European Journal of Internal Medicine 15 (2004) 348 – 357 www.elsevier.


Review article

White-coat hypertension: a clinical review
Hilde Celis*, Robert H. Fagard
Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven, U.Z. Gasthuisberg – Dienst Hypertensie, Herestraat 49, 3000 Leuven, Belgium Received 1 June 2004; received in revised form 15 July 2004; accepted 2 August 2004

Abstract White-coat hypertension (WCHT), also called disolated office or clinic hypertensionT, is defined as the occurrence of blood pressure (BP) values higher than normal when measured in the medical environment, but within the normal range during daily life, usually defined as average daytime ambulatory BP (ABP) or home BP values (b135 mm Hg systolic and b85 mm Hg diastolic). The prevalence of WCHT varies from 15% to over 50% of all patients with mildly elevated office BP (OBP) values. In untreated hypertensive patients, the probability of WCHT especially increases with female gender and a mildly elevated OBP level. The value of other possible determinants such as (non) smoking status, duration of hypertension, left ventricular mass, number of OBP measurements, educational level, etc. is less consistently shown. Although, for various reasons, studies evaluating the long-term effects of WCHT are not always easy to interpret, most data indicate that persons with WCHT have a worse or equal cardiovascular prognosis than normotensives, but a better one than those with sustained hypertension. WCHT is sometimes considered a prehypertensive state, but data on the long-term evolution of subjects with WCHT are scarce. Patients with WCHT and a high cardiovascular risk or proven target organ damage should be pharmacologically treated. Subjects with uncomplicated WCHT should probably not receive medical therapy, but a close follow-up, including regular assessment of other risk factors and measurement of OBP (every 6 months) and ABP (every 1 or 2 years), is warranted. D 2004 Elsevier B.V. All rights reserved.
Keywords: White-coat hypertension; Sustained hypertension; Ambulatory blood pressure; Home blood pressure; Diagnosis; Prognosis

Contents Definition and prevalence of white-coat Correctly diagnosing WCHT . . . . . . Identification of patients with WCHT . Prognostic relevance of WCHT . . . . 4.1. Target organ damage . . . . . . 4.2. Cardiovascular outcome . . . . 4.3. Relation to other risk factors . . 5. Evolution of WCHT . . . . . . . . . . 6. Treatment and follow-up of WCHT . . 7. What about the white-coat effect? . . . References. . . . . . . . . . . . . . . . . . 1. 2. 3. 4. hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348 349 350 351 351 351 351 353 354 354 355

1. Definition and prevalence of white-coat hypertension White-coat hypertension (WCHT) is defined as the occurrence and persistence of blood pressure values higher than normal (dhypertensiveT) when measured in the

* Corresponding author. Tel.: +32 16 34 36 31; fax: +32 16 34 37 66. E-mail address: (H. Celis). 0953-6205/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2004.08.001

some quality requirements should be implemented to assure accurate measurements [1. treated versus untreated subjects). but within the normal range during daily life [1.3.4]. due to the ABPM effect.. but different expert committees have used different cutoff points of normalcy [1. (4) the need for patients to engage in normal daily activities. Fagard / European Journal of Internal Medicine 15 (2004) 348–357 349 medical environment and in the presence of a physician [the so-called office blood pressure (OBP)]. Conversely. Five hundred and sixty five mild hypertensive subjects and 95 normotensive controls underwent two ABPM 3 months apart. some investigators propose to use an algorithm .g. These results suggest that diagnosing or refuting the diagnosis of WCHT using ABPM should not be based on only one ABPM since. Depending on the thresholds used to diagnose the condition and the characteristics of the study population (e.2]. (5) the need for patients to keep a diary in which symptoms and unusual events. normal dout of the officeT BP values are not. [15] also investigated the reproducibility of the diagnosis of WCHT. they may yield measurements that are not representative. normal average 24-h values (b125 mm Hg systolic and b80 mm Hg diastolic) [1. yet. but refrain from strenuous exercise. However. Recently. This so-called dABPMT or dpressorT effect increases BP on average by 7/4 mm Hg for the first 4 h of measurement and can persist for up to 9 h after the person starts wearing the device. the prevalence of WCHT varies from 15% to over 50% of patients with mildly elevated OBP [6–10].e. Some guidelines propose the alternative use of home (or self) blood pressure measurement (HBPM) to diagnose WCHT [1. Some authors question whether one ABPM (for only 24 h) is sufficient to properly characterize usual daily BP.4]. some investigators suggested using the term disolated office or clinic hypertensionT instead of WCHT [11–13]. As for ABPM. defined in a consistent way. (3) the need to obtain an adequate number of readings (the interval between readings should probably not exceed 30 min during day and night). The pressor effect is no longer obvious when hypertensive patients are evaluated for the second and subsequent times.4] have also been used as cutoff points.4].H. a 5-min rest period before measurements.3. etc. Due mainly to regression to the mean..4]. R. Home or self-measurement of BP has been proposed as a useful alternative for ABPM to detect WCHT. smaller cuff for lean adult arms and children). Home BP (HBP) values of 135/85 mm Hg should probably be considered as the upper limit of normalcy [1. Today. are noted.5]). [14] based on 48-h ABPM indicate that if a person wears an ABPM device for the very first time.2].3. The most important are: (1) the use of an accurate and internationally and independently validated device. BP during normal daily activities is usually evaluated by 24-h ambulatory BP (monitoring) [ABP(M)]. this significantly affects the BP measured.4]. Results from a study by Hermida et al. Correctly diagnosing WCHT The correct diagnosis of WCHT requires the application of several logical. Hermida et al. and BP measured in duplicate every morning and evening for a 7-day period. above 140 mm Hg systolic and/or above 90 mm Hg diastolic [1. the quality of HBPM should also be guaranteed by: (1) (2) (3) (4) the use of accurate and validated (preferably upper arm) devices. (2) the use of cuffs of appropriate size (larger cuff for obese arms. the use of a cuff of appropriate size. and have not always been. and keep the arm still during the measurement. Palatini et al. documented such an ABPM effect in 73% of their hypertensive patients. In a substudy of the HARVEST trial. This term takes into account that it is not only the dwhite coatT of the doctor that causes the difference between OBP and ABP. due to anxiety and subsequent familiarization with the new technique. Often measurements of the first day are not included in the statistical analysis because. but nevertheless important. i. such as (physical and mental) activity during the day and the circumstances of the measurement. Most experts agree on the definition of elevated OBP values. 58% of the 90 patients who were diagnosed as having WCHT based on the first ABPM (daytime ABP b130 mm Hg systolic and b80 mm Hg diastolic) became sustained hypertensives on repeated recording. These data indicate that the diagnosis of WCHT is subject to selection bias and that one ABPM may not always be sufficient to correctly identify persons with WCHT. and However. most experts define WCHT as an elevated OBP in the presence of a normal average daytime ABP (b135 mm Hg systolic and b85 mm Hg diastolic [2. 2. guidelines. usually at several visits [1. but that there are also other factors involved. If ABPM is used to diagnose WCHT. Instead of using either ABPM or HBPM to diagnose WCHT.H. Elevated OBP values should be confirmed on subsequent measurements. duration and quality of night sleep. 11% had daytime ABP below 130 mm Hg systolic and below 80 mm Hg diastolic on the second recording. using ABPM for the diagnosis of WCHT may also raise problems. average day ABP might be higher and patients could be mistakenly classified as having sustained hypertension (SHT) instead of WCHT. among the sustained hypertensives. Celis.

