Context Self-measurement of blood pressure is increasingly used in clinical
practice, but how it affects the treatment of hypertension requires further
Objective To compare use of blood pressure (BP) measurements taken in physicians'
offices and at home in the treatment of patients with hypertension.
Design, Setting, and Participants Blinded randomized controlled trial conducted from March 1997 to April
2002 at 56 primary care practices and 3 hospital-based outpatient clinics
in Belgium and 1 specialized hypertension clinic in Dublin, Ireland. Four
hundred participants with a diastolic BP (DBP) of 95 mm Hg or more as measured
at physicians' offices were enrolled and followed up for 1 year.
Interventions Antihypertensive drug treatment was adjusted in a stepwise fashion based
on either the self-measured DBP at home (average of 6 measurements per day
during 1 week; n = 203) or the average of 3 sitting DBP readings at the physician's
office (n = 197). If the DBP guiding treatment was above (>89 mm Hg), at (80-89
mm Hg), or below (<80 mm Hg) target, a physician blinded to randomization
intensified antihypertensive treatment, left it unchanged, or reduced it,
Mean Outcome Measures Office and home BP levels, 24-hour ambulatory BP, intensity of drug
treatment, electrocardiographic and echocardiographic left ventricular mass,
symptoms reported by questionnaire, and costs of treatment.
Results At the end of the study (median follow-up, 350 days; interquartile range,
326-409 days), more home BP than office BP patients had stopped antihypertensive
drug treatment (25.6% vs 11.3%; P<.001) with no
significant difference in the proportions of patients progressing to multiple-drug
treatment (38.7% vs 45.1%; P = .14). The final office,
home, and 24-hour ambulatory BP measurements were higher (P<.001) in the home BP group than in the office BP group. The mean
baseline-adjusted systolic/diastolic differences between the home and office
BP groups averaged 6.8/3.5 mm Hg, 4.9/2.9 mm Hg, and 4.9/2.9 mm Hg, respectively.
Left ventricular mass and reported symptoms were similar in the 2 groups.
Costs per 100 patients followed up for 1 month were only slightly lower in
the home BP group (€3875 vs €3522 [$4921 vs $4473]; P = .04).
Conclusions Adjustment of antihypertensive treatment based on home BP instead of
office BP led to less intensive drug treatment and marginally lower costs
but also to less BP control, with no differences in general well-being or
left ventricular mass. Self-measurement allowed identification of patients
with white-coat hypertension. Our findings support a stepwise strategy for
the evaluation of BP in which self-measurement and ambulatory monitoring are
complementary to conventional office measurement and highlight the need for
prospective outcome studies to establish the normal range of home-measured
A 1997 study1 reported that adjustment
of antihypertensive treatment based on ambulatory monitoring instead of conventional
blood pressure (BP) measurement at the physician's office led after 6 months
of follow-up to less intensive drug treatment with preservation of BP control,
general well-being, and inhibition of left ventricular enlargement but did
not reduce the costs of antihypertensive treatment. In comparison with ambulatory
monitoring, self-measurement of BP at home is less expensive. If applied in
a standardized way, self-measurement accomplishes several of the advantages
of ambulatory monitoring, including the greater number of BP measurements,
the absence of the white-coat syndrome, and, when automated devices are used,
the lack of observer bias.2 Furthermore, self-measurement
increases compliance with antihypertensive therapy and, compared with usual
management, may lead to fewer clinic visits.3
Few prospective cohort studies on the association between cardiovascular
outcome and self-measured BP have been published.4-6 Consensus
guidelines7,8 propose diagnostic
thresholds for the clinical application of self-measured BP, but these are
based on observational studies9-15 and
have never been tested in large-scale randomized clinical trials. The primary
objective of the Treatment of Hypertension Based on Home or Office Blood Pressure
(THOP) trial16 was to compare self-measurement
and conventional office measurement of BP as guides to initiate and titrate
antihypertensive drug treatment. The THOP trial extends our previous research
on ambulatory monitoring of BP.1
Study Design and Interventions
The ethics committees of the University of Leuven, Leuven, Belgium,
and the Beaumont Hospital, Dublin, Ireland, approved the protocol of the THOP
trial,16 which was conducted according to the
Helsinki declaration17 at 56 primary care practices
and 3 hospital-based outpatient clinics in Belgium and 1 specialized hypertension
clinic in Dublin, Ireland. At an initial screening, patients gave written
informed consent. Men and women with hypertension and a minimum age of 18
years were eligible if they were either untreated or being treated with no
more than 2 different antihypertensive agents. Potential candidates were invited
for 2 further run-in visits, 2 to 4 weeks apart, while their treatment status
and medications were held constant. They could be randomized if the last of
