High Blood Press Cardiovasc Prev DOI 10.1007/s40292-014-0044-5
How Should We Manage a Patient with Masked Hypertension? Paolo Palatini
Received: 28 November 2013 / Accepted: 28 January 2014 Ó Springer International Publishing Switzerland 2014
Abstract A number of studies have shown that masked hypertension (MH) confers an increased risk of target organ damage and of cardiovascular events suggesting that patients with MH would benefit from antihypertensive treatment. However, there is no general agreement about how this condition should be diagnosed. Although ambulatory blood pressure monitoring (ABPM) and self blood pressure measurement (SBPM) provide different and complementary clinical information, the recently published ESH/ESC guidelines for the management of arterial hypertension suggest that for initial assessment of the patient, SBPM may be more suitable in primary care and ABPM in specialist care. If SBPM provides borderline values it is advisable to confirm the diagnosis of MH with ABPM. As the prevalence of MH declines with repeated ABPMs the diagnosis of MH should be based on at least two ABPMs. Patients with MH should undergo a careful diagnostic work-up to assess the existence of additional risk factors including a worsened metabolic profile and the presence of target organ involvement. Treatment of the patient with MH should initially be addressed to improve the patient’s lifestyle in order to decrease out-of-office blood pressure and to ameliorate metabolic data. If nonpharmacological measures are insufficient to normalize blood pressure, MH may benefit from pharmacological treatment but no clinical trial has been implemented as yet with the specific purpose of testing this hypothesis. Despite this lack of evidence, the 2013 ESH/ESC guidelines have recommended that in patients with MH also drug treatment should be considered because in patients with MH the risk P. Palatini (&) Department of Medicine, University of Padova, via Giustiniani 2, 35128 Padua, Italy e-mail: [email protected]
of adverse outcome is very close to that in sustained hypertension. When ambulatory blood pressure is measured, pharmacological treatment may be modulated according to whether blood pressure is elevated during daytime hours or during sleep. Keywords Masked hypertension Ambulatory Blood pressure Management Out-of-office
1 Introduction The introduction of self-blood pressure (BP) measurement (SBPM) and of ambulatory BP monitoring (ABPM) in clinical practice have allowed the identification of two new clinical conditions that were previously unknown, the white-coat hypertension and the masked hypertension (MH). The definition of MH is a normal BP measured in the office by a doctor or a nurse and a high BP measured out of the office [1–3]. The fact that the diagnosis of MH relies on out-of-office BP measurement techniques explains why many patients with MH remain unrecognized. A body of evidence has documented that MH confers an increased risk of target organ damage and of cardiovascular events suggesting that patients with MH would benefit from antihypertensive treatment [4–8]. However, the correct identification of the patient with MH is not easy and there is no general agreement about how this condition should be diagnosed. In particular, many doubts still exist on the most appropriate algorithm for the use of the out-of-office BP measurement techniques and on the number of out-ofoffice BP measurements on which the diagnosis of MH should be based. In addition, there is still debate about the clinical variables that should be used for the screening of the normotensive subjects at increased risk of MH who
could benefit from systematic testing. In this review, I will examine the respective role of ABPM and SBPM for the diagnosis of MH and will gain insight into the methodological problems that can be encountered when identifying this condition. Another purpose of this article is to provide recommendations on how a subject with MH should be assessed for deciding whether he or she should be given antihypertensive treatment.
2 ABPM versus SBPM for the Diagnosis of MH As mentioned above, both ABPM and SBPM can be used to identify people with MH, but to what degree these two methods are interchangeable is still a matter for debate. A number of studies have shown that there is often disagreement between ABPM and SBPM in the diagnosis of MH suggesting that the two pressures may identify different types of MH [2, 3]. Stergiou et al.  reported that the diagnosis of MH was confirmed by both methods in only half of their patients. Using ABPM as the gold standard for the diagnosis of MH, Viera et al. reported that the sensitivity and specificity for detecting masked hypertension were 23 and 67 %, respectively, when SBPM was used to assess out-of-office BP . Both methods have advantages and disadvantages over each other. Night-time BP is a potent predictor of cardiovascular morbidity and mortality [11–14] and BP during sleep can be measured only with ABPM. Also, ambulatory BP is measured in freely moving subjects and may vary from one day to the other according to patients daily activities, environmental factors etc. In contrast, SBPM is performed under standardized conditions thereby avoiding the effect of occasional triggers. Although ABPM and SBPM provide different and complementary clinical information , a recent meta-analysis has shown that the prognostic impact of MH is similar for the two methods  although more patients with MH are detected by ABPM (14 %) than by SBPM (11 %) . According to the recently published ESH/ESC guidelines for the management of arterial hypertension, for initial assessment of the patient, SBPM may be more suitable in primary care and ABPM in specialist care . However, if SBPM provides borderline values it is advisable to confirm the diagnosis with ABPM, which is currently considered the reference for out-ofoffice BP.
