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European Perspectives
Circulation. 2013;128:f133-f138
doi: 10.1161/01.cir.0000440722.09306.51
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European Perspectives in Cardiology
Spotlight: Alicja Wolk, DMSc
“A Diet High in Fruits May Help Prevent Many Vascular Diseases,
and This Study Provides Evidence That a Lower Risk of Abdominal
Aortic Aneurysm Will Be Among the Benefits”
Copyright 2012
Stefan Zimmerman
A
Alicja Wolk, professor of nutritional epidemiology and head, Nutritional Epidemiology Unit
and coordinator of 5 units of Epidemiology and Biostatistics, Institute of Environmental
Medicine, Karolinska Institutet, Stockholm, Sweden, talks to Mark Nicholls.
licja Wolk, DMSc, is professor of
vascular diseases, and this study
nutritional epidemiology and
provides evidence that a lower risk
head, Nutritional Epidemiology Unit,
of abdominal aortic aneurysm will
and coordinator of 5 units of Epibe among the benefits.”
demiology and Biostatistics, Institute
Professor Wolk’s interest has
of Environmental Medicine, Karoalways been in preventive medicine
linska Institutet, Stockholm, Sweden.
and the study of modifiable lifestyle
risk factors related to major chronic
She is a passionate advocate of health
diseases, not only cardiovascular
promotion and prevention and the last
diseases, but also cancer, osteoporoauthor of a recent article in Circulation titled, “Fruit and Vegetable Professor Wolk with her PhD student, Nicola Orsini sis, obesity, age-related cataracts, and
(left), when he received the national prize for the best
preterm mortality. “These healthConsumption With Risk of AbdoPhD thesis in epidemiology in Sweden in 2009. Photominal Aortic Aneurysm,”1 which graph courtesy of Agneta Davidsson Ohlson.
related factors include diet, drinking
investigated fruit and vegetable conof alcohol, smoking, physical activsumption and the risk of developing abdominal aortic
ity/inactivity, and body weight,” she explains. “The comaneurysm among the prospective Cohort of Swedish Men of
mon denominator for all of them is that they are behaviour44317 men that Professor Wolk established, and the Swedish
related and thus can be changed, in contrast to our genetic
Mammography Cohort of 36109 women. Professor Wolk
characteristics.”
says, “In this prospective, population-based cohort study of
>80000 men and women, consumption of fruit but not veg“A Combination of Simple Healthy Behaviours Can
etables was inversely associated with the risk of abdominal
Prevent ≈77% of Myocardial Infarctions in Women,
aortic aneurysm. The reduction in risk associated with the
but Only 5% in Our Study Population Had All 5
disease was more pronounced for ruptured than non-ruptured
Healthy Behaviours Simultaneously”
abdominal aortic aneurysm. This is the first prospective study
Professor Wolk investigated type 2 diabetes mellitus for her
to report associations of fruit and vegetable consumption sepDMSc thesis in the Division of Cardiovascular Epiarately with risk of non-ruptured and ruptured abdominal aordemiology, Warsaw, Poland. She then moved to Sweden to
tic aneurysm. A diet high in fruits may help prevent many
work as a postdoc at the Karolinska Institutet before taking
On other pages...
Funding: French
Federation of
Cardiology—Teams
Recipients in 2012
describe the research
funded by the grant.
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other phenotype information collected directly
from study participants to good quality
national medical registers, for example, the
Myocardial Infarction Register started in
1964, to obtain information about the study
participants’ health status.”
