements (ABPM or home) to identify patients with white-coat hypertension (WCH) early on to avoid unnecessary treatment with antihypertensive drugs.12

WBW:

Yes, several professional groups that have ascertained the utility of ABPM have recommended that ABPM be done at least once in people with suspected stage 1 hypertension (Table 1) when they are being initially diagnosed to demonstrate whether they do or do not have WCH. This is a relatively recent recommendation in the United States,14 but it has been in use longer in England, Ireland, and Scotland,11 where they have accumulating data on how it has helped with a streamlined diagnosis and the utility of treatment. Eventually they should have outcomes data about its effect on stroke, heart failure, and heart attack. In the United Kingdom, they have a different setup, whereby ABPM devices are often provided via pharmacies, after the physician writes a prescription, instead of at doctors’ offices.

The typical office BP can be an imprecise tool for making decisions if you don’t have the information provided by ABPM. If I were a patient newly diagnosed with hypertension, I wouldn’t want to be treated with a lifelong medication without having knowledge of my out-of-office measurements.1518

P&T:

What is WCH? (See Figure 1A–B for an illustration of suspected WCH.) What is the difference between WCH and the white-coat effect?

WBW:

Making a distinction between WCH and white-coat effect is very important.20 WCH refers to people who are being newly diagnosed, not on antihypertensive medication, and have an in-office pressure within the range of stage 1 hyper tension, typically greater than 140 mm Hg systolic or 90 mm Hg diastolic or both, but who, on a 24-hour ambulatory BP study during the normal activities of daily living, have a 24-hour BP less than 130/80 mm Hg. That’s typically been the diagnosis for the last 10 or 15 years according to most guidelines in the U.S. and Europe.

In the situation in which someone has been treated with an antihypertensive drug, the phenomenon known as white-coat effect may be observed. It doesn’t mean the person is normotensive but rather that there is a pressor effect in the medical care environment that increases their BP to a value much larger than what it would be at anywhere else. This is very common. We see it quite regularly, particularly in older people. Overall, WCH is present in 8% to 10% of people, whereas the white-coat effect is present in 25% to 30% of people. We saw two or three people like this yesterday in my regular faculty practice. In the medical care environment, whether a medical technician or I took their BP, their systolic BP was over 160 mm Hg, but on the ambulatory monitor it was at least 30 mm Hg lower, averaged over the 24-hour period. It is very important to determine whether or not a person has the white-coat effect because other wise you will be up-titrating medications, but all the person is getting out of it are the side effects of the medications and not the benefits.

P&T:

A Spanish study using ABPM found that, among 8,295 patients thought to have (and who were treated for) resistant hypertension (office systolic BP greater than or equal to 140 or diastolic greater than or equal to 90 mm Hg, or both, while receiving more than two anti-hypertensive drugs), 62.5% of them truly had resistant hypertension, but the remaining 37.5% had white-coat resistance.21 What are the consequences of prescribing antihypertensives on the basis of elevated office BP measurements for a person who is a true white-coat hypertensive? Can patients be at risk of falling, for example?

WBW:

In some patients there would be such a risk because the only measurement being taken is the one in the doctor’s office. The clinicians might think they’re making headway with a small drop in BP measured in the office, but at home the person’s BP might be much lower. These patients might feel tired or dizzy because they’re being overtreated. That can certainly happen when physicians do not have enough BP data. This is dependent in part, however, on the class of medication used. Some drugs don’t typically lower a normal BP to a hypotensive value, whereas others do.

P&T:

The Canadian stroke specialist J. David Spence is a longtime critic of using a diagnosis of WCH as a reason for withholding drug therapy from patients who otherwise might be prescribed an antihypertensive on the basis of office BP measurements.2224 His most recent dissent came in response to an update of the Canadian algorithm for diagnosing hypertension.12 Dr. Spence contends that WCH is hypertension, that people with WCH should receive drug treatment, and that withholding antihypertensives from them would be a disservice. To what extent do Dr. Spence’s opinions reflect those of other researchers who study hypertension?