3 consecutive readings of diastolic BP (DBP) obtained in the sitting position
at each of the 2 run-in visits averaged 95 to 114 mm Hg. Patients with higher
DBP also qualified but were reexamined at shorter intervals. Women of reproductive
age had to practice a reliable contraception method. The exclusion criteria
encompassed heart failure, unstable angina pectoris, stage 3 or 4 hypertensive
retinopathy, a history of myocardial infarction or stroke within 1 year of
enrollment, severe noncardiovascular disease (eg, cancer or liver cirrhosis),
serum creatinine concentration higher than 177 µmol/L (2.0 mg/dL), mental
disorders, and substance abuse. Patients working night shifts also could not
After stratification by center, the study manager at the coordinating
office used a computerized random number function to assign patients to treatment
based on their BP measured at home vs at the physician's office. For the measurements
at home, patients used validated18 oscillometric
Omron HEM-705CP devices (Omron Inc, Kyoto, Japan), which the manufacturer
calibrated before use in the trial. The self-measured BP was the average of
all readings collected during the 7 days prior to each follow-up visit. After
5 minutes of rest in the sitting position, patients performed 3 consecutive
self-measurements of BP twice daily, in the morning between 6 and 10 AM and in the evening between 6 and 10 PM. They recorded
and printed the values of BP and pulse rate along with the time of day. The
office BP was the average of 3 consecutive BP readings taken by the physician
during the day during usual practice hours, after patients had rested for
5 minutes in the sitting position. The investigators' terminal digit preference
was monitored every 6 months. Regardless of randomization, both the home and
office BP were available at each visit. In addition, at randomization, at
6 months, and at the last follow-up visit, patients underwent 24-hour ambulatory
monitoring. Validated18 oscillometric SpaceLabs
90207 recorders (SpaceLabs Inc, Redmond, Wash) were programmed to obtain BP
readings at 15-minute intervals from 8 AM to 10 PM and
at 30-minute intervals otherwise. Day and night BP measurements were time-weighted
means computed for fixed clock-time intervals of 10 AM to 8 PM and from midnight to 6 AM, respectively.
After randomization, follow-up visits were scheduled at 1 and 2 months
and thereafter at 2-month intervals for up to 1 year. Depending on randomization
and in agreement with the treatment goals used in our previous trial of ambulatory
BP monitoring,1 the target for both the office-
and home-based BP measurement groups was a DBP of 80 to 89 mm Hg. To attain
this goal, physicians implemented a standardized drug regimen. After randomization,
all patients began or switched to monotherapy with lisinopril, 10 mg/d (step
1). At later visits, treatment could be stepwise intensified by doubling lisinopril
to 20 mg/d (step 2); by combining lisinopril with hydrochlorothiazide, 25
mg/d, or amlodipine, 5 mg/d (step 3); and, finally, by adding amlodipine,
5 mg/d, in patients taking the combination of lisinopril and hydrochlorothiazide
or prazosin, up to 6 mg/d, in other patients (step 4). In patients with known
contraindications to angiotensin-converting enzyme inhibitors, lisinopril
could be substituted by atenolol, 50 mg/d (step 1) or 100 mg/d (step 2).
Immediately after each visit, the clinical investigators transferred
all relevant information to the coordinating center in Leuven, including the
home and office BP values, current treatment, symptoms, signs, and new diagnoses.
One physician at the coordinating center who was blinded with regard to randomization
made all treatment decisions. He received only the values of either the office
or the self-measured BP, depending on the allocation of patients. The field
investigators subsequently implemented his treatment decisions. If the DBP
level guiding treatment was above the target (>89 mm Hg), medical treatment
was intensified by 1 step. If the DBP level was within the target range (80-89
mm Hg), medical treatment was left unchanged. If the DBP level guiding treatment
was below the target (<80 mm Hg), medical treatment was reduced by 1 step,
which for patients receiving step 1 treatment meant discontinuation of antihypertensive
drug treatment. The ambulatory BP values were disclosed only after completion
of the trial and were not considered in any treatment decision.
Other Clinical and Technical Measurements
At enrollment, at 2 and 6 months, and at the last visit, patients completed
a questionnaire to express their symptoms on a 5-point scale, using as qualifiers
"never," "a little," "moderately," "fairly," and "very." The questionnaire
covered neurosensory symptoms, such as dizziness, troubled vision, sleep disturbances,
and headache; circulatory symptoms, such as palpitations, hot flashes, and
ankle edema; urogenital complaints, including sexual dysfunction, changes
in menstrual cycle, and disturbed micturition; various symptoms related to
the upper and lower gastrointestinal tract; and disturbances of the upper
and lower airways, including cough. The 33 questions were combined into 1
overall and several organ-specific symptom scores by averaging the answers
to the individual questions.
