A commentary on the article ‘Antihypertensive drug treatment in white-coat hypertension: data from the Plaque Hypertension Lipid-Lowering Italian Study’

The white-coat effect is used to describe the difference between an elevated office blood pressure (BP) (treated or untreated) and a lower home or ambulatory BP in both untreated and treated patients. White-coat hypertension refers to the untreated condition in which BP is elevated in the office but is normal when measured by ambulatory blood pressure measurement (ABPM) or home blood pressure measurement (HBPM), or both [1]. Although masked hypertension patients should be considered and treated as hypertensive patients especially in prehypertensive range [2], consequences and treatment of white coat hypertension are not so well supported by evidences from clinical studies. New evidence contributing to clarify this issue is, therefore, welcome. Mancia and his colleagues investigated whether antihypertensive treatment lowers cardiovascular risk in white-coat hypertension within the Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS) [3]. It was shown that in white-coat hypertension (WCH) patients, antihypertensive treatment caused an early, marked and sustained reduction of office BP similar to that seen in patients with sustained hypertension. Although in sustained hypertension, the treatment-induced office BP reduction was associated with a reduction of 24-h, daytime and night-time BP, in WCH no ambulatory BP reduction was noticed. The reduction of BP was independent of the drug regime, which was used as it was proven also in other studies. Like in other studies before, the number of cardiovascular outcomes recorded in the PHYLLIS study was small, so it was impossible to directly analyse the relationship between the peculiar effects of treatment on the risk of cardiovascular outcomes [3]. The findings of Mancia and his colleagues would be important, especially for older fragile patients if effect on out-of-office BP would also be noticed. Often in this population, orthostatic hypotension is more expressed and lowering blood pressure could worsen patient's life quality by possible fall accidents and bone fractures, if doctor decides to start treatment of WCH. Physician's decision on treatment should be based on assessment of cardiovascular risk and medical treatment benefit so we think some more facts should be described. In 1988, Pickering reported that 21% of 292 patients with untreated borderline hypertension were found to have normal daytime ambulatory pressures [4,5]. Pickering's articles [6,7] raised the hypothesis that patients who showed an exaggerated response to the clinic environment might also exhibit a similar response to more regularly occurring types of stress, a concept that supported the clinical application of BP monitoring. However, a later study by the same group did not confirm the hypothesis that stressors might increase office but not daytime blood pressure [4]. Despite the use of varying criteria to define WCH, several, albeit not all publications suggest that on balance, cardiovascular risk is comparable in patients with white-coat hypertension and normotension, especially if low cut-off values for the (daytime) ambulatory BP are applied [8–10]. Staessen et al. in International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome (IDACO) (N = 7506) and in the study of Genetic and Phenotypic Determinants of Blood Pressure and Other Cardiovascular Risk Factors (GAPP) (N = 2044) assessed that the prevalence of WCH exponentially increased from 2.2 to 19.5% from age 18–30 to 70 years and over, with little sex differences. Cardiovascular disease risk in most persons with WCH was comparable to age-adjusted and risk-adjusted normotensive control individuals [11,12]. In the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study, where in individuals participating in the initial survey and seen again about 10 years later, WCH individuals exhibited a greater incidence of new-onset sustained hypertension [13], impaired fasting glucose state, overt diabetes, and (in individuals with an initially normal left ventricular mass index) echocardiographic left ventricular hypertrophy. Thus, they speculated that WCH is associated with a greater progression to a variety of high cardiovascular risk conditions, which makes the risk elevation with time greater than that because of aging per se [14]. Two studies in their substudy population have looked to this problem. In the Hypertension in the Very Elderly Trial (HYVET), 50% of participants fulfilled the established criteria for WCH. They have estimated that 50% of participants had WCH in the main study and speculated that this condition may benefit from treatment in the very elderly [15]. From the Ambulatory Blood Pressure Monitoring Side Project of the Systolic Hypertension in Europe (Syst-Eur) Trial, where ABP monitoring was included in its design, about one-quarter of patients had nonsustained, white-coat or isolated clinic systolic hypertension. They concluded that sustained systolic hypertension is more harmful than white-coat systolic hypertension in the elderly. However, the information if nonsustained systolic hypertension is innocuous compared with true normotension because of low number of events could not be provided. A statement that clinical blood pressure (CBP) decreases and ABP hardly changes when treatment is guided by CBP in patients with nonsustained isolated hypertension was confirmed and no negative effect of medical treatment was noticed [16–18]. Mancia et al.[19] added important information to management of WCH in our daily practice confirming no ambulatory SBP and DBP reduction occurred, independently of the drug choice as in previous ELSA study results. Nevertheless, because of the small number of cardiovascular events, the risk of cardiovascular outcomes is still unclear [3]. Accordingly, management of white-coat hypertensive patients should still follow ESC/ESH 2018 hypertension guidelines including closer follow-up and lifestyle changes [1]. However, if the presence of hypertension-mediated target organ changes would require medical treatment, based on the just presented results, it can be applied with better confidence. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.