Isolated clinic hypertension in a general population

In this issue of the journal, Niiranen et al. [1] describe the results of a study on the prevalence of isolated clinic hypertension (ICH) in a representative sample of the general adult population in Finland not treated for hypertension. Factors affecting the probability of ICH on the basis of psychological, demographic and clinical characteristics are also addressed. Their final conclusion is that the prevalence of ICH in the Finnish adult population is approximately 16% and that this condition is associated with mildly elevated systolic and diastolic blood pressure (compared to normotensive subjects), lower body mass index (BMI) and non-smoking status. No association with any psychosocial disorder was observed. Despite some methodological limitations that deserve a critical analysis, their study provides new information on the prevalence and determinants of ICH on a national level, at variance from most previous studies carried out in hypertension clinics or academic settings. However, before addressing this issue in detail, some more general considerations on ICH might be useful. Diagnosis and clinical implications of ICH The growing availability of ambulatory blood pressure monitoring (ABPM) or home blood pressure measurement, in combination with conventional clinic measurement, has allowed the identification of four different patterns when describing the blood pressure status of a population of subjects. These include true normotension, sustained hypertension, ICH (also known as white-coat hypertension) and its reverse phenomenon, so-called masked hypertension [2]. White-coat hypertension is a term often used to designate those subjects whose systolic/diastolic blood pressure, when measured in the doctor's office, is ≥ 140/90 mmHg whereas their 24-h ABP or home blood pressure is in the normotensive range [3]. It is unclear whether white-coat hypertension is really related to the white-coat effect, a phenomenon characterized by an increase in blood pressure that occurs in the medical environment regardless of differences in ABP levels [4]. Because numerous studies have found a limited association of white-coat hypertension with the alerting reaction induced by the presence of a physician or a nurse, it has been recommended that the alternative definition of ICH should be used [5,6]. ICH is a relatively common finding in patients with elevated blood pressure, but the prevalence obviously depends on how the condition is defined. In theory, the detection of ICH should be easily based on the evidence of abnormal clinic blood pressure measurements and normal ABP or home blood pressure readings. However, difficulties arise with regard to the definition of normality in blood pressure values outside the clinical setting, either at home or during ABPM. As for clinic blood pressure, normal ranges for ABPM and home blood pressure have been a matter of debate over recent years. A large body of evidence has shown that not only night-time and 24-h, but also daytime average ABP is usually several mmHg lower than office blood pressure in the population. Office blood pressure values of 140/90 mmHg approximately correspond to 24-h, daytime and night-time average ABP values of 125/80, 135/85 and 120/70 mmHg, respectively. However, thresholds values are more difficult to be established because they are markedly influenced by the subjects' activities performed during the day or night. As for ABP, normal values of home blood pressure are also lower compared to office or clinic blood pressure. With some degree of approximation, an average 24-h ABP level of less than 125/80 mmHg and an average home blood pressure level of less than 135/85 mmHg are generally regarded as normal. Even lower values are advocated as a possible target for treatment, particularly in high-risk individuals, such as patients with diabetes mellitus or nephropathy, but their precise definition is still a matter for future research [3,7]. ICH has been estimated to occur in approximately 20% of mildly hypertensive patients or even with a higher prevalence when its definition is based on less conservative criteria. According to cut-offs of <140/90 mmHg for normal clinic blood pressure and <135/85 mmHg for normal day-time ABP, the prevalence of ICH ranges from 15 to 45%. Dolan et al. [8] reported an overall ICH prevalence of 15% in a large population of hypertensives referred to an outpatient hypertension clinic over a 22-year period (Table 1). Verdecchia et al. [9] found a prevalence of ICH of 19% among 1333 patients when a daytime ABP cut-off level of 135/85 mmHg was used [9]. More recently, the same authors reported a significantly lower overall prevalence (10.4%) in a cohort of 1564 subjects with hypertension stage I, in whom ICH was defined according to a more conservative daytime ABP partition value of 130/80 mmHg [10]. In a study of 50 elderly and very elderly hypertensive patients that used more liberal criteria for normal clinical blood pressure and ABP (160/95 and 146/87 mmHg, respectively), the frequency of ICH was 18% [11].Table 1: Prevalence of isolated clinical hypertensionThe possible impact of the frequency of screening visits on the prevalence of ICH has been addressed in some studies. Fogari et al. [12] found that 26% of subjects with newly diagnosed hypertension were defined as having ICH after the first visit to the clinic and one ABP recording. This percentage progressively fell during the follow-up, down to 14% after the fifth visit. In spite of its remarkable prevalence, the clinical relevance of ICH is not yet fully established, and the question on whether an increased cardiovascular risk characterizes this condition still remains to be answered. The presence and degree of target-organ damage in arterial hypertension have proven useful in predicting prognosis. However, cross-sectional studies on the association between ICH and hypertension target organ damage have provided conflicting results. Some studies have indicated a significant association between ICH and hypertension target-organ damage [13,14], whereas others have provided evidence that cardiac and vascular structural features in individuals with ICH are no different from those of normotensive subjects, whereas they differ significantly from those characterizing age- and sex-matched sustained hypertensive subjects [15,16]. Furthermore, the degree of target organ damage in ICH is dependent on the thresholds used to define normal ABP levels [9]. For example, a strictly normal upper limit of ABP may more frequently detect ICH subjects without target organ damage who are at low risk of cardiovascular events than the adoption of higher ABP threshold levels. Data concerning cardiovascular prognosis in patients with ICH are also conflicting. Some outcome-based studies suggest that ICH is associated with a risk of events apparently comparable to that of clinic normotensive subjects, and lower than that of subjects with elevated daytime ABP [17,18]. However, other studies indicate that subjects with ICH may be at intermediate risk between