Is Prehypertension a Useful Clinical Category?

Dr Myerson is Director of Preventive Cardiology, St. Luke's-Roosevelt Hospital, Columbia University College of Physicians and Surgeons, New York, NY.

Since 1977, the National High Blood Pressure Education Program has issued 7 reports from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 1 through 7), each with a lower threshold value. Before 1984, a diastolic blood pressure (BP) of >105 mm Hg was the only established criterion for the diagnosis of hypertension. In 1984, "isolated systolic hypertension" was defined as systolic BP >160 mm Hg. JNC 7, issued in 2003, defines a BP of <120/80 mm Hg as "normal" and values from 120/80 to 140/90 mm Hg as a new category, "prehypertension."

Journal of Clinical Hypertension

JNC 7 may have led to more problems than solutions. Confusing the situation further was a position paper by the Hypertension Writing Group published in the (2005;7:505-512), the official publication of the American Society of Hypertension. The group expanded the JNC classification by integrating additional preclinical and clinical cardiovascular (CV) manifestations. Not only was there a numeric cut-off to identify individuals, there was also a global CV risk assessment. The authors felt that the threshold-based definition of hypertension failed to identify a large group of individuals with subclinical cardiovascular disease (CVD) that may precede chronic BP elevations.

The position paper proposed 4 categories of variables to classify patients: BP, CV risk factors, early disease markers, and target-organ damage. One of the stated goals of the writing group was to break up the JNC 7 "prehypertension" category into those who are genuinely at high risk and those who are at low risk.

J Clin Hypertens

Thomas Pickering, MD, DPhil, director of the Behavioral Cardiovascular Health and Hypertension Program at Columbia Presbyterian Medical Center, New York City, believes that the old definition, a BP >140/90 mm Hg, was clear. "The implication of the Hypertension Working Group classification is that patients (if we should really call them that) with stage 1 hypertension are sick. What we urgently need are better algorithms based on a few well-established risk markers that we can add to the prediction based on blood pressure. If we do need a new definition of hypertension, it should be based on improved measures of blood pressure, and should be separate from a new definition of risk" (. 2005;7:702-704).

J Clin Hypertens

Bringing up the implications of labeling, Dr Pickering asks, "Do we have to scare our patients to get them to comply with treatment? The consequences of screening for hypertension have been the subject of many studies, some of which have suggested that screening a population for hypertension may cause unintended harm" (. 2006; 8: 57-60).

Arch Intern Med

J Hypertens

Arch Intern Med

The designation of prehypertension represents a large number of people who would be labeled. By some estimates, 40% of men and 23% of women in the United States would qualify (. 2004;164:2126-2134). While the relative risk for this group is small, the absolute number is high for develop-ing CVD as shown by several studies (. 1998;16:2117-2124; . 1992;152:56-64).

The working group's strategy does have some support. The Second National Health and Nutrition Examination Survey (NHANES II) population who met the JNC 7 classification for prehypertension at baseline had a significantly increased risk for all-cause and CV mortality compared with those with normal BP at baseline. When data were adjusted for the presence of risk factors, however, mortality was not increased in individuals who had prehypertension without any additional CV risk factors.

N Engl J Med

There are limited data from large, placebo-controlled, randomized, clinical trials to suggest that treatment of prehypertension is beneficial. In the HOPE (Heart Outcomes Prevention Evaluation) trial, treatment based on angiotensin-converting-enzyme inhibitors compared with a regimen that did not include such therapy reduced the incidence of CV events and death from any cause among >9000 high-risk patients with or without elevated BP (. 2000; 342:145-153).

JAMA

In the CAMELOT (Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis) study, 1991 patients with angiographically documented coronary artery disease and an average baseline BP of 129/78 mm Hg showed a reduced incidence of CV events by 31% with an amlodipine (Norvasc)-based (10 mg) but not an enalapril (Vasotec)-based (20 mg) treatment regimen (. 2004; 292:2217-2225).

N Engl J Med

A recent study, the TROPHY (Trial of Preventing Hypertension), looked specifically at prehypertension (. 2006;354: 1685-1697). A total of 772 patients with high-end prehypertension were randomized to candesartan (Atacand), 16 mg, or placebo. After 2 years, the active treatment group stopped the medication and received placebo. Both groups were followed for another 2 years while taking a placebo. At the end of the first 2 years, 40% of those in the placebo group progressed to hypertension compared with only 14% in the candesartan group. At 4 years, 63% progressed to hypertension in the placebo group compared with 53% in the active drug group.

N Engl J Med

In an editorial accompanying the TROPHY publication (. 2006; 354: 1742-1744), Heribert Schunkert, MD, of the Medizinische Klinik, University of Lübeck, Lübeck, Germany, urges that some of the study data should be interpreted with caution. Dr Schunkert argues that in epidemiologic studies, the need for medical treatment is defined by using BP medications. However, he notes that candesartan was not on the list defining hypertension as the end point. If it were, he points out, perhaps the number of persons in the drug group with hypertension at the end of 4 years would have been higher. Inevitably, the profound decrease in BP induced by treatment with candesartan masked, rather than prevented, this end point in the first 2 years of the study, he writes.

New York Times

Times

New York Times

As if controversy in the medical community were not enough, the lay press also weighed in. The focus of the lay-papers' criticism was the funding by industry of the studies leading up to the new definition. An editorial titled "Industry's Role in Hypertension," published in the (5/30/2006), quotes reporter Stephanie Saul, who wrote, "If the American Society for Hypertension [ASH] hoped to devise an expanded definition of the condition that would be scientifically and ethically defensible, it sure picked the wrong way to do it. Virtually every key step in its efforts to redefine hypertension from mere high blood pressure to a broader syndrome has been financed by pharmaceutical companies that would gain by selling drugs to more people" (, 5/20/2006).

Should we routinely diagnose and treat prehypertension? Franz Messerli, MD, FACC, also a board member of ASH and director of the Hypertension Program at St. Luke's-Roosevelt Hospital of Columbia College of Physicians and Surgeons in New York City, says "not yet."

According to Dr Messerli, "There is not much evidence that treating prehypertension will have a benefit for morbidity and mortality. Despite the results of the TROPHY study, the morbidity and mortality benefit has not been established."

He adds, "If you have prehypertension and risk factors that are not easy to tackle, such as obesity and smoking, then it is a good idea to try and keep blood pressure low. Since the medications to treat blood pressure are now so benign, especially angiotensin receptor blockers, and the risk of harm is low, it is reasonable to consider treatment if appropriate. It is not like years ago when we only had clonidine (Catapres) or beta-blockers."

Dr Messerli also agrees that labeling a person with a disease may have an adverse effect. "Pre-anything, for example, precancer or prehypertension, has a negative connotation that you inevitably will get the disease."

Although experts disagree on what may ultimately be best, it will be several years before we have data to guide us in the management of prehypertension. Until then, keep in mind the following points:

? At this time, there is no clear evidence from randomized clinical trials to support routine use of medication to treat prehypertension.

? All patients with hypertension and prehypertension should be counseled on lifestyle factors?dietary salt, alcohol intake, exercise, stress, body weight, and tobacco use.

? Patients with known CVD or several risk factors may be considered for medical therapy if they have prehypertension.

? Generally, the same principles apply to the choice of medications to use for prehypertensive patients as for those with hypertension.