The Reproducibility of Average Ambulatory, Home

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The Reproducibility of Average
Ambulatory, Home, and Clinic Pressures
GARY D. JAMES, THOMAS G. PICKERING, LILY S.
YEE,
GREGORY A. HARSHFIELD, SUZANNE RIVA, AND JOHN H. LARAGH
SUMMARY The reproducibility of ambulatory, home, and clinic blood pressures was compared in
13 untreated mildly hypertensive and 14 normotensive subjects. Each subject had two sets of daily
ambulatory recordings, home self-measured readings (over 6 days), and clinic measurements taken 2
weeks apart. Comparisons over the 2 weeks within and among the methods of measurements were
made using a repeated-measures analysis of variance. The results showed that there was no consistent
average change in the ambulatory or home pressures and no change in clinic diastolic pressures, but
the clinic systolic pressure of the hypertensive subjects dropped 6 mm Hg (p<0.05), while that of the
normotensive subjects showed no significant change. Test-retest correlations of each of the three
methods were similar in magnitude, indicating a similar level of reliability. Test-retest correlations of
the ambulatory standard deviations, however, were low, indicating a low reliability of this measure of
daily pressure variability. These results suggest that the reproducibility of ambulatory pressures may
be as good or better than that of home or clinic measurements. They also suggest that the average
ambulatory pressure may be preferable as the measurement in clinical trials, since it may be less
influenced by measurement anxiety, particularly in hypertensive subjects.
Hypertension 11: 545-549, 1988)
KEY WORDS • ambulatory blood pressure
• blood pressure measurement
C
• reproducibility
surements made by the physician.8 The reproducibility
of averaged patient-measured home readings, however, generally has not been systematically investigated,
although available evidence suggests that among hypertensive patients they may stay about the same or
drop over time. 9 In addition, little information is available as to the prognostic potential of home pressures.
There is also a growing body of evidence suggesting
that average daily ambulatory recordings may give the
best characterization of a person's level of blood pressure and the risks associated with it.10- " The reproducibility of these recordings has been studied over periods as short as 48 hours12"14 and as long as 4 months15
using a variety of ambulatory pressure measurement
systems. These studies have shown that the average
pressure as well as the pattern of variation is reasonably reproducible.
In the case of casual and home pressures, the conditions of measurement are relatively standardized,
whereas with ambulatory readings made in free-ranging subjects, the situation is much less controlled. It
might be expected, therefore, that the reproducibility
of ambulatory pressure averages would be lower than
that of casual or home pressure averages. The purpose
of the present study was to compare, in the same subjects, the reproducibility of averaged clinician-mea-
ASUAL measurement in the clinic or office is
the most common method used to determine
blood pressure in clinical studies that examine
the risks associated with hypertension and the benefits
of treating it. Although they are easy to obtain, casual
pressures have low reproducibility for a variety of reasons. '•2 One of the problems associated with interpreting results of large-scale trials of the treatment of mild
hypertension has been that casually measured pressures tend to fall significantly with time, even in untreated persons.3"5
Repeated measurements of blood pressure taken by
the patient at home have also been used to evaluate
hypertension. The averages of these readings tend to
be lower than clinic pressures 6 ' 7 and may reflect the
overall level of pressure more reliably than do meaFrom the Cardiovascular Center, Cornell University Medical
College, New York Hospital, New York, New York.
Supported by Grant HL30605 from the National Institutes of
Health. Present address of Dr. Harshfield: Charles Drew Post-Graduate Medical Center, Department of Medicine, 1621 E. 120th
Street, Los Angeles, CA 90059.
Address for reprints: Gary D. James, Ph.D., Cardiovascular
Center, Cornell University Medical College, New York Hospital,
525 E. 68th Street, New York, NY 10021.
Received March 30, 1987; accepted February 23, 1988.
545
HYPERTENSION
546
sured, home-measured, and ambulatory-recorded
blood pressures using the same research design. The
reproducibility of the variability of the ambulatory recordings was also assessed. Both normotensive and
hypertensive subjects were included in the study.
