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Whitecoat Hypertension  

Conclusions:  Comparing matched BP groups, Isolated Office hypertensives have LV morphofunctional characteristics considerably different from normotensives and qualitatively similar to sustained hypertensives. Therefore, our results support the hypothesis that Isolated Office hypertension should not be considered as simply a benign condition.
Anna M. Grandi, etc.    Arch Intern Med. December 10/24, 2001;161:2677-2681

White-Coat Hypertension To Treat or Not to Treat - A Clinical Dilemma (Editorial)
Marvin Moser, MD            Arch Int Med Vol. 161 No. 22, December 10/24, 2001

IN THIS ISSUE OF THE ARCHIVES, Grandi et al¹ describe changes in left ventricular (LV) function and size in isolated office hypertensives compared with matched groups of normotensives and sustained hypertensives. Patients with in-office blood pressures (BPs) greater than 140/90 mm Hg but daytime ambulatory BPs less than 130/80 mm Hg were compared with normotensive individuals (in-office systolic BP <135 and/or diastolic <85 mm Hg and daytime ambulatory BP <130/80 mm Hg) and sustained or persistent hypertensives (in-clinic and daytime ambulatory systolic BP >140 and/or diastolic >90 mm Hg). Their findings are of more than academic interest.

Whether isolated office or clinic hypertension is of clinical importance and should be treated poses a dilemma "to treat or not to treat." In the past 10 years, numerous studies have addressed this problem. Some studies have suggested that casual office BP elevations with normal at-home or ambulatory BPs do not pose an important risk in terms of future cardiovascular events² and that these individuals do not manifest the physiologic changes associated with hypertension. On the other hand, some investigators have concluded that elevated office BPs (white-coat hypertension) is not a benign finding elevations of casual BPs seem to correlate with changes in vascular resistance and the presence of LV diastolic dysfunction and frequently have been associated with elevated triglyceride levels, low high-density lipoprotein and increased low-density lipoprotein cholesterol levels, insulin resistance, obesity, and other markers of the metabolic syndrome commonly noted in hypertensives.^{3, 4} Thus, opinion is sharply divided: one group advocates no specific therapy for white-coat hypertension, and the other maintains that these patients should not be ignored but that they should be treated, based primarily on office BP readings.

EVIDENCE FOR USING CASUAL BPs FOR MONITORING TREATMENT DECISIONS

pidemiologic evidence seems to favor use of the office or casual BP in determining risk, predicting prognosis, and determining therapy. In the Framingham Heart Study,⁵ for example, casual BPs taken in the clinic or office after a suitable period of sitting quietly were predictive of outcome: the higher the BP, the worse the prognosis. These predictive data were not based on the use of ambulatory or home BPs. In addition, in large-scale randomized clinical trials,^6-8 casual BPs were also the determinants of outcome: the higher the BP in the office or clinic, the more cardiovascular events occurred; the lower the BP, the fewer events.

The argument that too many people with so-called white-coat hypertension are being treated with medication when they need not be is often presented to justify a watchful waiting period in these patients. Approximately 20% to 25% of hypertensives have elevated office BPs and normal ambulatory or home BPs. Some investigators believe that resources could be saved and better care could be given if this subset of people who did not, in their opinion, require treatment (ie, white-coat hypertensives) could be defined. Grandi and colleagues1 conclude, after conducting a carefully designed study comparing 3 groups of individuals normotensives, in-office hypertensives, and (3) never-treated sustained hypertensives that the white-coat syndrome is not benign. Individuals were carefully matched not only by age, sex, and weight but also by mean clinic and daytime BPs. Many of the previous studies compared white-coat hypertensives whose in-office "elevated" BPs were considerably lower than those of sustained hypertensives. In this study, the in-office elevated BP group had BPs similar to those of sustained hypertensives. Although the numbers studied were small, as they have been in many of the studies of ambulatory BP, the authors conclude that in-office hypertensives with normal ambulatory BPs have more evidence of LV wall hypertrophy, increased LV mass, and altered diastolic function compared with normotensives. Although sustained hypertensives had considerably more evidence of LV mass, wall thickness increase, and diastolic dysfunction than did in-office hypertensives, this did not negate the fact that in-office hypertensives had demonstrated some physiologic adaptation to even transient elevations in BP. The authors conclude that in-office hypertension should not be considered a benign condition; by extrapolation, this entity should be treated. Other investigators have reached similar conclusions; but, as noted, many have not.

One problem with many of the reported studies is that normotensive controls have not been used. Comparative data in these trials include white-coat compared with persistent hypertensives. In these cases, the changes were greater in the latter group, as expected; similar findings are noted in the study by Grandi et al.¹ Another problem relates to the level of ambulatory daytime BPs that should be considered normotensive. Some studies suggest a BP of 130/80 mm Hg, and others suggest a BP of 135/85 mm Hg. Using different definitions brings about different results. Studies^{9, 10} suggesting that ambulatory daytime BPs correlate more closely with outcome than do casual BPs lack careful follow-up, data on specific treatments, etc. These studies have been quoted repeatedly to suggest that ambulatory BP should be a requisite in the evaluation of hypertensives.

WHICH BPs SHOULD BE USED TO GUIDE TREATMENT DECISIONS?

