AJH 1997;10:1302–1307 BRIEF COMMUNICATIONS White-Coat Resistant Hypertension Andrea Mezzetti, Sante D. Pierdomenico, Fabrizio Costantini, Ferdinando Romano, Anna Bucci, Mario Di Gioacchino, and Franco Cuccurullo Downloaded from https://academic.oup.com/ajh/article/10/11/1302/149451 by guest on 04 October 2021 The aim of this study was to evaluate whether hypertensives and 17 and 14, respectively, were sustained hypertensives with high clinic blood white-coat resistant hypertensives. Interestingly, in pressure, despite multiple drug treatment, show a white-coat resistant hypertensives the large true resistant hypertension or a ‘‘white-coat effect,’’ differences between clinic and ambulatory daytime and whether the pretreatment white-coat effect is blood pressure (white-coat effect), recorded before maintained despite pharmacological therapy. The treatment assignment, were not affected by drugs occurrence of resistant hypertension was and remained constant over time. Left ventricular determined in 250 consecutive essential mass index in white-coat resistant hypertensives hypertensives who had had an ambulatory blood was significantly lower than in truly resistant pressure monitoring before treatment assignment. hypertensives, suggesting that prognosis could Twenty-seven of 250 hypertensives with differ between these groups. In this study, using persistently high clinic blood pressure despite 3 either our internal standards or some other cutoffs months of adequate pharmacological therapy reported in the literature, the white-coat underwent further ambulatory blood pressure phenomenon was an important cause of resistant monitoring. Using our internal standards, seven hypertension. The use of ambulatory blood patients had a true resistant hypertension whereas pressure monitoring in these patients may avoid 20 subjects showed a large white-coat effect (white- misdiagnosis of resistant hypertension, coat resistant hypertension), ie, high clinic blood unnecessary overtreatment, and expensive pressure (>140/90) but ‘‘normal’’ ambulatory procedures to look for possible secondary daytime (<139/90 mm Hg) and 24 h (135/85 mm hypertension. Am J Hypertens 1997;10:1302–1307 Hg) blood pressure. Using other cutoff points for © 1997 American Journal of Hypertension, Ltd. ambulatory blood pressure, 134/90 and 135/85 mm Hg for daytime blood pressure, 10 and 13 patients, KEY WORDS: White-coat effect, ambulatory blood respectively, were reclassified as true resistant pressure monitoring, resistant hypertension. esistant hypertension has been defined as medical therapy, secondary hypertension, and non- uncontrolled blood pressure despite stan- compliance.5 It has also been reported that some pa- dard triple therapy,1,2 and its prevalence tients receiving antihypertensive therapy show a has been estimated to be approximately be- ‘‘white-coat effect’’6–8 that could cause an overestima- tweenR 2.9% and 13%.3,4 Drug resistant hypertension tion of their real blood pressure. The amount of this may be due to different causes, such as suboptimal phenomenon may be variable and its impact on the Received October 31, 1996. Accepted June 24, 1997. Address correspondence and reprint requests to Andrea Mezzetti, From the ‘‘Centro per lo Studio dell’ Ipertensione Arteriosa, delle MD, Istituto di Fisiopatologia Medica, Policlinico ‘‘S.S. Annun- Dislipidemie e dell’ Arteriosclerosi,’’ Istituto di Fisiopatologia Med- ziata,’’ Via dei Vestini, 66013—Chieti Scalo (Chieti), Italy; e-mail: ica (AM, SDP, FC, AB, MDG, FC) and the Chair of Hygiene (FR), [email protected] University ‘‘Gabriele D’Annunzio,’’ Chieti, Italy. © 1997 by the American Journal of Hypertension, Ltd. 0895-7061/97/$17.00 Published by Elsevier Science, Inc. PII S0895-7061(97)00318-X AJH–NOVEMBER 1997–VOL. 10, NO. 11, PART 1 RESISTANT HYPERTENSION 1303 occurrence of resistant hypertension (white-coat resis- an excessive stiffness of the large brachial arteries tant hypertension) has not yet been clearly evaluated. (pseudohypertension).13 Moreover, in previous studies,5–8 patients with white- coat hypertension,9–11 ie, high clinic blood pressure Ambulatory Blood Pressure Monitoring Ambulatory monitoring was performed with a portable noninva- but ‘‘normal’’ ambulatory blood pressure in the ab- 14 sence of drug treatment, were not clearly differenti- sive recorder (SpaceLabs 90207, Redmond, WA) on a ated from true hypertensives with a white-coat effect. day of typical activity after a clinic visit. Ambulatory Ambulatory blood pressure monitoring, performed blood pressure readings were obtained automatically before and after drug treatment, is the only method to at 15 min intervals from 6 am to midnight, and at 30 differentiate white-coat resistant hypertensives from min intervals from midnight to 