Subjects and Methods
Design
A repeated-measures design was employed in which
averages calculated from each of the three ways of
assessing blood pressure were compared 2 weeks
apart, with no intervention in the interim. A total of 27
subjects were recruited for the study. Fourteen were
normotensive volunteers, and 13 were patients with
mild essential hypertension from the Hypertension
Center at New York Hospital, who were off medication for at least 2 weeks before the study. Both normotensive and hypertensive subjects were familiar with
the clinic setting and none had previously worn the
Spacelabs ICR ambulatory blood pressure monitor
(Hillsboro, OR, USA). Table 1 presents some demographic characteristics of the study sample.
Procedures
Blood pressures were measured in each subject in
three different ways: 1) with a standard Baumanometer
mercury column (Baum, Copiague, NY, USA) and
stethoscope by a clinician trained according to the criteria of the Multiple Risk Factor Intervention Trial16
(using the stethoscope diaphragm), 2) at home by the
patient with an aneroid cuff and stethoscope (using the
stethoscope diaphragm), and 3) with an automatic
monitor (Spacelabs ICR 5200 model) over at least an
8-hour period during the course of a single day. At
each of two visits (2 weeks apart) to the Hypertension
Center of the New York Hospital, the same clinician
took three readings. The average of each set of readings was used as the two clinic measurements. For the
home measurements, subjects were supplied with a
calibrated aneroid sphygmomanometer (Bristoline,
Freeport, NY, USA) and instructed by a trained medical technician in its proper use. The appearance of
sound was recorded as systolic pressure, and the disappearance of any detectable sound (Korotkoff Phase V)
was recorded as diastolic pressure. After an adequate
TABLE 1.
Selected Demographic Characteristics of the Study
Sample
Variable
Sex (% men)
Ethnic group (% white)
Age (yr)*
Smokers (%)
Alcohol consumption
(% nondrinkers)
Coffee consumption (% drinkers)
Duration of hypertension (yr)*
•Values arc means ± SD.
Normotensive Hypertensive
(n=14)
(«=13)
46
29
85
79
57±12
24±5
0
0
29
50
0±0
39
54
7.6±7.7
VOL 11, No
6, PART 1, JUNE
1988
session of practice and validation of their technique,
subjects were instructed to take three seated pressure
measurements at home twice daily (three in the morning on arising, and three in the evening before bed for a
total of six per day) for 6 consecutive days. The average of these pressures was used as the home pressure.
Each subject repeated this protocol twice, the week
before and after the interim period of 2 weeks. Finally,
the subjects were twice fitted with the Spacelabs ICR
ambulatory automatic blood pressure monitor, before
and after a 2-week interim. Most of the subjects were
measured on the same midweek day, which for 23 of
them was one on which they went to work. The recorder was worn for as long as possible over each of the 2
days. Blood pressure was recorded automatically every 15 minutes during awake hours and every 30 minutes during sleep. Machine readings were calibrated to
those of a standard sphygmomanometer when subjects
were fitted with the device. In this procedure, a T tube
was used, which connected the machine to a mercury
column. The automatic pump in the machine inflated
the cuff, the pressure being registered on the mercury
column as well as in the machine. A trained listener
using a stethoscope placed just distal to the microphone from the recorder read the pressure from the
column. This listener was blinded from the machine
readings. The recorder was considered accurate when
five consecutive readings from the monitor agreed to
within 5 mm Hg of the listener's measurements for
both systolic and diastolic pressure. Measurements recorded during the ambulatory period by the monitor
were screened and edited for artifactual values based
on previously described criteria.17 Only those readings
that were taken during the same hours on each of the 2
days were used in the analysis. The arithmetic average
of the edited pressures taken during the same hours
was used as the ambulatory measurement. The standard deviation of these edited readings was also calculated for each subject and used as an indicator of the
variability of that subject's daily recorded pressure.
Table 2 summarizes the number of readings taken
each week for each pressure average. Although each
subject was compared over an equal time span from the
initial to the second week, different subjects wore the
ambulatory monitor for different lengths of time. Additionally, while each subject was to have taken 36
readings at home, not all complied perfectly with this
protocol. On average, 62 home pressures were measured and recorded by the subjects when 72 were required by protocol.
Data Analysis
To assess the reproducibility of the various pressure
averages, the differences between the initial and second averages were first calculated for each of the methods of pressure assessment. These differences were
then compared using a repeated-measures analysis of
variance in which the method of pressure measurement
(ambulatory recorded, home subject-measured, and
clinician-measured) and hypertensive status (normotensive or hypertensive) were included as fixed fac-
PRESSURE REPRODUCIBIUTY/Jame5 et al.