Professor Wolk’s focus at the Karolinska
Institutet was initially cancer, but from 2002
she began her cardiovascular research, which
now takes up almost 60% of her group’s time
and focuses on less-studied areas of cardiovascular disease in relation to modifiable lifestyle
factors, such as heart failure,3 stroke,4 and
more recently abdominal aortic aneurysm.1
Professor Wolk’s most enjoyable article,
which “is also significant from a public health
point of view,” analysed the combined effect
of 5 modifiable risk factors (diet, physical
activity, non-smoking, normal body weight,
Photograph at the residence of the president of Minnesota University during celebraand moderate alcohol consumption) on the
tions to mark the 5th Anniversary of the Frontiers in Biomedical Research
5
Partnership between Karolinska Institutet and Minnesota University in November risk of myocardial infarction in women. She
2012. Professor Wolk says, “I am sitting in the red jacket, the president of the says, “It is fascinating that a combination of
Karolinska Institutet, Professor Harriet Wallberg-Henriksson is in the yellow jacket, simple healthy behaviours can prevent ≈77%
the president of Minnesota University, Professor Eric W. Kaler, is sitting next to our of myocardial infarctions in women, but only
president, and others are professors from Karolinska, Minnesota University, and 5% in our study population had all 5 healthy
Mayo Clinic.” Photograph courtesy and copyright 2012, Tim Rummelhoff.
behaviours simultaneously.”
In terms of other diseases, Professor Wolk
up a temporary 1-year teaching position as a senior lecturer
and her colleagues were the first to find adverse associations
in human nutrition at Uppsala University, Uppsala,
between retinol intake and bone mineral density and
Sweden. This was followed by a position as a researcher at
between long-term dietary cadmium exposure (a recently
Uppsala University’s Cancer Epidemiology Department
proposed endocrine disruptor) and endometrial cancer. Her
where she started her own line of research and established
group was also the first to identify novel biomarkers for the
a research group investigating obesity and cancer in relaintake of dairy fat and whole grains. Professor Wolk has pubtion to modifiable lifestyle factors. Professor Wolk’s attenlished >400 original articles in peer-reviewed medical jourtion turned to cardiovascular diseases when, from 1995 to
nals, which have been cited >20 000 times. “According to
1997, she “deepened her scientific experience” as a visiting
the latest quantitative analysis of mass media (2012), I have
scientist at the Department of Nutrition, Harvard School of
been the most cited professor from Karolinska Institutet,
Public Health, Boston, MA, which led to a significant artinationally and internationally, spreading knowledge about
cle on dietary fibre and the decreased risk of coronary heart
modifiable health-related factors,” says Professor Wolk.
disease.2
Articles by other researchers that have had most impact
Professor Wolk rejoined the Karolinska Institutet in
on Professor Wolk’s work describe the effect of a Medi1997. A substantial research grant support from the Swedish
terranean diet on mortality.6,7 “Those studies, and many
Research Council allowed her to establish a Cohort of
others since, have shown how important the whole dietary
Swedish Men and extended the Swedish Mammography
pattern is, not just single foods or nutrients,” she says.
Cohort. As principal investigator of the 2 cohorts, Professor
Wolk explains that these 2 population-based longitudinal
“I Have Always Been Intrigued by the Big Questions—
(repeated measurements of exposures) cohorts of >110 000
Life and Death and the Fountain of Health,
participants are unique in comparison to other existing
Particularly in a Medical Context of Health
prospective cohorts because of the high response rates and
Promotion, Disease Prevention, and Healthy Aging”
because they are representative of the general Swedish popProfessor Wolk was born in a small town 80 km north-west
ulation. She says, “Moving to Sweden definitely helped
of the Polish capital Warsaw. She trained at the city’s unishape my career as an epidemiologist. Sweden and other
versity and after obtaining a Master of Science degree with
Scandinavian countries are known to be the best places to do
a specialty in human nutrition, she stayed at home for 3
epidemiological research because of the introduction of the
years to raise her daughter Katarina before resuming her
Swedish National Identification Number in 1947, covering
studies for her DMSc.
the total resident population of a country. This number
Research projects in Professor Wolk’s group, as well as
makes it possible to match data about lifestyle factors and
the maintenance and development of their 2 cohorts, are
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funded mainly by external research grants from
major governmental organisations. Her cancer
research work is financed by the Swedish
Cancer Foundation. Professor Wolk has recently
received a 5-year Distinguished Professor
Award at the Karolinska Institutet and is a
member of the Swedish National Committee
for Nutrition and Food Sciences at the Royal
Swedish Academy of Sciences. Professor Wolk
says, “Many inspiring research environments
in Poland, Sweden, and the United States, and
good opportunities in my professional life have
shaped my career. One of the important driving
powers has been my philosophical passion and
curiosity to get some answers for those basic
eternal questions about life (health) and death.
