Article Text
Abstract
Objectives Standard operating procedures for office blood pressure measurement (OBPM) vary greatly between guidelines and studies. We aimed to compare the difference between a single OBPM and the mean of the three following measurements. Further, we studied how many patients with possible hypertension may be missed due to short-term masked hypertension (STMH) and how many might be overdiagnosed due to short-term white coat hypertension (STWCH).
Design and setting In this cross-sectional, single-centre trial, 1000 adult subjects were enrolled. After 5 min of rest, four sequential standard OBPMs were performed at 2 min intervals in a quiet room in sitting position. We compared the first (fBPM) to the mean of the second to fourth measurement (mBPM). STMH was defined as fBPM <140 mm Hg systolic and <90 mm Hg diastolic and mBPM systolic ≥140 mm Hg or diastolic ≥90 mm Hg. STWCH was defined as fBPM systolic ≥140 mm Hg or diastolic ≥90 mm Hg and mBPM <140 mm Hg systolic and <90 mm Hg diastolic.
Results Complete measurements were available in 802 subjects. Between fBPM and mBPM, 662 (82.5%), 441 (55%) and 208 (25.9%) subjects showed a difference in systolic and 531 (66.2%), 247 (30.8%) and 51 (6.4%) in diastolic blood pressure (BP) values of >2 mm Hg, >5 mm Hg and >10 mm Hg, respectively. In 3.4% of initially normotensives STMH and in 34.3% of initially hypertensives, STWCH was apparent.
Conclusions There are significant differences between a single OBPM and the mean of consecutive BP measurements. Our study provides evidence that a single OBPM should not be the preferred method and should be discouraged in future guidelines.
Trial registration number NCT02552030;Results.
- hypertension
- cardiac risk factors and prevention
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Introduction
Standard operating procedures (SOPs) for office blood pressure measurement (OBPM) vary greatly depending on the guidelines (table 1).1–10 Similarly, outcome studies have used different methods to measure office blood pressure (BP) (table 2), which vary between single measurements11–14 and several measurements averaged,15–31 occasionally with the first measurement discarded.16 17 19 20 28 30 31 The 2011 National Institute for Health and Care Excellence (NICE) guidelines, for example, recommend in their short version multiple measurements only if the first measurement is elevated after 5 min rest;9 a recommendation for the number of measurements is not given in the long version.8 Despite general agreement across most guidelines for the need of repeated blood pressure measurements (BPMs), there is evidence that many physicians take only one BPM.32 33 Nonetheless, OBPM is used for clinical decision making including the diagnosis of arterial hypertension (AHT), initiation or titration of antihypertensive treatment.2–10 Recently, the use of automated office blood pressure measurement (AOBPM) has emerged. AOBPM is currently recommended in the Canadian guidelines,2 with the intention that it may better reflect daytime ambulatory blood pressure measurement (ABPM), may reduce systematic errors in BPM34 and may thus be used as an alternative to ABPM which is the current gold standard.35 To analyse the reliability of a single OBPM, we compared the BP values obtained by a single OBPM, as used in early outcome studies and many clinical settings, with the mean BP values obtained by repeated OBPM as done in the Systolic Blood Pressure Intervention Trial (SPRINT)15 and suggested by the Canadian guidelines.2 Additionally, we intended to study how many potentially hypertensive patients would be missed by a single OBPM due to short-term masked hypertension (STMH) and how many patients might be overdiagnosed and overtreated due to short-term white coat hypertension (STWCH).
Methods
Data collection
These data are part of the iPARR (iPhone-App compared with standard RR-measurement) trial. In this observational cross-sectional, single-centre trial, 1000 adult subjects were consecutively recruited from September 2015 until February 2016 at the Department of Internal Medicine and the Department of Obstetrics and Gynaecology at the University Hospital Basel (inpatient and outpatient units). After 5 min of rest, four consecutive BPM were taken with 2 min intervals in a quiet room in a sitting position in the presence of an operator according to a prespecified SOP (online supplementary figure 1, table 1). Thirteen physicians took BPM, and all of them were trained by one clinical hypertension specialist (TB). For the main trial, these measurements were compared with three photoplethysmographical recordings, using a smartphone camera to record the patient’s index finger. Subjects were blinded for the BPM results. The OBPM were taken using a validated standard device (Omron HBP-1300 professional BP monitor with the appropriate cuff size36). Only patients who had all four conventional measurements taken were included in this analysis, resulting in the exclusion of 198 subjects.
