Masked Uncontrolled Hypertension in the Elderly: A Dangerous Affair

Blood pressure (BP) values and thresholds are dependent on the setting in which BP is measured. When patients are categorized according to office and ambulatory or home BP, different combinations may result, with different prognostic significance. There is little doubt that patients with uncontrolled hypertension in the office and out-of-office have a worse prognosis than patients with controlled hypertension. Studies mainly performed in the general population, involving untreated or treated subjects, indicate that the incidence of cardiovascular events is not significantly different between individuals with white-coat hypertension and true normotension, whereas the outcome is worse in those with masked hypertension.1–3 Thus, each BP elevation carries an increase in risk which adds to that of other BP elevations, in a sort of “continuum” from normotension to sustained hypertension, passing through white-coat hypertension and masked hypertension. Such risk may vary in treated vs. untreated patients and in younger vs. older hypertensives.4,5 It is thus important to identify patients with masked hypertension or white-coat hypertension because failure to do so may result in significant misdiagnosis and mismanagement of hypertension, with increase in patients’ cardiovascular risk. In this issue of the American Journal of Hypertension, Pierdomenico and coworkers present results of a prospective study aiming at evaluating the impact of different BP phenotypes on long-term cardiovascular prognosis in elderly treated hypertensive patients.6 All patients were seen at an initial visit, where both clinic and ambulatory BPs were collected, together with clinical information. The occurrence of fatal or nonfatal cardiovascular events was recorded during a follow-up visit taking place after an average of 9.1 years. Patients with masked uncontrolled hypertension (MUCH, office BP <140/90 mm Hg + 24-hour average systolic BP ≥130 and/or diastolic BP ≥80 mm Hg) had a 60% larger risk of cardiovascular events than controlled hypertensives (CH, office BP <140/90 mm Hg + 24-hour average BP <130/80 mm Hg), a figure only marginally lower than the 81% increased risk observed in sustained uncontrolled hypertensives (SUCH, office systolic BP ≥140 and/or diastolic BP ≥90 mm Hg + 24-hour average systolic BP ≥130 and/or diastolic BP ≥80 mm Hg). Conversely, the cardiovascular risk of white-coat uncontrolled hypertensives (WCUCH, office systolic BP ≥140 and/or diastolic BP ≥90 mm Hg + 24-hour average BP <130/80 mm Hg) was only slightly and not significantly increased as compared to controlled hypertensives (+9%). The results of this study are quite unique because of the large sample of patients studied (1,191), the length of the follow-up, the event rate (3.63/100 patient-years) and the lack of such relevant data in the elderly. The only comparable study available so far in the literature is the SHEAF (Self measurement of blood pressure at Home in the Elderly: Assessment and Follow-up) Study which evaluated 4,939 treated hypertensives, aged 60 years or older, followed in general practices.7 At variance from the study of Pierdomenico et al., the SHEAF Study was based on home BP monitoring (HBPM), had a shorter mean follow-up (3.2 years) and consequently a lower overall rate of cardiovascular morbidity and mortality (event rate 2.22/100 patient-years). The prevalence of CH (14%), MUCH (9%), and WCUCH (13%) was smaller and that of SUCH (63%) larger than that showed in the study by Pierdomenico et al. (23% CH, 12% MUCH, 19% WCUCH, 46% SUCH). However, in the SHEAF Study as in the study presented in this issue of the journal, when compared to CH, the relative risk of cardiovascular events was larger in SUCH (1.96) and MUCH (2.06) than in WCUCH patients (1.18). Unfortunately, in the study by Pierdomenico and coworkers, all information on predictors of fatal and nonfatal events were collected only at baseline. No data on variations in patients’ health status and treatment during the follow-up is available. Thus, we cannot exclude that some patients belonging to a BP category may have shifted to another in the course of the study, this modifying the initial grade of cardiovascular risk. Additionally, some patients were followed-up in the hospital and managed by the team of the study investigators, whereas others were only seen by their family doctors. Thus, the intensity and efficacy of hypertension management may have not been comparable across patients. Finally, the average 24-hour BP level was used to categorize patients, and thus we do not know whether the prognostic impact of the different BP phenotypes may have changed by categorizing patients also according to day-time and night-time BP averages, as recommended by guidelines.8 This observation is clinically relevant, since it is well known that BP during the night is often elevated, particularly in treated individuals, and it is more closely related to the risk of cardiovascular outcomes than