6 am. Each time a patients with a true drug-resistant hypertension or reading was taken, subjects were instructed to remain motionless and to record their activity on a diary from subjects with white-coat hypertension. Downloaded from https://academic.oup.com/ajh/article/10/11/1302/149451 by guest on 04 October 2021 The aim of this study was to evaluate whether sus- sheet. On completion of ambulatory blood pressure tained hypertensives with high clinic blood pressure monitoring the data were analyzed by computer, us- despite multiple drug treatment show a resistant hy- ing a program designed to perform editing and inter- pertension or a white-coat effect, and whether the val statistics. All patients included in the study had pretreatment white-coat effect is maintained despite recordings of good technical quality. The following treatment. ambulatory blood pressure monitoring parameters were evaluated: average daytime (awake period) sys- METHODS tolic and diastolic blood pressure; average nighttime (sleep period) systolic and diastolic blood pressure; Patients and Study Design We studied 27 subjects and average 24 h systolic and diastolic blood pressure. (14 men and 13 women, age 56 6 11 years) with a White-coat resistant hypertension was defined as high previous diagnosis of true hypertension confirmed clinic blood pressure, despite triple treatment for at by ambulatory blood pressure monitoring, who had least 3 months, but ‘‘normal’’ ambulatory daytime and persistently elevated clinic blood pressure (.140/90 24 h blood pressure. There is no general agreement mm Hg) despite being on a rational triple drug concerning the normal limits of ambulatory blood regimen for at least 3 months. These patients under- pressure values, and different upper limits of nor- went a further ambulatory blood pressure monitor- malcy have been used in previous studies. Thus, ing to confirm the clinical diagnosis of resistant rather than using a previously reported cut-off point hypertension. They represented the 11% of 250 sus- and in light of possible influence of geographical lo- tained hypertensives who were consecutively sub- cation on blood pressure, we have chosen the blood mitted to ambulatory blood pressure monitoring pressure values representing the upper limits (mean 1 and were regularly followed by our secondary hy- 2 SD) of a clinically normotensive population coming pertension referral center. Patients referred to our from our geographical area (Chieti, Abruzzo, Italy). center for suspected resistant hypertension who had 9 The resulting upper limits for average 24 h and av- not been submitted to ambulatory blood pressure erage daytime ambulatory blood pressure were monitoring before treatment assignment, and those 135/85 and 139/90 mm Hg, respectively. Patients found to have secondary hypertension and white were also reclassified according to different upper coat hypertension, were excluded from the study. limits of ambulatory blood pressure.9,15 Only antihypertensive medications were being taken at the time of the study. All participants read Echocardiographic Study Echocardiographic exam- and signed an informed consent. ination was performed using a Hewlett-Packard 77030A (Andover, MA) ultrasound imaging system Measurements Office Blood Pressure Clinic systolic equipped with a 2.5 or 3.5 MHz transducer. Interven- and diastolic blood pressure recordings were per- tricular septum, posterior wall, and left ventricular formed on the same arm, with the patient sitting after 12 dimension at the end of diastole were measured ac- 10 min quiet rest, according to a standard technique. cording to the American Society of Echocardiography Phase V was used to determine diastolic blood pres- recommendations.16 Left ventricular mass was calcu- sure. Measurements were performed in triplicate and lated by the formula introduced by Devereux et al17 on the average value was used as the blood pressure for the basis of necropsy validation studies. The left ven- the visit. Resistant hypertension was defined as clinic tricular mass index (LVMI) was calculated by dividing blood pressure . 140/90 mm Hg, despite a triple drug the left ventricular mass by body surface area. regimen, in at least 3 visits (1 week apart). In patients with resistant hypertension the ‘‘Osler maneuver’’ Medication Adherence Assessment All subjects was used to differentiate true hypertensives from were interviewed to collect information about nutri- those with falsely elevated blood pressure because of tional history, smoking habit, and other relevant life- 1304 MEZZETTI ET AL AJH–NOVEMBER 1997–VOL. 10, NO. 11, PART 1 TABLE 1. CLINIC CHARACTERISTICS AND DRUG noncompliance, the exact prevalence of true resistant THERAPY OF PATIENTS WITH RESISTANT hypertension is reduced from