Circulatory Health magazine

Circulatory Health
Magazine
"I've never regretted
opting for the biological
heart valves"
37 researchers, patients, students and
healthcare professionals tell us
how to improve cardiovascular care
UMC Utrecht
Center for for Circulatory Health Health

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Contents
06 Promising research
into lower blood pressure thanks to
implant
07 Outpatient report complicated
hypertension
10 Heart-on-a-chip
12 The LVAD team:
who plays which role?
14 "I might even win another prize
some day"
16 Patients are partners
in care, research and education
18 Facts & Figures
20 Wealth of data
in Utrecht Cardiovascular Cohort
22 All information on hand in the
consulting room
23 "Not just for myself, but for
everyone"
24 News
26 I feel as if I'm carrying a time
bomb inside me”
30 Heart failure due to heart muscle
stiffness
32 Big Data @ Heart:
Sharing data and discovering trends
35 "Combining forces"
36 Joyce Browne studies high blood
pressure in pregnant women
37 Global Health:
Global insight into cardiovascular
diseases
38 The biological clock of the heart
40 Multidisciplinary outpatient
Center for Circulatory Health
42 "This daily check-up
reassures me"
43 A patch against a stroke?
44 Aspirin:
more than just a painkiller
46 U-Prevent:
smart website about customized
medication
49 Imaging of heart failure
28 "Locking in on promising
students"
Circulatory Health Magazine 3

4 Circulatory Health Magazine

Our heart's desire is…
...to give all our patients quality care, regardless of
whether they have clogged arteries or heart failure
...to develop methods that help
our patients
…to train doctors who have an eye for the
patient as a whole instead of just the disease
...to design methods that predict the
individual risk of cardiovascular disease
…to help patients change their lifestyle
…to train people around the world who
help patients with cardiovascular
disease, also in developing countries
…to conduct research that society
really needs
At the strategic theme Circulatory Health
of UMC Utrecht, we work hard every day
to fulfill this heart's desire one step at a time.
Circulatory Health Magazine 5

Promising research into lower
blood pressure thanks to implants
Deeply touched, a patient came to
consulting hour. Overjoyed. Because his
sky-high blood pressure had returned to
normal. And because he had found a job
again. This patient had been treated with
the Mobius implant, a therapy being
studied by internist-vascular physician
Wilko Spiering.
If your blood pressure remains high despite medication,
you may qualify for a Mobius implant. "And also if there is
no underlying cause, such as an adrenal gland disorder or
kidney failure," adds Wilko." A Mobius is a stent-like implant
that is placed in the carotid artery. It boosts the signals
from the baroreceptors, which lowers blood pressure,
immediately after implantation. To date, we see an average
and persistent lowering of the blood pressure of 24 points
(systolic pressure) and 12 points (diastolic pressure), in
addition to a need for less medication. I am hopeful about
this new treatment. But hope is not enough, we must
know for sure."
High blood pressure
increases the risk of
cardiovascular disease. High risk
(high blood pressure) is one of
the research themes of the
strategic theme Circulatory
Health. We pay special attention
to patients with high blood
pressure that is difficult to treat
or related to pregnancy.
With Wilko as leading scientist, an international study was
launched last year that leaves nothing to arbitrariness or
subjectivity. "The study is a double-blind one. This means
that neither the researcher nor the patient knows whether
the Mobius implant has actually been implanted. To this
end, an entire 'set' has been organized in the angio room
so that patients who do not receive the implant do
experience it as a real implantation when they're on the
operating table. They are given a line, they feel warmth in
their neck, the real thing. After all, high blood pressure is
not like a broken leg; emotions have a lot of impact. And
what we're seeing so far is that the blood pressure of those
who did get the implant decreased immediately, while that
didn't happen in patients who didn't get it. I'm enthusiastic
about this innovation, because I want to give my patients
the best possible treatment. That's also why I temper
myself: aren't I overly enthusiastic? Because you can only
achieve the best results in healthcare based on methodical
and objective research.”
6 Circulatory Health Magazine

Nicolasa follows a
comprehensive screening
program because of her
blood pressure
A 15-minute walk
"Great that they can really help me here," says Nicolasa Alejandro. She
has had high blood pressure for many years, with different examinations
and constantly changing medication. But her blood pressure remained
far too high. Now, Nicolasa is a patient at the outpatient clinic for
complicated hypertension of the Center for Circulatory Health. >
Circulatory Health Magazine 7

It is Tuesday morning, 7:45 a.m. Nicolasa enters through the revolving door of the UMC
Utrecht, together with her daughter-in-law Sharine. She's fifteen minutes late. "Traffic
jam", she explains, "everything was deadlocked" and despite her cane she hurries to the
Internal Medicine outpatient department. Sometimes she grimaces with pain, because
she has had a blood pressure monitor around her arm for 24 hours, which still continues
to pump up tightly. "I hardly slept because of it. It's great that it comes off soon."
"It started with a headache and pain in my
neck every day," Nicolasa remembers. "High
blood pressure, my family doctor told me. I
received medication, but my blood pressure
remained at 170/100. Far too high. And after
my accident, it got much higher still. I took
six different drugs. Eventually, I was referred
to the outpatient clinic for complicated
hypertension."
As Nicolasa was eligible for the
comprehensive screening program, she first
had to cut back her medication, to ensure
untainted research results. Nicolasa: "On
April 10, I had my first major medical, which
looked at risk factors. This was called SMART.
My blood and urine were tested, my waist
and hip circumference were measured, an
abdominal ultrasound was done, and an
ECG. Today is the second major examination.
For this, I had to start a 24-hour blood
pressure measurement yesterday, and I also
collected my urine over these 24 hours."
Upon arrival at the outpatient department,
she is greeted by nurse Marieke Pol, who
helps her to her bed.
"This study looks at the possibility of a
hormonal disorder in the adrenal glands,"
Marieke explains to Nicolasa. "Or whether
your adrenal glands produce too much of
the hormone Aldosteron. This hormone
regulates the salt and water metabolism in
the body, and, as such, blood pressure. To
measure this, you will be administered a total
of two liters of saline solution through a drip.
We will take blood samples and measure
your blood pressure at specific intervals.
Because Aldosteron is normally always
produced when you move, we must take the
measurements at rest. This means you will
have to stay in bed for four hours."
But first, Nicolasa has to take a 15-minute
walk. "Immediately afterward, we will take a
blood sample and measure your blood
8 Circulatory Health Magazine

pressure after this light exercise," says Marieke.
The 24-hour sphygmomanometer finally comes off,
and a drip needle is inserted. Nicolasa walks to the
outpatient laboratory, where she hands in her urine
sample and continues to the vascular medicine
outpatient clinic to hand in the sphygmomanometer.
Plus the log that she filled in yesterday, so that all
blood pressures can be linked to her activity level.
Back in the outpatient department, Nicolasa sits
down on the edge of the bed. First, the blood
pressure in her right arm is measured: 181/107.
Marieke asks Nicolasa whether she recognizes this
result. "Yes, that's normal," she whispers. Measuring
the other arm hurts. And the cuff keeps pumping
up. "That means the blood pressure is very high
and it is automatically measured again," explains
Marieke. She's right, the blood pressure peaks at
228/138. Marieke wants to take a blood sample
through an IV needle, but that does not work. "We
will take a separate sample." This, too, is not easy.
"This often happens," says Marieke, "the blood
vessels of people with high blood pressure are
tougher and more difficult to prick." But Marieke is
skillful and it's soon over, leaving Nicolasa to heave
a sigh of relief. After this first blood pressure
measurement and blood sampling, the saline
solution in Nicolasa's IV is administered. She lies
down for the next four hours. After a few weeks, all
outcomes will be discussed with her.
Circulatory Health Magazine 9

10 Circulatory Health Magazine

Heart-on-a-chip
Willem Suyker, department head of cardiothoracic surgery and
chairman of the Heart & Lungs division.
It is possible: repairing the heart while optimally
respecting the body. Willem Suyker repairs heart valves
using a robot, a minimally invasive technology that he
was the first to use in the Netherlands. Regeneration is
more difficult, but this research field is also evolving.
The latest of the latest is the heart-on-a-chip.
"I am especially interested in regenerative medicine
and surgery. It would be great if we could activate the
self-healing ability of the body, for instance, by having
the heart muscle tissue that has died grow again.
There are indications that this should be possible, but
a lot of research is required to find out how exactly
this can be done.
Printed heart muscle cells
The latest development in regenerative research is the
organ-on-a-chip. I am, of course, mainly interested in
the heart-on-a-chip. This is a chip, only a few
millimeters square, on which a patient's heart muscle
cells have been printed: a miniscule, three-dimensional
piece of cardiac tissue. That allows you to conduct a lot
of experiments, as the chips are relatively easy to make.
A liquid in the chip ensures that the substances that we
add reach the cultured tissue. What will happen if we
release substances that occur naturally in the body and
that are potentially self-healing onto the heart tissue?
Ultimately, we want to find those substances that can
repair a heart.
Fewer animal experiments
The heart-on-a-chip is a means to unravel the complex
human regenerative processes. This is the basis on
which we hope to be able to develop therapies. It
would be ideal, for instance, if people with an LVAD
would no longer need it because the regenerated or
newly grown heart muscle cells sufficiently improve
their cardiac function. But that's still in the future. For
now, we're working hard on the required research.
Another benefit is that for this research method fewer
animal experiments are needed. This is not only more
humane, but also faster and cheaper.”
Circulatory Health Magazine 11