3 How Many Out-of-Office Measurements? When SBPM is used to make the diagnosis of MH, it should be noted that duplicate morning and evening measurements for 7 days should be obtained, as suggested by
the ESH guidelines for home BP measurement . After discarding the first day measurements, the average of the readings obtained during the subsequent 6 days should be used. This provides a measurement that approximates to average daytime ABPM. For ABPM, there is still controversy about the appropriate number of ABPMs that should be made for a correct diagnosis of MH . In a study of adults with MH in which ABPM was performed twice, the prevalence of MH increased at repeat ABPM . However, of 25 subjects with MH in the first session 18 (72 %) remained ambulatory hypertensive in the second session. A noticeable contribution to our understanding of this phenomenon was given by the results of the CAMBO trial which evaluated the prevalence of MH over three ABPMs within 6 months in a group of patients with systolic hypertension randomized to management with automated BP measurement or continued conventional manual measurement in routine primary care practice . The prevalence of MH on any one of three visits calculated using systolic BP varied between 12 and 17 % in the automated BP measurement group and between 19 and 22 % in the manual BP measurement group. MH was present on both of the first two visits in 7 and 12 % and on all three visits in 6 and 7 % of the two groups, respectively. Similar results were obtained when the diagnosis of MH was based upon both systolic and diastolic BPs. These data show that the prevalence of MH declines with repeated ABPMs and suggest that a correct diagnosis of MH should be based on at least two ABPMs.
4 ABPM for the Diagnosis of MH: Day, Night, or 24-Hour? Although the diagnosis of MH with ABPM has usually been based on daytime BP, today there is controversy about the most appropriate ambulatory BP that should be used for this purpose. This issue has been debated in a recently published document on the use of ABPM in clinical practice . In keeping with the definition of white coat hypertension, it seemed inappropriate to exclude nocturnal BP from the computation of average ambulatory BP because of the important prognostic value of night-time BP. Thus, according to the authors of the document the definition of MH should be extended to include also 24-h BP values. Less attention was paid to isolated nocturnal hypertension, which was shown to predict adverse cardiovascular outcome in some studies [11–14]. The ESH document says that ‘‘BP increase at night triggered by obstructive sleep apnea has been suggested to contribute to MH, in particular when the latter condition is defined by considering 24-h or nighttime ABPM values as out-ofoffice BP reference levels.’’ , which implies that also
How Should We Manage a Patient with Masked Hypertension? Table 1 Risk factors for masked hypertension Demographic and lifestyle factors
Physiological and behavioural factors
High daytime physical activity
BP in the high-normal range
High daytime heart rate
Hyperreactivity to exercise
Increased arterial stiffness
Hyperreactivity to standing
Chronic kidney disease
High sodium intake BP blood pressure
5 How Can We Identify Subjects with MH? Several factors may have a greater impact on ambulatory BP than on office BP thereby selectively elevating ambulatory BP (Table 1). The difference between clinic and ambulatory BP tends to increase with aging [21, 22]. In a study by Rasmussen et al. , 82 % of men 41 to 42 years of age had higher daytime than office BP, whereas this was true of only 51 % at the age of 71 to 72 years. Thus, MH is less common among older people . Male gender is another determinant of MH [2, 3, 13]. Several lifestyle factors have shown a selective effect on ambulatory BP. Cigarette smoking [23, 24], alcohol use , contraceptive use in women , and sedentariety  have all been shown to selectively raise daytime and/or 24-h BP. High sodium sensitivity or an elevated amount of sodium intake may be other determinants of MH [28, 29]. In a Chinese general population of relatively healthy persons people with MH showed a higher salt intake and lower potassium intake than the normotensive group . In a study by Uzu et al.  in type 2 diabetic patients, a high dietary sodium intake was independently associated with an increased prevalence of masked uncontrolled hypertension. Job strain has been found to be associated with an increased risk of MH, as shown in a study of male white-collar workers . Physiological factors are other important determinants of ambulatory BP. In particular, a greater reactivity to the standing posture has been found to be significantly related to average daytime BP  and to be inversely correlated to the difference between clinic and daytime BP . Indeed, orthostatic hypertension has been recently found to be a strong risk factor for MH . These findings stress the importance of measuring standing BP in normotensive
Survival probability (%)
isolated nocturnal hypertension may be used to define MH. Indeed, the above mentioned European guidelines indicate that a sleep BP C120/70 mmHg is one of the conditions that allow the identification of MH.
80 Masked HT (10.3%) with CBP≥130/85
60 Masked HT (3.5%) with CBP