smoking habits. cholesterol. Indeed. However. Julius et al. LV mass and the prevalence of micro-albuminuria did not differ between those with WCHT (OBPz140 mm Hg systolic or z90 mm Hg diastolic and daytime ABPb135 mm Hg systolic and b85 mm Hg diastolic) and the normotensive control group. Pickering et al. A few years later. triglycerides. the prevalence and the determinants of WCHT (OBPz140 mm Hg systolic or z90 mm Hg diastolic and awake ABPb135 mm Hg systolic and b85 mm Hg . Fagard / European Journal of Internal Medicine 15 (2004) 348–357 using both of the above techniques [16–18]. a population-based cohort of men not treated with antihypertensive agents at baseline. All patients in the Martinez study were either untreated or had antihypertensive drugs withdrawn for at least 3 weeks. R. the optimal strategy for detecting WCHT has not yet been established and more research is needed.350 H. Staessen et al. among the subjects who had WCHT according to the dformalT definition (high OBP. and previous cardiovascular disease. Thus. All participants had to be free of diabetes. momentarily. Bjfrklund et al. if this shows normal values. [6] reported that in 292 subjects with diastolic OBP between 90 and 104 mm Hg.). OBP. Furthermore. Celis. [19] performed a joint analysis of the large HARVEST and PIUMA databases. In conclusion. and lower systolic and diastolic OBP values. According to this algorithm. and short duration of hypertension were independent predictors of WCHT. and several metabolic parameters (glucose. non-smoking status. Identification of patients with WCHT Although several investigators have tried to identify possible determinants of WCHT [9.42 [16]).H. but a rather low sensitivity (ranging from 43% [18] to 68% [17]). A few studies [16–18] that tested the above-proposed algorithm did report high specificity (ranging from 81% [16] to 93% [18]) and a high negative predictive value (ranging from 77% [16] to 97% [17]). In the group of 183 patients taking no antihypertensive medication. female gender. 3. Already in 1988. Subjects with WCHT did not. [21] showed that participants in the Tecumseh Blood Pressure Study (none of them receiving antihypertensive drug treatment) with WCHT (systolic OBPN140 mm Hg or diastolic OBPN90 mm Hg and HBP below the upper decile of the whole population) were very similar to those with SHT and differed significantly from normotensive controls. Martinez et al. although ABPM and HBPM may classify comparable percentages of patients as being WCHT or SHT. thus leaving an unacceptably high proportion of 32– 57% of WCHT undetected. Verdecchia et al. only 43% [18] to 68% [17] will be diagnosed when the proposed algorithm is used. patients with persistently high OBP values and no evidence of target organ damage should engage in HBPM (screening test). This means that. although high specificity and negative predictive value are important for a screening test. More recently.38 [17] to 0. etc. lower educational level. They also had elevated BP levels on previous examinations as compared to their normotensive counterparts. differ from normotensives with respect to reactivity to psychological stress or personality characteristics. They also reported that a lower BMI and a more favorable lipid profile characterized subjects with future development of WCHT (after 20 years) as compared to those with future SHT. and lower left ventricular (LV) mass on echocardiography were the sole independent predictors of WCHT. Multivariate logistic regression showed that female gender. patients with SHT and WCHT were similar with regard to BMI. They observed consistently higher heart rate. Both dhypertensiveT groups had higher weight. in a longitudinal way. and insulin levels. elevated total cholesterol. They showed that the probability of having WCHT (24-h ABP below the 95th percentile of a normotensive control group) was higher in women and was positively associated with age and inversely related to systolic and diastolic OBP values and to the number of visits and OBP measurements per visit. However. no official international or national guideline committees have endorsed this approach. normal ABP). young age. [24] analyzed a large international database consisting of 2492 subjects with OBP above 140 mm Hg systolic or above 90 mm Hg diastolic. it should predominantly have a high sensitivity. and a prevalence of abnormalities of glucose metabolism in both patients with WCHT and SHT as opposed to normotensives. the previous use of antihypertensives. faster heart rates. Conversely. They showed that the diagnosis of WCHT was independently related only to female gender. triglyceride. WCHT was defined as an OBP (on at least two visits) of 140–159 mm Hg systolic or 90–99 mm Hg diastolic and day ABP below 130 mm Hg systolic and below 80 mm Hg diastolic. the Kappa coefficient suggested only moderate agreement between HBPM and ABPM in the diagnosis of WCHT (Kappa coefficient ranging from 0. data allowing an estimate of the probability of WCHT according to patientsT characteristics are relatively scarce. [9] examined the clinical factors that may identify patients with WCHT (OBP 140–170 mm Hg systolic or 90–109 mm Hg diastolic on repeated measurement and day systolic ABPb135 mm Hg systolic and b85 mm Hg diastolic) in a primary care setting. family history of hypertension. it is generally accepted that. and lower HDL-cholesterol levels. both techniques nevertheless identify different subsets of WCHT patients. renal failure. [23] carried out a retrospective study including 670 treated and untreated hypertensive patients. however. lower diastolic OBP. [20] investigated.19–24]. Segre ´ et al. ABPM is done to confirm the diagnosis (diagnostic test).