The LVAD team:
who plays which role?
Cardiologist
The cardiologist and the patient together discuss what the
possibilities are in case of severe heart failure. If treatment with
medication and lifestyle rules do not work, an LVAD may help to
bridge the time until a heart transplant. The cardiologists
performs a number of examinations to see whether the heart can
be supported with a pump.
Cardiothoracic surgeon
The cardiothoracic surgeon performs the surgery to implant the
LVAD. Following the operation, the patient stays in intensive care.
Once the patient is stable and no longer requires artificial
respiration, they are transferred to the nursing ward.
Hospitalization in intensive care usually lasts one week, the stay in
the nursing ward an average of four weeks.
MCS* nurse practitioner or clinical nurse
specialist or specialized nurse
(MCS coordinator)
The nurse plays a central role throughout the process, from
implantation until removal of the LVAD. She discusses the new
lifestyle rules for living with an LVAD with the patient. An example
is that the nurse assists the patient and trains them in caring for
the wound where the wire exits the body. The nurse constitutes a
tight team with the LVAD engineer.
Annette Klinkert has the hereditary
heart muscle disease PLN.
This genetic disorder causes a
disease of the heart muscle that
significantly affects the pump
function of the heart muscle. She
received an LVAD to bridge the
period until a heart transplant.
The LVAD team supported
Annette in matters concerning
implantation of the LVAD. Who
participates in the LVAD team,
what is their position and what
role do they play?
LVAD engineer
(technical MCS coordinator)
The LVAD engineer gives the patient five or six lessons to explain
how the LVAD works. For instance, how long the batteries last
during the stay in hospital. Family and friends are also trained to
familiarize themselves with the equipment. The LVAD engineer
visits the patient daily and analyzes the data produced by the LVAD.
12 Circulatory Health Magazine

Social worker
The social worker visits the patient at least once. The social
worker can help with questions such as "How do I handle feelings
of fear, dependence and uncertainty?" "How will I be able to
function properly again when I'm back home?" The patient and
the social worker discuss these and other issues.
Physical therapist
Once the patient is awake in intensive care, the physical therapist
visits every day. The physical therapist helps the patient build up
muscle again. This starts with short exercises, such as finger
movements and slow cycling in bed. A patient must be able to
walk 200 meters, climb stairs and operate the LVAD equipment
independently before they can go home.
What is an LVAD?
An LVAD is a pump placed in the body that connects
the left ventricle and the aorta. The LVAD ensures that
sufficient blood can flow through the body again. The
pump is powered by electricity and is connected to a
cable that exits through the abdominal wall. The cable
is connected to a battery-powered controller (and on
mains current during the night).
UMC Utrecht implanted the first LVAD, a left
ventricular assist device, in 1993. Every year,
30 to 35 patients receive an LVAD. In the
Netherlands, 200 people have an LVAD, and
over half of them were treated in UMC Utrecht.
Heart failure is one of the research themes of
the strategic theme Circulatory Health.
*MCS: Mechanical Circulatory Support is a collective term for
long- or short-term support of blood circulation.
Circulatory Health Magazine 13

”I might even win another
prize someday”
Kiki's life revolves around
horseback riding. When she
suddenly fell ill, she didn't know
whether she would ever win a
competition again. Kiki (27): "Nine
months ago, I had open-heart
surgery to have a new type of
biological heart valve implanted.
Following surgery, I took
anticoagulants for a while. When
that stopped, I was back on my
horse within two days. My doctor
is very enthusiastic. During my
most recent check-up, he told
me: 'Just do your thing, I don't
want to see you until next year'."
14 Circulatory Health Magazine

Flu?
"Five years ago, I caught a bacterial infection. When I
had a 40 degrees fever, I first thought I had the flu. But
a month later my joints started to hurt. It appeared
I had a streptococcal infection that had also
affected my heart valves. We're living at a horse
farm, with 45 horses. They need to be cared for and
ridden full time. When I had ridden one horse, all I
wanted to do was sleep on the couch. My body was
worn out.
New heart valves
I had to have heart surgery. That was a real downer, I
was only 26. In consultation with the thoracic
surgeon, we opted for a new type of biological heart
valve. That choice had to do with my desire to have
children and above all with horse riding. With
mechanical heart valves, you have to take
anticoagulants your entire life. That makes horseback
riding more awkward. With a biological valve, you are
off anticoagulants quite soon. And they expect that
this new type lasts longer. I knew I wanted to go for it.
Everything for horseback riding
I was so happy when I opened my eyes in IC. I'd
made it, I could start building again. My studies to
become an equine sports teacher had been delayed
quite a bit. I started that again, going to school one
day and doing an internship two days a week. After
the surgery, I wanted to ride all the time, preferably
six horses a day. But I adjusted that a bit. I listen to
my body when it tells me I need rest. I keep one day
a week free. It's good to know I have that freedom.
No regrets
I've never regretted opting for the new biological
valves. I chose them because of my horse racing.
And it worked out well. The doctor told me: 'You're
so positive, it's infectious! It comes naturally.
Surgery like that isn't nothing. But it wears off and
becomes part of yourself. My life has gone back to
normal. And that's great."
Circulatory Health Magazine 15

Patients are partners in care,
research and education
"Not just looking at the medical problem that a
patient has, but at the entire cardiovascular
system, the human being as a whole. That is the
core of the Center for Circulatory Health. Every
week, we treat an increasing number of patients in
the Center for Circulatory Health and we learn a
lot from that." Providing state-of-the-art care is
one of the goals of the strategic theme Circulatory
Health. An interview with vicechairman of the
UMC Utrecht Executive Board Frank Miedema and
strategic theme chairman Rick Grobbee.
Rick: "Just imagine the position of a patient who's had a stroke, who has to
go to the vascular surgeon to have his carotid arteries checked, visit the
cardiologist for a heart rhythm disorder, and 'pop by' the internist for
diabetes. Before you know it, you're four months down the road until
you've seen all these doctors. Here at the Center for Circulatory Health, we
do things differently. What is more effective than having the neurologist,
vascular surgeon and cardiologist be involved from the start? And having
them consult intensively about these patients?” This is possible at the new
Center of Circulatory Health of the strategic theme Circulatory Health,
because all these specialists work at one and the same location.
It was organized based on the patients' perspective. That focus not only
applies to care, but also to research. Frank is clear about that. "Patients are
increasingly becoming partners in our research. Their voice and that of their
patient organizations are important for the choice of research we conduct.
That really feels different. But this is a large public debate. Everyone is
thinking about how we can get more from research, have a greater impact.
The logical consequence is that doctors always have to ask themselves
whether they really have the patients and their families on board.
Knowing, captivating and holding on to new talents
"Real changes and innovation in care require more than one specialty.
That is where the strategic themes come in. "They bring more doctors of
all sorts and conditions together, across departments, and teams
consisting of a wide variety of researchers, such as epidemiologists,
geneticists and imaging specialists. When they understand each other,
you can generate real changes."
There are more and more of these cross-disciplinary collaborations in
the hospital. The Jacob Jongbloed Talent Society is a good example.
This successful talent program for young post-graduates was named
16 Circulatory Health Magazine

after the professor who developed the
artificial heart at UMC Utrecht. Rick: "As
strategic theme, we have granted a sum of
money to the participants of this program
to have them draw up a research proposal
together. The common denominator is
their talent. The participants work in
different departments, from very basic to
highly applied research.
That inspires and helps them take further
steps.” Rick emphasizes that he believes
that each strategic theme must pay a great
deal of attention to education and talent
development. "You want to know, captivate
and hold on to these new talents."
“What is more
effective than having
the neurologist,
vascular surgeon
and cardiologist be
involved from the
start?”
Human side
The strategic theme is a key connector
in- and outside the hospital to reach a
common goal: improving human health
and creating the healthcare of the future.
Frank concludes by saying that the
patients' perceptions are extremely
important. "We'd lost sight of that a bit.
But with societal impact as our objective,
we have organized our strategic themes
in such a way that they emphasize this
human side. In care, research and
education.”
Frank Miedema and Rick Grobbee
Our mission: to play a leading role globally in
decreasing the burden of cardiovascular disease.
Our vision for realizing this is:
providing state-of-the-art and patient-centered care,
research and education to prevent and treat
cardiovascular diseases and to improve the quality of
life of patients with such diseases.
Circulatory Health Magazine 17

