PREVALENCE OF WHITE COAT EFFECT IN TREATED HYPERTENSIVE PATIENTS FROM CARAS SEVERIN COUNTY

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1 ORIGINAL ARTICLES PREVALENCE OF WHITE COAT EFFECT IN TREATED HYPERTENSIVE PATIENTS FROM CARAS SEVERIN COUNTY Ecaterina Usurel 1, Sorin Pescariu 2,3, Daniel Brie 2, Constantin Erimescu 2, Stefan I. Dragulescu 2,3 REZUMAT Obiectiv: Scopul studiului nostru a fost determinarea incidentei efectului de halat alb pe un lot de pacienti hipertensivi din judetul Caras Severin, a caror hipertensiune arteriala nu este controlata in ciuda tratamentului medicamentos administrat si determinarea incidentei evenimentelor cardiovasculare la acest grup de pacienti, dupa o perioada de urmarire de 48±6 luni. Material si metode: Studiul a inclus 469 de pacienti hipertensivi tratati cu unul sau mai multe medicamente antihipertensive care locuiesc in judeteul Caras Severin, dintre care numai 292 au intrunit criteriile de includere. Rezultate: Dintre cei 292 de pacienti inclusi efectul de halat alb a fost intalnit la 88 de pacienti (30,1%). Incidenta efectului de halat alb a fost mai mare la femei si la fumatori. Pe perioada urmaririi 27 de pacienti au prezentat evenimente cardiovasculare majore (11p cu accident vascular cerebral, 8p cu infact miocardic sau angina pectorala, 5p urgente hipertensive, 3p cu decompensarea fenomenelor de insuficienta cardiaca). Incidenta crescuta a evenimentelor cardiovasculare a fost asociata cu varsta avansata, sexul masculuin, fumatul, nivelul crescut al colesterolului seric si cu valorile crescute ale tensiunii arteriale la monitorizarea ambulatorie. Concluzii: In urma studiului consideram ca la pacientii hipertensivi care prezinta valori crescute ale tensiunii arteriale in ciuda tratamentului medicamentos administrat trebuie luata in considerare monitorizarea ambulatorie/24 h avand in vedere ca efectul de halat alb nu poate fi prezis cu acuratete. Nu a putut fi stabilita o asociere intre efectul de halat alb si incidenta evenimentelor cariovasculare la pacientii urmariti. Cuvinte cheie: efectul de halat alb, judetul Caras Severin, monitorizarea ambulatorie a tensiunii arteriale 24 h, rata evenimetelor cardiovasculare ABSTRACT Objective: The objective of our study was to determine the prevalence of white-coat effect (i.e., difference between clinic and ambulatory blood pressure, or a normal ambulatory blood pressure) in a population of hypertensive patient with treated hypertension from Caras Severin county, a region in Romania, whose clinic blood pressure remained uncontrolled despite therapy and the incidence of cardiovascular events in this group for a period of follow-up 48± 6 month. Material and methods: We included in our study 469 patients with treated essential hypertension, with one or more antihypertensive medications, who live in Caras Severin County, a region from Romania. They must have two or more clinic blood pressure readings of at least 140/90 mm Hg (either/or), 1 month apart but no greater than 200/120 mm Hg (either/or), were 18 years of age or more and had no target organ damage or left ventricular hypertrophy, as evidenced by echocardiography. Only 292 patients met the inclusion criteria. Results: 292 patients (100 men and 192 women; mean age, 55±12 years), all white, who met the inclusion criteria, were included in the study, from whom 88 patients (30.1%) had white coat response. The median duration of follow-up was 48±6 months. The incidence of white coat effect group was great in women (p<0.001) and in smokers (p<0.001) patients. During the follow-up, 27 patients had cardiovascular event (11 with stroke, 8 with coronary heart disease, myocardial infarction, or angina pectoris; 3 with progressive heart failure; 5 with hypertensive emergency). The higher incidence of cardiovascular events was associated with older age, male sex, current smoking, high cholesterol level and higher value on ambulatory blood pressure measurement. The incidence of cardiovascular events in group of patients with white coat effect was low. Conclusion: We consider that patients whose blood pressure remains high despite adequate antihypertensive therapy should be considered for 24-hour ambulatory blood pressure monitoring because a white-coat effect cannot be predicted reliably. The prevalence of white-coat effect is greater in female sex and in smokers. The rate of cardiovascular events over an observation period of 48±6 months did not show any association with the white coat effect. Key Words: white-coat effect, Caras Severin county, 24-hour ambulatory blood pressure monitoring, rate of cardiovascular events 1 County Hospital Resita, 2 Institute of Cardiovascular Medicine, Timisoara, 3 Victor Babes University of Medicine and Pharmacy, Timisoara Correspondence to: Ecaterina Usurel, Spitalul Judetean Resita, Stationar 2, Tel Received for publication: Jul. 06, Revised: Oct. 28, INTRODUCTION The measurement of blood pressure (BP) in the physician s office may trigger an alerting reaction and a rise in BP. 1 In a study, Mancia et al have shown that the rise in intra-arterial BP during the visit is, on average, 27/14 mm Hg; it is maximal during the first 4 minutes of the visit, disappears within 10 minutes, and persists over several visits. 2,3 The transient rise in BP from Ecaterina Usurel et al 263

