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Editorial White Coat Hypertension: Time for Action Thomas G. Pickering, MD, DPhil A Downloaded from http://circ.ahajournals.org/ by guest on September 12, 2016 lthough increased blood pressure is one of the most powerful predictors of cardiovascular morbidity, the prediction for the individual patient is relatively weak. One reason for this is the inherent variability of blood pressure and the distortions associated with clinic measurement. It is widely accepted that blood pressure measured in the clinic commonly overestimates pressure measured in nonmedical settings and that the discrepancy between the 2 varies greatly from 1 individual to another. On the grounds that it is the average level of blood pressure to which the circulation is exposed over prolonged periods of time that causes the adverse effects of hypertension, rather than the pressure at any 1 moment, such as during a clinic visit, it is logical to suppose that ambulatory blood pressure will give a better prediction of risk than clinic pressure. A subgroup of patients with mild hypertension whose blood pressure is high only in medical settings has been identified as having white coat hypertension; this group typically comprises '20% of the hypertensive population.1 This is a potentially useful concept because it may help to define a group of patients who are at relatively low risk of cardiovascular morbidity and hence do not merit antihypertensive drug treatment. However, the definition of white coat hypertension is arbitrary and depends both on the cutoff point chosen to define a hypertensive clinic pressure and a normal ambulatory pressure. study was the length of follow-up, which approached 10 years. There are 2 ways of analyzing the data obtained with ABPM in prognostic studies. One is to estimate the predictive value of ambulatory pressure after controlling for clinic pressure for the entire cohort; the other is to compare the event rates in patients with sustained hypertension and those with white coat hypertension. Khattar et al chose the latter approach in their analysis of the Northwick Park study. Theirs is actually the fifth published report of the prospective significance of ambulatory blood pressure; others are on the way. The first in the series, published by Perloff et al,3,4 used noninvasive monitoring performed during the day only and reported that those whose ambulatory pressure was low in relation to their clinic pressure were at lower risk of morbidity. The second, by Verdecchia et al,5 monitored a group of 1187 normotensive and hypertensive individuals for 3 years. The authors identified a subgroup of patients with white coat hypertension but used somewhat different criteria than Khattar et al. Verdecchia et al used a daytime blood pressure of 131/86 mm Hg in women and 136/87 mm Hg in men for defining the upper limit of normal ambulatory pressure, whereas Khattar et al used a 24-hour average of 140/90 mm Hg, which would be equivalent to a daytime pressure $145/95 mm Hg. Both groups used the same cutoff point for defining clinic hypertension (140/ 90 mm Hg). In the study by Verdecchia et al, the morbidity differences between white coat and sustained hypertensives were more pronounced than in the Northwick Park study: Verdecchia et al reported an event rate of 0.49 per 100 patient-years in white coat hypertensives (similar to the rate of 0.47 in the normotensives); a rate of 1.79 in hypertensive dippers, who constituted the majority of the study population; and a rate of 4.99 in nondippers. The Northwick Park event rate in white coat hypertensives was higher at 1.32 per 100 patient-years, which may be attributed to the higher cutoff point for defining white coat hypertension. This would tend to include a larger number of high-risk individuals. The third published prospective study of ABPM comprises the pilot results of a population study in Ohasama, Japan,6 which reported that ambulatory pressure was a better predictor of morbidity than screening pressure. No attempt was made to classify individuals as having white coat hypertension. The fourth7 is a study of patients with refractory hypertension, defined as a diastolic pressure .100 mm Hg while taking $3 antihypertensive medications. Patients were classified in 3 groups according to their daytime ambulatory pressure; those in the lowest tertile (,88 mm Hg) had a significantly lower rate of See p 1892 In this issue of Circulation, a study reported by Khattar et al2 on the follow-up of a cohort of hypertensive patients established by Dr Jim Raftery at Northwick Park Hospital in London throws new light on the role of 24-hour ambulatory blood pressure monitoring (ABPM) in predicting cardiovascular morbidity. The principal finding was that patients with white coat hypertension were at substantially reduced risk of morbidity compared with patients whose hypertension was sustained throughout 24 hours. The patients underwent ABPM by the intra-arterial technique, which is still considered the gold standard of blood pressure measurement but which is rarely used in epidemiological studies. A second important feature of this The opinions expressed in this editorial are not necessarily those of the editors or the American Heart Association. From the Hypertension Center, New York Hospital, New York, NY. Correspondence to Thomas G. Pickering, MD, DPhil, Hypertension Center, 525 East 68th St, New York, NY 10021. (Circulation. 