Reversed white-coat hypertension: definition, mechanisms and prognostic implications

In this issue of the journal, Wing et al. 1 properly mention that the condition they refer to as ‘reversed white-coat hypertension’ had already been described in previous studies. They also emphasize, however, the main novel finding of their study. While in previous studies ‘reversed white-coat hypertension’ was regarded as rare, in their study, this condition was found to have a noticeable prevalence (i.e. to characterize from approximately one-third to one-half of the hypertensive population based on systolic and diastolic blood pressure measurements, respectively). This means that when physicians find an elevated office blood pressure, the possibility that daytime ambulatory values are greater rather than lower (as it may seem logical from the distribution of the two pressures in the general population) (Fig. 1) 2 should be regarded as by no means remote. Interestingly, this is the case also in the elderly hypertensive individuals studied by Wing et al. in which the average difference between the higher office and the lower ambulatory blood pressure values is particularly pronounced 3.Fig. 1: Frequency distribution of the office systolic and diastolic blood pressure values (SBP and DBP, respectively) in the PAMELA population versus (a) home blood pressure, (b) 24 h average blood pressure, (c) daytime blood pressure and (d) night-time blood pressure. The upper limit of normality office blood pressure (140/90 mmHg) and the corresponding values on the home, 24 h, day and night blood pressure distribution curves are indicated. The portion of the distribution curves to the right of the upper normality values are indicated by dark or shaded areas. Adapted with permission 2. The ‘reversed white coat hypertension’ addressed by Wing et al. 1 leads to discussion of at least three issues on which evidence is limited and thus speculation is inevitable. The first issue concerns the mechanisms responsible for making daytime average blood pressure greater than office blood pressure, at variance to what happens in the majority of hypertensive individuals. Wing et al. 1 discuss this at length and offer several findings of interest. They found that ‘reverse white-coat hypertension’ was related to cigarette smoking and more frequent in individuals on antihypertensive treatment or in whom office blood pressure was closer to the threshold classically dividing hypertension from normotension. This can be explained by the results obtained in previous studies. These have shown that (i) cigarette smoking elicits a marked and prolonged (up to 30 min) pressor response 4–7. In heavy smokers, this can substantially elevate daytime average blood pressure 7,8 and bring it above office values which are normally taken after a few hours abstinence from smoking. (ii) In the general population, the difference between office and average ambulatory blood pressure is positively related to the former value 9 and, in hypertensive patients, it becomes less during antihypertensive treatment 10,11. This means a greater theoretical chance for ambulatory blood pressure to exceed office blood pressure, which is exactly what Wing et al. have demonstrated 1. The second issue is what should be the best definition of the condition characterized by an average ambulatory blood pressure greater than office blood pressure. My opinion is that ‘reversed white-coat hypertension’ is not appropriate because it focuses on the involvement of an alerting reaction and leads people to think that the one elicited by the monitoring device may be greater that the one brought about by measuring blood pressure in the clinical environment. We have shown, however, that, except for a short-lasting initial period, automatic ambulatory blood pressure measurements do not trigger any alerting reaction and pressor response 12. We have also shown that the difference between the greater office and the lower ambulatory blood pressure is not related to the true pressor response to blood pressure measurements by a doctor, which was accurately quantified by having the patients on beat-to-beat prolonged blood pressure monitoring 13. This led the WHO/ISH Guidelines to not use the term ‘white-coat hypertension’ for this condition but the less mechanistic and more descriptive term ‘isolated office hypertension’ 14, a similar semantic caution being probably desirable also for the opposite condition (greater ambulatory than office blood pressure) described by Wing et al. 1. This would avoid a conceptual inconsistency: namely, that the difference between office and ambulatory blood pressure obviously also depends on the latter and that an ambulatory value lower, similar or greater than the office value may be brought about by the effect on daily blood pressure of behaviours (physical activity, work, smoking, etc.) which have nothing to do with the alerting reaction to blood pressure measurements by a doctor or a nurse (Fig. 2).Fig. 2: Schematics showing that the differences between office and ambulatory blood pressure may increase or decrease in relation to a reduction or an elevation of ambulatory values, with no change in office blood pressure and thus no relationship with the white-coat effect. The third and last issue concerns the prognostic significance of an ambulatory blood pressure greater than the office one. The observations of Wing et al. 1 do not shed light on this issue, although the relatively large number of patients enrolled makes it possible that, in the longitudinal phase of the study, a relationship between this condition and cardiovascular morbid or fatal events will be established. In the meantime, Wing et al. 1 correctly emphasize that previous observations have shown subjects with an ambulatory blood pressure greater than office blood pressure to have a greater prevalence and severity of organ damage. Furthermore, we have recently observed that the PAMELA population subjects with an office blood pressure below 140/90 mmHg but with a 24-h average blood pressure above its upper normality value (and close to, similar to or greater than office blood pressure) had a prevalence of echographic left ventricular hypertrophy much greater than that of control individuals 15. Thus, this condition may have an adverse prognostic significance, making its identification clinically important. This implies that it may be useful to more regularly obtain information not only on office, but also on ambulatory blood pressure to properly identify cardiovascular risk diversities and thus more properly decide on treatment types and goals.