The intensity of antihypertensive drug treatment was evaluated by assigning
a score proportional to the dose of each of the study medications, with values
set at 1 for the maximum daily dose (20 mg of lisinopril, 100 mg of atenolol,
25 mg of hydrochlorothiazide, 5 mg of amlodipine, or 6 mg of prazosin) and
to 0 in untreated patients. For each patient and each visit, the scores of
all medications were summed. Patients' compliance with therapy was assessed
by tablet counts.
Left ventricular mass was noninvasively measured at the beginning and
end of follow-up. The R wave in lead aVL, the Sokolow-Lyon index,19 the Cornell index,20 and
the Cornell product21 were determined from
electrocardiograms. Four hospital-based clinics took part in imaging and Doppler
echocardiography. Mean left ventricular wall thickness, echocardiographic
left ventricular mass index, fractional shortening, and the ratio of the peak
left ventricular inflow velocities in early diastole (E) and at the atrial
contraction (A) were determined according to established conventions and formulas.22,23 For analysis, 3 to 5 heart cycles
Monetary rates of the Belgian health insurance system were applied to
estimate the costs of antihypertensive treatment based on home and office
BP measurements. Physicians' fees amounted to €30 per visit. In 2002,
1 month of treatment with 20 mg/d of lisinopril, 100 mg/d of atenolol, 25
mg/d of hydrochlorothiazide, 5 mg/d of amlodipine, and 6 mg/d of prazosin
necessitated expenditures of €25, €15, €3, €26, and €6,
respectively (€1 = US $1.27 on January 25, 2004). Home BP measurement
is not yet reimbursed by the Belgian health care system and was therefore
budgeted at the rate of depreciation of the Omron recorders during the trial
(€6.6 for 1 week of measurements). Because treatments could begin to
diverge only at the first follow-up visit, the calculations disregarded earlier
expenses. Two assumptions were made. First, if starting from any visit a patient's
BP remained well controlled and treatment remained unchanged until the end
of follow-up, we presumed that from this visit onward, the same treatment
schedule would be continued for a further 6 months without any reassessment.
Second, we assumed that physicians would reexamine their patients after 2
months if the BP at the last study visit still exceeded the target range.
These intervals were chosen because they are in line with current practice
at most specialized hypertension clinics in Belgium.
The primary efficacy measure of BP control was the 24-hour level. With
significance set at 5% and power at 85%, approximately 200 patients per treatment
group had to be randomized to detect BP differences of 5 mm Hg for systolic
BP (SBP) or 2 mm Hg for DBP, assuming standard deviations of 15 mm Hg and
10 mm Hg, respectively.16
Database management and statistical analyses were performed with SAS
software, version 8.1 (SAS Institute Inc, Cary, NC). Serial measurements were
analyzed using the difference between the entry and the last available measurement
as the main outcome variable.24 The between-group
differences in continuous measurements were calculated by subtracting the
mean changes from baseline in the office BP group from those in the home BP
group. Between-group comparisons involved the Mann-Whitney rank sum test for
non–normally distributed data and the t test
and analysis of covariance for normally distributed variables. Proportions
were compared by the χ2 statistic and longitudinal changes
in treatment status by Kaplan-Meier survival function estimates and the log-rank
test. The probability that treatment could be stopped was modeled in relation
to several explanatory variables using multiple logistic regression. Treatment
stoppage was defined as discontinuation of drug treatment until the end of
the study because the office or home DBP was less than 80 mm Hg and thereafter
remained at or below the target level (80-89 mm Hg).
As shown in Figure 1, 400
(66.0%) of 606 patients enrolled at the 60 centers met the entry criteria
and were randomized. Of the patients screened and randomized, 554 (91.4%)
and 373 (93.2%) were Belgian and 52 (8.6%) and 27 (6.8%) were Irish. At randomization,
the office BP (n = 197) and home BP (n = 203) groups had similar characteristics
(Table 1) and BP values (Table 2). Twenty-six office BP patients
(13.2%) and 27 home BP patients (13.3%) did not complete the study because
they dropped out (n = 30), experienced an adverse event (n = 2; Figure 1) or missed 1 or more follow-up visits (n = 21). Among the
400 randomized patients, the median follow-up was 350 days (interquartile
range [IQR], 326-409 days). In the office BP group, the median follow-up was
352 days (IQR, 323-411 days) and for the home BP group, it was 350 days (IQR,
Treatment Intensity and BP Control
More home BP than office BP patients could permanently stop antihypertensive
drug treatment (Figure 2) because
their DBP was less than 80 mm Hg and thereafter stabilized at or below the
target range (25.6% vs 11.3%; 2.2 vs 1.0 patients per 100 followed up for
1 month; log-rank P<.001). The opposite trend
was observed for patients proceeding to multiple-drug treatment (38.7% vs
45.1%; 3.3 vs 3.8 patients per 100 followed up for 1 month; log-rank P = .14).