WBW:

There are a couple of issues with regard to this. First, a lot of the studies done in the 1980s and 1990s on WCH used different definitions. We stuck to a very conservative ABPM value of 130/80 mm Hg or less, but other researchers used 135/85 or even 140/90 mm Hg. So if the BP was slightly greater than 140/90 mm Hg in the office but slightly less than 140/90 mm Hg on the ambulatory monitor, you were considered to have WCH. But these values are essentially the same, and people like this are actually at higher risk for future cardiovascular events. In our studies looking at heart disease and vascular disease in the brain, when we use 130/80 mm Hg, we see very low prevalence rates of vascular disease—no different than normotension. But if 135/85 mm Hg were used that wouldn’t be the case. Dr. Spence is relying on meta-analyses that incorporate these different populations.

Another issue is whether or not people were previously treated. Most of my original studies enrolled people who never had been treated, so I had a good estimation of their natural situation.

It also is important to take the length of follow-up into account. If a 40-year-old’s BP is 118/70 mm Hg on an ambulatory monitor but 150/90 in the clinic, I don’t say, “You have nothing to worry about, and I’ll never see you again.” Five or 10 years later, the situation could have changed. The BP of about 50% of patients diagnosed with WCH gradually increases over time, even on the ambulatory monitor. If I follow up white-coat hypertensives every two or three years with ABPM, in 10 or 15 years they might have systolic pressures greater than 135 or 140 mm Hg even on the monitor, not just in the doctor’s office, and then I’ll initiate therapy based on their 24-hour data. So it is correct that, overall, if you have a long enough follow-up period, you eventually will see a small increase in cardiovascular event rates in people who have WCH versus normotension.

But I also want to point out that about half of patients whose office BP and ambulatory BP is normal at age 40 will become hypertensive by the time they’re 65 or 70 years old. It’s not just the white-coat hypertensives who can progress to hypertension, it’s anybody.

P&T:

How aware are primary care physicians (PCPs) in the United States of WCH? If they fail to take it into account when hypertension is suspected, why do they do so?

WBW:

Most PCPs have heard about WCH—patients often use the term themselves—and PCPs understand it, but they don’t have access to any other measurement techniques, or they don’t have good faith in patients’ home BPs. Patients have to be their own advocates to seek a hypertension specialist or cardiologist to do 24-hour monitoring. I hate to say it, but the biggest problem is that PCPs are very busy and don’t have time to get the assessment process done.

P&T:

As a longtime white-coat hypertensive, I’m baffled by the idea that there are some people whose BP is normal in the physician’s office but elevated everywhere else. What’s behind this phenomenon known as masked hypertension?

WBW:

Masked hypertension is a very important clinical entity. It’s basically the opposite of WCH—a person whose BP is normal in the medical care environment but whose BP as measured by an ambulatory monitor is higher in other settings. Patients with masked hypertension do achieve hypertensive values in the non-medical environment. As many as 3% to 5% of normal healthy persons who aren’t on antihypertensive medication have masked hypertension. They might be very active physically or experiencing a lot of stress in their jobs or elsewhere. Smoking and consumption of caffeinated or alcoholic beverages also contribute to masked hypertension.

A larger group with masked effect consists of the treated hypertensive patient population. One would assume their BP is normal based on their office measurement, but the ambulatory monitor demonstrates otherwise, showing their BP control is inadequate. It could happen because the antihypertensive drug that they are taking is wearing off, or because of some of the other reasons just mentioned. Masked hypertension in these patients is a tough problem because they are undertreated and perhaps already have target organ disease. People with masked hypertension who are not thoroughly treated have more untoward outcomes.25 I’ve had a lot of professionals who have worn 24-hour monitors and have had remarkably high BPs while they’re at work. As soon as they get in the car to drive home it goes down 25 points.

We haven’t figured out a good way to deal with masked hypertension yet because it isn’t practical to put 24-hour BP monitors on every normotensive or borderline hypertensive person who walks into the office. We treat masked hypertension when we find it, but the challenge is finding it in the first place.

P&T:

What is the role of BP in general, and pulse pressure in particular, in maintaining normal cognitive function and in contributing to cognitive impairment?