Facts & Figures
The heart
There are some 1.4 million patients with cardiovascular
disease in the Netherlands.
Heart failure
Heart failure means
that the heart cannot
effectively pump blood
through the body. Every
year, about 40,000
people receive the
diagnosis heart failure.
53% of them are
women, 47% are men.
Stroke is a collective
term for TIA, cerebral
infarction and brain
hemorrhage. Every year,
some 41,000 people
suffer from a stroke.
That's about 113
people every day.
Weight
Over half of the Dutch
population is overweight.
Over 10% of them are
morbidly obese. A healthy
weight reduces the risk of
cardiovascular disease.
Aneurysm
About 300,000 people in the
Netherlands have a brain
aneurysm, a dilated artery in
the brain.
High risk: femalespecific
factors
1 in 4 women in the
Netherlands dies from
cardiovascular disease.
Every day, 306 women are
hospitalized because of a
cardiovascular disease.
In the Netherlands there
are approximately
670,000 women with a
cardiovascular disease.
In the Netherlands
57 women die from
cardiovascular disease
every day. That is more than
two women every hour.
The heart is a
pump that pumps
around 4 to 5 liters
of blood per
minute. The blood
contains oxygen
and nutrients for
all muscles and
organs.
Exercise reduces the risk
of cardiovascular disease
Exercise at least 2.5 hours
a week with moderate
intensity. For example, go
cycling or walking a few
days a week. Do activities
that strengthen your
muscles and bones at least
twice a week.
18 Circulatory Health Magazine

Blood vessels
An adult has 5 to 6 liters of
blood in their body. The heart
circulates this blood in a
vascular system.
Every year, 20 million
people around the world
die from cardiovascular
disease. Between 1990 and
2015, the mortality rate
increased by about 50%.
Blood vessels distribute the blood from the heart throughout the
body. The total length of all these blood vessels is 100,000 kilometers.
High risk: diabetes
Over 830,000 people in the Netherlands know they have
type-1 or -2 diabetes. It is estimated that another
200,000 people have type-2 diabetes without being
aware of it. Diabetes patients run a greater risk of
cardiovascular disease, such as a heart attack, heart
failure or a stroke. That risk is slightly greater in women
than in men.
High risk: blood pressure
1 in 3 people in the Netherlands
has high blood pressure; among
the over-60s, this is 2 out of 3.
High blood pressure increases
the risk of cardiovascular diseases
and kidney damage.
Over 100 principal investigators are active in the
strategic theme Circulatory Health, which has already
resulted in over 9,000 publications, and about
50 doctoral degrees every year.
Approximately
1 in
6 patients
in UMC Utrecht
has a cardiovascular
disease.
1 in
4 patients
with cardiovascular
disease receive care
from more than one
specialist (cardiologist,
vascular surgeon,
internist, vascular
physician,
neurologist).
Circulatory Health Magazine 19

20 Circulatory Health Magazine
Baukje van Dinther and Katrien Groenhof

Wealth of data in
Utrecht Cardiovascular Cohort
In healthcare, we collect a lot of data that we do not or hardly use for scientific
research. This changes with the Utrecht Cardiovascular Cohort (UCC). Baukje
van Dinther (manager UCC) and Katrien Groenhof (PhD student UCC) tell us
more about this.
Baukje, what is the UCC?
"The UCC is a collaboration of all of
the departments at the UMC Utrecht
that treat patients with a cardiovascular
disease or a risk factor for it.
We combine healthcare and scientific
research. For the UCC, we collect the
same data on all patients, regardless of
specialty. We adhere to the current
Dutch guidelines for cardiovascular risk
management. Because of the UCC, we
have a risk profile for cardiovascular
disease for each patient, which can
then be used for care. With the
patient's consent, we collect extra
blood for (future) scientific research.
That enables us to monitor the patient
over time. The UCC is about the
improvement of cardiovascular care in
the broadest sense of the word. It is
supported by the divisions that
participate in the strategic theme and
by ZonMW."
What does your work day look
like, Baukje?
"I facilitate the UCC at UMC Utrecht.
Facilitating this centrally, enables
uniform registration of the collected
healthcare data and the informed
consent. To that end, I talk to a lot of
people every day.” Katrien: "From
secretaries to professors, you connect
them all."
Preventing and treating
cardiovascular diseases can
be further improved if we use
medical data and
measurements from patient
care in our scientific research.
That is why UMC Utrecht set
up the Utrecht Cardiovascular
Cohort (UCC), a collaboration
of all departments and
divisions in the strategic
theme Circulatory Health.
What answers will the UCC be
able to provide?
"Healthcare professionals ask patients
for broad-ranging informed consent,
suitable for a wide range of research
questions. These questions are taken
from practice, such as the questions
Katrien is working on. It is good that
you came, Katrien, it really gives the
UCC a boost. As Katrien uses the data
and assesses the quality, it is also
possible to make improvements at an
organizational level. The data of the
UCC are from and for all specialties.
Everyone with a question to be
answered can use them. So if you have
a research question: let us know!"
(www.umcutrecht.nl/UCC)
Katrien, how long have you been
working for us?
"I was hired a year ago as a PhD
student at the UCC. In short, my thesis
is about improving care for
cardiovascular patients. These patients
see various specialists: cardiologist,
endocrinologist, geriatrician,
gynecologist, nephrologist,
neurologist, vascular surgeon and
vascular internist. And at different
times in their lives, from being a
pregnant woman to an elderly patient.
The UCC ensures that data on all these
patients are collected in the same
manner, which makes it easier to
discover differences and similarities
between them. Using the data
collected in the UCC, I can see how
effectively the LDL cholesterol ('bad
cholesterol') of our patients is treated
or how important family history is for
predicting cardiovascular diseases."
What is the aim of your research?
"Cardiovascular diseases do not end on
the threshold of one specialty or even
of the hospital. Cooperation is vital,
both in daily care and in scientific
research for the future. This project
facilitates that. That's why I think the
UCC is great!"
Circulatory Health Magazine 21

The Utrecht
Cardiovascular
Cohort (UCC) was
set up in 2015 and
is a growth model
Since the start:
Candidates invited:
4400
All information
on hand in the
consulting room
Number of people
seen: 3100
Informed consent:
1700
No informed consent:
1400
"The risk of getting a cardiovascular disease within ten years, is x percent. And with this
medication and quitting smoking, your risk will decrease significantly." This is how the
conversation between the patient and doctor may go in the consulting room, with
both looking at a dashboard together. The dashboard illustrates how treatment and a
change in lifestyle could benefit the patient's health.
EDEN is the name of the application created under the
supervision of cardiologist Folkert Asselbergs. The
application presents a single overview of all of the patient's
risk factors, linked to a personal risk score of getting a
cardiovascular disease within the next ten years.
"Getting at the best treatment and lifestyle together with
the patients - that's my aim," says Folkert. "To that end
digital support can be useful. Little exercise, age, smoking
and high blood pressure are examples of risk factors.”
There are numerous guidelines for all risk factors. Moreover,
there are different studies and new insights for each
guideline. Doctors know this, but do not immediately have
all data on hand in the consulting room. This application –
currently in HiX (electronic health record) – contains all the
up-to-date guidelines linked to the situation of each
individual patient, their weight, age, cholesterol values, etc.
EDEN shows patients at a glance, in a single overview
dashboard, what you're talking about, plus their personal
risk score."
22 Circulatory Health Magazine

"Not just for
myself
but for
everyone"
For the past year, Anja ter Avest (62) has
received treatment at the UMC Utrecht
for her high cholesterol level and an
abnormal cardiogram. During that period,
she participated in three scientific studies,
including the Utrecht Cardiovascular
Cohort (UCC). She does not mind doing
this, as she has a medical-biological
background through her studies and
work. "I know it's important to have
biological materials to achieve progress
in science. Moreover, I'm very curious
about how the body works and possible
solutions that are found for medical
problems. Not just for myself, but for
everyone."
"I don’t find it difficult to take part in
research into the risk factors of
cardiovascular diseases. I always look at
the UMC Portal to see the results. I'm
someone who wants to know things, and
preferably a little more than the doctors
want to tell me. When I see a UCC
questionnaire online, I always fill it out
immediately."
Circulatory Health Magazine 23

News reports
Talented researchers
receive scholarships
Scientists Leo Timmers and Jesper Hjortnaes
received a research grant, the Dekkerbeurs
scholarship, from the Heart Foundation. All in all,
13 talented scientists working for Dutch
knowledge institutes received a personal research
grant. The young researchers can use the money
for conducting innovative research into
cardiovascular disease.
Maarten-Jan Cramer is
Friend of the Year
Stichting Vrienden UMC Utrecht has nominated five
employees who have each in their own way
committed themselves to a good cause within the
hospital. According to staff members of UMC
Utrecht, cardiologist Maarten-Jan Cramer deserves
the title Friend of 2017. He has been getting on the
tandem bicycle with patients for years in aid of heart
failure research. An example for others.
Congratulations!
Quitting smoking after cardiovascular
disease extends life by five years
Two new
expertise centers
UMC Utrecht has two new
expertise centers: the
Center for Inherited
Cardiovascular Disease and
the National Expertise
Center for Pseudoxanthoma
elasticum (PXE). Patients can
come to these certified
expertise centers for rare
disorders for diagnostics,
treatment (if possible),
cross-disciplinary care and
assistance. Six to eight
percent of the population in
the Netherlands suffer from
a rare disorder.
Smokers with a cardiovascular disease who quit
smoking on average live five years longer than
non-quitters. And the chance of a next
cardiovascular disease is postponed by an
average of 10 years. This is the result of PhD
research carried out by Johanneke van den
Berg. She conducted a study among almost
5,000 patients with cardiovascular disease, a
third of whom continued smoking after a first
heart attack, cerebral infarction or angioplasty.
Test women who have had
pre-eclampsia earlier for
cardiovascular disease
Women who have had pre-eclampsia
should be tested earlier for cardiovascular
disease. Current practice is that women are
advised to go to their family doctor when
they turn 50. But research by UMC Utrecht
physician Gerbrand Zoet shows that these
women have a greater risk of heart attack or
stroke at a younger age.
Over the past three years, he studied over
160 women who have had pre-eclampsia.
24 Circulatory Health Magazine

