American College of Physicians: Internal Medicine — Doctors for Adults ®

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Prehypertension: Is new evidence a call to action?

From the September ACP Observer, copyright 2006 by the American College of Physicians.

By Bonnie Darves

What are you telling your prehypertensive patients? While new evidence shows that prehypertension quickly turns into hypertension, experts say that without clear evidence that intervention works, internists should not only watch what they do, they also should be careful what they say.

"When you tell a patient they are prehypertensive, make it clear that lifestyle changes are recommended to prevent hypertension and not medication to lower blood pressure," advised William C. Cushman, FACP, chair of the VA Hypertension Field Advisory Committee and chief of preventive medicine at the VA Medical Center in Memphis, Tenn. “You’re talking about a lot of money to treat these patients if suddenly they all started on drug therapy. Therefore, we need definitive outcome trials to prove whether we should treat prehypertension with drugs."

Others point to the Seventh Report of the Joint National Committee (JNC 7) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, issued in December 2003, and ask, "why should physicians wait to intervene?" That report substantially changed previous guidelines by classifying patients with "high normal" blood pressure as prehypertensive.

“Many doctors believed, even before the term 'prehypertension' was coined, that anything over 120/80 was not acceptable,” said Michael A. Weber, FACP, a study investigator and professor of medicine at the State University of New York Downstate College of Medicine in Brooklyn. He admitted that he—and many of his colleagues—initiate therapy in prehypertensive patients he suspects are headed for health troubles in the near term, particularly if other risk factors are present.

But for many the question of what to do or say—and when—is still up for grabs even as internists try to balance what they're seeing in their offices with changing views of prehypertension treatment and concerns about potential costs to the health care system.

Raising the bar

Prompting the latest discussions are the results of a study, published in the April 20, 2006, issue of The New England Journal of Medicine, showing that using angiotensin receptor blockers (ARBs) can prevent or postpone—to some degree—progression to full-blown hypertension.

The 772 participants in this Trial of Preventing Hypertension (TROPHY) were randomized to either candesartan or placebo for the first two years of study, and all received a placebo for the study's remaining two years. Two-thirds of those on a placebo only progressed to hypertension, compared to just over half of those on the ARB.

Given the increasing prevalence of prehypertention—an estimated 70 million Americans have the condition—even this relative risk reduction of 15.6% in those on the ARB is sparking debate.

Those who say it is a call for closer monitoring of prehypertensive patients—: who often are overweight, have blood pressure around 130/80, and may have abnormal blood glucose—note that there's everything to gain by taking a proactive approach. “You look at that patient and say, ‘even though you’re not yet diabetic and you’re not yet hypertensive, why should we wait for a heart attack or some other major event before we take action?’,” Dr. Weber said. “A lot of doctors already have that aggressive attitude today”.

Others urge caution in interpreting TROPHY's results, citing the study's limitations. For one, TROPHY was designed as a hypothesis-generating study, Dr. Weber said. In addition, the mean age of participants was 48, their mean body mass index (BMI) was 30 and the vast majority—about 90%—had additional health risks ranging from high cholesterol and triglyceride levels to abnormal glucose and insulin-to-glucose ratios.

“TROPHY was a fascinating attempt to … show that you can postpone development of real hypertension by treating prehypertension,” said Franz Messerli, FACP, director of the hypertension program at St. Luke’s Roosevelt Hospital in New York City and one of the study's investigators. “But does it have any major practical implications? I am not certain at the present time that it does.”

The findings would have been more relevant had the trial involved younger, less comorbid patients, for example, said Dr. Messerli, or had it been designed to compare candesartan with another agent, such as a statin.

Too soon for drug therapy?

What many are looking for is clear evidence showing that starting pharmacotherapy early actually prevents cardiovascular (CV) events. Unfortunately, TROPHY verifies the problem—patients in the upper half of the prehypertensive range clearly have near-term risk of developing hypertension—but doesn't give enough data to support starting drug therapy, according to Dr. Cushman. As a result, it’s premature to talk about recommending a strategy that would, at the least, be very expensive to the health care system, he said.

“It’s a higher-risk population, CV-wise, and one with a higher risk of developing hypertension. What we lack is prospective clinical trials saying that if you start a patient on drugs in that range that you will prevent CV events,” said Dr. Cushman, an author of the JNC 7 guidelines that first classified and defined prehypertension (see "How JNC 7 changed medicine's view of prehypertension").

For now, he cautioned against treating prehypertensive patients with antihypertensive medication unless the appropriate indication exists. “If you have a patient who has an indication for a drug that happens to be an antihypertensive drug, independent of blood pressure, you should treat him,” he said. The patient with nephropathy but no hypertension, for example, should be prescribed an ARB or an angiotensin converting enzyme (ACE) inhibitor, he explained; the patient with systolic dysfunction and heart failure would still receive the ACE inhibitor or beta-blocker–regardless of his blood pressure reading.

For patients with prehypertension, the decision to prescribe drugs may depend on the patient's other risk factors as well as the patient’s likelihood of changing unhealthy behaviors. Dr. Messerli decides how to proceed based on what such a comprehensive assessment of all risk factors uncovers.

“When you have a patient with metabolic syndrome or a smoker who is unwilling or unable to give it up, then a blood pressure in the prehypertensive range is probably a treatable entity,” he said. His thinking is that it’s “one risk factor that you can lower in this patient.” At that point, he added, the decision becomes whether to use a statin—studies have shown that statins reduce the risk of new hypertension—or an antihypertensive.

Complicating the discussion of whether to use drug therapy for prehypertension were news reports last spring that the American Society of Hypertension had received grants from pharmaceutical companies to host lectures promoting an expanded definition of hypertension to include prehypertension. The controversy prompted the society to require more detailed disclosure from its leadership about any grants received from industry.