31.23]. some investigators have examined the relation between WCHT and other traditional or novel CV risk factors. They showed that subjects with WCHT (high OBP. 46. age [6.33.28–31.37. different study designs (cross-sectional study versus follow-up study). the results of all these studies are not always easy to interpret because of the use of different definitions of WCHT (conservative versus liberal). Prognostic relevance of WCHT Several studies have tried to evaluate the long-term effects of WCHT on target organ damage (i. creatinine) [9.23. Trials on (CV) prognosis comparing WCHT to normotension are scarce and show an equal or worse prognosis in patients with WCHT [10.9–11.53–58] compare WCHT to SHT (Table 2) and most of them indicate a worse (CV) prognosis in those with SHT. Data indicate that persons with WCHT have a lower or similar LV mass compared to those with SHT. Fagard / European Journal of Internal Medicine 15 (2004) 348–357 351 diastolic) were assessed. number of OBP measurements [24]. and a higher or similar LV mass compared to normotensives.28–30. carotid arteriosclerosis by ultrasonography). Very recently.12.30.H. Evaluation of other possible determinants.10. educational level [9].45. R.19].43]. The prevalence of vascular retinopathy is reported to be lower or equal in WCHT as compared to SHT.47–51. Celis.35. large arteries. They show less or equal carotid artery damage in normotensive controls and more or equal carotid artery damage in subjects with SHT in comparison to those with WCHT. Trials assessing renal function (urinary albumin excretion.43. such as (non)smoking status [9. there was no association between WCHT and sex.23. difference in ABP between WCHT and normotension). Only one trial [54] reports a higher mortality in persons with WCHT than SHT. The majority of studies evaluating endothelial function indicate that endothelial dysfunction is more prevalent in WCHT than in normotension. family history of hypertension [9.24]. eye. More recently. LDL.9–11. high HBP) hypertension. 23.54. while there are no significant differences between subjects with WCHT and normotensives.19. The majority of data shows similar glucose and lipid profiles in patients with WCHT and SHT [7.24] and mildly elevated OBP levels [9.56]. differences in (baseline) characteristics between the study groups (difference in OBP between WCHT and SHT. Relation to other risk factors Several investigators compared traditional metabolic parameters that could influence CV risk. but that endothelial function is either equal [51. Target organ damage The majority of trials evaluated LV parameters (echocardiographically assessed LV mass. high HBP) or uncontrolled (high OBP.21. Evaluation of systolic or diastolic LV function or of the prevalence of LV hypertrophy gives comparable results. [58] assessed the prognostic value of HBPM in an elderly population treated for hypertension.47–49.9.H. [52] found lower circulating homocysteine levels in subjects with WCHT than in those with SHT. lipid profile.1. prevalence of LV hypertrophy) [7.10.2. a few trials report less favorable glucose and lipid levels in those with WCHT as compared to normotensives [28. subclinical lesions or functional deterioration of target organs such as the heart. Pierdomenico et al.33.33.43. triglycerides) [7.25–43]. WCHT was only significantly associated with familial history of hypertension.25. LV systolic or diastolic function. . Several trials compared carotid artery structure and function (intima-media thickness.56].13.42. but higher (only two trials) in WCHT than in NT.23]. Bobrie et al.36.43.54. We found only a few trials that looked at vascular retinopathy [23. the probability of WCHT especially increases with female sex [9. such as glucose and insulin levels and lipid profile (total cholesterol.49. 4.56].56]. Cardiovascular outcome The majority of trials on cardiovascular (CV) outcome [7. Overall. equal to those with controlled hypertension (normal OBP. some dnovelT CV risk factors have also been studied in WCHT. whereas no difference was found between WCHT and normotension. and indices of target organ damage such as echocardiographic parameters of LV mass. etc.47–52] usually indicate that persons with WCHT have fewer or equal signs of (early) renal damage as compared to those with SHT. and LV mass [19. etc.45. An overview of the trial results with respect to LV mass can be found in Table 1. age.28– 30.19.60] in SHT as compared to WCHT.59] or worse [47.23].29. lipid levels [9. In contrast.43–46].. different methods to quantify the long-term effects (LV mass by echocardiography. the previous data indicate that.e.40. normal HBP) and better than those with masked (normal OBP.54. 4. but the investigators used an unconventional definition of WCHT based on nursesT BP measurements. and kidney) and on the occurrence of future cardiovascular (CV) events.35. Moreover. changes in fundoscopy.24].33. prevalence of plaques) [7.45–51. was less consistently carried out and sometimes showed contradictory results. creatinine level.and HDL-cholesterol. C ¸ oban et al.35. normal HBP) have a good prognosis.3. 4. Overall. in untreated hypertensive subjects. [61] report higher levels of plasma fibrinogen and d-dimer in persons with WCHT than in 4.

