Office blood pressure (BP) is very frequently higher than that measured out of the office. This difference, recognized for more than 70 years , has been ascribed to an alert reaction in response to a situation that is unusual for the patient and has been termed the white coat effect. White coat hypertension (WCH), also described as isolated office or isolated clinic hypertension, is a condition in which the BP is elevated at repeated visits to the office and is normal when measured either on ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) in untreated hypertensive individuals. The Guidelines of the European Society of Hypertension and European Society of Cardiology for the treatment of hypertension  use the term WCH only for untreated hypertensive patients. We consider that the same definition should apply to treated hypertensive individuals. Conversely, BP can be normal in the office and elevated when measured by ABPM or HBPM; this situation is known as masked or isolated ambulatory hypertension and can be seen in untreated as well as in treated hypertensive individuals. In this case, it is termed masked uncontrolled hypertension (MUCH). This last term is not recognized by the above quoted Guidelines, which consider masked hypertension to only apply to untreated patients.
As can be seen from the position paper on ABPM of the European Society of Hypertension , to qualify an untreated or a treated patient as having WCH, the three values, 24-h ambulatory BP, awake ambulatory BP and a sleep ambulatory BP have to be below the normal limits on ABPM. To qualify a patient as having masked hypertension or MUCH the opposite is required, in that the three values need to be simultaneously above normal limits.
The great majority of data contained in the literature do not fulfil these criteria, and, in general, only the value of daytime or of 24 h ambulatory BP has been considered to qualify patients for one of the three groups described above.
Future studies, particularly those considering CKD, should to take into account separately night-time BP because it has been shown to be altered in CKD patients coincidentally with an increased pulse pressure (PP) [4▪]. CKD is characterized by a very high prevalence of arterial hypertension and, hence, the consequences of WCH, masked hypertension and MUCH are particularly important in this situation because they impact on achieving adequate control of BP, and remains a matter of debate in CKD . Indeed, CKD leads to a severe increase in morbidity and mortality  such that an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2 is among the five main causes of acute coronary syndrome  and of stroke . Consequently, in these patients, individual assessment of cardiovascular risk requires not only a broad evaluation of cardiovascular risk factors but also a careful assessment of BP, which should comprise not only office BP but also out-office BP, ideally including night-time BP.
This study reviews the usefulness of out-of-office BP for the diagnosis and the management of hypertension in patients with CKD. This is not to suggest that office BP should be disregarded and we will take the opportunity to stress how it could be improved.
DISCREPANCIES IN BLOOD PRESSURE CATEGORIZATION BETWEEN BLOOD PRESSURE MEASURED IN DIFFERENT SETTINGS IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Population-based studies reviewed by Fagard and Cornelissen  found an overall prevalence of WCH of 13%. This figure increases to 32% in hypertensive individuals. The prevalence of masked hypertension in untreated hypertensive individuals varies from 10 to 40% , while the prevalence of MUCH has been shown to be above 30% [11▪,12].
In comparison, the prevalence of WCH in patients with CKD was estimated in a meta-analysis of six studies to be 28%, whereas the estimated prevalence of masked hypertension was 8% . The figure for masked hypertension may be much higher in African-American patients  according to the data published during the same period. In more recent data , obtained from a single cohort of 14 382 treated and untreated hypertensive patients in Spain, as many as 5693 patients (39.5%, stages 1–5) exhibited, CKD defined by the presence of an estimated GFR (CKD-EPI) below 60 ml/min/1.73 m2 or albuminuria above 30 mg/g of creatinine. In this group of patients, 72.6% were treated, but in the remaining 27.4%, no drugs were being used. The vast majority of patients not treated corresponds to white coat hypertensive individuals. Masked hypertension, or predominantly MUCH, was seen in 32.1% of patients with office BP of less than 140/90 mmHg. It appears, therefore, that patients with CKD are more likely to have discrepancies between office and out-of-office BP measurement. In this study, analysis of ABPM was based on the mean of 24 h BP .