Further analyses explored whether sex, age, previous antihypertensive
treatment, and diastolic office BP or home BP at randomization could predict
the permanent discontinuation of antihypertensive drug treatment. In home
BP patients, the probability of stopping drug treatment increased 2.1-fold
for each 5-mm Hg decrement in the diastolic home BP at randomization (95%
confidence interval [CI], 1.6 to 2.8; P<.001).
After accounting for the diastolic office BP at randomization (P = .42), sex (P = .64), age (P = .86), and previous antihypertensive treatment (P<.001), the odds ratio was 1.2 (95% CI, 1.1-1.3; P<.001). Thus, in the home BP group, lower home DBP at entry and
the lack of previous treatment independently predicted permanent cessation
of antihypertensive drug therapy during follow-up. In the office BP group,
the office DBP at randomization did not predict discontinuation of treatment.
The odds ratios associated with a 5-mm Hg lower office DBP at entry were 1.3
(95% CI, 0.8-2.1; P = .21) before any adjustment
and 1.1 (95% CI, 0.9-1.2; P = .23) with adjustment
for home DBP at randomization (P = .67), sex (P = .62), age (P = .62), and previous
antihypertensive treatment (P = .004). Thus, in the
office BP group, only lack of previous treatment predicted stoppage of antihypertensive
treatment during follow-up.
The office, home, and ambulatory BPs decreased (P<.001) after randomization (Table
2). At the first follow-up visit (Figure 3), these decreases were similar in both treatment groups,
averaging 12.0/8.2 mm Hg for office BP and 8.4/5.2 mm Hg for home BP. After
the 1-month follow-up visit, drug treatment became more intense (P<.001) in the office BP than home BP group, although patients who
continued antihypertensive drug treatment used similar daily doses (Table 3). At the 2-month visit, SBP and
DBP were significantly higher in the home BP than office BP group (P = .02) with a similar trend for DBP at 4 months (P = .01). At 6 months (Figure 3),
the decreases in BP were of similar magnitude in the 2 randomized groups:
19.1/12.8 mm Hg for office BP, 14.3/8.6 mm Hg for home BP, and 11.6/7.5 mm
Hg for the daytime ambulatory BP. Thereafter, as summarized in Table 2 and Figure 3,
the BP reductions became consistently and significantly greater in office
BP than home BP patients. After adjustment for baseline BP, sex, age, and
body mass index, the final differences between the 2 treatment groups ranged
from 4.8 to 6.8 mm Hg for SBP and from 2.9 to 3.5 mm Hg for DBP (Table 2). Further adjustment for previous
antihypertensive treatment did not materially alter these estimates. Of the
51 home BP patients who could stop drug treatment, 33 (64.7%) maintained a
home DBP below 85 mm Hg. Office BP patients (n = 159) and home BP patients
(n = 169) with available pill counts took similar percentages of the prescribed
dosages of the study medications (89.3% vs 90.1%; P =
Symptoms, Adverse Events, and Left Ventricular Mass
During the entire follow-up, the mean symptom score decreased (P<.001) on a 5-point scale from 1.52 (SD, 0.36) to 1.40
(SD, 0.32) in the office BP group and from 1.60 (SD, 0.40) to 1.50 (SD, 0.41)
in the home BP group. The baseline-adjusted changes in the overall symptom
score were similar in both groups at 6 months (–0.07 vs –0.10; P = .39) and at the end of the trial (–0.10 vs –0.10; P = .99). The scores for dizziness, headache, palpitations,
and ankle edema and organ-specific symptoms also showed similar trends in
the 2 treatment groups. Major adverse events occurred in 13 office BP and
10 home BP patients (P = .52). Five patients experienced
major cardiovascular complications (office BP vs home BP, 1 vs 4) involving
the coronary (1 vs 2) or cerebrovascular (0 vs 2) circulation; 16 had major
noncardiovascular illnesses (10 vs 6) of the gastrointestinal tract (2 vs
0) or the musculoskeletal system (3 vs 2) or required noncardiovascular surgery
(1 vs 2); 2 patients developed major depression (2 vs 0).
