White-Coat and Masked Hypertension

White-Coat Hypertension

The BP rise associated with the alerting reaction during the medical visit, the so called “white-coat effect” (WCE) represents a major problem associated with conventional BP measurement because it may lead to overestimation of initial BP levels. As a consequence of this, there will be a significant number of subjects with elevated BP values in the office but with persistently normal out-of-office BP levels (a condition defined as “white-coat” hypertension, WCH, or “isolated office” hypertension). Traditionally, WCH has been defined as BP levels measured in the office persistently equal to or higher than 140 mm Hg for systolic and/or 90 mm Hg for diastolic, associated with persistently normal out-of-office BP values either on ambulatory or on home BP monitoring. Because BP levels are different during the day and night, and BP may be elevated during either of these periods or throughout the 24-hours, definition of normality in out-of-office BP levels must take into consideration the whole BP recording period. In recognition of this, as well as of the prevailing prognostic relevance of nighttime blood pressure levels over other components of ABPM, current European Society of Hypertension/European Society of Cardiology (ESH/ESC) hypertension guidelines and ABPM guidelines have expanded the definition of WCH, requiring normality in ambulatory BP values during either daytime (i.e., <135/85 mm Hg); 24-hours (i.e., <130/80 mm Hg) and nighttime (i.e., <120/70 mm Hg) and also normality in average home BP levels (i.e., <135/85 mm Hg) when this methodology is used ( Fig. 12.1 and Table 12.1 ).

Masked Hypertension

The condition characterized by normal in-office but elevated out-of-office BP levels has been defined as masked hypertension. For its diagnosis, conventional BP in the office is considered to be normal if it is less than 140/90 mm Hg. However, when defining elevation in out-of-office BP, according to recent guidelines, it is now considered inappropriate to exclude nocturnal BP and to focus on daytime BP levels only, as done in the past. Indeed, masked hypertension might be attributed not only to elevated daytime BP levels, but also to isolated nocturnal hypertension, which characterizes 7% of hypertensive individuals and can at present only be diagnosed with 24h ABPM. The definition of masked hypertension, has thus been extended to include elevation in ambulatory BP levels during either daytime (i.e., ≥135/85 mm Hg), and/or 24-hours (i.e., ≥130/80 mm Hg) and/or nighttime (i.e., ≥120/70 mm Hg); and/or elevation in average home BP levels (i.e., 135/85 mm Hg) (see Fig. 12.1 and Table 12.1 ).

Although, ABPM is currently considered the standard method for estimating out-of-office BP, and for assessing daily life BP control in treated hypertensive patients, it is not easily available everywhere and requires trained clinic staff and specialized equipment and software for its analysis. Conversely, HBPM could be easily used on a routine basis, as recommended by recent ESH guidelines. Indeed, when performed on a regular basis and following standardized protocols, repeated BP measures obtained by patients at home offer the possibility to accurately and frequently assess out-of-office BP not only during a single day, but also over several days, weeks, or months in a usual life setting, thus providing a reliable assessment not only of the degree but also of the consistency of BP control over time.

Besides, recent studies have indicated that HBPM is almost as reliable as ABPM in identifying WCH and MH although it provides complementary rather than superimposable information on out-of-office BP as compared with ABPM. Based on its undeniable advantages, as well as on the predictive value of HBP values over and above the information provided by OBP, current hypertension guidelines recommend the extensive use of HBPM not only for the initial diagnostic approach to hypertension, but also and more specifically, for the long-term follow-up of treated hypertensive patients as well as an additional useful method for assessment of WCH and MH. The currently proposed threshold values for definition of WCH and MH based on this methodology, are shown in Table 12.1 . Of note, the cutoff BP values of 135/85 mm Hg or higher for diagnosing hypertension pertain to both daytime ABPM and to average self measured BP values obtained through HBPM.

In particular, a report of the Pressioni Arteriose Monitorate e Loro Associazioni study, (PAMELA study) in which the initial diagnosis of WCH (identified as office BP ≥140/90 mm Hg with 24-hour BP mean <125/79 mm Hg or home BP <132/82 associated mm Hg) was reassessed 10 years later, showed similar results in the ability of HBPM and ABPM to identify WCH, sustained hypertension, true normotension and masked hypertension, even if a substantial percentage of subjects, changed from one category to another, including progression from normotension, WCH or MH to sustained hypertension (true hypertension) ( Fig. 12.2 ).

