In the past two decades, techniques for the measurement of blood pressure outside the medical setting have unmasked highly prevalent situations. A significant proportion of patients with office blood pressure levels above the thresholds for diagnosing hypertension or above the limits where those being treated are considered to be adequately controlled actually show normal ambulatory blood pressure levels. These patients have white-coat hypertension if untreated or false resistance to antihypertensive therapy because of the white-coat effect if treated. However, some individuals with normal office blood pressure measurements show elevated ambulatory blood pressure levels, and thus have masked hypertension if untreated or masked uncontrolled hypertension if treated. When looking for white-coat hypertension in patients with elevated office blood pressure levels or when looking for masked hypertension in office-controlled patients, up to one in three patients in each scenario would have white-coat or masked hypertension. Although related clinical factors, such as age, gender and global cardiovascular risk, are associated with both conditions, their abilities to predict such a misclassification are very low. Thus, assessing individual blood pressure levels by means of an ambulatory technique, particularly ambulatory blood pressure monitoring, is now considered a priority in diagnosing hypertension and in evaluating hypertension control.
Cardiovascular disease is the leading cause of mortality worldwide, accounting for 30% of all deaths.1 Having a blood pressure (BP) above optimal limits is the main risk factor for cardiovascular and renal diseases, thus constituting the main determinant of mortality and disability worldwide.2 In spite of the efforts made by health services to prevent cardiovascular disease, the prevalence of hypertension is growing, and it is expected to affect up to one in three adult individuals by 2025.3
The vast majority of the body of knowledge about hypertension has been built on the assessment of BP by means of the traditional auscultatory measurement at an office or clinic. Nevertheless, the main limitation of this technique, apart from observer bias, comes from offering only a momentary BP measurement, usually under circumstances that can influence the BP level.4 To improve the assessment of actual 24-h BP levels, techniques for obtaining automated BP profiles over 24 h and BP measurements at home have been developed. Ambulatory BP monitoring (ABPM) is now the gold standard method for evaluating true BP levels, providing a more accurate estimation of true individual BP.5, 6, 7, 8, 9, 10, 11, 12
The authors searched PubMed for ‘white-coat hypertension (WCH),’ ‘white-coat effect,’ ‘isolated clinic hypertension,’ ‘masked hypertension (MH)’ and ‘isolated ambulatory hypertension.’ Inclusion criteria for the present review were (1) studies from national and international registries of ABPM and/or home BP monitoring, and (2) studies containing information about the prevalence of WCH in hypertensive patients and the prevalence of MH in normotensive office-controlled patients, respectively.
Misclassification of blood pressure status in the office
In clinical practice, the main indication for ABPM is to accurately determine an individual’s BP.4 Misclassification of BP status can occur in one out of three hypertensive subjects.13, 14, 15 Disagreements between office and ambulatory BP assessments arise from two conditions, that is, WCH and MH.
The term WCH was introduced by Pickering et al.16 to describe the condition, in which untreated patients have high BP readings at their doctor’s office but normal BP levels outside the medical setting. This situation is also called isolated clinic hypertension. The term white-coat effect has been defined as the rise in BP that occurs in the medical environment; patients presenting with an office BP at least 20 mm Hg systolic and/or 10 mm Hg diastolic higher than the awake ambulatory BP have been designated as having a significant white-coat effect.4 Treated patients presenting with uncontrolled BP at the office but normal ambulatory BP values have been designated as pseudo-resistant or false-resistant hypertensives because of the white-coat effect.4 In the epidemiologic approach to hypertension control, this condition has been termed office-resistant control or underestimation of BP control at the office.13
MH is defined as untreated individuals with normal office BPs, usually <140/90 mm Hg, but elevated BPs on ABPM or home BP measurements, usually ⩾135/85 mm Hg for daytime values. MH and its related risks have previously been recognized for both treated and untreated subjects.4,15,17, 18, 19 For treated hypertensive patients, the preferred term is masked uncontrolled hypertension.