day sABPb134 and day dABPb90 sOBPz160 or dOBP z90. x: data only shown for cutoffs 130/80 and 135/85. d=dipper=reduction in average s and dABP from day to night of z10%. R. XbY: X better prognosis than Y. yet lower ones than in patients with SHT. SHT: sustained hypertension. awake sABPb135 and awake dABPb85 dOBPz90. 4 cutoffs: day dABPb90. day sABPb131 (U) and day dABPb86 (U) b136 (h) b87 (h) dOBPz90. intra-arterial 24 h sABPb140 sOBP 140–159 or dOBP90–99. day sABPb135. ABP: ambulatory blood pressure. the prognostic relevance of WCHT remains controversial. day sABPV130 and day dABPV80 sOBPz140 or dOBPz90 2 definitions: 24 h sABPb125 and 24 h dABPb79 or shomeBPb132 and dhomeBPb83 sOBPz140 or dOBPz90. s: systolic. day sABPV146 and day dABPV87 sOBPN140 or dOBPN90. by nurse: sOBPb140 and dOBPb90 0BP: mild to moderate HT. day sABPb139. NT: normotension. day sABPb140 and day dABPb90 dOBPz90.6 and day dABPb89.4 sOBPz140 or dOBPz90. day sABPb135 and day dABPb85. 3 definitions: 8 ABP criteria (see ref [42]) or day sABPb130 and day dABPb80 or day sABPb135 and day dABPb85 sOBPz140 or dOBPz90. Although WCHT might still be an innocent phenomenon. 24 h dABPb85 sOBPz140 or dOBPz90. r : for all definitions of WCHT.6 and day dABPb90. day sABPb135 and day dABPb85 and night sABPb125 and night dABPb70 by doctor: sOBPz160 or dOBPz95. day sABPb142 and day dABPb90 sOBP 140–174 and dOBP 90–104. 3 cutoffs day ABP-day sABPb130 and dABPb80 or day sABPb135 and dABPb85 or day sABPb140 and dABPb90 sOBPN140 or dOBPN90. XNY: X worse prognosis than Y. day sABPb135 and day dABPb85 Parameter LV mass index LV mass index LV mass index LV mass WCHT versus NT WCHT N NT WCHT N NT / WCHTcNT WCHT versus SHT WCHTbSHT WCHTcSHT WCHTcSHT WCHTbSHT d bSHT ndw WCHTcSHT WCHTbSHT WCHTbSHT WCHTbSHT WCHTbSHT WCHTbSHT / / WCHTbSHT WCHTbSHTx [28] [29] [30] [31] [32] [33] [34] [36] [7] [37] LV mass index LV mass index LV mass index LV mass index LV mass index LV mass index LV mass index LV mass index LV mass index LV mass index WCHTcNT WCHTcNT WCHTcNT WCHT N NT WCHTcNT WCHTcNT WCHTcNT WCHTcNT / WCHT N NTx [38] LV mass index WCHT N NT / [39] [40] LV mass LV mass index WCHT N NT WCHTcNTh (WCHTcSHT) WCHTbSHTh [41] [9] [12] [13] LV mass index LV mass index LV mass index LV mass index / / WCHT N NT WCHT N NT r WCHTbSHT WCHTbSHT (U) WCHTcSHT (h) WCHTbSHT WCHTbSHT r [42] LV mass index WCHT N NT r WCHTcSHT r [23] [43] WCHT NOT associated to LV parameters LV mass index WCHT N NT WCHTbSHT WCHT: white-coat hypertension. 24 h sABPb140 sOBPz160 and dOBPz95. In conclusion. day sABPb134 and day dABPb90 dOBPz90. h: for all four cutoff values. day sABPV136 and day dABPV86 sOBP 140–179 or dOBP 90–109. LV: left ventricular. XcY: X and Y comparable prognosis. Celis. but a lower (CV) risk than those with SHT. trials assessing LV mass by echocardiography Ref id [25] [26] [27] [10] Definition of WCHT dOBPN90.4. . d: diastolic. day dABPb95 sOBPN140 or dOBPN90. most available data suggest that persons with WCHT have a higher (CV) risk than normotensives. awake sABPb132 and awake dABPb84 sOBP 140–180.H. Fagard / European Journal of Internal Medicine 15 (2004) 348–357 Table 1 Prognostic significance of WCHT. day sABPb135 and day dABPb85 sOBPN140 or dOBPN90.352 H. day ABPb90th percentile healthy volunteers sOBPN140 or dOBPN90. OBP: office blood pressure. normotensive controls. w: nd=nondipper=reduction in average s and dABP from day to night ofb10%. 24 h sABPb135 and 24 h dABPb85 sOBP 145–190 or dOBP 90–114.