day-time BP.9 The results of the study by Pierdomenico and coworkers add to the current evidence in different ways. First, these data confirm that both masked hypertension and white-coat hypertension are not uncommon in treated hypertensives and that the former is not at all a benign condition. Previous systematic reviews have documented that the prevalence of masked hypertension lies between 8% and 20%, depending on the methods of BP measurement and threshold values, but can be up to 50% in treated hypertensive patients.10 White-coat hypertension occurs in 15% to 30% of subjects with an elevated office BP, and is reported in as many as one third of treated hypertensives with apparent resistant hypertension, when an ABPM is performed.11 The significant prevalence of both MUCH and WCUCH and the much more harmful consequences of MUCH, make it feasible to include elderly treated patients among those targeted for screening of masked and white-coat hypertension. Such evidence also strengthens the indications of current guidelines which suggest to offer ABPM to high risk patients with normal office BP for screening of masked hypertension or to low risk patients with raised office BP for screening of white-coat hypertension.8,12 Second, although an increased prevalence of masked hypertension has been observed among younger individuals,13 the present study documented that MUCH is not infrequent also in elderly treated hypertensive patients and carries the same level of cardiovascular risk observed in younger subjects. Elderly treated hypertensives should thus be included in screening programmes for masked hypertension as other individuals in which this phenomenon can be suspected because of co-existence of multiple risk factors for cardiovascular disease, including diabetes, obesity, dyslipidemia, male sex, cigarette smoking, alcohol drinking, or obstructive sleep apnea (a condition which may trigger sudden BP increases at night).8 Third, in 127 treated subjects aged 60 years of older of the IDACO (International Database on Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes population) Study with white-coat hypertension, identified on the basis of office and day-time BP, the risk for cardiovascular events was similar to that in treated normotensives (+9%) and matched that observed in the 230 WCUCH subjects of the present study.5 Although the IDACO study included only patients with isolated systolic hypertension, both the Study of Pierdomenico et al. and the IDACO confirm the more favorable prognosis of white-coat hypertension in a population of elderly treated hypertensive patients. The work of Pierdomenico et al. confirms that ABPM has a better prognostic value than office BP and thus should be regarded as the measurement method of choice for confirming the diagnosis of arterial hypertension before starting treatment and as the best tool to evaluate the efficacy of treatment once it is initiated. It also strengthens the recommendations of the current guidelines which list among the compelling indications for ABPM, white-coat, and masked hypertension in treated individuals (including false resistant hypertension) and assessment of hypertension in elderly individuals.8 However, current guidelines also support the use of HBPM in all treated hypertensives, because they acknowledge that the use of ABPM may be problematic in some situations. These include, for instance, the possible inability of elderly hypertensive patients to reach the hospital or the outpatient clinic where ABPMs are offered or the unavailability of such facilities in the community setting where the subject is dwelling. Indeed, although the prevalence of masked hypertension was slightly lower in the SHEAF study based on HBPM (9%) than in the study by Pierdomenico based on ABPM (12%), there is evidence from systematic reviews, that the prevalence of masked hypertension when determined by self-measurement of BP at home might be slightly larger than when assessed in ambulatory conditions (21% vs. 17%).4 Despite a possible different prevalence of the phenomenon between the 2 out-of-office BP settings, the 2 studies available so far in elderly treated hypertensives seem to suggest a similar prognostic impact of masked hypertension when estimation is based either on HBPM or ABPM. These results need, however, to be replicated in large prospective cohorts and well designed studies. In the meantime, ABPM, or HBPM when the former is not available or not feasible, should be offered to all treated elderly hypertensives in order to efficiently manage high BP and its dangerous consequences. However, in order to yield a reliable diagnostic accuracy, HBP should be measured daily on at least 3–4 days and preferably on 7 consecutive days, with 2–3 measurements in the mornings as well as in the evenings, in the week preceding the office visit.14 The approach based on either ABPM or HBPM, if properly applied, may be useful in particular to identify MUCH and to tailor antihypertensive treatment in order to achieve the best possible efficacy.