The addition of ambulatory blood pressure monitoring to conventional clinical measurement to define blood pressure status in clinical practice has added new complexity to the process, as the separation of normotension and hypertension can be assessed independently by each of the 2 methods. Thus, we have 4 potential groups of patients who are normotensive by both methods (true normotensives); second, hypertension in both (true or persistent hypertensives); thirdly, hypertensive according to clinical measurement and normotensive according to ambulatory measurement (white coat hypertensives); and fourth, normotensive measurement by clinical measurement and hypertension by ambulatory measurement. From a clinical point of view, the first 2 groups are easy to solve because both methods give the same classification. More interesting are the groups in which there is disagreement. A third group, usually referred to as white-coat hypertensives or, less commonly, isolated office hypertensives, has been extensively studied and is generally accepted as having a relatively low risk of cardiovascular morbidity,1 a view consistent with the notion that ambulatory pressure provides a better predictor of risk than clinical pressure.
Until now, little attention has been paid to the fourth group, whose condition has been given the infamous titles of "white coat reversal hypertension" or "white coat normotension." If it is true that ambulatory pressure provides a better classification of risk, this would mean that these individuals should be considered truly hypertensive, as discussed below. We also propose to call this phenomenon "masked hypertension" on the basis that hypertension is not detected by routine methods. "Undiagnosed ambulatory hypertension" is another possible name. But what evidence is there that this group deserves recognition as a separate entity, as opposed to being made up of people who had unusually high ambulatory pressure or low clinical pressure on that particular occasion? There are potentially several questions that could be asked to decide this issue. First, the phenomenon of masked hypertension would be more likely if it could be shown to be reproducible in repeated testing. To our knowledge, this issue has not been investigated. Second, patients with masked hypertension should show more extensive target organ damage than true normotensive subjects. We are on safer ground here. The first study to address this issue was our publication in 19992, in which we showed that the masked hypertensive group had left ventricular mass and carotid atherosclerosis that were greater than true normotensive subjects and that were similar to true hypertensives. Left ventricular mass index was 73 g/m2 in true normotensive subjects, 86 g/m2 in masked hypertensives, and 90 g/m2 in true hypertensives. Carotid plaque was present in 15% of right normotensives and in 28% of masked and right hypertensives. A recent analysis of PAMELA3 data, a population-based study of 3200 Italians, classified subjects into the 4 groups we described above. Subjects with treated hypertension were excluded from this analysis; 67% were true normotensives, 12% true hypertensives, 12% white-coat hypertensives, and 9% masked hypertensives. The mean clinical pressure in the masked hypertensives was 129/84 mm Hg, which, although still in the normal range, was higher than in the true normotensives (112/77 mm Hg). Left ventricular mass index was higher in masked hypertensives (91.2 g/m2) than in right normotensives (79.4 g/m2) and similar to that in right hypertensives (94.2 g/m2). A third question is whether masked hypertensives are at increased risk of cardiovascular morbidity. That has yet to be determined.
What factors can lead to masked hypertension? Basically, there are 2 groups of factors that are not mutually exclusive. First, clinical pressure may be relatively low relative to ambulatory pressure, or second, there may be factors that selectively increase ambulatory pressure. Regarding the first possibility, it is generally true that the daily ambulatory pressure is higher than the clinical pressure in truly normotensive subjects, but in hypertensive subjects the clinical pressure tends to be higher. One reason is "regression to the mean" because hypertension status is almost always based on clinical pressure. Many factors can selectively increase ambulatory pressure. For example, we showed many years ago that smokers tend to have high daytime ambulatory blood pressure (when they are likely to smoke) compared to clinical blood pressure (when they are unlikely to smoke).4 Second, subjects who are more physically active during the day will tend to have a higher daily pressure.
Several population-based studies have compared clinical and ambulatory blood pressure. 5-7 Some have shown that diurnal pressures are slightly higher than clinical pressure, while others have found the opposite. 8 One important finding from the Italian population-based study was that ambulatory pressure showed a much smaller increase with age than clinic pressure. 7 In a Danish study, 886% of men aged 42 years had daily pressures higher than clinic pressures, while age 72 only in 51%. Thus, the white coat effect (difference between clinic and ambulatory pressure) is more pronounced in the elderly, and since masked hypertension is equivalent to the negative white coat effect, it is reasonable to assume that masked hypertension will become less prevalent with increasing age.
The main problem concerns the prevalence of masked hypertension. Although there are no definitive numbers, the available information is alarming. In a study of 319 clinically normotensive volunteers, all of whom had 5 clinical measurements and 12-hour daily ambulatory blood pressure measurements, Selenta et al9 found that 23% had masked hypertension, defined as daytime blood pressure >135/85 mm Hg. Subjects with masked hypertension were mostly male, ex-smokers, and older, and consumed more alcohol. The issue of masked hypertension was also addressed by Belkic et al,10 who described it as occult hypertension in the workplace. We found that 36 of 267 men (13.5%) in the Cornell Worksite study had masked hypertension, defined as daily ambulatory diastolic pressure >85 mm Hg and clinic pressure <85 mm Hg. Two population studies have also described this phenomenon. The first was the Ohasama study, 11 conducted in a small Japanese city, which reported that 10.2% of subjects with normal screening blood pressure had ambulatory pressures in the “borderline hypertensive” range (>133/78 mm Hg on average over 24 hours). ) and another 3.2% in the definitely hypertensive range (24-hour blood pressure >144/85 mm Hg). The second was the PAMELA study cited above.
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