s: systolic.. leading to increased risk of arteriosclerosis (via endothelial dysfunction).38.5 years both in untreated subjects with WCHT and in a normotensive control group matched for age. The evolution to SHT was associated with female (2) (3) . approximately 75% of their study subjects with WCHT at baseline evolved towards dambulatory hypertensionT (daytime ABPN140/90 mm Hg). Celis. In contrast. SHT1 has day dABP 88–97 and SHT2 has day dABPN97. d: diastolic. [68] showed that 28% of 64 study subjects with WCHT spontaneously developed SHT after an average follow-up of 2.56] (although normal average ABP values). NT: normotension. 5. in WCHT. day dABPb88 sOBP 160–219 and dOBPb95. and other CV risk factors. weight. R. OBP: office blood pressure. such as: (1) increased BP variability [28. [67] report that over a 5. Recent evidence has shown sympathetic neural hyperactivity in SHT [64] and. masked HT is normal OBP and high home BP. Moreover. by nurse: sOBPb140 and dOBPb90 sOBPz140 or dOBPz90. Fagard / European Journal of Internal Medicine 15 (2004) 348–357 Table 2 Prognostic significance of WCHT. 56]. [36] assessed the evolution of OBP and ABP for about 3. Verdecchia et al. intra-arterial 24 h sABPb140 dOBPN100.H. Their data suggest that the percentage of patients with WCHT showing a spontaneous progression towards dambulatory hypertensionT (awake ABPz140/90 mm Hg) does not differ significantly from normotensive controls. SHT: sustained hypertension. 24 h sABPb130 and 24 h dABPb80 dDOBPz95.7 years. reduced anti-oxidant activity) [65]. ABP: ambulatory blood pressure. Bidlingmeyer et al. [66] did not find any difference in oxidative stress between persons with WCHT and normotensives. Associations between sympathetic hyperactivity and abnormalities of glucose and lipid metabolism have also been reported [21]. home sBPb135 and home dBPb85 Parameter CV events WCHT versus NT WCHTcNT WCHT versus SHT WCHTbSHT dbSHT ndw 353 [47] [7] [53] [48] [54] Silent cerebrovascular damage CV events CV events CV events Stroke Mortality / WCHTbSHT / / / / WCHTNNT WCHTbSHT WCHTbSHT1 WCHTbSHT2 WCHTbSHT WCHTbSHT WCHTNSHT (!) [49] Silent cerebral infarction Stroke CV events CV events Mortality (% Multiple) silent cerebral infarctions CV events WCHTcNT WCHTcNT / WCHTNNTx WCHTcNTx / WCHTbSHT WCHTbSHT WCHTbSHT WCHTcSHTx WCHTcSHTx WCHT(dmÀ)bSHT(dmÀ)b WCHT(dm+)bSHT(dm+) WCHTccontrolled HTb masked HTcuncontrolled HT r [55] [56] [57] [58] / WCHT: white-coat hypertension. day sABPb140 and day dABPb90 sOBPz140 or dOBPz90. Pierdomenico et al. 63]. day sABPb140 by doctor: sOBPN160 or dOBPN95.67]. XbY: X better prognosis than Y. XcY: X and Y comparable prognosis. However. but the evidence linking this with higher target organ damage is limited [28. trials evaluating dhard endpointsT Ref id [10] Definition of WCHT sOBPN140 or dOBPN90. enhanced oxidative stress (increased LDL-oxidation. but data on the long-term evolution of OBP and ABP of subjects with WCHT are limited and sometimes contradictory [36. CV: cardiovascular. dm+: with diabetes mellitus. to a lesser extent. 2 definitions: day sABPb135 and day dABPb90 or day sABPb135 and day dABPb85 sOBPN140 or dOBPN90. r : controlled HT is normal OBP and normal home BP. dmÀ: without diabetes mellitus. it is not yet clear whether this enhanced oxidative stress occurs before or after the development of (white coat) hypertension. x: comparable results for both cutoffs. day sABPb131 (U) and day dABPb86 (U) b136 (h) b87 (h) sOBPz140 or dOBPz90. which may lead to the development of target organ damage. uncontrolled HT is high OBP and high home BP. Different explanations for this intermediate risk profile of WCHT have been proposed. d=dipper=reduction in average s and dABP from day to night of z10%. XNY: X worse prognosis than Y. 24 h sABPb135 and 24 h dABPb80 sOBPz140 or dOBPz90. %: prevalence. Evolution of WCHT It has been proposed that WCHT is a prehypertensive state. w: nd=nondipper=reduction in average s and dABP from day to night of b10%. 24 h sABPb135 and 24 h dABPb80 sOBP 140–180. increased sympathetic activity [62. Polonia et 6-year follow-up period.H.