Serial electrocardiograms and echocardiograms of sufficient quality
were available in 355 and 54 patients, respectively (Table 4). After adjustment for baseline values, sex, age, and body
mass index, the between-group differences in the changes in most electrocardiographic
and echocardiographic measurements were small and statistically nonsignificant
(Table 4). At the end of the trial,
there was marginal benefit only for the echocardiographic E:A ratio (P = .02) in the office BP compared with the home BP group.
Costs of Medications and Follow-up Visits
The costs of the medications amounted to €2120 and €1688 (P = .002) per 100 office BP and home BP patients treated
for 1 month (Table 5). The mean
fees of the physicians were, respectively, €1789 and €1510 per 100
patient-months (P<.001). However, the potential
savings in the home BP group associated with less-intensive drug treatment
and fewer physician visits were partially offset by the costs of home monitoring.
Overall, expenditure was slightly but significantly higher for office BP compared
with home BP measurement (Table 5).
In this randomized clinical trial with a duration of 1 year, adjustment
of antihypertensive treatment based on home BP instead of office BP led to
less intensive drug treatment and marginally lower medical costs but also
to less long-term BP control with no differences in general well-being and
electrocardiographic or echocardiographic left ventricular mass. On the other
hand, compared with repeated assessment of BP at the physician's office, self-measurement
at home allowed the discontinuation of antihypertensive drug treatment in
twice as many patients. Thus, self-measurement helped to identify patients
with white-coat hypertension. These findings support a stepwise strategy for
the evaluation of BP.2 In keeping with current
guidelines,25 patients with elevated office
BP on repeat measurement and either target-organ damage or a high cardiovascular
risk profile should start drug treatment. However, when elevated office BP
is the only detectable abnormality or when patients with a normal office BP
show unexplained target-organ damage, self-measurement, ambulatory monitoring,
or both must be used to exclude white-coat hypertension (isolated clinic hypertension)
or masked hypertension (isolated ambulatory26 or
home5,26 hypertension), respectively.2
The final differences in SBP and DBP between the randomized groups averaged
6.8 and 3.5 mm Hg on conventional measurement at the physician's office and
4.9 and 2.9 mm Hg on 24-hour ambulatory monitoring. Blood pressure gradients
of this magnitude are clinically relevant for the long-term prognosis. Indeed,
in prospective observational studies, a 5- to 6-mm Hg decrease in usual DBP
was associated with 35% to 40% less stroke and 20% to 25% less coronary heart
disease.27,28 A meta–regression
analysis of 30 clinical trials in hypertensive or high-risk patients demonstrated
that a 5-mm Hg difference in SBP over 3 to 5 years changed the risk of all
cardiovascular complications and stroke by 25% to 30%.29 More
recently, the Blood Pressure Lowering Treatment Trialists' Collaboration confirmed
the importance of small BP differences in cardiovascular prognosis.30 Furthermore, in the Systolic Hypertension in Europe
Trial,31 with adjustments applied for antihypertensive
treatment, sex, age, cardiovascular complications at entry, and current smoking,
each 5-mm Hg increment in the 24-hour SBP at randomization was significantly
and independently associated with increases in the risks of all cardiovascular
events and fatal and nonfatal stroke by 9% and 18%, respectively.
To facilitate extrapolation of our results, most THOP patients were
recruited at family practices and antihypertensive treatment was either initiated
or continued on the basis of hypertensive BP values confirmed by repeated
conventional measurements at the physician's office. The choice of the BP
component (DBP) and its target range (80-89 mm Hg) might partially explain
why in the long run BP control was less in the home BP than office BP group.