clinic normotensive individuals and those with sustained hypertension [19,20]. Therefore, the relevant issue of whether ICH should be regarded as a benign condition remains unresolved to date. This contributes to stimulating the interest of researchers in this area. Interest and limitations of the study In their paper, Niiranen et al. [1] evaluate the prevalence and determinants of ICH in a randomly selected nationwide population. Subjects (n = 1440, aged 45–74 years) included in their study underwent a clinical interview, determination of serum glucose and lipids, measurement of clinic and home blood pressure, and psychometric evaluation for depressive symptoms and related disorders. The diagnosis of ICH was based on a single clinic blood pressure measurement ≥ 140/90 mmHg and a home blood pressure < 135/85 mmHg, determined as the mean of 14 measurements taken on 7 consecutive days. According to this design: (i) the prevalence of ICH was 15.6% in the Finnish adult general population and 37.5% among untreated clinical hypertensives; (ii) metabolic risk factors of individuals with ICH were intermediate between those of the hypertensive and normotensive subjects; and (iii) mildly elevated clinic systolic and diastolic blood pressure, lower body mass index and non-smoking status, but not psychosocial disorders, were independent predictors of ICH in the population. These findings deserve a number of comments. The first interesting issue raised by the results of this study, carried out in a general adult population, is the relatively high prevalence of ICH, comparable to that of previous studies performed in selected groups of hypertensive patients. The overall prevalence of ICH was superimposable to that of the PAMELA study (15%), a study carried out in a northern Italian cohort where ICH was detected by ABPM [21]. Although the study by Niiranen et al. [1] provides new information on the frequency of ICH on the basis of a nationwide survey that included a fairly large number of subjects, an important criticism of their study is that clinic blood pressure was measured on only one occasion, thus leading to an overestimation of this phenotype. Because a decrease in blood pressure after repeated clinic visits has been widely documented, a correct diagnosis of ICH should be based on at least three visits to a doctor's office or clinic. Moreover, in their study, clinic blood pressure was assessed by the auscultatory technique, making use of a mercury manometer, whereas home blood pressure was monitored by means of an automated oscillometric device. The known differences between these blood pressure measurement techniques are likely to have contributed to the differences in clinic and home blood pressure levels, and thus to the estimate of ICH prevalence. A further potential limitation is related to ICH definition made by using home blood pressure monitoring instead of ABPM. Home blood pressure monitoring has been proposed as a useful alternative to ABPM in the detection of ICH, but the finding of a normal home blood pressure in certain hours of the day does not exclude the possibility that blood pressure might be higher at other times of the day. Although a similar magnitude of the white-coat effect and a similar reactivity to laboratory and clinical stressors have been reported when ICH was defined on the basis of either home blood pressure and ABPM, this was associated with disagreement in the blood pressure classification of a substantial number of patients [22,23]. Furthermore, no study has been specifically designed to test the usefulness of home blood pressure as a screening test for the diagnosis of ICH. A second interesting finding of the study by Niiranen et al. [1], which confirms and extends previously published data, is that subjects with elevated clinic blood pressure but normal ABP have more pronounced alterations in serum fasting glucose and lipid profile compared to sustained normotensives. This is in line with observations showing that part of the increased cardiovascular risk in ICH is attributable to other coexisting risk factors rather than to the raised office blood pressure per se. In particular, cross-sectional studies have provided evidence for the presence of metabolic disturbances in young ICH patients compared to their age-matched normotensive counterparts. On the other hand, the observation that individuals with ICH have significantly lower BMI than sustained hypertensives also suggests that normal blood pressure values outside the clinic may reflect a healthier life-style status. A third interesting contribution provided by the study comprises the attempt to identify what might be the more likely profile of subjects with ICH. Only a limited number of studies have assessed the probability of ICH in relation to psychological, clinical and demographic characteristics. An Italian study, including 1564 subjects with hypertension at stage I, showed that ICH was most frequent among women, non-smokers and subjects with low clinic blood pressure and smaller left ventricular mass [10]. From an international database of 2492 subjects with clinic blood pressure ≥ 140 or 90 mmHg, the probability of ICH was greater among women and older adults [24]. In a large cohort of 5716 selected patients, a higher prevalence of ICH was seen among older adults, females, non-smokers and subjects with clinic systolic blood pressure between 140 and 159 mmHg [9]. According to the results of the present study, ICH should be suspected in non-smoking, non-overweight subjects with mildly elevated clinic blood pressure. This clinical profile is in agreement with most previous reports. The inverse association between cigarette smoking and the probability of ICH may be related to the known effect of smoking on daytime blood pressure patterns. No independent connections have been found between age or gender and ICH. The lack of correlation between age and ICH may depend on the fact that younger subjects (< 45 years) were excluded from this study. Although many previous studies in hypertensive patients have demonstrated a greater prevalence of ICH in women, this survey, in line with the PAMELA study, failed to find an association between female gender and ICH. Finally, an interesting observation made by Niiranen et al. [1] is that ICH is not associated with any specific psychological characteristics, in particular with anxiety and related disorders. This appears to exclude the possibility that subjects' psychological features might help in identifying those individuals who are more likely to have ICH. In conclusion, the findings reported by Niiranen et al. [1] again emphasize the importance of out-of-clinic blood pressure measurements in the initial evaluation of subjects with elevated clinic blood pressure. This appears to be particularly the case in non-obese, non-smoking individuals with mildly elevated clinic blood pressure. However, given that this study was not free from limitations, further research is needed to find the optimal strategy for detecting ICH in the general population, as well as in a hypertension clinic setting.