1998;97:1834-1836.) © 1998 American Heart Association, Inc 1834 Pickering Downloaded from http://circ.ahajournals.org/ by guest on September 12, 2016 morbidity over the next 4 years despite similar clinic pressures. Thus, although these 5 prognostic studies differed widely in design, ranging from a population study to a study of refractory hypertensives, the results all point in the same direction, namely, that ambulatory pressure gives a better prediction of prognosis after controlling for clinic pressure. The corollary is that patients with white coat hypertension have a more benign prognosis than those with sustained hypertension. It has been suggested that white coat hypertension may simply be a precursor of sustained hypertension.8 Although there will undoubtedly be some true hypertensives who are misclassified as having white coat hypertension on initial assessment, the literature on this is inconsistent at present. In the Northwick Park study, no attempt was made to repeat ABPM during follow-up, but a substantial proportion of patients had a comprehensive assessment of target organ damage after an interval of 9 years. The assessment showed that only 11% of white coat hypertensives had left ventricular hypertrophy compared with 38% of sustained hypertensives, and there were similar differences in carotid artery thickening. The lesser degree of target organ damage in white coat hypertensives is not altogether surprising, since these patients had lower clinic pressures than did sustained hypertensives upon entry into the study (156/96 mm Hg compared with 164/101 mm Hg), although final clinic pressures were the same in the 2 groups. In addition, white coat hypertensives were receiving less antihypertensive medication than sustained hypertensives. All of these points are consistent with the idea that white coat hypertension is, in most individuals, a benign condition. An argument sometimes raised against the concept of white coat hypertension is that if patients are seen a sufficient number of times in the clinic, blood pressure will return to normal. Again, this may be true in a minority of patients, but there are many in whom clinic pressure will remain high indefinitely. Thus, in the Northwick Park study, the majority of white coat hypertensives must have been considered by their physicians to be truly hypertensive during the course of the study, because 82% were taking antihypertensive medication at the end of the follow-up period. How should these findings be put into practice? One of the trends in management of mild hypertension in recent years has been the attempt to select patients according to their overall level of risk rather than treating everyone with a clinic pressure above a certain value. Thus, the widely quoted New Zealand recommendations9 are to treat people whose risk of cardiovascular morbidity over 10 years is .20%, unless blood pressure is .170/100 mm Hg, in which case they should be treated anyway. The rationale for the recommendations is that the benefits of treating blood pressure below this level are very small. In the Northwick Park study, the 10-year risk was 7.9% in white coat hypertensives and 22% in sustained hypertensives. Under the New Zealand guidelines, white coat hypertensives would not be prescribed antihypertensive medication, whereas those with sustained hypertension would. Although there is still no consensus, most experts accept the idea that patients with white coat hypertension do not November 3, 1998 1835 require antihypertensive drug treatment. Furthermore, there is evidence that even if treated, the drugs lower clinic pressure but have little effect on ambulatory pressure.10 One implication of this is that the cost of performing ABPM in clinical practice can be offset by the savings resulting from avoiding unnecessary drug treatment in patients identified as having white coat hypertension. It has been estimated in a survey of a general medical practice in Michigan that on the basis of the prevailing costs of antihypertensive drug treatment and the prevalence of white coat hypertension, the break-even cost for performing ABPM in newly diagnosed hypertensives would be $188.11 The actual cost of a single recording