Ambulant versus unattended & attended office versus self-home blood pressure measurement

CVD remains the leading cause of death globally (31,4%). Ischemic heart
diseases (16.6%), followed by stroke (10.2%) account for 85% of all CVD-related
deaths. High BP is the dominant risk factor for CVD. Prevalence of high BP
globally is a staggering 31% for all adults. For people over 65 years of age
the prevalence rises above 50% and reaches values of 70%.

Discussion about treatment thresholds and which BP measurement methods to use,
especially in different patient subpopulations and age categories, has always
been a topic of scientific debate. Recently the *Systolic BP Intervention
Trial* (SPRINT) has complicated this discussion even further by unintentionally
adding another factor into the mix: the protocol of BP measurement methods.
The initial results of the SPRINT-trial were compelling. However, a debate
about the method used to measure BP in the trial quickly ensued and caused
concerns about the generalizability of the results into clinical practice. How
did their unattended automated BP method compare to the most used conventional
(attended and semi-automated) BP method? And what does this mean for the
generalizability of the compelling results? The 120 mmHg systolic BP
measurement threshold might even be equivalent to 140 mmHg using conventional
office BP methods critical investigators argued.
The discussion about the method of BP measurement is very relevant as more and
more BP devices in clinical practice use automated measurements. The problem
however is that each device has different hardware installed and per
manufacturer the software algorithms for determining BP after multiple readings
are different (and often secret for marketing purposes). On top of that, many
different instruction protocols for measuring BP exist. Variation can be seen
on the time rested before taking the actual measurement, posture of the
participant, attended versus unattended, the number and time between
measurements, single or both arm measurements and on-site circumstances (clinic
versus home). So, each method has their own unique way of measuring BP.
Creating a subset of uniquely different BP measurements within a single
patient. Considering all of the above and the fact that office BP measurements
cannot detect the important hypertension phenotypes white coat and masked
hypertension, we should search for better implementation of more reliable and
better reproducible BP methods such as out-of-office BP measurements.
There is consensus out-of-office BP measurement methods, either ABPM or HBPM,
are the best methods to diagnose and follow up hypertension. ABPM however is
cumbersome, time consuming and expensive. HBPM is considered a more patient
friendly alternative and cheaper than ABPM. The recent updated guidelines for
the management of arterial hypertension (ESC/ESH 2018) advice the use of ABPM
and HBPM interchangeably when performing out-of-office BP measurement. HBPM
leads to significantly better BP control. The effect on BP control is even
bigger when self-monitoring is accompanied by other (co)interventions such as
telemonitoring and app support.

The UMC Utrecht has developed a new, state of the art, method for HBPM. An
important feature is the integration of a protocolled 7-day measurement as
advised by the ESH practice guidelines for home blood pressure monitoring. This
7-day protocol, which leads to a standardized 7-day BP average, is also advised
as the preferred HBPM method protocol in the already mentioned recent updated
guidelines for management of arterial hypertension.
Our HBPM method uses a validated BP measurement device together with a newly
developed CE certified app. The app provides the user BP measurement
instructions and, among other things, visual representation of BP values, cloud
storage, facilitates remote telemonitoring services, in-app messaging functions
and reminder options (email, text message or in-app notifications). Our HBPM
method is state of the art and innovative because it uses a combination of
validated hardware, ICT techniques and an evidence based guideline-advocated BP
measurement protocol not seen before to our knowledge.
In light of the discussion earlier about troublesome heterogeneity of BP
methods and protocols, we designed the AMUSE-BP study. The AMUSE-BP aims to
compare the agreement between the five most used modern BP methods in a
randomized five-way crossover design. Our primary objective will be the
comparison, expressed as the agreement, between ABPM and our newly developed
HBPM method. The five BP methods used are: ABPM, attended and unattended
automatic office BP management (a/u-AOBP), HBPM and 30mBP. Results of the
AMUSE-BP study will help researchers answer the question if and how we can use
our newly developed HBPM method in comparison with ABPM and different office BP
measurements for the treatment of patients with raised blood pressure.

Objective:
Primary:
To investigate the agreement between HBPM and ABPM for measuring BP in patients
with hypertension.

Secondary:

a) To investigate the agreement between HBPM and daytime ABPM for measuring BP
in patients treated for hypertension

b) To investigate the agreement between HBPM and a-AOBP for measuring BP in
patients treated for hypertension.

c) To investigate the agreement between HBPM and u-AOBP for measuring BP in
patients treated for hypertension.

d) To investigate the agreement between HBPM and 30mBP for measuring BP in
patients treated for hypertension.

e) To investigate the agreement between ABPM and a-AOBP for measuring BP in
patients treated for hypertension.

f) To investigate the agreement between ABPM and u-AOBP for measuring BP in
patients treated for hypertension.

g) To investigate the agreement between ABPM and 30mBP for measuring BP in
patients treated for hypertension.

h) To investigate the agreement between attended AOBP and u-AOBP for measuring
BP in patients treated for hypertension.

i) To investigate the agreement between a-AOBP and 30mBP for measuring BP in
patients treated for hypertension.

j) To investigate the agreement between unattended AOBP and 30mBP for measuring
BP in patients treated for hypertension.

k) To investigate if a different protocol instead of a standard 7-day HBPM
protocol results in clinically acceptable (<3 mmHg) average systolic and
diastolic BP readings as compared to the ABPM and awake ABPM

The study will have a controlled randomized 5-way cross-over design. The 5
different periods each contain 1 out of 5 different BP methods:

(1) HBPM (7-day home measurement)

(2) ABPM (24-hours)

(3) a-AOBP (single office measurement visit)

(4) u-AOBP (single office measurement visit)

(5) 30-minute AOBP (single 30-minute unattended office measurement visit)

Patients will be asked to participate in a randomized 5-way crossover design
study with a total of 5 different BP methods (corresponding with the *5-way* as
described above). Total length of the study will be a minimum of 15 and a
maximum 29 days, depending on the randomization arm and planned measurement
schedule. All BP methods are safe, already used in clinical practice in all
participating centers and generally very well accepted by patients. Elevated BP
is the dominant risk factor for the development of cardiovascular disease,
which is in turn the number one cause of death worldwide. Patients treated for
hypertension need frequent BP measurements for follow-up and therefore
participation in this study is fully justifiable. No new or prolonged methods
other than already used by healthcare professionals will be used. All methods
are performed with CE certified and validated BP devices and by authorized and
trained local personnel. Potential benefit for the participants is insight in
available BP methods and corresponding BP values. High acceptability of
patients for BP devices and methods improves adherence too. Patients in this
study could benefit from new insights in different BP methods and through
shared decision making choose their own preferred BP measurement method for
follow-up.