Another extremely important factor was my
unlimited academic freedom. I could move
with my salary where I wanted—the only conProfessor Wolk with members of her research unit. Photo courtesy of Anna Persson.
dition was to do good research.” Professor
Wolk’s high school was named after Marie
Sklodowska-Curie, who has been an inspirational figure in
research profile from studies of middle-aged people to
Professor Wolk’s life. “I was exposed to her work quite
studies of old and very old people and successful aging. In
early, and her achievements, characterised by a deep paswell-phenotyped subjects with a known genetic profile,
sion to research,” says Professor Wolk.
researchers will explore short-term effects of diet on
Professor Wolk lives in Stockholm and is married to
metabolism, enzymes, and gene expression to better underWincenty. Away from medicine, her interests include art
stand the mechanisms behind observed associations and to
exhibitions and concerts, and whenever travelling on busidevelop personalised nutrition/medicine.”
ness, she tries to allow time to visit local museums and exhiProfessor Wolk says, “As a young student, I loved lecbitions. She has a number of relatives in medicine, including
tures on philosophy and history of science. I have always
Katarina, who is specialising in dermatology. She says, “For
been intrigued by the big questions—life and death and the
a career in medicine or any other field of science you have to
fountain of health, particularly in a medical context of
love what you do. You have to be passionate about your
health promotion, disease prevention (both primary and
work. Then you do an excellent job and your career follows:
secondary), and healthy aging.”
it is a natural consequence of your great work. Choose your
work place carefully and then be very engaged.”
References
1. Stackelberg O, Björck M, Larsson SC, Orsini N, Wolk A. Fruit and vegProfessor Wolk aims to further develop and follow up
etable consumption with risk of abdominal aortic aneurysm. Circulation.
her 2 longitudinal cohorts, which from a scientific point of
2013;128:795–802.
2. Wolk A, Manson JE, Stampfer MJ, Colditz GA, Hu FB, Speizer FE,
view, are “extremely valuable.” She says, “When we estabHennekens CH, Willett WC. Long-term intake of dietary fibre and
lished the cohorts, the participants were 40 to 79 years of
decreased risk of coronary heart disease among women. JAMA.
age at baseline, Now the ‘youngest’ are 65 years of age,
1999;281:1998–2004.
3. Levitan EB, Yang AZ, Wolk A, Mittleman MA. Adiposity and incidence
and the oldest will be 100 years of age next year. We have
of heart failure hospitalization and mortality: a population-based prospecaccumulated a lot of information about their lifestyle and
tive study. Circ Heart Fail. 2009;2:202–208.
health status. Longitudinal cohorts are like a good
4. Larsson SC, Orsini N, Wolk A. Long-chain omega-3 polyunsaturated
fatty acids and risk of stroke: a meta-analysis. Eur J Epidemiol.
wine—the older they are, the more valuable they are. We
2012;27:895–901.
will study factors/predictors related to healthy aging.”
5. Akesson A, Weismayer C, Newby PK, Wolk A. Combined effect of lowIn terms of future developments in her field of work,
risk dietary and lifestyle behaviors in primary prevention of myocardial
infarction in women. Arch Intern Med. 2007;167:2122–127.
Professor Wolk comments that the interplay between
6. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a
nature and nurture has not developed as rapidly as she had
Mediterranean diet and survival in a Greek population. N Engl J Med.
hoped in terms of general disease prevention or treatment.
