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Journal of Human Hypertension (2008) 22, 438–440 & 2008 Nature Publishing Group All rights reserved 0950-9240/08 $30.00 www.nature.com/jhh

RESEARCH LETTER

Blood pressure levels correlate with intraindividual variability using an automated device in early pregnancy Journal of Human Hypertension (2008) 22, 438–440; doi:10.1038/sj.jhh.1002302; published online 29 November 2007

This study reports on the interdependence of intraindividual blood pressure (BP) variability and the BP level in early pregnancy. The higher the BP the more exaggerated the drop from the first to the second reading and the higher the intra-individual standard deviation (s.d.). Pregnancy is a window of opportunity to screen for essential hypertension by measurement of BP. However, accurate assessment of BP has been hindered by the considerable variability that BP exhibits within each individual. Patients with higher BP have higher variability1 and a more exaggerated response to stressful stimuli.2 During BP measurement at rest the first recording is usually the highest and this decreases as the patients become more familiar with the procedure.3–6 It is therefore recommended that a series of BP measurements should be made until a pre-specified level of stability is achieved.7 However, there is evidence that a high first measurement may not be a benign finding and can be predictive of subsequent development of hypertension and cardiovascular disease.1,8,9 The study was undertaken to demonstrate the interdependence of intra-individual BP variability assessed with an automated device and the BP level as a useful tool to predict a woman to be hypertensive in early pregnancy. A validated automated device (3BTO-A2, Microlife, Taipei, Taiwan) which was calibrated before and at regular intervals during the study10 was used to measure BP in 4402 women with singleton pregnancies attending for routine antenatal care at 11 þ 0–13 þ 6 weeks of gestation. The women were in the seating position, their left arms were supported at the level of the heart and an appropriate size cuff was used depending on the mid-arm circumference.7 After a 5-min rest a series of recordings were made at 1-min intervals until variations between consecutive readings fell within 10 mm Hg in systolic (SBP) and 6 mm Hg in diastolic BP (DBP).7 The women were divided into five groups according to the number of recordings needed. In group A only two recordings were needed, in group B three,

in group C four, in group D five and in group E six. Similarly, the women were divided into five groups according to the level of SBP (o110, 110–119, 120–129, 130–139 and X140 mm Hg) and DBP (o60, 60–69, 70–79, 80–89 and X90 mm Hg). The per cent decrease between the first and second measurement was calculated for each subject. The s.d. of the BP measurements within each subject was calculated as a measure of variability of their BP (intra-individual s.d.). The Cuzick’s trend test was used, first, to examine the significance of trends in BP at the first, last and average of all recordings between groups A–E and second, to examine the trend between the BP groups in the per cent reduction between the first and the second BP measurements and the intra-individual s.d. There were 3753 (85.3%) women in group A, 510 (11.9%) in group B, 87 (2%) in group C, 39 (0.8%) in group D and 13 (0.3%) in group E. In each of the five groups, the mean BP at the first recording was significantly higher than the one at the last recording, apart from the DBP and mean arterial pressure (MAP) in group E (Table 1). In addition, there was a significant increase in the mean BP from group A towards group E for the first recording, the last recording and the average of all recordings (Supplementary Figure w1; Cuzick’s trend test Po0.0001, Table 1). With increasing BP there was a progressive increase in the per cent decrease from the first to the second measurement (Supplementary Figure w2; Cuzick’s trend test Po0.0001) and between first and last measurement (Cuzick’s trend test Po0.04). With increasing BP there was a progressive increase in the intra-individual s.d. (Supplementary Figure w3; Cuzick’s trend test Po0.0001). In the total population the BP was 140/90 mm Hg or more in 177 (4.0%) cases in the first recording and in 77 (1.7%) in the last recording. On the extreme assumption that the suspicion of hypertension should be based on the results of the first recording then a policy of recording the last measurement would detect 43.5% of affected cases, and the use of the average of the first two measurements, the last two measurements or the average of all measurements would detect 60.5, 39.5 and 53.7% of affected cases, respectively (Supplementary Table w1). In contrast, if the suspicion of hypertension is based on the results of the last

Research Letter 439

Table 1 First and last two measurements of SBP, DBP and MAP according to the number of measurements required (mean and s.d.) Measurements

Blood pressure Systolic

Diastolic

Mean

Group A (n ¼ 3753)

First Second

114.6 (10.5)a 112.6 (10.0)

69.5 (7.6)a 68.8 (7.4)

84.5 (7.8)a 83.4 (7.6)

Group B (n ¼ 510)

First Second Third

122.2 (13.9)a 116.2 (11.9) 115.2 (11.6)

74.2 (9.7)a 71.0 (8.8) 71.0 (8.5)

90.2 (9.8)a 86.1 (9.1) 85.7 (8.8)

Group C (n ¼ 87)

First Third Fourth

121.6 (15.9)a 116.0 (12.8) 115.6 (12.5)

73.2 (11.5)a 70.5 (9.0) 70.3 (8.6)

89.4 (11.6)a 85.7 (9.6) 85.4 (9.2)

Group D (n ¼ 39)

First Fourth Fifth

129.3 (18.7)a 120.2 (14.2) 120.2 (14.6)

77.2 (13.3)a 71.6 (11.9) 71.3 (11.6)

94.5 (13.5)a 87.8 (12.1) 87.6 (12.0)

Group E (n ¼ 13)

First Fifth Sixth

137.5 (17.0)a 127.0 (14.8) 127.5 (12.1)

77.5 (12.8) 77.4 (9.0) 75.6 (10.4)

97.5 (13.1) 93.9 (10.1) 92.9 (10.5)

a

Significant differences between the first and last measurement.