Current definitions of white-coat hypertension and masked hypertension
Until now, many definitions have been used in assessing WCH and MH. Initially, studies defined WCH as having an office systolic BP ⩾140 mm Hg and/or diastolic BP ⩾90 mm Hg and an out-of-office daytime (awake) BP <135/85 mm Hg. More recently, studies have defined WHC as an elevated office BP but a 24-h ambulatory BP <130/80 mm Hg, recognizing that nocturnal BP has a remarkable impact on a patient’s prognosis.
The current definition of WCH, as recently proposed in an ad hoc position paper of the European Society of Hypertension Working Group on BP monitoring, includes normality in the three conventional ABPM periods, that is, daytime, nighttime and 24 h, to diagnose WCH.4 As mentioned above, the term WCH, or isolated clinical hypertension, should be reserved for untreated patients; thus, the term is used mainly for diagnostic purposes. Treated patients with an office BP ⩾140/90 mm Hg and normal ambulatory BP values should be designated as having pseudo-resistant or false-resistant hypertension because of a white-coat effect. By contrast, MH should be defined in untreated patients who have normal office BP levels but a daytime BP ⩾135/85 mm Hg, nighttime BP ⩾120/70 mm Hg or 24 h BP ⩾130/80 mm Hg. When this situation occurs in a treated patient, the term ‘masked uncontrolled hypertension’ should be used.4,15 These definitions are summarized in Table 1.
Differences between office and ambulatory blood pressures
As stated above, many patients present with a stress reaction when visiting a doctor or nurse, or even when performing a self-automated BP measurement in a medical environment, and show an office BP that may be significantly higher than their BP levels during normal daily activities. Data from 51 573 hypertensive patients included in the Spanish ABPM Registry showed that daytime BPs were ≈16/8 mm Hg lower than office BPs, and this difference reached ≈20/10 mm Hg when comparing office and 24 h BPs (Figure 1). The higher the BP or global cardiovascular risk level, the greater the difference between office and ambulatory BP values, as shown by our group in the comparison between patients with high-risk hypertension and patients with low-to-moderate-risk hypertension. These data are summarized in Table 2.20 We also discovered significant gender differences between office and ambulatory BP levels. Women showed higher office BP values than men, despite receiving the same amount of antihypertensive treatment. These office differences were related to a more advanced age (63.9 vs. 60.1 years) and a higher prevalence of obesity (44.4 vs. 37.3%) in women. Nevertheless, rounded differences between office and 24 h BP levels were 18/9 mm Hg in men and 22/13 mm Hg in women. Consequently, women showed higher control rates of ambulatory BP levels than men.21
Prevalence of white-coat hypertension in the Spanish ABPM Registry
The Spanish ABPM Registry was developed in 2004 with the goal of promoting the use of ABPM in primary care settings. More than 1200 general physicians were trained in the ABPM technique and in the use of a web platform (www.cardiorisc.com) that receives ABPM data and clinical records from individual patients and generates a results report in real time. Data are stored in a safe database and have been used for a series of investigations including the assessment of WCH in general treated hypertensives,13 as well as different hypertensive populations, that is, untreated hypertensives,14 treated male versus female hypertensives,21 hypertensives with coronary heart disease,22 very elderly hypertensives,23 resistant hypertensives,24 diabetics25 and hypertensives with chronic kidney disease.26 The prevalence of WCH ranged from 15.5 to 29.2% in untreated patients, and the prevalence of false-resistant hypertension due to the white-coat effect ranged from 24.2% in treated males to 37.5% in hypertensives resistant to three or more drugs. Complete data about the prevalence of WCH and false resistance due to the white-coat effect are displayed in Table 3. In one of the analyses, the abilities of physicians to predict WCH in untreated hypertensives was assessed but yielded discouraging results. When WCH was suspected, only 33.7% of the results obtained were positive, and when it was not suspected, 26.0% of patients displayed WCH. Predictors of WCH as a cause of false office resistant control are displayed in Table 4. The most consistent variables associated with WCH were age, female gender, a higher body mass index, and less target-organ damage or established cardiovascular disease.
