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White Coat Hypertension and Target Organ Involvement: the Impact of Different Cut-Off Levels on Albuminuria and Left Ventricular Mass and Geometry

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White Coat Hypertension and Target Organ Involvement: the Impact of Different Cut-Off Levels on Albuminuria and Left Ventricular Mass and Geometry Journal of Human Hypertension (1998) 12, 433–439 1998 Stockton Press. All rights reserved 0950-9240/98 $12.00 http://www.stockton-press.co.uk/jhh ORIGINAL ARTICLE White coat hypertension and target organ involvement: the impact of different cut-off levels on albuminuria and left ventricular mass and geometry AHøegholm, KS Kristensen, LE Bang and JW Nielsen Department of Internal Medicine, County Central Hospital, N{stved, Denmark The aim of this cross-sectional study which took place atory daytime BP of 135.6/90.4 mm Hg was found to cor- in a hypertension clinic at a district general hospital in respond to an office BP of 140/90 mm Hg in normal con- Denmark was to make a pragmatic definition of white trols; used as a cut-off level in patients with newly coat hypertension. A total of 420 patients were referred diagnosed hypertension it separated 19% as white coat consecutively from general practice with newly diag- hypertensives. The end-organ involvement of these nosed untreated essential hypertension and 146 normal white coat hypertensives differed significantly from subjects were drawn at random from the Danish those with established hypertension but not from the national register. The following measurements were normal controls. Lower cut-off levels were less efficient taken: office blood pressure; 24-h ambulatory blood in this respect, as was the case when the systolic BP pressure (BP) monitoring; echocardiography with deter- was not taken into account. mination of left ventricular mass index and relative wall In conclusion a pragmatic definition of white coat thickness; and early morning urine albumin/creatinine hypertension should—apart from well-established ratios. hypertensive office measurements—include a cut-off Four different cut-off levels were studied. An ambul- level close to 135/90 mm Hg ambulatory daytime BP. Keywords: white coat hypertension; target organ damage Introduction morbid and mortal events4,8 and intervention stud- ies;9 a value of 140/90 mm Hg is widely accepted for Blood pressure (BP) measured under standardised adults.10,11 In contrast, no similar large scale studies conditions at the office and BP during daily life as on morbidity/mortality and ABP exist, and hence measured by ambulatory monitoring often give dif- cut-off values for ABP have not gained consensus.12 ferent results. The correlation between values from This dilemma had led to a disputable practise in these two measurement modalities is relatively low which cross-sectional studies on ‘normal popu- with reported coefficients of correlation around 0.5– lations’ of limited size have been the substrates for 0.7.1–3 It is unsolved which measure is ‘true’, ie, 4 different types of computations. Most often a per- which best reflects the ‘usual’ BP and prognosis. centile or standardised deviation from the mean of The lack of identity between the two methods of the distribution is computed, in other cases a BP of measurement yields a group of patients with the 140/90 mm Hg at the office has been used to calcu- combination of hypertensive office BP and normal late a corresponding ABP value. Some studies make ambulatory BP (ABP), which is generally referred to conversions for different gender and age groups sep- 5,6 as ‘white coat hypertension’. The literature has arately, which makes the results less easy to handle shown numerous definitions of this condition and, in clinical practice.2 Evidently, the varying cut-off consequently, great variation in the characterisation levels give very large differences in the frequency of 7 of the group has evolved. The primary explanation white coat hypertension, ie, 7–52%.13–16 for these diversities is the lack of widely accepted In the absence of large scale longitudinal studies ABP normalcy limits. The cut-off values between and generally accepted cut-off values we have made normal and hypertensive office BP has been deter- the present analysis on BP and surrogate end-points mined on the basis of major epidemiological longi- with the purpose of examining the effect of different tudinal studies regarding BP level and frequency of cut-off levels for the definition of normalcy and hence white coat hypertension. Our cohort of patients offers a potential for describing a white coat Correspondence: Dr A Høegholm, Medicinsk Afdeling, Centralsy- group with a normal level of target organ involve- gehuset, DK-4700 N{stved, Denmark ment, in that it includes a genuine normal control Received 26 January 1998; revised 7 April 1998; accepted 16 group and has data on both albuminuria and echo- April 1998 cardiography. White coat hypertension and target organ involvement AHøegholm et al 434 Subjects and methods were obtained, but all ambulatory readings were considered acceptable, defined as at least 18 day- In order to estimate the frequency of white coat time readings from outside the office. hypertension we have performed 24-h ABP monitor- The monitorings