Supplementary file 1
Additional information about cardiovascular (CV) risk factors, concomitant disease and medication was collected.
Registration
This trial was registered on clinicaltrials.gov (NCT02552030) and approved by the local ethics committee (EKNZ 2015–287).
Statistics
We compared the first measurement out of four (fBPM) to the mean of the last three measurements (mBPM) using Bland-Altman plots and intraclass correlation. Continuous and dichotomous data were analysed using Mann-Whitney U or Fisher’s exact test as appropriate. Results of different measurement methods were compared using Wilcoxon signed-rank test. All calculations were done using SPSS V.22.
Outcome measures
STMH was defined as a systolic fBPM<140 mm Hg and diastolic fBPM<90 mm Hg and a systolic mBPM≥140 mm Hg or diastolic mBPM≥90 mm Hg. STWCH was defined as a systolic fBPM≥140 mm Hg or diastolic fBPM≥90 mm Hg and a systolic mBPM<140 mm Hg and diastolic mBPM<90 mm Hg. Sustained normotension (SNT) was defined as a systolic fBPM<140 mm Hg and diastolic fBPM<90 mm Hg and a systolic mBPM<140 mm Hg and diastolic mBPM<90 mm Hg. Sustained hypertension (SHT) was defined as a systolic fBPM≥140 mm Hg or diastolic fBPM≥90 mm Hg and a systolic mBPM≥140 mm Hg or diastolic mBPM≥90 mm Hg (figure 1).
Results
Complete measurements were available in 802 subjects (figure 2). Baseline characteristics are shown in table 3. Median age was 46.5 (IQR 32–61) years, 48.6% of subjects were male and 32.5% had a history of AHT.
Systolic measurements
Values of systolic BP and accuracy criteria comparing fBPM and mBPM are shown in table 4. There was a significant difference between the systolic fBPM and mBPM (P value<0.0005). Over the entire group, there was good correlation between the two measurement methods, as seen in an intraclass correlation coefficient of 0.852 (95% CI 0.832 to 0.870, P value<0.0005). The Bland-Altman plot showed a high variability between the measurement methods (online supplementary figure 2). Comparing the methods, both a decrease and increase of BP values were observed (figure 3). The fBPM was higher in the group without an increase>5 mm Hg of the BP over the measurements (fBPM 129 (117–140) mm Hg vs fBPM 119 (108–137) mm Hg; online supplementary table 2). A similar picture was seen in patients with a significant decrease of BP (ie, >5 mm Hg), who had a higher fBPM. However, there were significantly more patients with a history of AHT who demonstrated a decrease of systolic BP in mBPM compared with fBPM (online supplementary figure 3).
Diastolic measurements
Values of diastolic BP and accuracy criteria comparing fBPM and mBPM are shown in table 4. There was a significant difference between diastolic fBPM and mBPM (P value<0.0005; table 4). Over the entire group, there was good correlation between the two measurement methods, as seen in an intraclass correlation coefficient of 0.870 (95% CI 0.853 to 0.886, P value<0.0005). The Bland-Altman plot showed a high variability between the measurement methods (online supplementary figure 2). Comparing both methods, both a decrease and increase of BP values were observed (figure 3; online supplementary tables 4 and 5). The fBPM was higher in patients presenting without increase or with a decrease from fBPM to mBPM. There was a higher prevalence of history of AHT in patients showing a decrease of BP in mBPM compared with fBPM.
Blood pressure classification
Out of the 802 subjects, 510 (64%) subjects were sustained normotensive and 180 (22%) subjects were sustained hypertensive (figure 2).
Short-term masked hypertension
We identified 528 (65.8%) subjects with a normotensive systolic fBPM <140 mm Hg and diastolic fBPM of <90 mm Hg. Of those, 18 (3.4%) subjects with a normotensive fBPM had a STMH (figure 2).