Prevalence of white-coat hypertension in other national and international registries
Most cited information about WCH diagnosed by means of ABPM in national registries comes from Italy,18,27, 28, 29 Ireland,30 Japan31,32 and Denmark.33,34 Furthermore, the Finn-Home and Didima studies assessed WCH using self-administered home blood pressure monitoring.35,36 Finally, the International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes (IDACO) study included a large number of subjects from several countries.37
Data about WCH within subjects with office hypertension are summarized in Table 5. The prevalence of WCH ranged from ≈10 to ≈50%, depending on the definition of normal for ambulatory BPs and/or on the studied population. All of these studies showed that WCH occurred very frequently, supporting the previous idea that 30–40% of the subjects classified as having hypertension in a medical environment have normal ambulatory BPs.38 Consequently, ABPM has been indicated as the first step for diagnosing hypertension after the detection of an office BP ⩾140/90 mm Hg by current British NICE (National Institute for Health and Clinical Excellence) recommendations.39 Moreover, recent guidelines from the European Societies of Hypertension and Cardiology defined hypertension by both office and ambulatory thresholds and indicates assessing ambulatory BPs to rule out WCH in a broad range of situations, such as grade 1 hypertension at the office or high office BPs in individuals without asymptomatic organ damage and at low cardiovascular risk.40 Furthermore, ambulatory-based assessments of hypertension control are far better than office-based ones, conveying the encouraging message to physicians that the patients are faring better than shown by the data retrieved in in-office evaluations.13 In some specific patients, such as resistant hypertensives, the prevalence of the white-coat effect could be even higher than within the general hypertensive population,24 so assessing ambulatory BPs has also been considered to be the first procedure for diagnosing resistant hypertension.41
Prevalence of masked hypertension in national and international registries
MH is considered to be the opposite of the more commonly recognized WHC. As stated before, the term MH should be used for untreated individuals who have normal office BPs but elevated ambulatory BPs. For treated patients, this condition should be termed masked uncontrolled hypertension.4,15 Assessing the prevalence of MH in whole samples of a population of hypertensives would underestimate the magnitude of the problem. The MH prevalence in population studies averaged 13%19 and was previously estimated as <10% of the global hypertension population (Figure 2). Nevertheless, when looking for MH within office-controlled patients, up to 1 in 3 could have MH. Table 6 shows data regarding the prevalence of MH in various cohorts of controlled hypertensives from the Spanish ABPM Registry.15,21, 22, 23, 24, 25, 26 Table 7 shows corresponding data from other national and international registries, including those mentioned in the WCH section,18,27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 and 3 other studies from Sweden, Japan, and France.42, 43, 44
Patients with WCH are at risk of being managed as true hypertensives, undergoing laboratory tests, and overtreatment. On the other hand, patients with MH are at risk of under-detection and under-treatment. Because over one in three office-controlled patients could have MH, predictors of this condition are of key importance to detecting an ambulatory lack of BP control. In a recent analysis of the Spanish ABPM Registry, the clinical profile of patients with MH included male gender, obese, longer duration of hypertension, smoking habit, and diabetes: that is, patients with a high risk of an adverse cardiovascular event. Office BPs in the high-normal range (systolic 130–139 mm Hg and/or diastolic 85–89 mm Hg) also predicted MH.15 These findings were consistent with data from previous studies looking for predictors of MH.19,43,44
Physicians are prone to two types of misclassifications when assessing BP statuses solely at the office. WCH and MH are highly prevalent conditions that could be present in up to one in three patients with seemingly uncontrolled BP and one in three with controlled BP, respectively. Patients with WCH are more frequently women, older, obese and have a low cardiovascular risk profile. Patients with MH are more frequently men, younger, obese, smokers, and have high-normal BPs at their doctor’s office and a higher cardiovascular risk. Nevertheless, many patients with any of these predictors could have WCH or MH. Assessing ambulatory BPs using ABPM (and possibly by home BP monitoring if ABPM is not available) should be encouraged in the current management of hypertensive patients, both for diagnosis and for evaluation of BP control.
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Gorostidi, M., Vinyoles, E., Banegas, J. et al. Prevalence of white-coat and masked hypertension in national and international registries. Hypertens Res 38, 1–7 (2015). https://doi.org/10.1038/hr.2014.149
- ambulatory blood pressure monitoring
- blood pressure control
- masked hypertension
- white-coat hypertension
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