TABLE 2. Number of Measurements per Length of Time for Each
Blood Pressure Average
Blood
Week measured
pressure
Second
average
Initial
48± 13(15±4hr)
Ambulatory*
49 ± 15 (15±4hr)
Home
31± 10 (6 days)
31± 10 (6 days)
Clinic
3(1 visit)
3(1 visit)
Ambulatory and home pressures expressed as mean number of
readings ± SD; ambulatory time is expressed as mean number of
hours ± SD.
*Seven hypertensive and five normotensive subjects had sleep
readings.
tors. Test-retest correlations were calculated for each
method of pressure measurement to assess their reliability and the reproducibility of the average pressure
distributions.18 A paired t test and test-retest correlations were used to examine the reproducibility and
reliability of the standard deviation of the ambulatory
averages.
Results
Table 3 shows the pressure comparisons from the
analysis of variance models for all three means of
pressure assessment in both the normotensive and hypertensive subjects. Pressures have been rounded to
the nearest millimeter of mercury. As indicated, the
average level of ambulatory and home subject-measured pressures (both systolic and diastolic) changed
very little over the 2 weeks (all changes < 3 mm Hg;
p = NS). However, there was a statistically significant
( / J < 0 . 0 5 ) drop of 6 mm Hg in clinician-measured
systolic pressure among the hypertensive subjects.
Table 4 shows the test-retest correlations for each
pressure average as well as the correlations among the
averages calculated from the initial and second week of
measurement. For both systolic and diastolic pressures, the test-retest correlations were similar among
the methods, indicating similar levels of reliability;
that is, the distributions of pressure averages for each
method of measurement remained relatively stable
over the 2 weeks in this sample. Ambulatory pressures
tended to correlate better with home subject-measured
pressures than with clinician-measured pressures,
while the correlations between clinician-measured and
subject-measured home pressures tended to be some-
547
what higher than those between subject-measured and
ambulatory pressures. However, all the correlations
among the different measurements were of the same
magnitude, indicating a similarity in the distributions
of the measurements of the different methods.
An examination of the reproducibility of the standard deviations of the ambulatory averages showed
that there was no significant difference in this measure
of individual pressure variability over the 2 weeks in
either normotensive (systolic, 10 vs 10 mm Hg; diastolic, 9 vs 8 mm Hg) or hypertensive subjects (systolic, 14 vs 13 mm Hg; diastolic, 10 vs 8 mm Hg). The
test-retest correlations were quite low (r = 0.36 for
systolic, r = 0.16 for diastolic), which suggests that,
in this study group, the position of subjects in the
limited distributions of standard deviations changed
over the 2 weeks.
Discussion
Although several studies have reported on the reproducibility of noninvasively measured ambulatory
blood pressure, few if any have compared its reproducibility with that of the other two commonly used modes
of assessing blood pressure (home and clinic readings). Comparisons of normotensive and hypertensive
subjects in this context have also not been made. In the
present study, the pressures compared were those most
commonly collected in clinical practice: a set of clinic
readings, several days of home readings (in this case,
six), and a daily ambulatory recording.
The reproducibility of the ambulatory pressures was
evaluated on days that were representative of a subject's normal activity, which for most was a working
day. No special instructions were given to the subjects
as to how to spend their day. It was anticipated that,
because the circumstances in which the ambulatory
pressures were taken were more variable, the reproducibility of the average daily ambulatory pressures
might be lower than that of the home and clinic pressures. This expectation was based on previous findings
suggesting that activity is a major predictor of individual blood pressure measurements taken over 24 hours
with an ambulatory monitor." It was gratifying to find
that the ambulatory average was as reproducible as the
clinic and home averages and that all three methods
had high test-retest correlations.
Another important finding was that there was no
TABLE 3. The Average Pressures in Normotensive and Hypertensive Subjects as Determined by Each Method of
Measurement Compared Over the 2 Weeks
Clinic
Ambulatory
Home
HT
NT
NT
HT
Measurement
NT
HT
Systolic BP (mm Hg)
134±11
119±17
140±14
Initial
158 ±23*
111±11
114±9
Second
132±12
113±8
118±13
143±13
152 ±20
110±10
Diastolic BP (mm Hg)
85+10
76 + 7
Initial
70±7
76±10
86±12
93+11
Second
86 ±10
73±7
87±12
91 ±10
70±9
76+10
Values are average ± SD. NT = normotensive; HT = hypertensive; BP = blood pressure.