We adjusted antihypertensive treatment only according to DBP, which, in comparison
with SBP, is more difficult to measure by the Korotkoff method and which is
not measured but is calculated by oscillometric devices.8 However,
most outcome trials of hypertension implemented this option.29 In
persons younger than 60 years32 and even in
older persons,28 DBP determines cardiovascular
risk. Had both SBP and DBP been used, the treatment strategy should have been
more complex. Furthermore, in analogy with the Ambulatory Blood Pressure and
Treatment of Hypertension (APTH) trial,1 treatment
was adjusted to achieve the same range of DBP (80-89 mm Hg) in the office
BP and home BP groups. In the APTH trial,1 the
goal of treatment was either an office DBP or an average daytime DBP of 80
to 89 mm Hg. These design features allowed 1 physician at the study coordinating
center to propose adjustments in treatment in a blinded fashion. Although
most current guidelines8,25 define
a normal BP on self-measurement as less than 135 mm Hg SBP and 85 mm Hg DBP,
observational studies rather than prospective evidence support these operational
In a meta-analysis of the summary statistics of published articles,11 the self-recorded BP averaged 115/71 mm Hg in normotensive
persons and 119/74 mm Hg in untreated persons not selected on the basis of
their BP. In an international database of self-recorded BPs,12 the
95th percentile in 2401 normotensive persons was 136/85 mm Hg for measurements
taken in the morning, 139/86 mm Hg for readings obtained in the evening, and
137/85 mm Hg when the time of day was disregarded. Other experts9,10,13-15 proposed
thresholds approximately ranging from 12513 to
14015 mm Hg for SBP and from 8013 to
9015 mm Hg for DBP. To the best of our knowledge,
only 2 published studies with a prospective design addressed the relation
between cardiovascular risk and self-recorded BP. In a population-based study
in Ohasama, Japan,4 the self-measured BP was
a better predictor of total mortality than the BP measured at screening by
a nurse. A retrospective analysis of the baseline data of the SHEAF study
(Self-measurement of Blood Pressure at Home in the Elderly: Assessment and
Follow-up) suggested that older patients (≥60 years) with white-coat hypertension
(isolated clinic hypertension) had fewer cardiovascular risk factors and a
lower prevalence of previous cardiovascular complications than those with
isolated home hypertension or uncontrolled hypertension.5 The
patients were followed up from February 1998 until early 2002. The results
of the prospective SHEAF component have not yet been fully published, but
preliminary analyses6 confirmed that self-measurement
at home improved the prognostic accuracy of office BP. Multiple standardized
office BP readings might predict target organ damage with accuracy similar
to that of automated techniques of BP assessment.33 One
limitation of the Japanese4 and French5,6 studies is the small number of office
BP readings (1 reading at a single visit4 and
2 readings at each of 2 visits,5 respectively)
used for the comparison of prognostic precision with home BP.
The APTH trial compared treatment strategies for hypertension based
on office BP and the average daytime ambulatory BP.1 In
the present study, ambulatory BP values were only disclosed after completion
of the trial and were not used to adjust treatment. Nevertheless, the similarity
between the APTH1 and THOP trials with regard
to protocol, conduct and settings, and baseline characteristics of the patients,
as well as the intended matching of the target ranges of DBP on 3 types of
BP measurement, enable comparison of the results of both trials. In the APTH
study,1 a strategy guided by ambulatory monitoring
instead of office BP measurement, after a median follow-up of 6 months, led
to less intensive drug treatment with preservation of general well-being and
inhibition of left ventricular hypertrophy, but without cost savings in the
group randomized to ambulatory monitoring. In the APTH trial, the final between-group
differences in SBP and DBP also tended to be in favor of the office BP group.
They averaged 3.3 mm Hg (95% CI, –0.1 to 6.7 mm Hg; P = .06) and 1.4 mm Hg (95% CI, –0.5 to 3.3 mm Hg; P = .16) for office BP measurement and 2.8 mm Hg (95% CI, 0.6-5.1 mm
Hg; P = .02) and 1.6 mm Hg (95% CI, 0.2-3.0 mm Hg; P = .03) for the 24-hour ambulatory BP. In the present
trial, median follow-up increased from 6 to 12 months with less BP control
at the final visit in patients randomized to self-measurement than observed
in APTH patients randomized to ambulatory monitoring. One might speculate
that had follow-up in the APTH trial been longer, the BP gradient between
the randomized groups might have been larger. We reported the APTH trial with
the conclusion that these small between-group differences in BP control, albeit
statistically significant, probably did not matter in terms of prognosis because
there were no differences in left ventricular mass between the randomized
groups. In view of more recent evidence from prospective population studies27,28 and outcome trials,29,30 this
point of view is no longer tenable. Thus, if automated BP measuring techniques
are used to initiate or adjust antihypertensive treatment, lower BP targets
must be pursued, which should probably be below 130 mm Hg SBP and 80 mm Hg
DBP. At these levels, the incidence of cardiovascular complications is similar
in patients with white-coat hypertension diagnosed by daytime ambulatory monitoring
and normotensive controls.34 Physical activity
and the stress of daily life raise the level of the daytime ambulatory BP
in comparison with the BP measured at home, so that the operational threshold
proposed for daytime ambulatory monitoring cannot be extrapolated to self-measurement.35
The present study must be interpreted within the context of its limitations.