WBW:

As people get older, there is an increase in memory impairment and the ability to engage in what is called executive function—doing calculations, solving problems. This obviously bothers people a great deal because they can’t do what they used to do or want to do. We and other research centers around the globe have been studying this for some time. There’s definitely a relationship between 24-hour BP and the development of cognitive impairment. The first change detected is in executive function, rather than changes in depression scales or long- or short-term memory loss.

P&T:

You have suggested that 24-hour systolic BP might be a target for intervention to reduce the risk of cerebrovascular disease and cognitive decline in the elderly (mean age, 82 years).26 In this study, white-matter hyperintensity volume was a matter of interest. What is white-matter hyperintensity, and why is it important?27

WBW:

Researchers are interested in learning whether we can keep mild cognitive impairment from progressing by targeting 24-hour BP, or should we instead focus on people whose cognitive function is normal but who are at high risk of cognitive impairment because they have family members with cognitive impairment or because they have so-called white-matter hyperintensity (WMH) lesions in the brain (Figure 2). Using magnetic resonance imaging (MRI), we also test the integrity of brain tissue adjacent to WMH lesions that looks normal but may also be a risk factor for cognitive impairment.

WMH lesions are found deep in the subcortical part of the brain—the neurons in these lesions are not functioning. Meanwhile, the fibrous glial cells that coat these neurons remain alive, creating white spots on an MRI. In contrast, after a stroke the neurons and glial cells are both gone, creating a black hole on the MRI.

When white-matter disease is present, the transmission of signals from the back of the brain to the front of the brain may be slowed. For example, your vision center is in the occipital lobe in the back of the brain. It might be intact. Let’s say that you are walking along a sidewalk and see an obstacle. Your normal reaction would be to move quickly to avoid the obstacle. If the transmission from the occipital cortex in back to the motor cortex in the front of the brain is slowed by white-matter disease, perhaps your response time is slowed and balance is impaired—hence, you fall and may sustain an injury. Those problems are clearly happening to older people with vascular disease of the brain, and they are more strongly related to 24-hour BP than to clinical BP.26

P&T:

Now you are involved in a study, INFINITY (Table 3), which also includes a measure of WMH as an outcome, along with measures of mobility and cognitive function.27,28 What is unique about this study?

INFINITY is the first trial to use 24-hour ABPM to guide antihypertensive treatment intended to reduce damage in the subcortical white matter associated with hypertension. We started the study in 2012 to determine whether or not we could target the systolic ambulatory BP at 130 versus 145 mm Hg in older people. The hypothesis is that lowering the systolic BP to 130 mm Hg on the ambulatory recorder will lead to better outcomes, particularly the accumulation of white-matter disease. The primary outcomes deal with functional issues: Can we improve patients’ mobility—their stability while walking, speed of walking, ability to get up and down from a chair without using their arms, ability to go up and down stairs? We also use a sophisticated series of standardized cognitive tests, which are administered by neuro psychologists at baseline, 18 months, and 36 months. In addition, we use quantitative MRI of the brain and diffusion tensor imaging to assess the integrity of cells adjacent to damaged areas as well as the damaged areas themselves. We make a regional assessment of the parts of the brain affected by the hypertension and their functional role in the daily activities of elderly people.

This study is very interesting, but it’s also very challenging because we have to see people quite regularly to make sure they’re still reasonably healthy and can stay in the trial. The enrollees range in age from 75 to nearly 100. Once people are in their high 80s and low 90s, bad things happen—pneumonias, fractures, intestinal problems, heart disease. We knew that would be the case, but our drop-out rate actually has not been high over the past four years.

P&T:

Is hypertension under-recognized and undertreated among people ages 75 and older?

WBW:

I don’t know if it is under-recognized but it certainly is undertreated because people are allowed to have BP that’s higher than it should be for long periods of time. If you don’t treat older people with hypertension, they will be at increased risk for stroke and heart failure. There’s no doubt about it.

P&T:

It sounds as though INFINITY has the potential to greatly improve people’s quality of life without a lot of expense.

WBW:

We hope so. In the original cohort that we studied before we started INFINITY, we looked at many other risk factors—cholesterol, blood sugars, expensive biomarkers of blood vessel disease—but only systolic BP on the 24-hour monitor and low-density lipoprotein-cholesterol were predictive of the progression of vascular disease in the brain.