Staessen et al. It can be as high as 30 mm Hg. but patients with WCHT. the recommendation not to (pharmacologically) treat patients with WCHT thus seems reasonable [5]. Treatment and follow-up of WCHT Most experts agree that antihypertensive drug treatment should be instituted in subjects with WCHT and a high CV risk (20% over 10 years) or documented target organ damage [4. it increased with higher body mass index and with advancing age.41. The maximal rise takes place 1–4 min after the doctorTs arrival. regular OBP measurements (at least every 6 months). led to less intensive drug treatment in the ABP group. which are absent when the true (strict) WCE is considered. A WCE can occur in both normotensive and hypertensive persons. In addition. or a poor one. 7. The development of SHT on followup could not. Although WCHT is a consequence of the WCE. between the above surrogate measures of the WCE and a direct measure of the WCE as assessed by noninvasive.73]. They did not find any difference in general well-being or in electrocardiographic or echocardiographic LV mass.8 for OBP) is considered clinically relevant. The transient BP rise occurring as an alerting or defense or anxiety reaction associated with the presence of a doctor is called the WCE.42. such as lipid profile. On the basis of the abovementioned studies. The size of the WCE varies greatly in different subjects. however. Moreover. but caution is warranted. but usually averages about 20 mm Hg systolic and 10 mm Hg diastolic.79–81] or CV morbidity or mortality [82]. showed no significant benefit from medical therapy. . What about the white-coat effect? Some confusion exists concerning the terms WCHT and white-coat effect (WCE). and is not substantially influenced by reassurance and familiarization with the technique or the circumstances of the BP measurement. Active drug treatment lowered OBP in all patients but had very little effect on ABP in patients with dnon-sustainedT (white coat) hypertension. data [76– 78] seem to indicate that the WCE does not predict future target organ damage [72. persons with a light or moderate OBP elevation and a small WCE may show a normal ABP level and thus have WCHT [1.2]. This disagreement is probably due to the fact that ABP monitoring also includes BP responses to daily life activities (mental or physical stress). Antihypertensive drug treatment reduced the rate of stroke in patients with SHT. R. [83] showed that the surrogate (ambulatory and home) WCE is attenuated by antihypertensive treatment but does not predict the treatment- 6.4. BP control and inhibition of LV enlargement were equal in both groups. there is no automatic association between the two.H. However.41].71]. recent data also show that there is no correlation. however. In 1997. In a recently published similar trial. Fagard / European Journal of Internal Medicine 15 (2004) 348–357 gender and older age. Methods using ABP or HBP to diagnose a significant WCE (usually at least 20 mm Hg systolic or 10 mm Hg diastolic) are. These two terms are sometimes erroneously used as synonyms. [75] showed that the ambulatory WCE was greater in women than in men. their long-term prognosis might not be equal. Den Hond et al. Nevertheless. However. and during the study period both OBP and ABP measurements were taken. and probably yearly or 2-yearly ABPM to detect whether SHT occurs [1. since the final difference in BP between the two treatment groups (ranging between 3. other methods of estimating the WCE were soon evaluated. is absent in many individuals. regular assessment of other risk factors. but it should be stressed that they are different entities. including initiation of life style changes. Further intervention studies are needed to determine whether subjects with WCHT will benefit from drug treatment to prevent the future development of organ damage and risk of CV events. Celis. continuous (beat-to-beat) finger BP measurements (true WCE) [72. and is usually accompanied by a parallel increase in heart rate. The first attempts to quantify the WCE were done by intra-arterial ABP measurement [72]. such as the difference between OBP and (daytime) ABP (ambulatory WCE) [72–74] or between OBP and HBP (home WCE) [72. and appropriate treatment if (metabolic) abnormalities are present.74].354 H. who experienced a very low stroke rate whether or not they were treated. be predicted on the basis of OBP values since these tended to decrease during follow-up. The (systolic) home WCE was also significantly higher in females and showed a slight increase with higher body mass index and with older age. [69] showed that adjustment of antihypertensive treatment. but also to worse BP control at the end of the 12-month treatment period. the same authors [70] found that adjusting antihypertensive treatment on the basis of HBP instead of OBP led to less intensive drug treatment.5 and 6. based on either ABP or OBP. can persist for up to 10–15 min. evidence to date does not allow us to make firm recommendations regarding drug treatment in patients with uncomplicated WCHT in whom medical therapy seems unnecessary. Further evidence comes from the ABPM substudy of the Syst-Eur trial [48]. Most. though not all. and in treated than in untreated patients. In patients with WCHT in whom antihypertensive drug treatment is not started. Several investigators assessed the prognostic significance of the dsurrogateT or dtrueT WCE. elderly patients with isolated systolic hypertension were randomized to be treated with a dihydropyridine calcium antagonist or placebo. reported to disagree in this diagnosis in up to 20% of the subjects [74]. Persons with a high OBP and a large WCE may show elevated ABP levels and thus have SHT. Parati et al. In Syst-Eur. Because of practical problems.73. a close follow-up should certainly be implemented.