Within the entire cohort, 412/802 (51.4%) subjects had no history of AHT and had a normotensive fBPM and 116/802 (14%) had a history of AHT and a normal fBPM, respectively. In the group without a history of AHT, STMH was present in 13/412 (3.2%) compared with 5/116 (4.3%) in the group with a history of hypertension (P value 0.545). Subjects with STMH had a higher fBPM compared with subjects with a stable or falling mBPM, but no differences in other clinical parameters (online supplementary table 6). On the individual level, we found that subjects with a low BP range<130 mm Hg systolic in fBPM could still show STMH (online supplementary figure 3).
Short-term white coat hypertension
We identified 274 (34.2%) subjects with a systolic fBPM of ≥140 mm Hg or a diastolic fBPM of ≥90 mm Hg. In 94/274 (34.3%) subjects, STWCH was present (figure 2).
Within the entire cohort, 145/802 (18.1%) subjects had a history of AHT and an elevated fBPM and 129/802 (16.1%) had no history AHT and an elevated fBPM, respectively. In the group with a history of AHT, STWCH was present in 29/145 (29.7%) compared with 51/129 (39.5%) without a history of hypertension (P value 0.086). Patients with STWCH were younger, lighter, smoked less and had lower systolic and diastolic fBPM in comparison with patients with SHT (online supplementary table 7). On the individual level, we found that subjects with a fBPM>160 mm Hg systolic could still show STWCH (online supplementary figure 4).
Discussion
Our main findings are that there are clinically significant differences in BPM results depending on the method applied to calculate the BP values within one measurement session. More than half of our patients had a difference of >5 mm Hg between the systolic fBPM and the mBPM and almost a third in their diastolic values. By measuring BP only once, as is often done in daily clinical practice and as it is recommended by the NICE guidelines, when the measurement reveals a normotensive value, possible hypertension can be missed in every 30th putative normotensive patient. Additionally, STWCH, as seen in 34.2% of our subjects with an elevated fBPM or in 16.5% of all patients with known AHT, can lead to overtreatment. However, we may underestimate the effect in the real world because one main error in clinical practice is not waiting 5 min before measurements.32 33
The recommendations for measurement methods vary highly according to the different guidelines (table 1). However, all guidelines give recommendations for treatment based on OBPM.3 5 7 10 Some acknowledge differences between OBPM, ambulatory and home measurements regarding cut-off values for hypertension,3 7 10 whereas some do not comment on methods at all.5 The strength of our study is the strict protocol for the BPM session, which allowed us to compare a single BPM—most frequently used in clinical routines32 33—with the mean of three consecutive measurements, after discarding a first measurement, which is very close to the SOPs used in the SPRINT study and recommended by the Canadian guidelines.2 15
In daily practice, patients report that 77% of physicians took a first measurement without waiting and 56% of physicians took only one measurement.32 Similar numbers have been reported for home measurements, where 60% of patients took their first measurement without waiting and again 40% only measured once.32 It has been reported that 30% of primary care physicians only take one BPM per session.33 Newer guidelines recommend ABPM, in different clinical situations, for example, ‘in patients with an elevated,8 a high normal OBPM2 or not only, but especially in case of elevated OBPM’.7 Considering that a systolic BP reduction of 2 mm Hg translates into a risk reduction of 7% in ischaemic heart disease mortality and a 10% risk reduction in stroke mortality37 and that per 10 mm Hg reduction of systolic BP a relative risk reduction of 20% in major CV events may be expected,38 a difference of ±5 mm Hg in OBPM depending on the measuring method applied may influence decision making when diagnosing and starting treatment. Regarding the different SOPs applied in different outcome studies and observational trials (table 2), the optimal cut-off value for hypertension in OBPM remains questionable as well as the optimal measurement technique. However, there is evidence that the very standardised approach of AOBPM correlates best with ABPM daytime values.34
Masked and white coat hypertension are discussed in the different guidelines.3 7 Masked hypertension is generally defined as a normal BP obtained in a clinic, which is in contrast elevated in an ambulatory BPM.7 Masked hypertension is associated with a prognosis comparable with true hypertension, partially explained by underdiagnosis and thereby undertreatment.39 40 Masked hypertension may be associated with increased physical activity, mental stress, smoking and alcohol.41 Additionally, it may be a sign of increased arterial stiffness, inflammation and endothelial dysfunction.41 Out of these possible pathomechanisms, mostly mental stress could be expected to account for short-term reactions, that is, STMH. In our cohort, the only predictor for STMH was the absence of a very low fBPM. Hence, we cannot exclude that a patient with a normal fBPM may have elevated measurements later on. These patients might in fact have a true masked hypertension and should undergo further diagnostics. Based on our results, the algorithms presented in the NICE guidelines,8 which recommend only one measurement, when the first measurement is normotensive, may be questionable in the individual patient.