2 before to during the visit is usually defined as whitecoat effect or white-coat phenomenon, whereas the coexistence of persistently high office BP with normal ambulatory blood pressure measurement (ABPM), regardless of the extent of the white-coat effect, is often referred to as white coat hypertension (WCH). WCH, which is also referred to as office hypertension or isolated clinic hypertension is generally defined as a persistently elevated office BP in the presence of a normal BP outside the office. 4,5 From a practical standpoint, it is worth noting that the whitecoat effect is a measure of BP change from before to during the visit, whereas white coat hypertension is an operative definition of clinically hypertensive subjects at a low potential risk because of apparently normal mean BP levels during daily life. 2,3,6 A reliable estimate of the white-coat effect may be carried out through intra-arterial or noninvasive techniques, with beat-bybeat measurement of the BP rise from immediately before to during the visit. 2,3,7 White coat hypertension is a common finding in hypertensive populations and in the population at large. The incidence has variably been recorded between 12% and 50%, depending on definitions. 5 The importance of the condition lies in the relatively benign cardiovascular risk with which it is associated compared with established hypertension. 8 The phenomenon of white coat effect or hypertension may reflect an abnormally vigorous sympathetic response to the environment of the measurement, especially the presence of the measuring nurse or physician. 3,9 A document issued by the American Society of Hypertension had defined normalcy of ABP (i.e., average daytime BP <135 mm Hg systolic and <85 mm Hg diastolic). 10 These values correspond to an office BP of 140/90 mm Hg. Depending on the upper limit set for mean daytime ambulatory blood pressure, the prevalence of white-coat response can range from 18% to 60% in populations with untreated hypertension. 11 Most studies of white-coat response have been conducted in subjects with normal blood pressure and those with borderline hypertension who were not receiving drug treatment. Recently, however, Myers and Reeves have found that 70% to 73% of treated patients showed a white-coat response, and 31% to 32% exhibited a marked white-coat effect. 12,13 Thus, white-coat response remains a consideration even among patients with treated hypertension. The objective of our study was to determine the prevalence of white-coat effect (i.e., difference between clinic and ambulatory blood pressure, or a normal ambulatory blood pressure) in a population of hypertensive patient in our area, with treated hypertension whose clinic blood pressure remained uncontrolled despite therapy and the incidence of cardiovascular events in this group for a period of follow-up 48 ± 6 months. MATERIAL AND METHODS We have conducted our study in Caras Severin County, a small region in Romania, after having been approved by the Ethics Committee of University of Medicine and Pharmacy Victor Babes, Timisoara. All patients gave written informed consent. All decisions concerning the study design, the collection, analysis, and interpretation of the data, and the intellectual content of the manuscript were made independently, without the involvement of the pharmaceutical industry sponsors. We included in our study 469 patients with treated essential hypertension, with one or more antihypertensive treatment. They must have had two or more clinic blood pressure readings of at least 140/90 mm Hg (either/or), one month apart, but no greater than 200/120 mm Hg (either/or), were 18 years of age or more and had no target organ damage or left ventricular hypertrophy, as evidenced by echocardiography. Criteria for exclusion were: suspicion of secondary hypertension, recent acute myocardial infarction, recent stroke (occurring within the previous three months), recent hospitalization for chronic heart failure, recent revascularization or planned cardiovascular intervention during the succeeding three months, chronic obstructive pulmonary disease, any coexisting diseases that might seriously reduce life expectancy, pregnancy, and no cooperation to undergo repeated ambulatory blood-pressure monitoring. Only 292 patients meet the inclusion criteria. All patients had a complete clinical workup at the beginning of the study to rule out secondary hypertension and to assess the presence of end-organ damage. Information about traditional cardiovascular risk factors, history of cardiovascular events, current medications, demographic and anthropometric data were collected. At that time, a sample of venous blood was drawn to assess baseline factors and routine 12- lead electrocardiogram was obtained. BP was measured with a mercury sphygmomanometer in a quiet environment, with the patient in a sitting position after 5 minutes of rest, following the recommendations of the British Hypertension Society. 14 Systolic BP (SBP) and diastolic BP (DBP) (Korotkoff phase I and phase V, respectively) represented in each visit the mean of three different readings measured at 5-minute intervals. ABPM was performed with the use of an oscillometric monitor 264 TMJ 2010, Vol. 59, No. 3-4