UMC Utrecht discovers treatment for PXE patients
UMC Utrecht has discovered an effective treatment for a rare hereditary disease, PXE. Patients with this
disease suffer from calcification of the skin, blood vessels and retina. This can cause skin lesions,
vascular disorders and severe vision loss. Researchers at UMC Utrecht have now discovered that an
existing medicine, etidronate, inhibits calcification.
Collaboration with family doctors
UMC Utrecht regularly consults family doctors about the
organization and methods of the Center for Circulatory Health.
Together, the specialists and family doctors determine who
provides what type of care and discuss developments. This
collaboration enables them to realize innovations and develop
clever ideas to improve patient care: 'the right care in the right
place'.
Large-scale European study into
the best dialysis therapy for kidney
failure
Headed by the UMC Utrecht, a study will
be conducted over the next four years
among 1800 kidney patients to find the
best dialysis therapy. As part of its Horizon
2020 program, the European Commission
has awarded a grant of over 6.4 million
euros to an international consortium
headed by UMC physician Peter
Blankestijn. The researchers intend to
demonstrate that a relatively new dialysis
method, hemodiafiltration, not only
reduces the risk of getting the disease and
dying from it, but also improves kidney
patients' quality of life.
Interactive
e-module 'Life
after a heart
attack'
In the Netherlands, 30,000 people are
hospitalized because of a cardiovascular disease
every year. Patients must then cope with lifestyle
rules about nutrition, exercise and medication
that reduce the risk of a second heart attack. This
information has now been combined in the
e-module 'Life after a heart attack' which patients
can read at their leisure, either in the hospital or
at home. UMC Utrecht and Stichting Vrienden
UMC Utrecht created the e-module together with
the Harteraad patient association.
New man/woman differences found in detecting
heart failure
If you lump together research results for men and women, you
miss relevant information to detect heart disease earlier. This is the
result of PhD research by Aisha Gohar, conducted with support
from the Hartstichting, the Dutch Heart Foundation. She
discovered new difference between men and women with arterial
calcification and heart failure. Moreover, she demonstrates that
man/woman differences are often still ignored in cardiac research.
Circulatory Health Magazine 25

"I feel as if I'm carrying a
time bomb inside me"
Ellen Pauëlsen has dilated carotid arteries. Last week, a scan was done
to see if the aneurysms had grown or shrunk. Professor in vascular
surgery Gert Jan de Borst is a specialist.
26 Circulatory Health Magazine

"How are you doing?," asks Gert Jan. Ellen Pauëlsen
(64) from Hollandsche Rading is being treated by him
for an aneurysm of the carotid arteries on both sides.
Last year, the annual scan was done to check whether
the aneurysms had grown or shrunk over the past year.
"I'm fine," she answers. "I'm happy with the result of the
scan; everything has remained stable. Yet I sometimes
visualize how everything is looking on the inside. And I
feel as if I'm carrying a time bomb inside me."
An aneurysm, or
bulge in an
artery, is a common
disorder. Aneurysm is
one of the four
research themes of
the strategic theme
Circulatory Health.
We provide
customized treatment
and conduct research
into aneurysms in the
brain, carotid artery
and aorta.
Expertise Center
UMC Utrecht became an expertise
center in 2014. Research data on
patients from all over the world are
collected in a database. Gert Jan puts
his patient's mind to rest: "A neck
aneurysm usually does not grow and
the chance that it ruptures is negligible.
Unless a patient has a predisposition
for connective tissue disorders. And
you don't." Ellen wonders if it is
possible that clots will form. "There is
hardly ever any clot formation in
aneurysms in the carotid arteries,"
answers Gert Jan. "Moreover, your
aneurysms are relatively small."
Tinnitus
The disorder is often discovered by
accident. This was also the case with
Ellen. She had tinnitus. The ENT
physician did a scan to find out the
cause. "Of course I was glad that I
didn't have a tumor," she says. But the
scan did expose the aneurysms." She
wonders whether an aneurysm could
cause the tinnitus. "It sometimes
sounds like I can hear my blood flow to
the rhythm of my heartbeat." Gert Jan
tells her that this was studied once in
another patient with tinnitus. In that
case, the carotid artery was closed off
for a short while using a small balloon.
"The patient still heard the swishing
sound," he explains. "So the aneurysm
is not the cause."
Distracted
"How much does your tinnitus bother
you?" asks Gert Jan. "It regularly
hinders me in my activities," says Ellen.
"And it can make me tired and grumpy."
The ENT specialist has told her that a
hearing aid might help. But that's a
decision she prefers to postpone for
now. According to Ellen there also is a
psychological component. She
recounts: "Yesterday, the sun was
shining, and I went out to work in the
garden. I'm a real outdoorsy type.
When the birds are singing and the
bees are buzzing, it doesn't bother me
as much. Then I'm distracted in a
pleasant way.”
Stents
Ellen finds it reassuring to have a scan
every year. She wonders what will
happen if the aneurysms grow. Gert
Jan: "We can operate on the neck to
remove the aneurysm or place a stent.
We are conducting research to
continually improve these stents. To
this end, we make a three-dimensional
image of the neck of an anonymized
patient. We then print a life-like mold
with which we experiment. Is the
newly developed stent flexible and
sturdy enough? Does it stay in place?
Are any blood clots formed when it is
placed?"
Anticoagulants
Ellen comes back to the danger of
blood clots associated with aneurysms.
"Wouldn't it be better to take
anticoagulants, just to be safe?
Because if a clot does form, it might be
too late." Gert Jan explains that
anticoagulants also have drawbacks.
"They can cause a hemorrhage. And in
your case, we don't want to take that
risk." "I feel that I am in safe hands,"
says Ellen. "But it's still a bit scary. At
the same time, you learn to deal with
it. I keep telling myself that there are
worse things in life."
Circulatory Health Magazine 27

Sanne de Jong – University lecturer, Medical Physiology department
Caroline Pham, first-year Master's student of Biology of Disease
"Locking in on promising students"
"I can conduct my own research!"
Sanne de Jong teaches students of biomedical sciences and medicine
with an interest in cardiovascular diseases. These regularly include
people that UMC Utrecht is pleased to train and employ as
cardiovascular researchers or physicians.
How do you do this?
"We not only teach basic knowledge of the cardiovascular system, we
also link it to scientific research, right from the Bachelor's phase. We
have, for instance, developed the elective programs 'Cardiac
pathophysiology' and 'Vascular biology' for our Bachelor's students.
Cardiovascular researchers contributing to these programs are all
involved in current scientific strategic theme research. They give
lectures and mentor students in writing their thesis. This way, we
introduce students to everything that's going on in terms of
cardiovascular medicine from an early stage. That can be very basic, at
cell level, but also translational – such as animal model studies – or a
clinical study with patients.
In the Bachelor's phase, students mainly attend lectures. However,
during their Master's research internship, they are really responsible for
part of the research. This way, they learn in a practical setting how to
conduct research and what it involves. This hands-on involvement in
high-quality scientific research is extremely interesting for these
students. But it's good for UMC Utrecht as well: this way, we can lock in
on promising students early on. And that's important, because we'd love
to welcome them as researchers or physicians. That's why we offer an
attractive curriculum in UMC Utrecht, from the Bachelor's phase until
the rest of their career. It's great to pass on my passion for the
profession to the students. And it's great to see what excellent
cardiovascular doctors and researchers UMC Utrecht trains and retains.”
"As a Master's student, I have the freedom to
develop into a researcher in the discipline of
cardiovascular medicine. During my Bachelor's
in Biomedical Sciences, I designed and set up a
cardiac arrhythmia study. Now, during my
Master's internship, I get the chance to actually
perform this study. Which is great! My tutor is
Marc Vos, Professor of Medical Physiology. His
knowledge and experience in cardiovascular
research has helped me become a good
researcher. I am learning different research
techniques, and there is a lot of attention to
scientific thinking, writing and presenting.
These are important skills for a researcher.
And what's also great is that in cardiovascular
education you are encouraged to do research
abroad. A chance I won't miss for the world! In
January 2019, I will go to Melbourne to continue
developing my expertise in cardiac arrhythmia.
What do I think of this form of education?
Versatile, in depth, and aimed at current
research. The lecturers are specialized in their
disciplines and often involved in scientific
research themselves. As a student, you are in
direct contact with cardiovascular experts. This
delivers high-quality education and helps you
build a scientific network."
28 Circulatory Health Magazine