White-coat hypertension and cardiovascular risk.24:101 – 5. Atkins N. J Hypertens 1993. Reid JL. Pini R. Different metabolic predictors of white-coat and sustained hypertension over a 20-year follow-up period. Laragh JH. Mormino P. Am J Hypertens 2003.289:2560.2:262 – 71. et al. [8] Verdecchia P. [39] Muscholl MW. Bettencourt PM. [34] Rizzo V. [24] Staessen JA. et al.14:45 – 53. Guida L. J Hypertens 1997. Skeva II. Cottone S. [25] Cardillo C. Circulation 2001. Papamichael C. [28] Weber MA. Nielsen JW. et al. Arq Bras Cardiol 2003. Circulation 1994. et al.23:106. Asmar R.12:743 – 8. O’Brien ET. Skjaerpe T. Am J Hypertens 1999. Papaconstantinou H. Ciucci A. J Hum Hypertens 1996. Porcellati C. Cardiovascular outcome in white-coat versus sustained mild hypertension—a 10-year follow-up study. Devereux RB. [36] Polonia JJ. [32] Soma J. R. Left ventricular changes in isolated office hypertension. White WB. Lancet 1996. detection. Borgioni C. Neutel JM. Lithell H. Circulation 2002. Rossvoll O. J Am Coll Cardiol 2002. Nardi E.21:1011 – 53. et al.19:1015 – 20. Brfckel U.16:87 – 91. 31:57 – 63. Jamerson K. Colombo S. James GD. [15] Palatini P.106:63 – 8. and treatment of high blood pressure. On behalf of the dAd HocT working group. Dahl L. et al.2:545 – 9. [17] Den Hond E. 161:2677 – 81. et al. White-coat hypertension: a selection bias? J Hypertens 1998. Left ventricular systolic and diastolic function assessed with two-dimensional and Doppler echocardiography in ’white coat’ hypertension. et al. Target-organ damage in stage I hypertensive subjects with white coat and sustained hypertension: results from the HARVEST study. [5] Verdecchia P. et al. Fernandez JR. Campia U. J Hum Hypertens 2004. [37] Palatini P. et al. Vessby B. [18] Nesbitt SD. Gudbrandsson T. Fagard / European Journal of Internal Medicine 15 (2004) 348–357 355 induced improvement in LV changes. Diagnostic value of strategy for the detection of white coat hypertension based on ambulatory and home blood pressure monitoring. Blood Press Monit 1997. Martin JC. Frequency and determinants of white coat hypertension in mild to moderate hypertension. Staessen JA. Properly defining white coat hypertension. 12:251 – 9. White coat hypertension: a follow-up. JAMA 2003.10: 293 – 8. [23] Segre CA. Santos AR.16:977 – 84. J Hypertens 2003. Short report: ambulatory blood pressure in normotensive compared with hypertensive subjects. Arch Intern Med 2001. Broggi R. Martins LR. et al. Bianchi A. Palatini P. White coat hypertension. et al. Basto F. Circulation 1998. Ambulatory blood pressure: an independent predictor of prognosis in essential hypertension. [7] Khattar RS. Andre ´ n B. Calvo C. Effect on the carotid artery structure. [27] Trenkwalder P. FMUSP. Black HR. Hypertension 1994. Santonastaso M. Graettinger WF. Roman E. Lind L. Innocuous or adverse phenomenon? Eur Heart J 2000. Schillaci G. Ueno RK. Mountokalakis TD. Rees KR. Lancet 1996. Ayala DE. Beilin L.104:1385 – 92. [30] Pierdomenico SD.26: 413 – 419. Curzio JL. Roman MJ. Schillaci G. White-coat hypertension as a cause of cardiovascular dysfunction. [13] Sega R. Eur Heart J 2001. Evaluation of the extent and duration of the ’ABPM effect’ in hypertensive patients. Schwartz JE. Imai Y. J Am Coll Cardiol 1996. Data from the general population (Pressione Arteriose Monitorate E Loro Associazioni [PAMELA] Study). Suzuki Y. J Hypertens 2001. [20] Bjfrklund K.10:1270 – 80. Self-measured versus ambulatory blood pressure in the diagnosis of hypertension. Alterations of cardiac structure in patients with isolated office. [29] Cavallini MC.15:979 – 85. Hypertension 1998. Kristensen KS. Dfring A. Celis H. A primary care-based study. evaluation. Lahiri A. ambulatory and home blood pressure measurement. Rodriguez SA.21:836 – 44. J Hypertens 2003. Bang LE. Am J Hypertens 1997. Boddie C. bWhite coatQ hypertension and alerting reaction in elderly and very elderly hypertensive patients.317:565 – 70. Lydtin H. Harshfield GA. Dorigatti F. Isolated clinic hypertension is not an innocent phenomenon. Hense H-W. Independent predictors of isolated clinic (dwhite coatT) hypertension. [38] Owens PE.11:1289 – 97. Fujusawa A. Elliott HL. [2] Verdecchia P.26:801 – 7. Celis. Alamara CV. White-coat hypertension and normotension in the league of hypertension of the Hospital das Clı ´nicas. European society of hypertension recommendations for conventional. Part A Theory Pract 1992.80:122 – 6. White-coat hypertension and cardiac organ damage in elderly subjects.21:1647 – 8. Schork N. Target organ status and serum lipids in patients with white coat hypertension. Guglielmi MD. Am J Hypertens 1999.40:710 – 7. Amerena JV. [22] Mancia G. Pessina AC. Folli G. Mormino P. Fagard R. [33] Glen SK. How common is white coat hypertension? JAMA 1988.18:85 – 9. Warde KR. Isolated office hypertension and end-organ damage.348:1444 – 5. et al. O’Brien ET. [16] Stergiou GS. References [1] O’Brien ET.90:2291 – 8. Garcia-Puig J. Amery KA. ambulatory. Porcellati C. Home blood pressure as a predictor of future blood pressure stability in borderline hypertension. Lanzarotti A. Schillaci G. O’Brien ET. Plaschke M. Riegger GAJ. Systemic arterial hypertension and vascular reactivity: diagnosis of mild hypertension by ambulatory blood pressure monitoring. Wideroe TE. [3] Chobanian AV. Gama GM. Lapenna D. Pickering TG. Ruilope LM. Hypertension 1993. Senior R.21:717 – 22. or home hypertension. [31] Cerasola G. 2003 European Society of Hypertension — European Society of Cardiology guidelines for the management of arterial hypertension. Bakris GL. [4] Guidelines Committee. [21] Julius S.12:245 – 50. Hypertension 1995. et al. White coat hypertension and target organ involvement: the impact of different .1997:289 – 95. Is elevation of clinic blood pressure in patients with white coat hypertension who have normal ambulatory pressure associated with target organ changes? J Hum Hypertens 1998. [12] Grandi AM. Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey. BMJ 1998. [26] Kuwajima I. [10] Verdecchia P. White coat effect.24:793 – 801. DeFelice F. et al. Blank S. Ciccinetti P. clinical and demographic characteristics. Schunkert H. Porcellati C.98:1892 – 7. Clin Exp Hypertens. Kuramoto K.22:826 – 31. The Tecumseh study.H. [11] Zakopoulos N. [35] Ferrara LA. Steffes-Tremer I. [19] Verdecchia P. When can the practicing physician suspect white coat hypertension? Statement from the working group on blood pressure monitoring of the European society of hypertension. Prevalence. [40] Hoegholm A. Psychophysiological reactivity and cardiac end-organ changes in white coat hypertension. Lyons SP.H. J Cardiovasc Risk 1995. Is white coat hypertension innocent? Hypertension 1993. [9] Martinez MA. This observation also supports the hypothesis that the (surrogate) WCE is of marginal clinical significance. [14] Hermida RC. Is white coat hypertension associated with arterial disease or left ventricular hypertrophy? Hypertension 1995. Lopez JE. Pickering TG. O’Brien E. Trocino G. J Hypertens 2003. Grant E. Follow-up clinic and ambulatory blood pressure in untreated white-coat hypertensive patients (evaluation after 2–5 years). et al. et al. [6] Pickering TG. 259:225 – 8. Smith DHG. The seventh report of the joint national committee on prevention.348:654 – 7.21:821 – 48. Pasanisi F. Blood Press 1993.

