Clinical significance of white-coat hypertension

This issue of the Journal of Hypertension[1] reports the results of a meta-analysis of studies that have addressed the prognostic significance of white-coat hypertension (WCH), that is, a condition characterized by an elevation of office blood pressure (BP) with normal ambulatory or home values [2]. Based on 14 studies for a total of 29 100 participants, the results confirm the previous findings [2] that in WCH, the risk of outcomes is substantially less than in both in and out-of-office (‘sustained’) hypertension. They further show, however, that in WCH individuals, 1) the incidence of overall cardiovascular events was 6.0% compared with the 4.0% seen in normotensive patients, with a 73% increase in risk (P < 0.001); 2), the incidence of fatal cardiovascular events was 4.0 and 1.2% in the two groups, respectively, with an even greater cardiovascular risk increase (+179%, P < 0.001); and 3) albeit the difference did not reach statistical significance, all-cause mortality went in the same direction, the WCH individuals exhibiting a 50% greater risk than the normotensive ones. Although some methodological aspects of the meta-analysis (e.g. choice of a too high cut-off BP to divide 24-h BP normality from elevation) may be open to criticism, there is no question that these data support the view that WCH is not an innocent clinical condition. Despite the conclusion of the authors that the cardiovascular mortality and morbidity associated with WCH may be ‘slightly’ higher compared with normotension, they may also indicate that WCH has a more than marginal adverse prognostic nature. This has also been the conclusion of another recently published long-term observational study, which has found that in WCH the cumulative outcomes lay in an intermediate position between normotension and sustained hypertension [3]. Starting a long time ago, a considerable body of evidence has accumulated on the clinical characteristics of WCH that make its association with a higher than normal cardiovascular risk by no means surprising. Compared with normotensive patients, WCH individuals have on average a higher prevalence of asymptomatic organ damage [2] with prognostic importance [4], including, at a vascular level, an increased carotid intima–media thickness and, at the cardiac level, an increased left ventricular mass, an increased left atrial diameter, and a reduced ventricular diastolic distensibility (Fig. 1) [5]. They exhibit higher serum cholesterol, triglycerides, and glucose values that, together with an increased body mass index, raise the metabolic-dependent risk [6] (Fig. 2). Their 24-h BP variability (another independent risk factor) [7] is abnormal whereas ambulatory and home BP mean values, although confined within the normality range, are several mmHg higher than in normotension (Fig. 3) [6]. Finally, WCH has been shown to favour new-onset diabetes and to more easily progress to sustained hypertension [8,9], thus being prone to the development of high cardiovascular risk conditions that can further impact on event occurrence, particularly over the long term. Thus, the adverse nature of WCH is supported by both epidemiological and pathophysiological evidence.FIGURE 1: Cardiac and vascular alterations in white-coat hypertension (WCH) and normotension (NT). Data from a meta-analysis of available studies in which diastolic function (E/A ratio), carotid intima–media thickness (IMT), left ventricular mass index (LVMI), and left atrial diameter (LAD) were measured in the two groups. SMD, standardized mean difference. (Adapted from [5].)FIGURE 2: Metabolic variables in normotension (NT), white-coat hypertension (WCH), and sustained hypertension (HT). Data from individuals of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) population study. Patient categories were identified based on office vs 24-h (h) blood pressure mean or office vs home blood pressure. Chol, cholesterol; DM, diabetes mellitus; IFG, impaired fasting glucose; MS, metabolic syndrome. (Adapted with permission from [6].)FIGURE 3: Office 24-h (h) and home systolic BP and diastolic BP values in normotensive (NT) patients and white-coat hypertensive (WCH) individuals from the PAMELA population. For either BP the left panels refer to identification of WCH by office ambulatory while the right panels refer to the identification of WCH by office vs home BP. The dashed horizontal line refers to the upper normality value for each pressure. Δ refers to the difference between blood pressure (BP) values. Data are shown as means ± standard deviation. (Adapted with permission from [6].)WCH accounts for a considerable portion of hypertensive patients, particularly when hypertension is mild or age is more advanced [4], which means that physicians have to deal with this condition on a daily basis and must therefore be correctly advised on what to do after its detection. Owing to its overall adverse clinical nature, no support should be offered to the Guidelines that advise WCH individuals to just undergo another visit after several years, like one would do in individuals with normal BP [10]. On the contrary, because cardiovascular risk can markedly differ between WCH individuals (see the between-study heterogeneity reported by the present meta-analysis) [1], physicians should perform an extensive assessment of cardiovascular risk factors to identify the fraction with a risk above average in whom a closer follow-up may be required. In addition to measuring traditional risk factors, this can be obtained by performing more than one office visit and collecting both ambulatory and home BP values because cardiovascular risk has been found to be greater if the elevation of office BP is confirmed at a second set of measurements [11] and only one of the two out-of-office BPs is normal (Fig. 4) [12].FIGURE 4: Cumulative incidence of cardiovascular (CV) and all-cause mortality in normotensive (NT), sustained hypertensive (HT), and true and partial white-coat hypertensive (WCH) individuals from the PAMELA population over an average follow-up of 16 years. True WCH refers to individuals in whom both home and 24-h BP were normal. Partial WCH refers to individuals in whom only one of the two out-of-office BPs was normal. Numbers above incidence curves refer to number of events, % in parentheses. Other explanations as in preceding figure captions. (Adapted with permission from [12].)The most difficult step, however, concerns the decision whether in WCH physicians should start antihypertensive drugs because although detailed information is available that in this condition treatment can cause a long-term effective office BP reduction [13], no study has been able to conclusively answer the question whether this translates into a reduction of outcomes [14], given that out-of-office BP does not concomitantly fall [13]. A protective effect of treatment may find support in the observation that in some studies, office BP has shown a prognostic value independent of ambulatory or home BP [8,11]. In addition, antihypertensive treatment has exhibited its protective effect also under circumstances in which WCH is especially common such as in mild hypertension [15,16] and in very elderly patients [17]. This indirect support should not exempt but rather stimulate the medical world to conduct a properly designed trial capable to provide scientifically founded data on the therapeutic decision to take in WCH. It is hoped that the evidence offered by the present meta-analysis on the abnormal nature of WCH [1] will also operate in this direction. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.