has been estimated to be much lower than this—$65.12 The number of studies demonstrating the clinical value of ABPM continues to grow. Thus, there is evidence that ABPM is not only superior in selecting patients for treatment but also in assessing the effects of treatment. In a study of 206 patients treated with lisinopril, it was found that changes in ambulatory pressure correlate more closely with regression of left ventricular hypertrophy than clinic pressure.13 The only reliable method of diagnosing white coat hypertension is ABPM. It is unfortunate that this procedure is still not recognized for reimbursement by Medicare and most other payers despite the fact that its clinical utility has been recognized in the last 2 reports of the Joint National Committee of the National High Blood Pressure Education Program14,15 and by bodies such as the American Society of Hypertension16 and the American College of Cardiology.17 In many other countries, ABPM is a recognized and reimbursed procedure. If its use is properly regulated and the reimbursement rate kept low, there is no reason why ABPM should not be recognized as a clinically useful test in the United States. References 1. Pickering TG, James GD, Boddie C, Harshfield GA, Blank S, Laragh JH. How common is white coat hypertension? JAMA. l988;259:225–228. 2. Khattar RS, Senior R, Lahiri A. Cardiovascular outcome in white-coat versus sustained mild hypertension: a 10-year follow-up study. Circulation. 1998;98:1892–1897. 3. Perloff D, Sokolow M, Cowan R. The prognostic value of ambulatory blood pressure. JAMA. l983;249:2793–2798. 4. Perloff D, Sokolow M, Cowan RM, Juster RP. Prognostic value of ambulatory blood pressure measurements: further analyses. J Hypertens. 1989;7(suppl 3):S3–S10. 5. Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A, Santucci C, Reboldi G. Ambulatory blood pressure: an independent predictor of prognosis in essential hypertension. Hypertension. 1994;24:793– 801. 6. Ohkubo T, Imai Y, Tsuji I, Nagai K, Watanabe N, Minami N, Itoh O, Bando T, Sakuma M, Fukao A, Satoh H, Hisamachi S, Abe K. Prediction of mortality by ambulatory blood pressure monitoring versus screening blood pressure measurements: a pilot study in Ohasama. J Hypertens. 1997;15:357–364. 7. Redon J, Campos C, Narciso ML, Rodicio JL, Pascual JM, Ruilope LM. Prognostic value of ambulatory blood pressure monitoring in refractory hypertension: a prospective study. Hypertension. 1998;31:712–718. 8. Bidlingmeyer I, Burnier M, Bidlingmeyer M, Waeber B, Brunner HR. Isolated office hypertension: a prehypertensive state? J Hypertens. 1996; 14:327–332. 9. Jackson R, Barham P, Bills J, Birch T, McLennan L, MacMahon S, Maling T. Management of raised blood pressure in New Zealand: a discussion document. BMJ. 1993;307:107–110. 1836 White Coat Hypertension 10. Pickering TG. White coat hypertension. Curr Opin Nephrol Hypertens. 1996;5:192–198. 11. Yarows SA, Khoury S, Sowers JR. Cost effectiveness of 24-hour ambulatory blood pressure monitoring in evaluation and treatment of essential hypertension. Am J Hypertens. 1994;7:464 – 468. 12. Pickering TG, Harshfield GA, Alpert BS, O’Brien E, De Swiet M, Shennan AH. Ambulatory Blood Pressure. SpaceLabs Medical; 1994:149. Biophysical Measurement Series. 13. Mancia G, Zanchetti A, Agebeti-Rosie E, Benemio G, de Cesaris R, Fogari R, Pessina A, Porcellati C, Salvetti A, Trimarco B. Ambulatory blood pressure is superior to clinic blood pressure in predicting treatmentinduced regression of left ventricular hypertrophy. Circulation. 1997;95: 1464 –1470. 14. Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda, Md: National Institutes of Health; 1993. Publication 93–1088. 15. Sixth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda, Md: National Institutes of Health; 1997. Publication 98 – 4080. 16. Pickering TG, Kaplan NM, Krakoff L, Prisant LM, Sheps S, Weber MA, White WB, American Society of Hypertension Expert Panel. Conclusions and recommendations on the clinical use of home (self) and ambulatory blood pressure monitoring. Am J Hypertens. 1996;9:1–11. 17. Sheps SG, Clement DL, Pickering TG, Krakoff LR, White WB, Messerli FH, Weber MA, Perloff D. ACC position statement: ambulatory blood pressure monitoring. J Am Coll Cardiol. 1994;23:1511–1513. KEY WORDS: pressure Editorials n hypertension n follow-up study n blood Downloaded from http://circ.ahajournals.org/ by guest on September 12, 2016 White Coat Hypertension: Time for Action Thomas G. Pickering Downloaded from http://circ.ahajournals.org/ by guest on September 12, 2016 Circulation. 1998;98:1834-1836 doi: 10.1161/01.CIR.98.18.1834 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1998 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/98/18/1834 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. 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