We did not record the time of day at which the field investigators measured
the office BP. General practitioners recruited most patients, and about half
of those randomized were taking antihypertensive drugs. This might explain
why the changes in electrocardiographic and echocardiographic left ventricular
mass were small. However, a substudy of left ventricular mass in the Losartan
Intervention for Endpoint Reduction (LIFE) trial36 demonstrated
that prior treatment was neither associated with greater left ventricular
mass at entry nor with a lesser degree of mass reduction during follow-up.
More importantly, long-term outcome studies should firmly establish the advantage
of further integrating self-measurement and ambulatory monitoring into the
routine care of hypertensive patients. Until such evidence becomes available,
conventional sphygmomanometry at the physician's office executed according
to published guidelines8 remains key to the
diagnosis and treatment of hypertension. Ambulatory BP monitoring and self-measurement
are useful to confirm the diagnosis and to diagnose white-coat hypertension
or masked hypertension.2 In keeping with the
THOP procedures and recent recommendations,7,8 the
clinical application of self-measurement requires the use of validated and
properly calibrated devices (excluding error-prone wrist devices), patient
education, a standardized protocol, at least 3 days of observation,37,38 a printed or electronic report of
the readings, and medical supervision. We scheduled self-measurement during
the week preceding clinic visits because BP responses to changes in antihypertensive
treatment reach their full magnitude only after several days to weeks and
because home BP and office BP measurements taken within a short interval are
less likely to be confounded by factors affecting the long-term BP variability
and can therefore be more readily compared.
In conclusion, adjustment of antihypertensive treatment based on home
BP instead of office BP led to less-intensive drug treatment and marginally
lower costs but also to less BP control, with no differences in general well-being
or left ventricular mass. Self-measurement helps to identify patients with
white-coat hypertension. Our findings support a stepwise strategy for the
evaluation of BP in which self-measurement and ambulatory monitoring are complementary
to conventional office measurement. They highlight the need of prospective
studies to establish the normal range of home BP, including the operational
thresholds at which drug treatment should be instituted or can be discontinued.
Until such prospective data become available, management of hypertension exclusively
based on home BP cannot be recommended.
Staessen JA, Byttebier G, Buntinx F.
et al. Antihypertensive treatment based on conventional or ambulatory blood
pressure measurement: a randomized controlled trial. JAMA.1997;278:1065-1072.
Staessen JA, Wang J, Bianchi G, Birkenhäger WH. Essential hypertension. Lancet.2003;361:1629-1641.
Chatellier G, Dutrey-Dupagne C, Vaur L.
et al. Home self blood pressure measurement in general practice: the SMART
study. Am J Hypertens.1996;9:644-652.
Ohkubo T, Imai Y, Tsuji I.
et al. Home blood pressure measurement has a stronger predictive power for
mortality than does screening blood pressure measurement. J Hypertens.1998;16:971-975.
Bobrie G, Genès N, Vaur L.
et al. Is "isolated home" hypertension as opposed to "isolated office" hypertension
a sign of greater cardiovascular risk? Arch Intern Med.2001;161:2205-2211.
Chatellier G, Genès N, Clerson P.
et al. Home blood pressure measurement has a better prognostic value than
office blood pressure results of the SHEAF study (Self Measurement of Blood
Pressure at Home in the Elderly Assessment and Follow-Up) [abstract]. J Hypertens.2003;21(suppl 4):S9.
Asmar R, Zanchetti A. Guidelines for the use of self-blood pressure monitoring. J Hypertens.2000;18:493-508.
O'Brien E, Asmar R, Beilin L.
et al. European Society of Hypertension recommendations for conventional,
ambulatory and home blood pressure measurement. J Hypertens.2003;21:821-848.
Mancia G, Sega R, Bravi C.
et al. Ambulatory blood pressure normality. J Hypertens.1995;13:1377-1390.
De Gaudemaris R, Chau NP, Mallion JM.for the Groupe de la Mesure–French Society of Hypertension. Home blood pressure: variability, comparison with office readings and
proposal for reference values. J Hypertens.1994;12:831-838.
Thijs L, Staessen JA, Celis H.
et al. Reference values for self-recorded blood pressure: a meta-analysis
of summary data. Arch Intern Med.1998;158:481-488.
Thijs L, Staessen JA, Celis H.
et al. The international database of self-recorded blood pressures in normotensive
and untreated hypertensive subjects. Blood Press Monit.1999;4:77-86.
Weisser B, Mengden T, Düsing R, Vetter H, Vetter W. Normal values of blood pressure self-measurement in view of the 1999
World Health Organization–International Society of Hypertension Guidelines. Am J Hypertens.2000;13:940-943.