White coat hypertension is the opposite of masked hypertension with elevated OBPM but normal ABPM.7 In contrast to masked hypertension, white coat hypertension is thought to have a CV risk profile more similar to true normotension rather than SHT.39 40 White coat hypertension can lead to overdiagnosis and overtreatment, which wastes resources and exposes patients to unnecessary medications and their side-effects. Usually, guidelines focus on the reduction of the probability of white coat hypertension in the individual patient by recommending repeated measurements when there is a relevant difference between a first and a second measurement, as stated in the 2013 ESH guidelines on the management of AHT,42 without specifying what a relevant difference means.
Surprisingly, we found that even after 5 min of rest, 55% of subjects showed a difference of >5 mm Hg in systolic BP and 31% regarding diastolic BP comparing fBPM against mBPM. This effect was seen especially in subjects with a history of AHT.
Veloudi et al compared a single measurement against two to three measurements in 20 716 patients.43 Similarly, they reclassified 3% of younger and 12% of older apparently normotensive subjects to hypertension and 70% of younger and 44% of older apparently hypertensive subjects to normotensive subjects. However, they took only two measurements in most subjects and added a third measurement only if the first measurements differed by more than 10 mm Hg. Our study therefore provides more reproducible data, as all included subjects had four standardised measurements taken and thus methods applied and compared were consistent in all subjects.
Limitations
Our data do not prove which method, a single BPM or discarding the first measurement and taking the mean of three subsequent measurements, is superior. Therefore, we cannot comment as to which method properly reflects the true BP value and serves as the best predictor of a patient’s CV risk. To answer these questions, studies comparing the different procedures to ABPM and also a prospective long-term follow-up would be needed. However, given our results and that most studies used and guidelines proposed repeated measurements, taking only a single measurement should be discouraged in clinical practice and in future guidelines.
Conclusion
There are significant differences in the results of the two different ways to calculate BP leading to a discrepancy of more than 5 mm Hg in more than half of the patients in one measurement session. Hypertension could potentially be missed in up to 3% of patients when taking only one measurement. Therefore, single BPM should be discouraged even in case of normal values. Also, there exists a clear need of a universally accepted SOP for OBPM in future trials and guidelines. Accordingly, utilisation of out-of-OBPMs, especially ABPMs, may help in clinical decision making.
Key messages
What is already known on this subject?
Currently, standard operating procedures (SOPs) for measuring office blood pressure show a high variability due to differences in guidelines. Data comparing the various SOPs are scarce.
What might this study add?
Our study is the first to use a very strict SOP with four office blood pressure measurements (BPMs) in all subjects included. This allows direct comparison between the most often clinically applied measurement, that is, a single measurement, and the mean value of repeated measurements as recommended by most guidelines.
How might this impact on clinical practice?
This study highlights the unreliability of a single BPM. It may lead clinicians to improve their BPM routine and could thus contribute to a better identification of patients with insufficiently treated or true hypertension. Ideally, this could be leading to a better long-term outcome and avoid unnecessary healthcare costs.
Acknowledgments
Many thanks to A. Winterhalder for the study coordination and to Dr Thenral Socrates for language editing. We would also like to thank all of the study participants.
References
Footnotes
Contributors TB: conception and design of the work, analysis and interpretation of data, drafting the work, revising, final approval. MM: critical revision of intellectual content, final approval. CW: conception and design of the work, critical revision of intellectual content, final approval. LL: conception and design of the work, data collection, critical revision of intellectual content, final approval. JE: conception and design of the work, critical revision of intellectual content, final approval. ASV: conception and design of the analysis and interpretation of data, drafting the work, revising, final approval.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Ethical committee northwestern and central Switzerland (EKNZ 2015-287).
Provenance and peer review Not commissioned; externally peer reviewed.