2003;348:2599–608.
7. Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O,
However, she believes that “over the next few decades, perMenotti A, van Staveren WA. Mediterranean diet, lifestyle factors, and
sonalised medicine will transform healthcare, offer the pos10-year mortality in elderly European men and women: the HALE projsibility to improve health outcomes, and have the potential
ect. JAMA. 2004;292:1433–1439.
to make healthcare more cost-effective. We are also movContact details for Professor Wolk:
ing in the direction of studies of epigenetic changes of DNA
E-mail:
[email protected]
related to our diet, lifestyle, and other environmental expoMark Nicholls is a freelance medical journalist.
sures. Furthermore, we are changing our interdisciplinary
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Funding: French Federation of Cardiology—Teams
Recipients of French Federation of Cardiology—Team grants in 2012 describe the research funded by the
grant to Jennifer Taylor, BSc, MSc, MPhil.
T
he French Federation of Cardiology (FFC) has an
annual call for projects to be funded. In 2012, the FFC
awarded 7 grants of ≈€20 000 each to research teams for
the purchase of equipment or to finance the operating costs
of research projects. It also awarded 2 grants of €40 000
each to the Reflection Group on Cardiovascular Research.
The projects are reviewed by a scientific committee of 13
expert cardiovascular researchers and clinicians who work
in different regions of France in a wide range of specialties.
Grants for Research Teams
myotonic dystrophy type 1 mice. The €16 000 grant from
the FFC allowed the purchase of a new patch clamp setup.”
The research also involved Alain Coulombe, PhD, Elise
Balse, PhD, and Frédéric Sebag, MD, from INSERM
UMRS-956, Pierre and Marie Curie University, Paris 6,
Cardio-Metabolism and Nutrition Institute, Paris.
Evaluating the Diagnostic and Prognostic Potentials of
Various Collagen Markers in Heart Failure and
Preserved Ejection Fraction
“The Grant Allowed the Purchase of a New Patch
Clamp Setup”
Dr Bauer with his colleagues. Photo courtesy of Dr Bauer.
Dr Algalarrondo (right) with his colleagues, from left to right: A.
Coulombe, E. Balse, and Professor Hatem, V Algalarrondo.
Photo courtesy of Dr Algalarrondo.
Vincent Algalarrondo, MD, cardiologist, INSERM UMR-S
769, Labex Lermit, Faculty of Pharmacy, IFR141,
University Paris-Sud, Chatenay-Malabry, France, received
an FFC grant towards a research project conducted in 2
INSERM units directed by Rodolphe Fischmeister, PhD,
and Professor Stéphane N. Hatem, MD, PhD. Myotonic
dystrophy type 1 is strongly associated with cardiac
arrhythmias, mainly conduction blocks, and less frequently
with dilated cardiomyopathy. The molecular mechanism is
nuclear accumulation of mutant triplets CTG causing aberrant alternative splicing of pre-mRNAs, but the mechanisms underlying cardiac arrhythmias remain unknown.
In collaboration with Geneviève Gourdon, PhD,
INSERM unit UMR-S 781, and Karim Wahbi, MD, PhD,
and Professor Denis Duboc, MD, Cardiology Division,
Cochin Hospital, APHP, Paris Descartes University, Paris,
France, the group is studying the cardiac phenotype of an
original murine model of myotonic dystrophy type 1 with
constitutive CTG expansion. The study included cellular
action potential recordings and whole cell patch clamp
analysis of ionic current in isolated myocytes.