The sheer cost of treating a population of 70 million individuals, Dr. Weber contended, “makes the whole issue rather intimidating, because if we treated them it would be extremely costly. Still, if evidence appears to show that this strategy saves lives, we might have no choice other than to take whatever steps are necessary to protect these people.”

Physicians at the forefront

But in lieu of clear guidance from TROPHY, some physicians are now either considering an earlier start with antihypertensives or are being more aggressive about starting medication in patients who have other risk factors.

For example, Pennsylvania general internist Sarah Gustafson Thompson, ACP Member, hasn’t changed her management of prehypertension on the basis of the TROPHY results: She initiates drug treatment when blood pressure hits 130/80 mmHg only in patients with renal disease or diabetes. But she seriously discusses progression to hypertension and risk reduction with all prehypertensive patients, while assessing for underlying causes for blood pressure elevation.

Dr. Thompson, who practices in a Radnor, Pa., clinic affiliated with University of Pennsylvania, where she is an assistant professor of clinical medicine, counsels all of her prehypertensive patients about reducing weight and sodium and getting regular exercise. She encourages them to adopt the DASH (Dietary Approaches to Stop Hypertension) eating plan, which features fruits, vegetables, whole grains, and other foods that are heart healthy and lower in salt. But once a patient's blood pressure hits 140/90, she switches from behavior changes to pharmacotherapy.

“I tell patients, ‘studies have shown that the long-term risk of you developing high blood pressure in your lifetime is relatively high," she said, "and it’s important to start making changes now to reduce your risk."

The TROPHY results may not resolve all the issues of how to treat prehypertensive patients, noted Dr. Weber, but it certainly adds to the discussion.

"In fact, just by waiting for a few months,": he said, "the diagnosis will usually become clear and lead to an appropriate form of treatment.”

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Six strategies that can help your prehypertensive patients

Some internists say finding the right message for the right patient as well as these other strategies help their prehypertensive patients better understand and manage their condition:

  • Talk about it sooner. “I think it’s important to raise patients’ awareness of prehypertension at a younger age and at a lower blood pressure level than we have in the past,” said Cynthia Ferrier, MD, a general internist with GreenField Health System in Portland, Ore. That's the perfect time to introduce the lifestyle-modification issue--exercise, stress reduction and weight loss, she said. "Say, 'Do these things now and you can possibly avoid or delay having to take medication,” she noted.

  • Know your patients. For patients who are medication averse, this approach works well, Dr. Ferrier said. “Some of my patients will do anything rather than go on medication,” she said. “I think you can pretty much predict from the initial conversation who will be receptive to lifestyle changes and who will respond" to this approach.

  • Go for dramatic results first. Most internists know that while lifestyle changes do work, and can even reduce blood pressure significantly in the near term, recommending modifications doesn't guarantee that it will happen. For that reason, William Cushman, MD, chair of the VA Hypertension Field Advisory Committee and chief of preventive medicine at the VA Medical Center in Memphis, Tenn., works with his patients to choose modifications that may be easiest to tackle and yet can produce dramatic differences in a matter of weeks.

  • Try reducing alcohol. "Alcohol reduction is an often overlooked intervention—and it’s something people can count and can more easily characterize [than reducing dietary sodium or pursuing complicated eating plans] when they do it,” Dr. Cushman said. It also can have a noticeable payoff. A recent VA study found reducing alcohol consumption from five or six to two or three drinks daily could significantly and fairly quickly decrease blood pressure, he said.

  • Encourage self-monitoring and reporting. Both Dr. Ferrier and Pennsylvania general internist Sarah Gustafson Thompson, ACP Member, encourage their “high-range” prehypertensive patients to monitor their own blood pressure a few times a week for a month or six weeks, and report readings via e-mail or fax. Not only will the internist stay up-to-date, but the patient who is making lifestyle changes can see how quickly the effort can pay off. It also addresses “white-coat hypertension,” which Dr. Ferrier’s said occurs in more than half of her patients.

  • Increase communication. Experts say that patients with prehypertension, especially those with other health risks and those who agree to attempt lifestyle changes, should have more frequent office visits or communication with their physician. That might mean a monthly check-in for the prehypertensive patient who is also overweight, or an office visit every two or three months for those with just prehypertension.

    “I wouldn’t just send them away for six to 12 months—-I would want them to come back every four to six weeks,” said Michael A. Weber, FACP, professor of medicine at the State University of New York Downstate College of Medicine in Brooklyn. “You're giving them a strong message that you really care about the elevated blood pressure.”

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How JNC 7 changed medicine's view of prehypertension

Thinking about prehypertension underwent a sea change in late 2003 thanks to two significant statements in the “Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure,” now known as the JNC 7.

The JNC 7 classified prehypertension for the first time, defining it with specific numerical ranges—systolic blood pressure of 120-139 mmHg and diastolic of 80-89. The report also called for initiating pharmacotherapy for Stage 1 hypertension rather than watchful waiting and lifestyle modification only.

Both the reclassification and the treatment recommendations were intended to increase awareness—among clinicians and patients—of the increasing prevalence of what used to be called “high normal” blood pressure, which affects an estimated 70 million Americans.

In a move that surprised many, JNC 7’s authors called for using the older thiazide-type diuretics as first-line therapy for uncomplicated hypertension, while recognizing the efficacy of newer drug classes—angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and calcium channel blockers—as initial therapy or co-therapy when other compelling indications or comorbidities exist.

The guidelines also promoted self-monitoring for patients taking antihypertensive medication and for those who may experience white-coat hypertension.

A copy of the JNC 7 guidelines can be downloaded at the National Heart, Lung and Blood Institute’s Web site.

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