However, as mentioned previously, although HBPM shares many of the advantages of ABPM, resulting more cost-effective for the diagnosis of WCH and MH, it cannot be considered as a substitute but rather a complement to ABPM, as these methods are likely to pick up different moments of BP behavior in a subject’s daily life.

White-Coat Hypertension

WCH or isolated office hypertension (IOH) has been shown to be a rather common phenomenon, reasonably reproducible when properly studied with OBP measurements along with real-life ABPM or HBPM. The prevalence reported in literature for WCH is quite variable across different studies, ranging from less than 10% to more than 60% with several intermediate values. After the evidence from several population studies and their metaanalyses supporting a threshold value equal or higher than 135/85 mm Hg to define hypertension with average daytime ambulatory BP, the frequency of WCH has been reported to range from 9% to 16% in the general population (average 13%) and from 25% to 46% (average about 32%) among hypertensive subjects defined only based on OBP. The frequency of WCH has been shown to increase in the presence of certain clinical characteristics, such as office systolic (S)BP in the range of 140 to 159 mmHg or diastolic (D)BP in the range of 90 to 99 mm Hg ; female sex; increasing age ; nonsmoking status; hypertension of recent diagnosis; limited number of BP measurements in the doctor’s office; and normal left ventricular mass at echocardiography. It should be emphasized that despite having home and ambulatory BP within “normal” limits, subjects with WCH have nevertheless slightly higher out-of-office BP levels than normotensive controls ( Fig. 12.3 ).

Masked Hypertension

Overall, the prevalence of masked hypertension in the general population ranges from 8.5% to 16.6%, and may increase up to 30.4% in populations with high normal clinic BP. The variability in prevalence estimates is attributed to the heterogeneous definition of masked hypertension, and to differences in the characteristics of the populations being investigated across studies. In the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (IDACO) study, the prevalence of MH was 44.5% among middle-aged and elderly patients (mean age, 64 years). A subsequent report of the IDACO showed a prevalence for MH of 18.8% among subjects from a nondiabetic population, and of 29.3% among normotensive diabetic patients. Masked hypertension is more likely to occur in elderly male patients with increased BP variability, in whom a marked reduction in OBP immediately after a large meal may contribute to a diagnosis of MH ; in subjects who experience mental stress at work or at home (i.e., BP rise to hypertensive levels during working hours with normal BP at the time of conventional office measurements) ; in smokers, further supporting a previous observation from our group that smoking one cigarette may increase ambulatory BP over 15 minutes ; in case of excessive alcohol consumption ; in sedentary obese individuals who are characterized by poor exercise tolerance throughout the daytime activities, whereas they often display normal BP values while at rest in the physician’s office ; the presence of metabolic risk factors or diabetes mellitus ; in chronic kidney disease ; in association with shortened sleep time, or obstructive sleep apnea and with other conditions characterized by isolated nocturnal hypertension, nondipping or rising nocturnal BP patterns whenever these patterns are associated with normal conventional office BP values.

White-Coat Hypertension

Population studies have indicated that compared with true normotension, WCH may increase the risk of developing sustained hypertension leading to consider this condition as a prehypertensive state ( Fig. 12.4 ).

Moreover, compared with sustained normotension, patients with WCH have been shown to exhibit a greater prevalence/severity of alterations in glucose and lipid metabolism (blood glucose, serum cholesterol, impaired fasting glucose or diabetes mellitus, etc.), albeit less than in patients with true hypertension that make the overall cardiovascular risk profile of this condition unfavorable when compared with the true normotensive fraction of the population ( Fig. 12.5 ).

Evidence has also been provided that compared with sustained normotension, WCH is associated with an increased risk of development and progression of renal, cerebral, vascular and cardiac organ damage (i.e., increased left ventricular [LV] mass index and carotid intima-media thickness). Besides, most population studies (although not all) and their metaanalyses have also indicated that WCH is associated with an increased risk of cardiovascular morbidity and mortality compared with true normotension, although such a risk remains lower than that of MH and sustained hypertension ( Fig. 12.6 ). Thus, on the background of the evidence summarized above, the idea that WCH is a clinically innocent condition that should be regarded as not being substantially different from true normotension, cannot be supported.