THE SIGNIFICANCE OF WHITE COAT HYPERTENSION, MASKED HYPERTENSION AND MASKED UNTREATED HYPERTENSION IN PATIENTS WITH CHRONIC KIDNEY DISEASE
It remains a matter of debate whether WCH is an innocent phenomenon , although masked hypertension and MUCH are well recognized as situations accompanied by an elevation in global cardiovascular risk . In this context, it is important to stress that night-time BP is more closely related to cardiovascular risk than 24 h and day-time BP . This is noteworthy, as patients with CKD frequently exhibit elevated night BP levels and a nondipping pattern [4▪,18]. In a recent publication, Minutolo et al.[19▪▪] studying 489 consecutive patients with CKD (stages 1–5) described the effect of having clinic or ambulatory BP as not addressing the cardiorenal risk. A composite cardiovascular event outcome consisting of fatal and nonfatal myocardial infarction and stroke, congestive heart failure, revascularization, peripheral vascular disease and nontraumatic amputation, together with a composite renal outcome including maintenance dialysis therapy and death, were analysed during a median follow-up of 5.2 years. The findings showed that WCH was a low-risk condition, whereas MUCH was associated with a higher cardiorenal risk similar to that observed in patients with simultaneous elevation of office and ambulatory BP.
Knowing that masked hypertension and MUCH are associated with an increased risk, it would very useful to be able to predict among patients with CKD who is the most prone to exhibit those conditions. In one cross-sectional study of 1116 people with CKD, age was reported to be of the main determinant of masked hypertension, which was associated with target organ damage (lower eGFR and higher left ventricular mass index) . This observation is in agreement with the description of an increase in both PP and night-time BP in patients with CKD, again in association with more severe organ damage [4▪].
Most data supporting the use of ABPM in CKD have been accumulated in adult patients. It is however relevant that the same applies to children with CKD who have evidence of masked hypertension in 35% of cases .
All these data taken together show convincingly that ABPM should be the standard procedure to assess BP and cardiovascular risk in patients with CKD, keeping in mind that at present more data are needed. It is particularly important that future studies investigate which part of WCH develops to normotension or to established hypertension . There is also the need for additional studies to assess the capacity of the different classes of antihypertensive agents alone or in combination to control masked hypertension and MUCH.
THE SIGNIFICANCE OF WHITE COAT HYPERTENSION AND MASKED HYPERTENSION ASSESSED BY HOME BLOOD PRESSURE MONITORING
HBPM, using an adequate technique, has become very popular in recent times and it is well accepted as a tool to detect WCH and masked hypertension . Furthermore, it has been proposed that HBPM could substitute for office BP measurement . Data regarding the use of HBPM in CKD are scarce and it is unfortunately not yet clear whether we can extrapolate observations made in hypertensive individuals with preserved renal function [24,25] to patients with CKD. A major shortcoming of HBPM in CKD is the lack of data on night BP levels that makes this technique less accurate for an optimal evaluation of cardiovascular risk in CKD. At present, HBPM appears useful to assess the quality of BP control during chronic treatment, after the initial detection of WCH, masked hypertension or MUCH.
THE NEED TO IMPROVE OFFICE BLOOD PRESSURE MEASUREMENT
Clinical practice guidelines have traditionally recommended manual BP measurement as the standard method for diagnosing hypertension. At present, BP cannot be estimated using a mercury sphygmomanometer in many countries due to safety concerns related to mercury. Auscultatory or oscillometric semiautomatic sphygmomanometers are used instead. These devices should be adequately validated and checked periodically through calibration. The advent of automated office BP (AOBP) represents a new alternative to obtain a more adequate evaluation of BP levels in the office [26,27▪]. AOBP is performed by obtaining multiple BP readings using a fully automated sphygmomanometer with the patient resting quietly and alone. AOBP provides more accurate BP readings and correlates better with ABPM and HBPM values as well as with the presence of target organ damage .
If ABPM and HBPM are not available, it is important to increase the number of office BP readings obtained at every single visit.
Precise assessment of BP is particularly relevant in patients with CKD in whom cardiovascular and renal risks are closely linked to BP levels. Among the techniques available to measure BP, ABPM should become the standard for detection not only of WCH but also of masked hypertension and MUCH. In particular, ABPM is important to evaluate night-time BP for a nondipping pattern as well as masked hypertension and MUCH. This is not to say that we should not use HBPM nor office BP measurement. The first is adequate for the follow-up of BP control beyond the initial detection of WCH, masked hypertension or MUCH. Repeated measurements of office BP at every single visit are required to improve the reliability of this technique. In the future, even if techniques for office BP measurement improve, ABPM will remain essential for several reasons, including particularly the evaluation of night-time BP.
Financial support and sponsorship
This work was supported by grants from Instituto de Salud Carlos III (PI11/02432, PIE13/00045, PI14/01841, CP15/00129), Fundación Mutua Madrileña, Fundación Eugenio Rodriguez Pascual and Fondos FEDER.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
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