*p<0.05, significantly different from second reading.
548
TABLE 4.
HYPERTENSION
Correlations Among the 27 Pressure Measurements
Systolic pressure Diastolic pressure
Associated variables
0.93
AMBP 1 vs AMBP 2
0.87
0.96
Home 1 vs Home 2
0.94
0.94
0.87
Clinic 1 vs Clinic 2
0.87
0.72
AMBP 1 vs Home 1
0.76
0.68
AMBP 1 vs Clinic 1
0.84
0.77
Home 1 vs Clinic 1
0.88
0.77
AMBP 2 vs Home 2
0.77
0.73
AMBP 2 vs Clinic 2
0.77
0.90
Home 2 vs Clinic 2
AMBP = ambulatory blood pressure; 1 = initial average;
2 = second average.
pronounced order effect in the ambulatory measurements, in contrast to the clinic pressures, which did
show such an effect, particularly among hypertensive
subjects. These results support the findings of most
earlier studies.12"15 The implication of this result is that
the average daily pressure may be a better measure
than clinicreadingsfor evaluating the effects of antihypertensive treatment, whether pharmacological or nonpharmacological, since any differences observed between successive recordings are likely to be due to the
intervention, rather than random variation or an order
effect. The stability of the daily ambulatory average
also implies that it is likely to be a more valid measure
for comparison with indices of target organ damage10' " or psychosocial and biochemical variables.
The variability of blood pressure during ambulatory
monitoring, as reflected in the standard deviation of
the ambulatory average, had a low reliability, a finding
consistent with other studies.1213 This result is not
surprising since blood pressure is subject to a number
of sources of variation, some cyclical, others not. Possible cyclical sources include respiratory oscillations
of pressure,20 ultradian rhythm,21 and diurnal variations.19 Noncyclic sources might include posture, activity, and emotional variation.22 Intermittent sampling
of blood pressure at a frequency typically used with
noninvasive ambulatory recorders (about one every 15
minutes for a total of perhaps 50 to 100 pressures
depending on the length of time worn) can also only
obtain a crude estimate of the true levels of variability;
thus, estimates of variability from these measurements
may be invalid as well. This point is readily apparent
when one considers that, if it were possible to record
each pressure beat to beat (approximately 1-2/second), one would obtain some 90,000 to 100,000
measurements per person over a 24-hour period. It is
highly unlikely that a nonrandom sample constituting
5/100ths of 1% of the possible measurements will reflect the true extent of the variability of pressure. There
is considerable interest among behavioral scientists in
the differences of cardiovascular reactivity to standardized physical and mental stimuli measured in laboratory studies. An unresolved question is the extent to
which these responses arerepresentativeof blood pressure variability during everyday life. Because it is unreliable and invalid, the variability of blood pressure
defined from intermittently sampled measurements
VOL 11, No
6, PART 1, JUNE
1988
should not be compared with laboratory measures of
reactivity.
Finally, the methods of pressure measurement examined in this study may define different aspects of a
person's blood pressure; hence, comparisons of their
reproducibility might be considered inappropriate. The
average ambulatory pressure may reflect a central
point around which pressure varies over the course of a
day. The subject-measured home readings reflect an
average level of pressure over an extended period (1
week), when measurements are made under similar
and usually quiescent circumstances. The clinicianmeasured pressurereflectsa point measure of pressure
under a singularly peculiar circumstance. The inappropriateness of the comparisons may also extend to the
fact that each of the three averages compared in this
study are based on different numbers of measurements. For example, the fact that there are far more
ambulatory measurements (even though they are collected under variable circumstances) than there are
clinic measurements may make the ambulatory average more reproducible, since the greater number of
measurements makes it less sensitive to extreme single
readings. Among the hypertensive subjects, ambulatory, home, and clinic pressure measurements were
different, yet the ambulatory and home measurements
were very similar in their reproducibility. Despite the
similarity in reproducibility, however, if change or
percent change in pressure is the focus of study, the
present findings suggest that the ambulatory pressure
average may be the best measure to use, since it may
reflect a central pressure of the cardiovascular system,
is composed of a large number of readings taken under
many circumstances, and is also likely to be independent of factors that increase measurement error,
such as digit preference, observer-subject interaction,
and measurement anxiety.
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