Should clinicians accept the data of Grandi and colleagues and others which show that isolated office hypertension is not a benign phenomenon and that its occurrence correlates with evidence of organ system involvement, specifically LV changes,^{1, 3, 4} or should they make treatment decisions based on data from other investigators² which indicate that isolated office hypertension is benign and not associated with either LV changes or other findings relating to the hypertension syndrome?

A careful review of available data dealing with this dilemma indicates that despite differences in study results, baseline data, definitions, and results, it seems that, on balance, patients with casual BP elevations in a physician's office or clinic are different from normotensives (ie, normotensive BP levels in the office and at home either on ambulatory BP monitoring or on patient- or family-recorded BPs).¹¹ Vascular resistance seems to be slightly higher and LV diastolic function compromised, and there is more evidence of other features that accompany hypertension (eg, obesity, metabolic disorders, and insulin resistance). As noted in the article by Grandi et al,1 changes in white-coat hypertensives are less than in those in persistent hypertensives, but there is a difference between these individuals and normotensives. These observations, plus long-term epidemiologic data and prospective treatment data, support the concept that white-coat hypertensives should be treated.⁶

We await a long-term, carefully conducted prospective trial to obtain a definitive answer. At present, we believe that if lifestyle interventions are not effective in reducing casual office BP to less than 140/90 mm Hg (or lower in patients with diabetes mellitus or renal disease), the patient should be treated with medication. Treatment today is relatively simple, may not be expensive, need not involve frequent physician visits or procedures, and can be undertaken at low risk to the patient. The possible benefit of long-term treatment of these patients seems to outweigh the maximal risk.¹¹

One way to limit the number of patients who might be treated unnecessarily if casual BPs are used to determine therapy (without using ambulatory or home BPs to make a decision) is to reevaluate BPs over time. One large study¹² noted that approximately 12% of patients initially screened as hypertensive became normotensive within 3 to 6 months. It is, therefore, reasonable, if the patient has stage 1 office hypertension (BP 140-160/90-100 mm Hg and no other significant risk factors, such as diabetes mellitus, history of cardiovascular disease, hyperlipidemia, or a smoking history), to follow the patient on lifestyle modifications (weight loss, sodium restriction, etc) alone for this period and then begin medication therapy if BPs remain greater than 140/90 mm Hg. However, as suggested in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure,¹³ even patients with stage 1 hypertension should be treated with medication in addition to lifestyle interventions simultaneously if they are diabetic or have any evidence of cardiovascular disease. The Joint National Committee report does not suggest routine use of ambulatory BP monitoring in the evaluation of hypertensives.

The study by Grandi et al1 does not settle the argument, but it does present data to reinforce the concept of treating patients based on in-office BPs. There are several reasons for using home BPs to follow patients (eg, if there are symptoms, if BP levels are not controlled, or to help motivate patients), but, in general, casual BP is still the measure that should be followed. At present, with our knowledge of the benefits of lowering BP and the realization that this usually does not involve complicated or dangerous regimens, it is good policy to treat white-coat hypertensives.

Marvin Moser, MD
13 Murray Hill Rd, Scarsdale, NY 10583

REFERENCES

1.  Grandi AM, Broggi R, Colombo S, et al.
Left ventricular changes in isolated office hypertension: a blood pressure–matched comparison with normotension and sustained hypertension.  Arch Intern Med. 2001;161:2677-2681.

2.  Gosse P, Promax H, Durandet P, Clementy J. "White coat" hypertension: no harm for the heart.
Hypertension. 1993;22:766-777.

3.  Julius S, Mejia A, Jones K, et al. "White coat" versus "sustained" borderline hypertension in Tecumseh, Michigan.
Hypertension. 1990;16:617-623.

4.  Palatini P, Mormini P, Santonastaso M, et al, for the HARVEST Study Investigators.
Target organ damage in stage I hypertensive subjects with white coat and sustained hypertension: results from the HARVEST Study.  Hypertension. 1998;31:57-63.

5.  Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham Study.
Am J Cardiol. 1976;38:46-51.

6.  Hypertension Detection and Follow-up Program Cooperative Group.
Five-year findings of the Hypertension Detection and Follow-up Program (HDF), 1: reduction in mortality of persons with high blood pressure, including mild hypertension.  JAMA. 1979;242:2562-2571.

7.  SHEP Cooperative Research Group.
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension.
JAMA.  1991;265:3255-3264.

8.  Straesen JA, Fagard R, Thijs L, et al, for the Systolic Hypertension Europe (Syst-Eur) Trial Investigators.
Morbidity and mortality in the placebo-controlled European Trial or Isolated Systolic Hypertension in the Elderly.
Lancet. 1977;350:757-764.

9.  Mancia G, Sega R, Bravi C, et al.
Ambulatory blood pressure normality: results from the PAMELA Study.
J Hypertens.  1995;13:1377-1390.

10.  Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Porcellati C.
White-coat hypertension: not guilty when correctly defined.  Blood Press Monit. 1998;3:147-152.

11.  Moser M.  Ambulatory blood pressure monitoring: how important is it in estimating risk or guiding therapy?
J Clin Hypertens. 2001;3:11-13.

12.  The Australian Therapeutic Trial in Mild Hypertension. Lancet. June 14, 1980:1261-1267.

13.  Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.  Arch Intern Med. 1997;157:2413-2446.

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