recording a policy of an alternative method of computing the result would lead to a false-positive diagnosis in 0.2–2.3% of cases. The frequency distribution of the SBP in the first recording in each group (A–E) is shown in Supplementary Figure w4. Similar patterns were observed for DBP and MAP. On the extreme assumption that the diagnosis of suspected hypertension should be based on the results of the first recording, the BP was 140/90 mm Hg or more in 72 women (1.9%) of group A, 70 women (13.7%) of group B and 35 women (25.5%) in the combined data of groups C, D and E. Consequently, the contribution of the groups in the total of 177 cases was 40.7% for group A, 39.5% for group B and 19.8% for groups C, D and E. If the diagnosis of suspected hypertension was based on the results of the last recording the prevalence of the disease would be 46 (1.2%) in group A, 19 (3.7%) in group B and 12 (8.6%) in groups C, D and E. Consequently, the contribution of the groups in the total of 77 cases was 59.7% for group A, 24.7% for group B and 15.6% for groups C, D and E. The first clinical visit in pregnancy has a potential for screening half of the adult population for essential hypertension. Our findings highlight the difficulties in defining the risk of such women on the basis of their BP measurement since the incidence of suspected hypertension is more than twice as high if the first rather than the last recording of their pressure is used. The findings that the higher the first BP measurement the bigger the drop between the first and second measurements and the greater the intra-individual s.d. suggest that a high first measurement is associated with cardiovascular hyper-responsiveness, which is a

recognized predictor of subsequent development of hypertension and its complications.11,12 The exogenous stress associated with the routine 11 þ 0–13 þ 6 weeks scan and the measurement of BP unmasked a group of women requiring three or more recordings of their BP. This group which constituted 15% of the total contributed about 60% of those with a BP of 140/90 mm Hg or more at the first recording and 40% of those with high BP at the last recording. What is known about this topic K Blood pressure lability and hyper-responsiveness to stressful stimuli are associated with subsequent development of hypertension. K The initial higher blood pressure measurement has been considered as bias in determining the ‘true’ blood pressure, and it has been recommended that to determine the latter a series of measurements should be made in an attempt to reduce the effect of the first measurement. K Despite the fact that the first trimester of pregnancy is a window of opportunity to screen for undiagnosed hypertension, there is no evidence regarding the influence of blood pressure lability and hyper-responsiveness on computing blood pressure levels. What this study adds K In the first trimester of pregnancy the prevalence of BP of 140/90 mm Hg or more may vary from 4 to 1.7% depending on whether the first or the last recording in a series of measurements is used for the diagnosis. K The mean BP at the first recording is significantly higher than the one at the last recording. The degree of reduction between the first and subsequent measurements is higher in women with higher blood pressure, possibly suggesting the hyper-responsiveness to the effect of the clinical visit. K Women with high variability in blood pressure levels are more likely to be truly hypertensive. Abbreviation: BP, blood pressure. Journal of Human Hypertension

Research Letter 440

The introduction of reliable automated BP devices facilitates repeated measurements and eliminates operator bias, but there is uncertainty regarding the number of recordings to be made and the best way of estimating the true BP from such a series of recordings. If one assumes that the last of a series of measurements represents the value closest to the baseline at rest, then the difference between the first and the last recording is a measure of the cardiovascular response to the stress of the antenatal visit. Further studies are needed to examine whether a method combining the last recording with the difference between the first and the last measurement would provide more effective screening for hypertension-related complications, than each measurement individually or even their simple average. LCY Poon, N Kametas, CM Valencia, IV Pandeva and KH Nicolaides Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, Denmark Hill, London, UK E-mail: [email protected] Published online 29 November 2007

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3 Huang YC, Morisky DE. Stability of blood pressure: is a sequential blood pressure reading protocol efficient for a large-scale community screening programme. J Hum Hypertens 1999; 13: 637–642. 4 Myers MG. Automated blood pressure measurement in routine clinical practice. Blood Press Monit 2006; 11: 59–62. 5 Wietlisbach V, Rickenbach M, Burnand B, Hausser D, Gutzwiller F. Combining repeated blood pressure measurements to obtain prevalences of high blood pressure. Acta Med Scand Suppl 1988; 728: 165–168. 6 Reeves RA. The rational clinical examination. Does this patient have hypertension? How to measure blood pressure. JAMA 1995; 273: 1211–1218. 7 National Heart Foundation Australia. Hypertension Management Guide for Doctors 2004. http://www. heartfoundation.com.au/index.cfm?page ¼ 36 (accessed 15 November 2006). 8 Rabkin SW, Mathewson FA, Tate RB. Relationship of blood pressure in 20–39-year-old men to subsequent blood pressure and incidence of hypertension over a 30year observation period. Circulation 1982; 65: 291–300. 9 Trembath CR, Hickner JM, Bishop SW. Incidental blood pressure elevations: a MIRNET project. J Fam Pract 1991; 32: 378–381. 10 Reinders A, Cuckson AC, Lee JT, Shennan AH. An accurate automated blood pressure device for use in pregnancy and pre-eclampsia: the Microlife 3BTO-A. BJOG 2005; 112: 915–920. 11 Treiber FA, Kamarck T, Schneiderman N, Sheffield D, Kapuku G, Taylor T. Cardiovascular reactivity and development of preclinical and clinical disease states. Psychosom Med 2003; 65: 46–62. 12 Schneider GM, Jacobs DW, Gevirtz RN, O’Connor DT. Cardiovascular haemodynamic response to repeated mental stress in normotensive subjects at genetic risk of hypertension: evidence of enhanced reactivity, blunted adaptation, and delayed recovery. J Hum Hypertens 2003; 17: 829–840.

Supplementary Information accompanies the paper on the Journal of Human Hypertension website (http:// www.nature.com/jhh)

Journal of Human Hypertension