3 on a regular working day, during the normal intake of the usual antihypertensive treatment. Following the standard protocol, readings at intervals of 30 minutes between 08:00 and 20:00 and at intervals of 60 minutes between 20:00 and 08:00. Daytime ambulatory blood pressure was defined as that between 08:00 and 20:00, and nighttime ambulatory blood pressure as that between midnight and 06:00. The average of SBP, DBP, and mean blood pressure were calculated for every one of the periods. Before starting the study, reliability of BP values measured with the monitor were checked against simultaneous measurements with a mercury sphygmomanometer. Differences of < 5 mm Hg were allowed. Those patients with recordings showing an error rate in > 25% of the total readings were excluded from the study. Subjects were identified as exhibiting white-coat response if their mean daytime ambulatory systolic/ diastolic blood pressure was 139/89 mm Hg (both) or lower, or if the systolic/diastolic pressure was at least 20/15 mm Hg (both) lowers than the clinic reading. All other subjects were considered to have sustained hypertension. Statistical analysis For each variable, values are expressed as mean±sd. Differences between groups were sought 2 by using t test and for discontinuous variables. Event rates for new cardiovascular events, fatal plus nonfatal, during the time of follow-up are presented as the number of events per 100 patient-years, based on the ratio of the observed number of events to the total number of patient-years of exposure. A p value of less than 0.05 was considered significant for all analyses. RESULTS 292 patients (100 men and 192 women; mean age, 55 ± 12 years), all white, who met the inclusion criteria, were included in the study, from whom 88 patients (30.1%) had white coat response. The median duration of follow-up was 48 ± 6 months. Characteristics of the patients according to category of white coat response or sustained hypertension are summarized in Table 1. Eighty-eight patients (30.1%) with treated hypertension from our subjects had white coat effect. The incidence of patients with effect group was greater in women (p<0.001) and in smokers (p<0.001) patients. During the follow-up, 27 patients had a cardiovascular event (11 with stroke, eight with coronary heart disease, myocardial infarction, or angina pectoris; three with progressive heart failure; five with hypertensive emergency). (Table 2) The higher incidence of cardiovascular events was associated with older age, male sex, current smoking, high cholesterol level and higher value on ambulatory blood pressure measurement. The incidence of cardiovascular events in the group of patients with white coat effect was lower than in those with sustained hypertension (p<0.001). Table 1. Baseline characteristics of participants. Characteristics Risk factor White coat effect (n=88) Sustatined hypertension (n=204) Age (yr) 53±10 yr 56±9yr NS Female sex 62/88 (70.5%) 100/204 (49.01%) P value <0.001 Body mass index 30 ± 5 29 ± 4 p=0.14 Current smoking (%) Total serum cholesterol concentration (mg/dl) Office BP (mm Hg) 68% 40% < ± ± 8 p=0.24 Systolic 150 ± ± 9 NS Diastolic 92 ± 4 93 ± 5 NS ABPM 24 H systolic 126 ± ± 8 < H diastolic 82 ± 8 93 ± 7 <0.001 Daytime systolic 128 ± ± 8 <0.001 Daytime diastolic 84 ± 3 95 ± 5 <0.001 Nighttime systolic Nighttime diastolic 118 ± ± 6 < ± 7 84 ± 6 <0.001 Values are means ± SD; the body-mass index is the weight in kilogram divided by square of height in meters. Ecaterina Usurel et al 265

4 Table 2. Cardiovascular events developed during the follow-up period. Cardiovascular events group C (n=26) White coat effect (n=88) Stroke 0 11 Coronary heart disease 1 7 Progression of cardiac failure 1 2 Hypertensive emergency 0 5 Sustained hypetension (n=204) Total events 2 (2.27%) 25 (12.57%) p <0.001 DISCUSSION The white coat effect and white coat hypertension differ in their definitions, pathophysiological mechanisms, and clinical significance. White coat effect is defined as of BP change from before to during the visit. 2,3 White coat hypertension is an attempt to define a low-risk stratum of clinically hypertensive subjects with normal BP levels out of the medical setting, regardless of their rise in BP from before to during the visit. 5,6 A white coat effect was found in total of 36% of our subjects, whose clinic blood pressure remained high, despite antihypertensives. Other investigators have reported prevalence rates of white-coat response of 21% to 73%. 