Staessen JA. Mezzetti A. [78] Palatini P. Fukudo S. [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] .160:1507 – 12.21: 1714 – 8. Curgunglu A. Stroke 2003. Altinisik S.11:352 – 6. Nardi E. A matching study. Pascual JM. Clinic-daytime blood pressure difference and cardiovascular damage. Penzo M.8:37 – 40. Oxidative stress in white coat hypertension. blood pressure and mortality in men: prospective cohort study. Levels of plasma fibrinogen and ddimer in subjects with white-coat hypertension. Eur Heart J 2000.12:817 – 22. Celis H. Hypertension 1998.12:307 – 13. White coat effect: semantics. Burnier M. Crivaro M. Borgioni C. Mountokalakis TD. O ¸ it F.16:498 – 501. O’Brien E. [63] Smith PA. No harm for the heart. Muldoon MF. Campos C. doi:10. Canali C. Cardiovascular prognosis of "masked hypertension" detected by blood pressure self-measurement in elderly treated hypertensive patients. Nocturnal fall of blood pressure and silent cerebrovascular damage in elderly hypertensive patients: advanced silent cerebrovascular damage in extreme dippers. Cardiovascular risk in white-coat and sustained hypertensive patients. JAMA 2004. Kristensen KS. 17:124. et al.17:165 – 70.19:389 – 97. J Hum Hypertens 2004.167:231 – 5. Karter Y. [75] Den Hond E. Chatellier G. Cottone S. Clementy J. Aydı ´n S. Saito Y.31: 621 – 6. Schillaci G. [77] Mule ` G. Antihypertensive treatment based on blood pressure measurement at home or in the physician’s office. Strandberg TE. Sympathetic neural mechanisms in white-coat hypertension. J Hypertens 2003. Matsuo T. Cuccurullo F. J Hum Hypertens 1999. Low-density lipoprotein oxidation and vitamins E and C in sustained and white-coat hypertension. Murray S. Mezzetti A.102:1139 – 44. Costantini F. Bucci A.278:1065 – 72. Rı ´os Blanco JJ. Kotsis VT. Lopez-Barreiro L. et al. Silent and clinically overt stroke in older japanese subjects with white-coat and sustained hypertension. Lip GYH. Interactive action of the white-coat effect and the blood pressure levels on cardiovascular complications in hypertension. et al. et al. Bobrie G. J Hum Hypertens 2003. Am J Hypertens 2002. Kario K. Circulation 1996. Mendez-Naya I. Mancia G.356 H. DeCesare D. Am J Hypertens 2004. Stoker JB. Gene ` s N. Iannuzzi R. [72] Parati G. Schwartz JE. Am J Hypertens 2003.21:481 – 6. J Am Coll Cardiol 2001. O’Brien ET. High prevalence of Chlamydia pneumoniae antibodies in white-coat hypertensives. [80] Gosse P. et al. et al. Karter Y. Target organ damage and changes in arterial compliance in white coat hypertension. Eguchi K. Roussias LG. Celis. Mary DASG. Beevers DG. Ruilope M. J Am Coll Cardiol 2002. et al. Blood Press 1999. Durandet P. Waeber B. [69] Staessen JA.34:2471 – 4. et al. White coat hypertension is a cardiovascular risk factor: a 10-year follow-up study. Nunokawa T. Pitiriga VC. Estevez-Nunez JC. Graham LN. Pessina AC. Salomaa V. Celis H. Imaya M. [68] Verdecchia P. O dysfunction in patients with white coat hypertension.18: 383 – 389. Aydı ´n S. Karter Y. Kario K. White coat hypertension. Thijs L. Mary DASG. Rushton L.14:327 – 32. Bidlingmeyer M. Am J Med 1997. Ertqrk NT. Shimada K. J Hum Hypertens 2003. Circulating homocysteine levels in sustained and white coat hypertension. Hypertension 1996. Manning G. Clinical implications of white coat hypertension: an ambulatory blood pressure monitoring study.38: 238 – 245. Staessen JA. White coat effect. Reassessment of definition and prognosis of white-coat hypertension. Beevers M. Yoshinaga K. J Hum Hypertens [advance online publication: 26 February 2004. Stoker JB.17:217 – 22. Pierdomenico SD. Relationship between ambulatory white coat effect and left ventricular mass in arterial hypertension. Lapenna D.40:304 – 9. Review: white coat hypertension: understanding the concept and examining the significance. ¨ zdogan M. et al. [71] Tsai P-S. Fagard R. Shimada K. role of paraoxonase. Akc [61] C ¸ oban E. Arch Intern Med 2000. [65] Uzun H. JAMA 2004. Gayet C. Staessen JA. Den Hond E.291:955 – 64. Hypertension 2002. Kobayashi H. Mackintosh AF. Bang LE. [62] Smith PA. Cuccurullo F. J Hypertens 1999. Go ´ mez-Cerezo J.15:946 – 52. [70] Staessen JA.40:126 – 32. Am J Hypertens 2003. Celis H. Noninvasive study of endothelial function in white coat hypertension. White-coat hypertension and carotid artery atherosclerosis. Sagar G. Difference between office and ambulatory blood pressure or real white coat effect: does it matter in terms of prognosis? J Hypertens 2000. Manuck SB.18:71 – 2. Coleman I-C. J Clin Nurs 2002. Pierdomenico SD. ¨ zdogan M. A randomised controlled trial. Ito N. Greater impact of coexistence of hypertension and diabetes on silent cerebral infarcts. Dorigatti F. Rodicio JL.jhh. for the THOP investigators. Brunner HR. J Hypertens 2001.22:766. Pose-Reino A. Vandenhoven G. et al. Staessen JA. Thijs L. Mackintosh AF. JAMA 1997. Sua ´ rez Garcı ´a I. Argyraki CK. Milon H. Letter to the Editor: Endothelial dysfunction in sustained and white coat hypertension. Landray MJ. Shimada K. Graham LN.17:811 – 7. Hoegholm A. Isolated office hypertension: a prehypertensive state? J Hypertens 1996. Pardaens K. Gustavsen PH. et al. [76] Munakata M. Hoshide S. Timuragaoglu A.H. Lapenna D. Response to antihypertensive therapy in older patients with sustained and nonsustained systolic hypertension. Sacchi N.25:343 – 9. Nazzaro P.1001697]. R. Circulation 2000. Narciso ML. Promax H. Papamichail CM. Clinical significance of blood pressure response triggered by a doctor’s visit in patients with essential hypertension.18:291 – 2.16:892 – 3. Redon J.1038/ sj. Sutton-Tyrrell K. Hypertension 1998. Celis H. Fagard RF. Am J Hypertens 2004.103: 208 – 16.291: 1342 – 9. Relation between central sympathetic activity and stages of human hypertension. assessment and pathophysiological implications. Fagard / European Journal of Internal Medicine 15 (2004) 348–357 cut-off levels on albuminuria and left ventricular mass and geometry. Atherosclerosis 2003. Prognostic value of ambulatory blood pressure monitoring in refractory hypertension: a prospective study. Blood Press Monit 2003.12:433 – 9. Relationship of heart rate and heart rate variability with conventional and ambulatory blood pressure in the population. Research letter: Endothelial C ¸ oban E.8:134 – 40. White coat hypertension and carotid atherosclerosis.11:715 – 22. Hypertension 1993. Antihypertensive treatment based on conventional or ambulatory blood pressure measurement. Cipollone F. Blood Press 2002. [73] Lantelme P. Bucci A. Bucci A. [74] Stergiou GS.11:144. Ciucci A. et al. Byttebier G. Determinants of white-coat syndrome assessed by ambulatory blood pressure or self-measured home blood pressure. Millar-Craig MW. Endothelial function in sustained and white coat hypertension. Diagnostic criteria of white-coat hypertension (WCH): consequences for the implications of WCH for target organs. Hypertens Res 2002. J Hum Hypertens 1998. Matsuo T. Efstathiou SP. [64] Fagard RF.94:I340. 17:331 – 7. Kario K. [79] Guida L. Is white coat innocent? Blood Press 2003. Matsuo M. Buntinx F. White coat effect in treated versus untreated hypertensive individuals: a case control study using ambulatory and home blood pressure monitoring.27:130 – 5. [66] Pierdomenico SD. Pickering TG. Rodriguez-Fernandez M. Reboldi G. [67] Bidlingmeyer I. Blood Press 2002. Vernet M.31: 712 – 8. J Hum Hypertens 2004.

Fagard / European Journal of Internal Medicine 15 (2004) 348–357 [81] Verdecchia P. Schillaci G. Ulian L.H. R. Schillaci G. Sampieri L. Am J Hypertens 1995. Hypertension 1997. Porcellati C.35:614 – 20. . Celis. Hypertension 2000. et al.8:790 – 8. et al. 357 [83] Parati G. White coat hypertension and white coat effect: similarities and differences. Attenuation of the ’white-coat effect’ by antihypertensive treatment and regression of target organ damage.H. Ciucci A. Borgioni C. [82] Verdecchia P.29:1218 – 24. Prognostic significance of the white coat effect. Borgioni C.

Sign up to vote on this title
UsefulNot useful