Evaluation of the *auto-cuff* response in outpatients with and without hypertension

The diagnosis of hypertension is hampered by intrinsic blood pressure (BP)
variability and anxiety responses that may systematically influence BP
measurement, such as the white coat effect. Both influence the diagnostic value
of BP measurement and the prediction of cardiovascular disease. Recently we
showed that ~20% of patients referred for out-of-office BP measurement have a
significantly higher home and office BP compared to ambulatory measurement. The
differences between home and ambulatory BP do not relate to hypertensive organ
damage. In addition, patients with a difference between home and ambulatory BP
more frequently had a white coat effect. This suggests that anxiety responses
upon the self-measurement of BP may exist. Recently we have shown the existence
of such an *auto-cuff* response during semi-automated self-measurement, however
evidence regarding the possibility of such an *auto cuff * response based on
fully-automated blood pressure measurement is lacking.

In theory, self-measurement of BP could evoke an anxiety response, similar to
that observed with the white coat effect during office BP measurement. These
*cuff responses* may be larger during active self-measurement compared to
fully-automated measurements. Anticipating a BP reading could induce a pressor
response at home as may happen in the clinic. Such an *auto-cuff* response may
be less significant during fully-automated ambulatory BP measurement, where
recording is nearly continuous and less influenced by emotional factors such as
anxiety. Recently, we showed a significant increase in BP during
self-measurement using a semi-automatic device compared to baseline in patients
with a large difference (10 mmHg systolic and/or 5 mmHg diastolic) between home
blood pressure measurement (HBPM) and ambulatory blood pressure measurement
(ABPM), but also in patients without this difference. This increase in BP
during self-measurement was accompanied by both an increase in cardiac output
(CO) and heart rate (HR) compared to baseline. Overall, BP decreased after
repeated self-measurements but still remained higher compared to BP before
self-measurement.
These results support the existence of an *auto-cuff* response during
semi-automated self-measurement. Whether this *auto-cuff* response persists
during fully-automated BP measurements remains to be determined. It*s important
to know if this *auto-cuff* response also exist in fully-automated
self-measurement, alias ABPM, to better understand the differences in HBPM and
ABPM but more important to prevent patients misdiagnosed with hypertension.

Does the *auto-cuff* response persist during automated consecutive blood
pressure recording in patients who have been referred for out of office BP
measurements as a potential explanation for the difference between HBPM
(active-measurement) and ABPM (passive measurement)?


Primary Objective: To assess differences in average systolic BP response during
semi-automated and fully-automated BP measurement in patients who are referred
for out-of-office BP measurement.

Secondary Objectives: To assess differences in average diastolic BP, heart rate
(HR), cardiac output (CO) and systemic vascular resistance (SVR) during
self-measurement. To assess the maximal increase in systolic and diastolic BP
during self-measurement.

This study is designed as a single centre, one visit, cross-over study. After
screening for eligibility and given informed consent, all subjects will receive
cardiovascular risk assessment. Two groups will be randomly made using a
computerized randomization scheme. Thereafter, all subjects will undergo a 30
minutes continuous non-invasive finger arterial BP recording with Nexfin
(BMEYE, Amsterdam, The Netherlands) at the dominant arm. A finger cuff will be
placed on the mid phalanx of the middle finger, the arm will be placed in a
sling at the height of the heart.

After 5 minutes of rest while seated, participants will be asked to perform
three semi-automated and three fully-automated BP measurements using the
Microlife watch BP device with an in-build possibility to measure blood
pressure in a full- and semi-automated way. Each participant will receive a
blood pressure cuff at the non-dominant arm in order to perform blood pressure
measurements. The order of the measurements will be randomized. After 5 minutes
rest, the second measurement will be made. During the semi-automated
measurement, the patient uses the semi-automated mode to perform three blood
pressure readings by actively pressing the button. In the fully-automated mode,
patients will press the button once and the device will automatically perform
three blood pressure measurements after a 5 minute waiting period. The study
consists of a single visit of approximately 45 minutes.

The sequence will be randomly assigned using www.random.org. Participants and
the executive researcher are aware of the classification. In order to mark the
start of a semi-automated record or a fully-automated record the researcher
will use a stopwatch and shall keep an eye on the participant from another
room.

Continuous non-invasive measurement with Nexfin
Devices for continuous non-invasive finger arterial BP measurement, like Nexfin
(BMEYE, Amsterdam, The Netherlands), have been largely validated in a variety
of clinical settings and resulted to be as reliable as previously used invasive
methods in detecting BP changes and autonomic responses. The measurement of BP
is performed with an inflatable finger cuff with a build-in plethysmograph
using the volume clamp method. The cuff pressure follows the finger arterial
pressure to keep the finger arterial blood volume constant which is controlled
by the plethysmograph, and supported by the automatic physiological calibration
technology and the measurement of the difference in hydrostatic pressure
between the finger and the heart. Then, the arterial BP in the brachial artery
will be reconstructed from the finger arterial BP, with adjustment for finger
pressure distortion and brachial finger pressure decrement. BP measures
obtained with Nexfin are acceptably accurate as compared to measures obtained
using the common auscultatory as well as the intra-arterial (invasive) methods.
Continuous measurement of BP is the basis for the estimation of haemodynamic
parameters. These estimates are comparable with measures obtained using the
worldwide accepted invasive thermodilution method.

Heart rate variability (HRV) is a phenomenon of oscillations of both
RR-interval and instantaneous heart rates and is used to investigate the
autonomic influences on the functioning of the heart. The heart rate (HR) is
defined as the inverse of the interbeat interval. Indices of blood pressure
variability (BPV), expressing arterial BP fluctuations, provide further
parameters used to investigate the autonomic influence on the cardiovascular
system. To calculate the cardiac output (CO), the stroke volume (SV) will be
determined by the pulse contour method (Nexfin CO-trek). CO is defined as SV
divided by the interbeat interval and the systemic vascular resistance (SVR)
will be calculated as the ratio of mean arterial pressure (MAP) and CO. All
these indexes have been used in literature to evaluate autonomic responses to
certain stimuli.

The results of this study will contribute to improve the quality of BP
monitoring and to better understand the characteristics of self-BP measurement
and ABPM responses in order to better identify susceptible subjects. Individual
subjects will gain no direct benefit from this study. The risk and burden of
participating in this study is negligible since all the measurements that will
be performed are safe and non-invasive and the study comprises only one visit
of approximately 45 minutes including questionnaire and measurements. This
visit will be combined with an out-clinic visit.