Stergiou GS, Thomopoulou GC, Skeva II, Mountokalakis TD. Home blood pressure normalcy: the Didima Study. Am J Hypertens.2000;13:678-685.
Mejia AD, Julius S, Jones KA, Schork NJ, Kneisley J. The Tecumseh blood pressure study: normative data on blood pressure
self-determination. Arch Intern Med.1990;150:1209-1213.
Celis H, Staessen JA, Buntinx F.
et al. Antihypertensive treatment based on home or office blood pressure measurement. Blood Press Monit.1998;3(suppl 1):S29-S35.Google Scholar
Forty-First World Medical Assembly. Declaration of Helsinki: recommendations guiding physicians in biomedical
research involving human subjects. Bull Pan Am Health Organ.1990;24:606-609.Google Scholar
O'Brien E, Waeber B, Parati G, Staessen J, Myers MG.for the European Society of Hypertension Working Group on Ambulatory
Blood Pressure Monitoring. Blood pressure measuring devices: recommendations of the European Society
of Hypertension. BMJ.2001;322:531-536.
Sokolow M, Lyon TP. The ventricular complex in left ventricular hypertrophy as obtained
by unipolar precordial and limb leads. Am Heart J.1949;37:161-186.Google Scholar
Casale PN, Devereux RB, Alonso DR, Campo E, Kligfield P. Improved sex-specific criteria of left ventricular hypertrophy for
clinical and computer interpretation of electrocardiograms: validation with
autopsy findings. Circulation.1987;75:565-572.
Molloy TJ, Okin PM, Devereux RB, Kligfield P. Electrocardiographic detection of left ventricular hypertrophy by the
simple QRS voltage-duration product. J Am Coll Cardiol.1992;20:1180-1186.
Sahn DJ, De Maria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography. Circulation.1978;58:1072-1083.
Devereux RB, Alonso DR, Lutas EM.
et al. Echocardiographic assessment of left ventricular hypertrophy. Am J Cardiol.1986;57:450-458.
Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. BMJ.1990;300:230-235.
European Society of Hypertension/European Society of Cardiology Guidelines
Committee. 2003 European Society of Hypertension/European Society of Cardiology
guidelines for the management of arterial hypertension. J Hypertens.2003;21:1011-1053.
Sega R, Trocino G, Lanzarotti A.
et al. Alterations of cardiac structure in patients with isolated office,
ambulatory, or home hypertension. Circulation.2001;104:1385-1392.
MacMahon S, Peto R, Cutler J.
et al. Blood pressure, stroke, and coronary heart disease, I: prolonged differences
in blood pressure. Lancet.1990;335:765-774.
Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality. Lancet.2002;360:1903-1913.
Staessen JA, Wang JG, Thijs L. Cardiovascular prevention and blood pressure reduction: a quantitative
overview updated until March 2003. J Hypertens.2003;21:1055-1076.
Blood Pressure Lowering Treatment Trialists' Collaboration. Blood Pressure Lowering Trialists' Collaboration: results of prospectively-designed
overviews of randomised trials. Lancet.2003;362:1527-1535.
Staessen JA, Thijs L, Fagard R.
et al. Predicting cardiovascular risk using conventional vs ambulatory blood
pressure in older patients with systolic hypertension. JAMA.1999;282:539-546.
Franklin SS, Larson MG, Khan SA.
et al. Does the relation of blood pressure to coronary heart disease change
with aging? Circulation.2001;103:1245-1249.
Fagard R, Staessen J, Thijs L, Amery A. Multiple standardized clinic blood pressures may predict left ventricular
mass as well as ambulatory monitoring. Am J Hypertens.1995;8:533-540.
Verdecchia P, Schillaci G, Borgioni C.
et al. White-coat hypertension. Lancet.1996;348:1444-1445.
Staessen JA, Bieniaszewski L, O'Brien ET, Imai Y, Fagard R. An epidemiological approach to ambulatory blood pressure monitoring:
the Belgian population study. Blood Press Monit.1996;1:13-26.
Aurigemma GP, Devereux RB, Wachtell K.
et al. Left ventricular mass regression in the LIFE study. Am J Hypertens.2003;16:180-186.
Celis H, De Cort P, Fagard R, Thijs L, Staessen JA. For how many days should blood pressure be measured at home in older
patients before steady levels are obtained? J Hum Hypertens.1997;11:673-677.
Den Hond E, Celis H, Fagard R.
et al. Self-measured versus ambulatory blood pressure in the diagnosis of
hypertension. J Hypertens.2003;21:717-722.