were edited for supposedly arti- ing in 420 consecutive patients with newly diagnosed factual measurements, ie, single measurements asso- mild-to-moderate hypertension. The inclusion cri- ciated with either an unexplained pulse rate above terion was that their general practioner had planned 120/min, or an unexplained systolic or diastolic to start anti-hypertensive treatment, but had not yet pressure deviation exceeding 30% compared with instituted it. In order to avoid confounding, patients the readings immediately before and after. The sub- with other known reasons for albuminuria, eg, jects did not wear activity monitors or the like, but known diabetes or renal disease, were excluded from according to their diaries almost everybody was the statistical analyses regarding albuminuria data. awake throughout the period between 08.00 am to No patients with major cardiovascular diseases 09.59 pm, which was subsequently defined as the were included. daytime period, and the daytime ABP was the aver- As part of a multicentre study to establish the dis- age of the readings obtained in this period. tribution of ABP in the population,17 we performed 24-h BP monitoring in subjects drawn at random from the Danish national register. There was an Echocardiography intended similar number of subjects in different gen- One hundred and thirty-two (132) of the 146 normal der and age strata from 20–79 years. Subjects with subjects (90.4%) and 333 of the 420 hypertensive known renal or cardiovascular disease, diabetes, patients (79.3%) were examined with echocardio- hypertension or other condition necessitating ther- graphy. The same experienced physician examined apy with drugs with anti-hypertensive effects had all subjects with an Aloka 720 SSD mechanical sec- been excluded, leaving 146 monitorings. tor scanner (Aloka, Tokyo, Japan). All the examin- The study was in accordance with The Second ations were videotaped. In the parasternal short-axis Declaration of Helsinki, and was approved by the view two to four M-mode photographs were taken local ethics committee. All participating subjects at the optimum perpendicular plane just below the gave their informed consent. tips of the mitral leaflets. These photographs were evaluated independently by two observers, who Blood pressure measurements were blind regarding the age, gender, size, and BP of the subjects. The two observers could individually All the referred patients were considered by their inspect the videotapes, if it was felt necessary. All general practioner to have hypertension, and were evaluations were performed in the same batch; scheduled to start anti-hypertensive treatment in the hence, the readings were different from the data pre- near future. No patient had for the 5 weeks prior to viously reported.21 The reason for the blinding pro- the study received any anti-hypertensive drug; no cedure was to assure an estimate free from bias, but patient was taken off medication in order to enter of course at the cost of lower accuracy which, how- the study, but, a third had previously been on such ever, is of less importance due to the relatively high medication (most often because of previous hyper- number of subjects. No patient was excluded from tension, but also large numbers because of palpi- analysis because of difficulties in obtaining images, tations, oedema and tremor) which had been taken although 55 (11.4%) were considered of minor tech- for median 3 years. The BP of the patients who had nical quality. Interventricular septal thickness never been on anti-hypertensive medication had (IVST), posterior wall thickness (PWT), and end- been followed by the general practitioners for diastolic left ventriculum internal diameter (LVID) median 4 months. The practitioners had determined were determined according to the Penn-conven- the BP at least three times (median 4) with at least tion.22 Left ventricular mass was computed as 1.04 weekly intervals. Nearly everybody used a standard [(IVST + LVID + PWT)3 − LVID3] − 13.6 g22 and was size cuff (12 × 35 cm) and in the sitting position; indexed for body surface area (BSA) (left ventricular approximately a third used aneroid sphygmoman- mass index (LVMI)); relative wall thickness (RWT) ometers, the remainder mercury columns. The aver- was computed as 2 × PWT/LVID.23 age of the diastolic BP measured in this way was The between-observer coefficients of variation above 90 mm Hg in all subjects. were 10.8% and 9.5% for LVMI and RWT, respect- The office BP of the normotensive subjects was ively. The mean of the measurements of the two determined as a mean of five measurements with a observers was used for data analysis. Hawksley ‘random zero’ sphygmomanometer (Hawksley and Sons Ltd, Lancing, UK),18 performed Urinalysis in the sitting position after 15-min of rest in the hypertension clinic. All the subjects were asked to bring with them an The subjects wore TM 2420 ABP recorders (A&D, early morning urine sample, defined as the first Tokyo, Japan)19,20 for at least 24 successive hours on voided specimen on arising; 127 of the 146 normal working days, during which period they performed subjects (87.0%) and 302 of the 420 hypertensive their habitual daily activities; the recorders took patients (71.9%) complied in this regard.
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