Elective programs
for students
Julius de Poel, third-year Bachelor's student of Biomedical Sciences
"This basic knowledge means that I'm well prepared"
"Last year, I took two elective programs about
cardiovascular diseases. Both were so
interesting that it made me realize that this is
what I want to do. The lectures are given by
enthusiastic speakers who know a lot about
cardiovascular research, and the lecturers are
always willing to talk to you.
What's also great is that, as a student, you are
free to choose the subject of your research
proposal or essay, which means you can
choose your preferred subject. In my case this
is cardiomyopathy, which literally translates as
'diseases of the heart muscle'. We know very
little about the underlying biological
mechanisms and genetics of these diseases. It's
very interesting to think about what kind of
research could improve diagnosis and
treatment. I think the Bachelor's program
prepares you well for your research internship
during your Master's, which involves at least
one internship cycle in a research group. This
requires sound basic knowledge to help you
understand what you're doing. And perhaps
even contribute ideas. It would be great to find
out after – or maybe even during– my Master's
what the causes of cardiomyopathy could be."
The strategic theme Circulatory
Health supports three elective
programs for Medicine and
Biomedical Sciences students.
The program 'Cardiac diseases:
from cause to treatment' is aimed
specifically at the heart muscle
and related disorders (heart
failure, arrhythmia).
The program 'The role of the
vessel wall and blood flow'
focuses on normal blood
circulation and the effect of
circulatory disorders. The
program ‘Cardiac
pathophysiology’ is aimed at the
molecular basis, prevention,
diagnosis and treatment of heart
disorders.
Talent development is a key theme in
the strategic theme Circulatory Health.
Every year, the strategic theme publishes an
educational brochure for students of
Medicine, SUMMA (Selective Utrecht
Medical Master) and Biomedical Sciences.
www.umcutrechthartenvaatcentrum-onderwijs.nl/
Circulatory Health Magazine 29

Heart failure
due to heart
muscle
stiffness
Cardiovascular disease researcher Hester den
Ruijter studies heart failure in women. "I try to
answer the question of why heart muscle
stiffness affects women more than men."
The signals in women
"Heart failure as a result of a stiff heart muscle is a very
serious disease," explains Hester. "People can hardly
climb the stairs or ride a bicycle and are very short of
breath. This form of heart failure, called diastolic heart
failure, occurs more often in women than in men. At
molecular level, we don't understand – yet – what's
happening. We know far too little, which is why it is
important to prevent the heart muscle from
becoming stiff.
Understanding the risks
Hester wants to find out who runs an increased risk of
heart muscle stiffness. "We have completed a thorough
review of the literature. This showed that there
isn't a single study on the early stages of heart failure
that distinguishes between men and women. We're
also analyzing the data on patients referred to a
cardiology center by their family doctor. We review
ultrasound images, we keep track of who is hospitalized
for cardiovascular disease and who dies from it.
Insight into the risks and the development pathways
toward heart failure in men and women offers a solid
basis for further research into the treatment of heart
failure due to heart muscle stiffness."
"Of course I am curious as a researcher," Hester
concludes, "and I want to know exactly what's going
on. But our research is urgent as well, in that the
prognosis for this form of heart failure is very poor.
There is no effective medication. Less than half the
patients are still alive after five years. Our goal is to be
able to really make a difference for these patients.
1
2
3
4
5
6
7
8
9
pain in the upper abdomen, jaw,
back or neck
shortness of breath
extreme fatigue
dizziness
restlessness
anxiety
pain between the shoulder blades
nausea
vomiting
There are different mechanisms at work in
the cause of cardiovascular diseases in men and
women. High risk (female-specific factors) is one of the
research themes of the strategic theme Circulatory
Health. The research is aimed at discovering
cardiovascular diseases in women earlier, treating it
more effectively and, where possible, preventing it.
30 Circulatory Health Magazine

Four women talk about their heart
"I survived breast cancer, but the chemo
has caused heart failure. I was given an
LVAD, and now I've fortunately gotten a
donor heart.
I hope that research can help prevent
heart damage after chemo in the future."
Hilda van der Veen
"I got the same heart problems as my
brother. It was discovered by means of
a test for hereditary diseases that I have
the hereditary heart muscle disease
PLN. I understand that a test can be
scary, but it can help prevent serious
consequences like mine."
Annette Klinkert
"I encourage women in my environment to go see a
doctor if they run an increased risk of heart
problems. Go to the hospital, have a check-up, and
don't let yourself be told off if age and symptoms do
not exactly match."
Loes van der Veen
"I had high blood pressure for years, but no
drug or treatment helped. The risk of heart
failure kept increasing. I got a new implant in
my carotid artery to lower my blood
pressure. My blood pressure has decreased
enormously, and it has given my life an
enormous boost."
Claire Labberté
"Cardiovascular
diseases are one of
the main causes of
death in women. It's
vital that more
research is done into
the female heart.
That's why I
wholeheartedly
support studies
aimed at discovering
cardiovascular
diseases in women
earlier, treating them
better and, where
possible, preventing
them."
Neelie Kroes
Ambassador of research
into the female heart
Circulatory Health Magazine 31

Big Data @ Heart:
Sharing data and
discovering trends
The explosive growth in the quantity of
digital data in our society is the new
driver of innovation. This also applies to
Big Data @ Heart. "We are living in a
world full of fragmented data files, but
once you share them, you pave the way
for answering clinical questions within a
short time frame."
With his current research, cardiologist
in training and clinical epidemiologist,
Stefan Koudstaal seeks to unravel the
patterns that exist in the years prior to
discovering that patients suffer from
cardiac failure. What are the type of
complaints that prompt them to go see
a doctor? Or what type of medication
have they been prescribed? Stefan:
"We hope to find the answers to these
questions at Big Data @ Heart over the
next few years."
What are these big data exactly? Stefan:
"To us, these are large quantities of data
that are not stored in a standardized
manner. They are basically very rough
data on a lot of patients. They are not
suitable for in-depth conclusions, but
we can use them to look at certain
patterns that help us identify diseases
earlier and treat them better. At Big
Data @ Heart, we study these patterns
using data from Great Britain, Sweden,
Spain and the Netherlands. Data from
Sweden and Great Britain have already
been compared as to the chances of
survival after an acute myocardial
infarction. These were corrected for
how ill patients were when they were
32 Circulatory Health Magazine

Forty-kilometer tandem
ride for research
Stefan remarks that patients are increasingly involved in
research, based on their concerns and questions, and in
crowdfunding. "At special congresses for patients, we
tell them in terminology they can understand what we
have studied. It tells you whether your research
question really addresses the patients' questions. An
example of a study designed together with the patients
is the study aimed at detecting heart failure earlier to be
able to slow it down at an early stage.
admitted to hospital, and showed that
survival rates in Great Britain were far
lower than in Sweden. The fact that this
difference between two countries can
be measured using big data shows that
they are very suitable as a research
method."
Always the same number
"How do we do this? We use electronic
health records. These contain data that
have been standardized for research of
all patients who want to participate." He
gives an example of health records kept
by family doctors in Great Britain,
>
Our UMC Utrecht tandem tour is the perfect time to
discuss the study with patients while we are cycling.
For this June tradition, doctors and patients ride a
tandem together to raise money for heart failure
research. This way, we combine attention to heart
failure and attention to the importance of exercise.
Participants in the tandem tour are the first to learn
about the results of the study they designed together
with Stefan's research group."
Further information on Stefan's study:
https://www.bigdata-heart.eu/
Circulatory Health Magazine 33

where they are a step ahead of the
Netherlands: the diagnostic codes
family doctors enter into the records
can be used directly for research.
"The British government regulates and
subsidizes a lot of this. Every patient
has an identifier, a number that is
always used, for every research
cohort."
Although Stefan and his colleagues
usually do not have highly accurate
data, such as an ultrasound or certain
blood test results, they do always have
information on blood pressure and
medicine use in the health records.
"These are what we target within Big
Data @ Heart. We are essentially a large
international consortium in which
several research groups cooperate.
The ICT companies in the consortium
enable us to compare the data.
Together, we pave the way for
answering the right clinical questions
within a short time frame. It would
make me very proud if we were to
achieve this within the 5-year project
term!"
“We really have global data. Patient data from
these family doctors and cardiologists are all in
these research files."
Rick Grobbee
"When you look at multiple layers, you start to see
the differences"
Rick Grobbee, chairman of strategic theme Circulatory
Health: "We conduct a series of studies, such as Big Data
@ Heart, to try to understand differences between
patients better. We have a relatively effective but also
somewhat simple idea of a patient with cardiovascular
disease. For instance, we use six categories for which we
have ten essential drugs. But when you take a closer look,
there are differences: such as in reaction to therapy, in
prognosis and whether we find a clear risk factor. While
they all are patients suffering from cardiovascular
disease, there is something different behind them all. We
believe that the use of large databases such as Big Data @
Heart will enable us to create a clear picture of smaller
groups. It's the way forward, partly because of new data
analysis technologies."
"It is the strength of the 24 million data in Big Data @
Heart and the diversity in this data that enable us to look
at a patient from different angles. This gives us a
360-degree picture based on the patient's genetic
information, the interaction between genes and the
environment, and the impact of metabolism and
molecules. You only see the differences when you look at
multiple layers."
34 Circulatory Health Magazine