P&T:

Without 24-hour ABPM, it probably would be very hard to do a study like INFINITY.

WBW:

It would not be possible, actually. A lot of people have perfectly normal BP in the office but then they go up to 160/80 mm Hg at night or even higher. A high proportion of people in INFINITY have masked hypertension as opposed to WCH. If we didn’t have ABPM to learn their nocturnal BP, we wouldn’t know how to get them under the best BP control possible.

P&T:

Earlier you said ABPM has been used for the past 20 years or so in clinical trials of antihypertensive drugs. Does ABPM also have a role in the evaluation of noncardiovascular drugs?

WBW:

Yes, ABPM is used when there is a concern that a drug might raise BP. I’ve helped sponsors of drug discovery design many trials when they’re concerned that there may be a safety issue with a drug for noncardiovascular indications such as cancer, arthritis, or depression, for example, that have the potential to raise the BP. If a study uses 24-hour monitoring, a much smaller number of people can be enrolled compared to if clinical measurement is used—this is because ABPM results are much more reproducible and with less noise, the statistics become more powerful.

So, ABPM has become popular with the Food and Drug Administration as an assessment of non cardiovascular drugs. We’ve looked at drugs for Parkinson’s disease that may raise BP, for type-2 diabetes that may lower BP as well as blood sugar, and drugs for fibromyalgia and depression, because the mechanism that helps those problems might also raise BP.

Figures and Tables

Portrait of a Suspected White-Coat Hypertensive

Between November 2013 and May 2015, a healthy and physically active white male in his early 60s made 29 visits to an orthopedic surgeon for evaluation and treatment of Dupuytren’s contracture. Throughout this period, the patient was not taking antihypertensive medications or any other prescription drugs, nor did he smoke, then or ever. During each visit, blood pressure (panel A) and pulse rate (panel B) were recorded after a single measurement by a technician or nurse. Because of a family history of stroke and because some primary care physicians previously had suggested that antihypertensive drugs might be beneficial in light of high in-office blood pressures, for several years the patient had adopted the habit of monitoring his blood pressure nearly every morning at home using an automatic digital device approved by a nurse at the primary care office. These pressures (the lowest of multiple systolic pressures and the corresponding diastolic pressure) are displayed. For the 29 office visits, mean BP was 163/82 mm Hg—high enough to warrant drug treatment per JNC 8 (Table 2).19 For the 28 home measurements made on those days, mean BP was 113/67 mm Hg—well within the normal range. Ambulatory BP monitoring was performed to determine whether the office or the home readings were the “true BP.” The average 24-hour mean BP was 118/72 mm Hg—thus avoiding excessive treatment. On the x-axis in each panel, the distance between data points is not proportional to time elapsed between visits. Visits within a few days of each other represent visits for the injection of Xiaflex (collagenase clostridium histolyticum, Auxilium Pharmaceuticals) followed by manipulation of the injected joint; all other visits were for evaluation only. The last three visits were follow-up visits after palmar fasciectomy in early April 2015 to address the problem surgically.

Assessment of White-Matter Hyperintensity (WMH) Segmentation in the INFINITY Trial26,27

Shown is a series of brain images from an 80-year-old man with small vessel disease of the brain. Two methods were used to show the presence of white-matter hyperintensity (WMH). The first three images in each row were obtained with magnetic resonance imaging; the last image in each row is a three-dimensional model. WMH segmentation appears in pink, while the blue areas indicate where there is cerebrospinal fluid.

T1 MP-RAGE = T1-weighted magnetization-prepared rapid gradient-echo; T2 FLAIR = T2-weighted fluid-attenuated inversion recovery.

JNC 7 Definitions of Hypertension and Prehypertension13

BP Category* BP Range
Normal SBP < 120 and DBP < 80 mm Hg
Prehypertension SBP 120–139 or DBP 80–89 mm Hg
Stage 1 hypertension SBP 140–159 or DBP 90–99 mm Hg
Stage 2 hypertension SBP ≥ 160 or DBP ≥ 100 mm Hg

BP = blood pressure; DBP = diastolic blood pressure; JNC 7 = Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; SBP = systolic blood pressure.

