What stands behind masked hypertension?

The diagnosis and treatment of hypertension are traditionally based on blood pressure (BP) readings taken by a doctor. There are many good reasons to rely on such readings. They are a valuable indicator of cardiovascular risk, and long-term reduction of these office or clinic BP (referred to below as casual BPs) markedly diminishes the occurrence of cardiovascular and renal complications. Even the most recent interventional outcome trials have used casual BPs as inclusion and target BPs [1,2]. Routine measurement of BP in everyday practice remains essential not only to detect hypertensive patients, but also to monitor the impact of lifestyle changes and antihypertensive therapy. To be reliable, casual BPs should be obtained in standardized conditions using validated devices, and repeated on different visits at several weekly or monthly intervals, unless the severity of hypertension or the presence of target organ damage requires a prompt BP lowering [3]. Casual BPs often differ greatly from those prevailing while the patient goes through his everyday activities in his usual environment [4–7]. In the individual patient, the magnitude of the BP changes elicited by the presence of a doctor is largely unpredictable. Most often BPs measured by the patient himself at home or monitored during 24 h using a portable recorder (referred to below as ambulatory BPs) are lower than BP readings taken by a doctor. Actually, many subjects considered as hypertensive based on casual BPs are not truly hypertensive as they have normal ambulatory BPs (white-coat hypertension). Conversely, ambulatory BPs may be higher than casual BPs in some individuals, and the diagnosis of hypertension may even be missed by taking into account only casual BPs (masked hypertension) [8,9]. Bobrie and his colleagues [10] have examined in their review the clinical significance of this latter condition, which is hidden unless 24-h ambulatory BP monitoring or self-measurement of BP is performed. This is a critical issue as BPs measured outside the medical setting are better correlated with target organ damage than casual BPs [11–13]. As recalled by the authors, a variety of terms have been proposed to describe the phenomenon characterized by elevated BPs in the face of normal casual BPs, but ‘masked hypertension’ has become the most widely used [14,15]. Other denominations, such as ‘isolated home hypertension’ or ‘isolated ambulatory hypertension’ have the advantage of describing more explicitly this type of BP behavior. Some patients might exhibit an increase in both casual and ambulatory BPs, with the latter being higher than the former. This pattern may be described as a ‘reverse white-coat effect’, but not as a ‘masked hypertension’, since hypertension is present regardless of the condition of BP measurement. The analysis of Bobrie and his colleagues [10] shows that the prevalence of masked hypertension detected in the general population by ambulatory BP monitoring or self-BP measurement varies between 10 and 20%. The values are very similar in treated hypertensive patients. Patients with masked hypertension carry an increased cardiovascular risk compared with normotensive individuals, close to that of patients with established hypertension [14–18]. A systematic screening for this common clinical entity would therefore be expected to have important implications in terms of public health. There exists an analogy between masked hypertension and white-coat hypertension, both conditions being characterized by divergent casual and ambulatory BPs. Fig. 1 represents schematically the BP pattern of a patient with white-coat hypertension (patient 1) and a patient with masked hypertension (patient 2). The example is based on systolic BP. The thresholds for defining casual and ambulatory hypertension are 140 and 135 mmHg, respectively. A 5 mmHg difference between the two types of BPs may occasionally suffice to ascribe a given patient to the diagnosis of white-coat or masked hypertension. But what does a 5 mmHg BP difference really mean, considering the normal circadian rhythm of BP and the physiological changes in BP occurring during physical exercise and mental stress? The reproducibility of casual BPs is moderate, and for sure, worse than that of ambulatory BPs. This is well illustrated in Fig. 2, taken from a study which aimed to assess the 1 month reproducibility of ambulatory BPs in 75 untreated hypertensive patients [19]. Differences in casual BPs exceeding 5 mmHg and even 10 mmHg were common. With regard to ambulatory BPs, differences were still existing, but of smaller magnitude. This better reproducibility can be explained by the large number of measurements obtained during ambulatory BP monitoring, the mean of all readings being less sensitive to marked BP fluctuations.Fig. 1Fig. 2The arbitrary character of the definition of BP normalcy is another source of confusion. No doubt that a 2 mmHg difference in BP is, when considering the general population, clinically relevant in terms of cardiovascular risk. In the individual subject, however, a 2 mmHg difference does not necessarily bear a relationship to long-term prognosis. Is a patient with a casual systolic BP of 141 mmHg and an ambulatory systolic BP of 134 mmHg truly different from a patient with a casual systolic BP of 139 mmHg and an ambulatory systolic BP of 136 mmHg? The former would be categorized as having white-coat hypertension, and the latter masked hypertension. This theoretical example illustrates an extreme situation, but nevertheless leading us to wonder whether white-coat and masked hypertension represent, in some cases, a statistical problem linked to the inherent variability of BP and the ‘yes or no’ cut-off values used to discriminate normohypertension and hypertension. White-coat hypertension is widely accepted as a clinical entity, which is reflected by the fact that recent guidelines for the management of arterial hypertension acknowledge the usefulness of self-measurement of BP and 24 h ambulatory BP monitoring in certain conditions, in particular when there is a large variability of casual BPs or high casual BPs in subjects otherwise at low cardiovascular risk [20]. It is far more difficult to position masked hypertension. On the basis of the present knowledge, the search for this ‘abnormal’ BP pattern in every individual with normal casual BPs is for sure not justified, and would be anyway impossible due to practical constraints. Ambulatory BP measurements may be included in the work-up of subjects with normal casual BPs if there is evidence for target organ damage inappropriate for BP levels, or if multiple cardiovascular risk factors coexist [20]. Masked hypertension seems to be frequently associated with male sex, stress or increased physical activity during daytime, obesity, excessive tobacco or alcohol consumption [14]. The occasional detection of masked hypertension in a subject with no target organ damage should urge one to implement or intensify lifestyle measures and ensure a regular follow-up: such an attitude appears fully justified, even if the definitive data to support this claim are still missing. The analysis of Bobrie and his colleagues [10] provides a balanced view on masked hypertension and points to the need for further trials to establish in which circumstances the identification of masked hypertension should be encouraged. Masked hypertension is a new ‘black box’ for the practicing physician, and it remains unclear whether opening it would provide benefit to the patients. At present, there is no reason to systematically search for target organ damage in subjects with normal casual BPs, no reason therefore to screen routinely for masked hypertension.