12,13,15,16 The variable definitions of white coat effect may be the explanation of this wide range of value. Several studies have suggested that white-coat hypertension is benign and that antihypertensive therapy is not required, whereas other studies have suggested that it may not be innocent In our study, the white coat effect was found to be associated with low incidences of cardiovascular events in our study population. In a study, Myers and Reeves found a significant difference in the prevalence of the response between women and men. 13 However, other studies have not demonstrated any difference in prevalence among men and women. 16 In our study, women were associated more than man with white coat effect. Several investigators have been used psychological testing, mental stress testing, exercise testing, or examination of levels of anger, anxiety or depression to test for blood pressure variances between patients with a white-coat response and those with sustained hypertension We did not use such a test in our study. The rate of cardiovascular events over an observation period of 48 ± 6 months did not show any association with the white coat effect. CONCLUSION We consider that patients whose blood pressure remains high despite adequate antihypertensive therapy should be considered for 24-hour ambulatory blood pressure monitoring because a white-coat effect cannot be predicted reliably. The prevalence of whitecoat effect is greater in female sex and in smokers. The rate of cardiovascular events over an observation period of 48±6 months did not show any association with the white coat effect. REFERENCES 1. Ayman D, Goldshine AD. Blood pressure determinations by patients with essential hypertension: the difference between clinic and home readings before treatment. Am J Med Sci 1940;200: Mancia G, Bertineri G, Grassi G, et al. Effects of blood pressure measured by the doctor on patient s blood pressure and heart rate. Lancet 1983;2: Mancia G, Parati G, Pomidossi G, et al. Alerting reaction and rise in blood pressure during measurement by physician and nurse. Hypertension. 1987;9: Guidelines Subcommittee. World Health Organization International Society of Hypertension guidelines for the management of hypertension. J Hypertens. 1999;17: Pickering TG, James GD, Boddie C, et al. How common is white-coat hypertension? JAMA 1988;259: Pickering TG. White-coat hypertension in a changing era of medical care. Blood Press Monit 1996;1(Suppl 2):S27-S Parati G, Ulian L, Santucciu C, et al. The difference between clinic and daytime blood pressure is not a measure of the white-coat effect. Hypertension. 1998;31: Verdecchia P, Schillaci G, Borgioni C, et al. White coat hypertension and white coat effect: similarities and differences. Am J Hypertens. 1995;8: Middeke M, Lemmer B. Office Hypertension: abnormal blood pressure regulation and increased sympathetic activity compared with normotension. Blood Pressure Monitoring 1996;1: Pickering T, for an American Society of Hypertension Ad Hoc Panel. Recommendations for the use of home (self) and ambulatory blood pressure monitoring. Am J Hypertens 1996;9: Verdecchia P, Schillaci G, Boldrini F, et al. Variability between current definitions of normal ambulatory blood pressure: implications in the assessment of white coat hypertension. Hypertension 1992;20: Myers MG, Reeves RA. White coat phenomenon in patients receiving antihypertensive therapy. Am J Hypertens 1991;4: Myers MG, Reeves RA. White coat effect in treated hypertensive patients: sex differences. J Hum Hypertens1995;9: Petrie JC, O Brien ET, Littler WA, de Swiet M. British Hypertension Society. Recommendations on blood pressure measurement. BMJ 1986;293: Pierdomenico SD, Mezzetti A, Lapenna D, et al. White coat hypertension in patients with newly diagnosed hypertension: evaluation of prevalence by ambulatory monitoring and impact on cost of health care. Eur Heart J 1995;16: Pierdomenico SD, Lapenna D, Guglielmi MD, et al. Target organ status and serum lipids in patients with white coat hypertension. Hypertension 1995;26: Cavallini MC, Roman MJ, Pickering TG, et al. Is white coat hypertension associated with arterial disease or left ventricular hypertrophy? Hypertension 1995;26: TMJ 2010, Vol. 59, No. 3-4

5 18. Gosse P, Promax H, Durandet P, Clementy J. White coat hypertension: no harm for the heart. Hypertension 1993;22: Bidlingmeyer I, Burnier M, Bidlingmeyer M, et al. Isolated office hypertension: a prehypertensive state. J Hypertens 1996;14: Kuwajima I, Suzuki Y, Fujisawa A, Kuramoto K. Is white coat hypertension innocent? Structure and function of the heart in the elderly. Hypertension 1993;22: Cerasola G, Cottone S, Nardi E, et al. White-coat hypertension and cardiovascular risk. J Cardiovasc Risk 1995;2: Verdecchia P, Schillaci G, Borgioni C, et al. Prognostic significance of the white coat effect. Hypertension 1997;29: Lerman CE, Brody CS, Hui T, et al. The white-coat hypertension response: prevalence and predictors. J Gen Intern Med 1989;4: Siegel WC, Blumenthal JA, Divine GW. Physiological, psychological, and behavioral factors and white coat hypertension. Hypertension 1990;16: Schneider RH, Egan BM, Johnson EH, et al. Anger and anxiety in borderline hypertension. Psychosom Med 1986;48: Ecaterina Usurel et al 267

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