‘Combining forces’
"The strategic theme's ambition is
to be socially relevant for people
with cardiovascular disease. We
make an impact with new
knowledge resulting from
scientific research, specialized
educational programs and a clear
care profile. Together with
healthcare professionals, we want
to offer our care in a serviceoriented
manner and with a high
degree of patient satisfaction.
To achieve this, collaboration with
healthcare professionals in and
outside the region is a key focus,"
says Marco Houterman, program
manager of the strategic theme
Circulatory Health.
The role of the program office is to develop policies for the
strategic theme and facilitate research, care and education.
"We work as a linking pin in the hospital. If we work
together effectively, we can provide high-quality care, for
instance for patients with multiple cardiovascular diseases.
Researchers develop a research strategy together based on
the four research themes: heart failure, aneurysm, stroke,
and high risk. And students can learn about the discipline
of cardiovascular medicine at an early stage.”
Team
"Our committed team works daily on this role. Healthcare
adviser Wendy Gouw-Ellenbroek focuses on extending
the cross-disciplinary outpatient Center for Circulatory
Health. Baukje van Dinther is manager of the Utrecht
Cardiovascular Cohort. Marti Bierhuizen is coordinator of
research/education and focuses on elective programs for
students and supporting research groups of the research
themes. Heleen Romeijn, Marketing & Communication
adviser, is dedicated to positioning and presenting the
Center for Circulatory Health. As program manager, I am
responsible for projects of the program office and
contribute to developing the strategy of our theme.
Reducing cardiovascular disease
"As a driver, facilitator and problem-solver, our team
contributes in its own way to reducing the burden of
cardiovascular disease. That's why we come to UMC
Utrecht every day."
Circulatory Health Magazine 35

Joyce Browne studies high blood
pressure in pregnant women
Around the world, some 350,000 women die during childbirth, labor or the
postpartum period every year. An important cause is high blood pressure during
pregnancy. Research physician Joyce Browne wants to minimize this risk.
High blood pressure in pregnancy can result in
pre-eclampsia, which could put the health of mother
and child at risk. Joyce conducts research among
800 women who are between 26 and 34 weeks
pregnant. She wants to find out whether it is possible
to predict which women benefit from giving birth as
soon as possible when they are ill, and for which
women delivery can be postponed. Every day in the
womb gives the child a better start in life.
Health of mother and child
She performs a second study among 400 women
a year after childbirth. She studies how many of
them still have high blood pressure, as well as the
general health status of mother and child.
She compares the results with those of 100 women
who had a normal childbirth. Joyce conducts the
first study in Ghana, the second in Nigeria. Not
because no pregnant women die from the effects
of high blood pressure in the Netherlands, but
because this happens far less frequently than in
the African countries: 7 out of 100,000 live births,
compared to 340 in Ghana and 814 in Nigeria.
Solid healthcare structure
The second reason for choosing these countries is
that they have a solid healthcare structure. Most
women visit a midwife at least once. Moreover, the
hospitals are fairly well organized, so that Joyce
can carry out her research there and
improvements in healthcare can be implemented.
Joyce works together with local doctors and
researchers. She's had to adapt to their different
cultural backgrounds, but also finds this very
instructive. "There is more of a hierarchy and
people are not as direct. That has made me more
careful. I no longer say: 'I suggest we do this or
this'. That's become: 'Would it be an idea if we did
this or this?'
Joyce expects to present the results of both
studies in 2020. She doesn't yet know what she will
do afterward: "But it will be a job in which I can
continue to make a meaningful contribution to
improving the health situation of women. This
currently matches perfectly with conducting
research."
36 Circulatory Health Magazine

Senior university lecturer Kerstin Klipstein-Grobusch
Global Health: global
insight into
cardiovascular diseases
Contributions to global health for everyone. That's the mission of
the researchers at Julius Global Health. How? By performing
clinical epidemiological research.
By coming up with innovative solutions in healthcare technology.
And by training new generations of professionals in healthcare.
These are the words of senior university lecturer Kerstin
Klipstein-Grobusch. "Global Health looks for new solutions in
the prevention and treatment of diseases, such as cardiovascular
diseases.
Cardiovascular health is a key theme of Julius Global Health research. Does
the development of babies and children affect their cardiovascular health
as adults?
What do we learn when we compare diabetes and cardiovascular disease
and their risk factors internationally? And can we find ways to prevent
cardiovascular diseases and diabetes in high- and low-income groups?
These are the three questions on which cardiovascular research at Global
Health centers. The researchers always take the life-cycle perspective as a
basis: the development from fetus, baby and child into adult.
In the strategic
theme Circulatory
Health heart and blood
vessel health is a key
theme. Our global target
is research and education
in the fields of diabetes
and cardiovascular
disease. Global Health
researchers cooperate
with local and
international partners.
Kerstin explains that there are ongoing projects all over the world aimed at
preventing cardiovascular diseases and diabetes. "Global Health researchers
are involved in studies in Asia/Pacific and Africa, where they work together
with local and international partners. In Oxford, Sydney and other cities,
they conduct research into the effects of gender differences on common
risk factors for cardiovascular disease. Or into the relationship between
ethnicity and the prevention of cardiovascular diseases. In the RODAM
study of obesity and diabetes among African immigrants, researchers
compare Ghanaians with their compatriots in Amsterdam, London and
Berlin. This way, they find out more about the complex interaction between
environment and genetics that plays a role in the development of type-II
diabetes and obesity. Research projects in Asia are aimed at improving the
quality of stroke care in an environment that is lacking resources. And a
study in South-Africa targets changes in the risk of high blood pressure in
the long term in rural and urban population groups."
Circulatory Health Magazine 37

The biological
clock of
the heart
38 Circulatory Health Magazine

Did you know that the cells in our body have a 24-hour
rhythm? And that this internal clock influences such functions
as the regenerative ability of cells? Cardiologist Linda van
Laake studies this fact and all of its implications. "There are
indications that cardiac cells can handle a lack of oxygen
better in the afternoon than in the early morning."
Not only people, but also animals, plants and
individual cells in our body - even when they
are isolated on a Petri dish - appear to live by
this 24-hour rhythm. A greater understanding
of that rhythm could have a major impact for
the medical world.
Linda: "Heart cells appear to have a fixed
circadian rhythm. Simply speaking, you could
say that they are active during the day and
rest in the evening. This could mean that the
regenerative ability of cells, for instance after
surgery, could also vary depending on time."
Internal clock
There is a lot we don't know yet about this
'internal clock', but researchers suspect that
the body prefers to perform certain tasks, such
as repairing cells, at times that it does not have
to be on stand-by for sudden action, such as
running to catch a train. In some diseases, this
circadian rhythm becomes unbalanced. This
appears to be the case with heart failure, which
decreases the pump function of the heart, after
Heart failure is a
chronic disease,
gradually decreasing
the pump function of
the heart. Heart failure
is one of the four
research themes of the
strategic theme
Circulatory Health. By
doing research, we
want to improve the
detection, prognosis
and treatment of heart
failure.
a heart attack for example.
Linda: "We currently study whether heart failure
can be treated more effectively if you take the
phase of the heart cells into account. This also
provides an opportunity to solve a different
problem: "The 24-hour rhythm and the resulting
differences in cellular activity may explain why
heart failure cannot be cured yet with stem cells."
Stem cells are our body's primitive cells: they
can still develop into all kinds of cells, such
as blood, skin or heart cells. Scientists have
been trying for years to repair the piece of
heart muscle that has died after a heart attack
using these stem cells. But that appears to be
more difficult than we thought. "My focus is on
improving the heart muscle cells cultured from
stem cells using the 24-hour rhythm. In other
words: transplanting the cells when they are
in their 'optimal phase' in terms of therapeutic
properties. Or manipulating them to make this
optimal phase continuous."
Early days
While it is still early days for this research, the
results so far are promising. Linda emphasizes:
“It is important to realize that there are circadian
rhythms. If we can work them out and adjust
medical treatment to them, we stand to gain an
advantage."
Circulatory Health Magazine 39

Pieter Doevendans
> Linda van Tellingen
Cross-disciplinary outpatient
Center for Circulatory Health
> Esther de Haan
> Suzanne Elstgeest-Grootenboer
40 Circulatory Health Magazine