*For any diagnosis, clinician should repeat testing during at least two visits with patient in seated position.

JNC 8 Thresholds for Pharmacological Treatment of Hypertension19

Age in Years Population Threshold for Initiating Drug Treatment to Lower BP BP Goal
≥ 60 General SBP ≥ 150 or DBP ≥ 90 mm Hg SBP < 150 and DBP < 90 mm Hg
< 60 General DBP ≥ 90 mm Hg DBP ≤ 90 mm Hg
< 60 General SBP ≥ 140 mm Hg SBP < 140 mm Hg
≥ 18 CKD SBP ≥ 140 or DBP ≥ 90 mm Hg SBP < 140 and DBP < 90 mm Hg
≥ 18 Diabetes SBP ≥ 140 or DBP ≥ 90 mm Hg SBP < 140 and DBP < 90 mm Hg

BP = blood pressure; CKD = chronic kidney disease; DBP = diastolic blood pressure; JNC 8 = Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; SBP = systolic blood pressure.

Intensive Versus Standard Blood Pressure Lowering to Prevent Functional Decline in Older People (INFINITY; NCT01650402)26,27

Enrollment 300
Design Randomized, open-label therapy, blinded endpoint assessment
Arms Intensive therapy
  • Multiple antihypertensive therapy (diuretics, beta blockers, angiotensin-converting enzyme inhibitor, calcium-channel blocker) to achieve 24-hour systolic BP ≤ 130 mm Hg
Standard therapy
  • Single or multiple antihypertensive therapy (diuretics, beta blockers, angiotensin-converting enzyme inhibitor, calcium-channel blocker) to achieve 24-hour systolic BP ≤ 145 mm Hg
Outcome measures Primary
  • Change from baseline in mobility parameters (self-paced walk and stance times)
  • Change from baseline in cognitive function (executive function, processing speed)
Secondary
  • Accrual of WMH over course of trial (36 months), including degeneration of tissue, using MRI technology known as diffusion tensor imaging
Inclusion criteria
  • Age ≥ 75 years
  • At risk for cerebrovascular disease (history of smoking, dyslipidemia, type-2 diabetes, longstanding hypertension, family history). Must have visible WMH lesions (> 0.5% WMH/entire brain volume) on screening MRI
  • Seated clinic systolic BP > 150 mm Hg in the untreated state

  • ° To maintain 24-hour systolic BP < 140–145 mm Hg in the standard treatment group or systolic BP < 125–130 mm Hg in the intensive treatment group, patients will be eligible if: 1) clinic systolic BP is 150–170 mm Hg, and they are taking 0 to 2 antihypertensives; or 2) systolic BP is > 170 mm Hg, and they are taking 0 to 1 antihypertensives.
Exclusion criteria (selected)
  • Uncontrolled diabetes mellitus (hemoglobin A1c > 10%)
  • History of stroke, dementia, or clinically impaired gait
  • Body mass index > 45 kg/m2 and/or arm circumference > 44 cm
  • Poor kidney function (estimated glomerular filtration rate < 30 mL/minute)
  • Active liver disease or serum transaminases > 3 times upper limit of normal
  • Major cardiovascular event (e.g., myocardial infarction) or procedure (e.g., cardiac bypass surgery) in past 3 months; stroke with residual gait abnormality
  • Uncompensated congestive heart failure (New York Heart Association class III or IV or documented ejection fraction < 30%)
  • Chronic atrial fibrillation that disallows ambulatory BP monitoring to be successfully performed
Principal investigators
  • William B. White, MD; Pat and Jim Calhoun Cardiology Center, University of Connecticut Health Center
  • Leslie Wolfson, MD; Department of Neurology, University of Connecticut Health Center
Sponsors and collaborators
  • University of Connecticut School of Medicine
  • National Institute on Aging

BP = blood pressure; MRI = magnetic resonance imaging; WMH = white-matter hyperintensity.

Author bio: 
The author is a freelance editor and medical writer living in Durham, Connecticut.

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