"This is the
healthcare of
the future”
Nurse practitioner:
for the best care as
well as service
“My colleagues and
I are the linking pin
in patient logistics"
Pieter Doevendans Linda van Tellingen & Esther de Haan Suzanne Elstgeest-Grootenboer
"We're here for the patients," says
Pieter Doevendans, Professor of
cardiology and responsible for
care within the strategic theme.
"In addition to providing the best
possible care, it's the experiences
of our patients that counts. They
must be seen by different
specialties and disciplines within
a few hours and have to feel
comfortable with that.
A pleasant patient experience and
improving the quality of care,
these are the main goals of the
cardiovascular outpatient clinic,
says Pieter. "We work with
different specialists, such as
internal medicine, vascular
surgery, neurology and cardiology.
It is essential that we use uniform
guidelines, which can differ
significantly for the individual
specialties. But with the outpatient
clinic that's a thing of the past,
which also benefits science.
Providing this much care within
such a short period of time hinges
on the logistics. Logistics must be
perfect, so that we can effectively
collect all data and draw up a
treatment proposal together. In
addition, patients must be
included more in science, for
instance so that their DNA can be
used for other genetic
cardiovascular research. The times
that a patient would go from
consulting room to consulting
room and specialists would
determine what happens, are over.
In the multidisciplinary outpatient
clinic, focus is on the patient: this
is the healthcare of the future.”
Even though patients in the
outpatient Center for Circulatory
Health see several healthcare
professionals, they always have a
nurse practitioner as permanent
contact. "We know everything
about every individual patient,"
says Linda van Tellingen.
"They come to us first with their
questions about care and
treatment."
"We conduct the necessary
preliminary work before a patient
visits the specialist," explains Linda.
"I update the medical history." Has
the patient been hospitalized
before, and for what? I review lab
results and identify risk factors. Is
the patient overweight, do they
have a high blood pressure, do
they smoke? To sum up, we focus
on risk management. Because all
patients who enter these doors
have one thing in common: they
are either already suffering from or
run a high risk of cardiovascular
disease. In addition to curative
treatment, we also pay a lot of
attention to prevention."
Nurse practitioners also monitor
cross-disciplinary cooperation.
Linda: "When I notice during triage
that we need a cardiologist in
addition to the vascular surgeon,
I see to it that the cardiologist is
available the same morning. It's
key that patients here receive the
best care as well as service."
From aneurysms and heart failure
to vascular claudication: the
outpatient Center for Circulatory
Health sees different patient
groups for a combination of
specialties. The team of medical
assistants ensures that patient
logistics run like a well-oiled
machine. "Patients must be able
to have all necessary
examinations and interviews
within half a day, like an express
train," says medical assistant
Suzanne Elstgeest-Grootenbroer.
"The process starts with
registration of the patient by the
family doctor," Suzanne explains.
"Or by a specialist in our or an
external hospital.
The referral is assessed by the
attending physician. They
determine which examinations and
appointments with other
specialties are necessary. My
colleagues and I are the linking pin
in the process of a patient's visit to
the clinic. Teamwork is vital for
this. We receive the patient and
answer any questions they may
have. But we also measure blood
pressure, if necessary, and the
pressure in the ankle and arm, the
so-called ankle-brachial index, in
preparation for the consultation
with the doctor. We also arrange
everything concerning wound
care, from A to Z. And after the
consultation, we conclude the visit
to the clinic and schedule a
follow-up appointment. All in all,
the medical assistants are involved
in the entire outpatient process.”
Circulatory Health Magazine 41

“This daily
check-up
reassures me”
Every morning, patient Alfred Hagedoorn places
his upper body on a special pad that connects to
the sensor implanted in his pulmonary artery. That
sensor measures the pressure and the results are
sent directly online to his cardiologist at UMC
Utrecht. "It feels safe to be checked at home every
day and receive feedback from the hospital. It
reassures me."
In the spring of last year, Alfred had been short of
breath for a while. He also suffered from dizziness.
"I used to swim intensively every week. Until it went
wrong in September: I thought I was choking. I had
cardiac asthma, which means that leaking heart
valves had weakened the left part of my heart to the
extent that it could not process fluid sufficiently. This
caused my lungs to fill up. I was hurried to UMC
Utrecht by ambulance. After a few very scary
breathless episodes, mitraclips were implanted
through a groin catheter. These reduce the leaking
of the heart valves. My health improved, but it wasn't
optimal yet. In December, things went wrong again.
I had cardiac asthma again and was rushed to UMC
Utrecht. It turned out that because of the leaks in
the heart valve, the two halves of my heart were no
longer working synchronously. To remedy this, it
was decided to implant a CRT-D pacemaker to
synchronize the two ventricles. I really feel a lot
better now."
Computer in a pad
Alfred also had a CardioMEMS HF system implanted,
a miniature sensor in the pulmonary artery that
directly measures pressure. When heart failure
worsens, pressure in the pulmonary artery increases.
Alfred: "I have a trolley at home, with a computer in
a pad. I lie down on this every day; a voice tells me
whether I'm positioned correctly. Information about
the pressure in my pulmonary artery is sent through
the implanted miniature sensor to the cardiologist.
This means I don't have to go to hospital as often,
while at the same time my doctor can react quickly
if necessary. I'm only called when adjustment is
necessary. I've had the system for two months now,
and I'm called about once every two weeks, when
the pressure appears to be too high and my
medication is adjusted. This immediately prevents
my heart failure from getting worse. With the attacks
that I've had, this daily check-up is reassuring, for me
and my family."
42 Circulatory Health Magazine

A patch against a
stroke?
Every year, some 41,000 people in The
Netherlands have a stroke. This can be a
cerebral infarction or a brain
hemorrhage. A cerebral infarction is
caused by a clot that closes off a blood
vessel; a hemorrhage is caused by a
bursting blood vessel. Neurologist Bart
van der Worp: "Fortunately, new
treatments have greatly improved the
prognosis for a brain infarction in recent
years. Injecting an anticoagulant within
4.5 hours can prevent a lot of brain
damage. In addition, the clot can
sometimes be removed through a
catheter in the groin. The earlier you
intervene, the better the prognosis."
Stroke is a collective term for TIA,
cerebral infarction and brain hemorrhage.
Stroke is one of the four research themes of
the strategic theme Circulatory Health. We
study how we can improve treatment
methods to reduce or eliminate the
consequences of a stroke.
Patch
Unfortunately, only a small percentage of patients reach the
hospital in time to get the anticoagulant, and the clot can
only be removed in 10% of patients. "We are looking for
complementary treatment," says Bart. One of the options is a
nitroglycerin patch applied by ambulance staff.
We started a trial in April: MR ASAP.
Nitroglycerin has a vasodilating effect. Bart hopes that this
means that patients with a cerebral infarction reach the
hospital in a better condition. It also lowers the blood
pressure, which may help in the event of a brain hemorrhage.
Cheap and safe
One medication for two different causes of a stroke - that
almost sounds too good to be true. Bart thinks so too. "Two
small-scale British studies have shown that the results appear
to be favorable," he says. "We hope to be able to confirm this
with this larger study."
Nitroglycerin has been used as a medicine for over 100 years.
It opens the coronary arteries in case of an imminent heart
attack. Van der Worp: "It's also used in mining, to blast rock.
But that requires several kilos, compared to only milligrams
used in our research. In the clinic, nitroglycerin is cheap and
safe. The damage following a stroke is usually very debilitating.
We hope the patch limits the damage."
Circulatory Health Magazine 43

Neurologist in training Annemijn Algra
Aspirin: more than just a painkiller
Patients with a cerebral infarction or a precursor
of this disease should immediately take aspirin,
says clinical epidemiologist Ale Algra. He has been
researching this drug throughout his career.
And his interest has passed to his daughter
Annemijn.
One of the ingredients in aspirin is salicin, a substance
originally produced from willow. It has an antifebrile
and analgesic effect. The Greek doctor Hippocrates
(approx. 400 BCE) already prescribed potions made
from willow bark to counter pain. It had a bitter taste
and patients would get stomach aches. In 1897,
synthetic salicin was produced for the first time and
made into the medication 'aspirin'. "A weird and
wonderful medicine," says Ale. "It does not only work
as a painkiller, it is also a platelet aggregation inhibitor,
preventing platelets from sticking together to form
clots that enter the bloodstream."
Blood clot
A blood clot may be caused by diseases such as
atherosclerosis, or hardening of the arteries. The body
sends platelets to the damaged vessel wall to repair it.
These platelets clot together. "Sometimes a piece of a
clot breaks away," explains Ale. "If this occurs in the
carotid artery, it travels to the blood vessels of the
brain. The longer the blood flow is interrupted, the
greater the risk of severe brain damage."A small clot
causes a TIA, a transient ischemic attack, with
temporary symptoms of weakness and numbness.
"A TIA is often a warning of a much more serious
infarction," says Ale. "The likelihood of a recurrence is
greatest during the first days after a TIA or cerebral
infarction."
Not tomorrow, but today
Patients who run an increased risk of clots are
prescribed aspirin for life. But Ale discovered that
taking aspirin is most effective immediately after a TIA
or cerebral infarction. In low doses: preferably 75 mg.
Together with his colleague from Oxford, Prof.
Rothwell, he recently published his findings in the
medical journal The Lancet. Ale: "The earlier you take
aspirin, the greater the chance of preventing another
infarction. Do not wait for the doctor. No. Take aspirin
44 Circulatory Health Magazine

Clinical epidemiologist Ale Algra
immediately." This recommendation was included in
the protocol for strokes last year. Incidentally, this
advice has been in place for much longer for people
who had a heart attack. Ale: "We always have a box of
aspirin in the kitchen cupboard."
Drawbacks
But aspirin also has its drawbacks. As the medication
makes platelets less 'sticky', there is a greater risk of
internal bleeding, particularly in the stomach and
intestines. So everyone who takes the medicine daily
and has an increased risk of bleeding is also
prescribed a stomach protector. Moreover, the
symptoms of a cerebral infarction – such as face
drooping, trouble speaking, paralysis of the arm –
may also be the result of a brain hemorrhage; only a
scan can provide certainty in the event of 'a stroke'.
Aspirin is counterproductive for a brain hemorrhage.
Ale: "The risk of a hemorrhage is much smaller than
that of an infarction. Moreover, a single aspirin does
not do a lot of harm in case of a brain hemorrhage."
Cancer prevention
The passion for aspirin has passed from father to
daughter: Annemijn Algra is neurologist in training
and performed a literature review into the effects of
aspirin. Annemijn: "Research with Professor Rothwell
shows that people who take aspirin develop fewer
tumors and that mortality among them is lower. I also
found evidence for this in the literature. Aspirin
reduces the risk of all types of cancer by almost 20%;
for intestinal cancer this is almost 50%. It is still too
early for a theory to explain this, but a possible
mechanism could be that aspirin prevents metastases.
Some guidelines recommend that people in their 50s
take a low dose of aspirin every day by way of
preventive medication.”
Two-by-two
A father and daughter who both work at the UMC
Utrecht and who both have an above-average interest
in aspirin sometimes causes confusion at home.
Annemijn: "I get emails addressed to 'Dear colleague
Algra', or my dad is asked to give consultations."
Annemijn inherited the love for science from her
father. "He used to have all kinds of gauges, to
measure rainfall in his garden for instance. And when
we hiked through the mountains he calculated how
much altitude we had gained per minute. Ale gave me
his two favorite mottos: Keep it Stupidly Simple and
Think two-by-two. You can reduce all your questions
to a single table."
Circulatory Health Magazine 45

A healthy lifestyle is usually the best way of living to
a ripe old age in one piece. Some people must take
medication to prevent cardiovascular diseases in
addition to living a healthy lifestyle. But for whom
are they useful?
46 Circulatory Health Magazine

U-Prevent
Smart website
about
customized
medication
internist in training
Jannick Dorresteijn
and Professor
in vascular medicine
Frank Visseren
In the event of cardiovascular disease or a risk of cardiovascular disease, treatment
comprises of not only adopting a healthy lifestyle, but also anticoagulants,
anti-hypertensives and cholesterol-lowering products. Internist and professor in
vascular medicine Frank Visseren and internist in training Jannick Dorresteijn treat
patients in the outpatient clinic. "We know from large-scale studies that they are very
effective and safe medicines," says Jannick. "But the medication is fitted for the
average patient and does not work as effectively for everyone."
Old-fashioned
According to Frank, even though we are living in 2018, we are still practicing very
old-fashioned medicine. "Just imagine," he says. "A large-scale study shows that a
patient group gets 30% less cardiovascular disease when using a certain medicine.
That's an average figure, based on the results of tens of thousands of patients. We
then prescribe this medication for the entire patient population. Because we don't
know in advance who will benefit from it and who won't. We also don't yet recognize
the patients for whom it would be useful to lower blood pressure and cholesterol to
below the target values. And that's a shame, because you'd want to intensify
treatment for this group."
U-Prevent
"We must do better," Frank and Jannick thought about nine years ago. The result is
U-Prevent, a smart website that calculates exactly how much an individual patient
will benefit from medication to prevent cardiovascular diseases.
To create the website, they analyzed data from various large-scale international
research cohorts and trials. Frank: "We use our Utrecht SMART cohort and work
together with researchers in the Netherlands and abroad. We now have access to
data from more than a million patients, for whom all kinds of measurements have
been performed for these studies. We also know how they did over five or ten years'
time. And that's a veritable treasure trove of information."
Calculation models
Together with professor Yolanda van der Graaf of the UMC Utrecht Julius Center,
they made several algorithms of these enormous quantities of individual data, using a
heavy-duty computer. These algorithms constitute arithmetical models that can be
used in practice. Jannick: "We converted these into an attractive and practical
application that healthcare professionals can use as soon as they consider
prescribing preventive medication. They can use it to predict and show the effect of
the medicine for this individual patient: "If you take this medication, you will >
Circulatory Health Magazine 47

postpone a heart attack or stroke by an average of three years. If you combine this
with a second medicine, the expected gain is as much as five years."
Revolution
According to Frank, the availability of this type of big data will trigger a revolution in
medicine. "It enables us to very accurately predict the effect of drugs in individual
patients," he says. "We can even make life-time predictions: this is the effect if you
use this drug until you're 85." According to the two internists, it is becoming
increasingly important to make a better individual assessment when prescribing
medication. Jannick: "For instance, there are new cholesterol-lowering drugs and
anticoagulants that are more effective, but that can also entail more risks and higher
costs. You'd want to prescribe them to the right patients."
Healthy lifestyle
Can U-Prevent also be used to measure the effect of a healthy lifestyle? "No," says
Frank. “Because a healthy lifestyle is good for everyone. A healthy weight, more
exercise, no smoking. That's the first step. Smoking in particular is a key factor. Only
when everything has been done in terms of a healthy lifestyle will U-Prevent come
into view. Incidentally, there are also people who have a very healthy lifestyle but
nevertheless benefit greatly from drugs that reduce the risk of cardiovascular
disease. We can show this effect. For patients with or without cardiovascular disease,
with or without diabetes, for young and old.
A real difference
Jannick has noticed that many doctors in the outpatient clinic give their patients
comprehensive information about the potential adverse effects of drugs. "But they
never discuss the advantages as comprehensively," he says. "Perhaps because there's
so little they can be certain of." Opting for medication may mean you have to take it
for life and visit a specialist for a check-up occasionally. Jannick: "That's why it's good
that we show patients what the effects of treatment will be. Many people do not
realize that medication increases their chances of staying healthy until they're old.
For everyone all over the world
U-Prevent is expected to be available from July 2018. On the internet, in
different languages and accessible for everyone all over the world. Frank:
"We created the website with support from the Heart Foundation and ZonMW.
We want to generate added social value with it, which matches the philosophy
of science in transition.” The developers have every confidence in the future
of U-prevent. Jannick: "It can be used by family doctors, nurse practitioners,
cardiologists, internists and all kinds of other specialists. And by patients
themselves, if, once they're back home, they want to check in peace and quiet
what exactly the doctor said."
The Netherlands has some 1.4 million patients with
cardiovascular disease.
The strategic theme Circulatory Health pays a lot of attention to
prevention of cardiovascular diseases and performs research into risk
factors and healthy lifestyle to enable us to prevent the risk of
cardiovascular disease even better.
48 Circulatory Health Magazine

Imaging of
heart failure
Faster, more detailed and more patient-friendly cardiac
MRI imaging. That is what professor of cardiovascular
radiology Tim Leiner wants to achieve with his study of
new techniques for optimal imaging of heart and blood
vessels. "So that we gain insight into heart failure -
which, unfortunately, is still a poorly understood
disorder - and treat patients better."
When we refer a patient to the cardiologist, they usually
do an ultrasound of the heart. "This already tells us a lot
about the heart and blood vessels," says Tim. "But
sometimes it is not enough to make a diagnosis. The
cardiologist needs a better picture and requests a
cardiac MRI from radiology." To do an MRI of the heart,
the patient is injected with contrast agent and lies on
the MRI table for about an hour, so that the radiologist
can produce all images needed to answer the clinical
questions. Tim: "We may be looking for a disorder of
the heart valves, coronary artery disorder or genetic
disorder. Or diastolic heart failure, which is when the
heart muscle does not relax enough during the resting
phase of the heart. This mainly affects women."
New MRI technology
At UMC Utrecht, we use the latest, state-of-the-art MRI
equipment, says Tim. "Better than this is not possible -
at this time. So what we envisage for our research must
still be built. To this end, we work closely together with
cardiologists - from other UMCs - as well as
technological companies. Together, we want to develop
new MRI technology with which we can make images
of the heart and blood vessels more quickly, in much
less time than one hour. We also want to make more
detailed images, such as images of heart muscle fibers.
That will enable us to detect the early stages of diastolic
heart failure sooner and treat it more effectively. MRI of
the heart plays an increasingly important role in
detecting and determining the severity of heart failure
and, consequently, in treating it."
Circulatory Health Magazine 49

He has a heart of gold I mean it from the bottom
of my heart Doing something
with heart and soul It breaks my heart
A man after my own heart I have everything
my heart desires Find it in your heart to
forgive Her heart is in the right place Wearing your
heart on your sleeve Stay close to your heart
My heart is not in it Home is where the heart is
She holds a special place in my heart
Losing your heart to someone
Have a heart-to-heart Out of the goodness of my heart
Letting your heart rule your head My heart
skipped a beat Putting your heart at rest
50 Circulatory Health Magazine

Colophon
Publication 2018
PUBLISHED BY
Strategic theme Circulatory Health, UMC Utrecht
EXECUTIVE EDITORS
Rick Grobbee, Marco Houterman, Bas Kooman,
Elke Lautenbag, Heleen Romeijn
DESIGN
Barbara Hagoort,
marketing & communication, UMC Utrecht
IMAGE COORDINATION
Jelle Westerhoff,
marketing & communication, UMC Utrecht
TEXT
Sigrid Dekker, Riëtte Duynstee, Karin Fleuren,
Sandra Genet, Lonneke Homfeld, Elke Lautenbag,
Heleen Romeijn, Marjon Waller
PHOTOGRAPHY
UMC Utrecht, marketing & communication:
Erik Kottier, Thirza Luijten, Ivar Pel,
Ed van Rijswijk, Rogier Veldman
ILLUSTRATIONS
Thinkstockphotos.com
PRINTING
De Bondt grafimedia communicatie, Barendrecht
CIRCULATORY HEALTH PROGRAM COMMITTEE
Rick Grobbee, Gert Jan de Borst, Pieter Doevendans,
Tim Leiner, Folkert Asselbergs, Yvonne van der Schouw,
Frank Visseren and Bart van der Worp
CONTACT
Marco Houterman, program manager
Strategic theme Circulatory Health
Room number Str. 5.109, internal mail number Str. 6.131
T +31 88 75 593 84
E hartenvaten@umcutrecht.nl
www.umcutrecht.nl

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