Dr Algalarrondo says, “Our results highlighted the role
of sodium current alterations in the cardiac phenotype of
Fabrice Bauer, MD, PhD, head of the Heart Failure and
Pulmonary Hypertension Clinic, Cardiology Department,
Rouen University Hospital, Rouen, France, received a
grant to help in a study of the significance of collagen
metabolism in predicting outcome in patients with heart
failure with preserved ejection fraction. He says, “In our
view, the pathophysiological mechanism of heart failure
with preserved ejection fraction is mainly based on
increased left ventricular diastolic stiffness caused by exaggerated collagen accumulation.” From 2010 to 2012, 90
consecutive, acutely decompensated patients were enrolled
in a prospective trial and cardiac collagen was quantified
using imaging procedures and blood samples. This research
is collaborative, conducted by the Cardiology and Radiology Departments, as well as INSERM U1096 in association with INSERM U744 in Lille, France. Collaborators
include cardiologists Bertrand D’héré, MD, and Dimitr
Stepowski, MD; radiologist Jérôme Caudron, MD; Professor Jean-Nicolas Dacher, MD, PhD; head of INSERM
U1096 unit, Vincent Richard, PhD; research technician,
Charlotte Vallet; and Professor Helene Eltchaninoff, MD,
head of the Cardiology Department.
Dr Bauer says, “This work evaluates the diagnostic and
prognostic potentials of collagen markers in patients with
heart failure and preserved ejection fraction. Depending on
the outcome, the ensuing key therapeutic paradigm would
focus on attenuating or activating aberrant collagen metabolism and secondary left ventricular remodelling.”
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Investigating Plasma Aldosterone Levels in Patients
With Implantable Cardioverter Devices and
Occurrence of Sudden Cardiac Death or LifeThreatening Ventricular Arrhythmia After 6 Months
Professor Beygui and his colleagues. Photo courtesy of Professor Beygui.
Farzin Beygui, MD, PhD, MPH, FESC, professor of cardiology and head, Cardiology Research Unit, Caen University Hospital, Caen, France, received the FFC grant for
an investigation of plasma aldosterone levels and lifethreatening ventricular arrhythmia in patients with
implantable cardioverter devices (ALDO-ICD study), a
prospective observational 2-centre cohort study.
Professor Beygui says, “If the hypothesis of the study is
confirmed, plasma aldosterone levels may allow identification of a group of patients at high risk of sudden cardiac
death who benefit from implantable cardioverter devices,
and further support the hypothesis of the benefit of systematic mineralocorticoid receptor blocking in the prevention
of ventricular arrhythmia.”
The study is conducted in Caen University Hospital
(Professor Beygui; Alain Lebon, MD, MS; Paul Milliez,
MD, PhD; Leila Benouda, MD; Sylvie Gibert, BSc) and in
Pitié Salpêtrière University Hospital (Professor Gilles
Montalescot, MD, PhD; Estelle Gandjbakhch, MD, PhD;
Guillaume Duthoit, MD, MS; Francoise Hidden-Lucet
MD; Maguy Bernard, MD; Nicolas Vignolles, BSc), in
association with INSERM UMRS 937, Paris, and the
ACTION academic research group (www.actioncoeur.org).
Advancing Understanding of the Mechanisms of
Action of Rehabilitation and Investigating Possible
Surrogate Markers to Assess the Effects of Training
Professor Cohen Solal (left) and his exercise physiology research
team (right). Photos courtesy of Professor Cohen Solal.
Alain Cohen Solal, MD, PhD, professor and head, UMR-S
INSERM Unit 942 “Biomarkers and Heart Failure” and
head, Cardiology Department, Lariboisiere Hospital, Paris,
received an FFC grant to evaluate the effects of a physical
training programme on plasma biomarkers and arterial system properties in chronic heart failure. The research
involves 150 patients over 2 years and a collaboration with
the Centre for Rehabilitation of la Brie in Villiers St Denis
(Jean-Yves Tabet, MD), the CHU of Besançon (MarieFrance Seronde, MD), and the Rehabilitation Centre Leon
Berard in Hyères (Lamia Tartière-Kesri, MD).
Professor Cohen Solal says, “The effects of rehabilitation on arterial parameters can be studied by tonometry.
Rehabilitation improves pulse wave velocity but no study
has looked at the evolution of these arterial parameters
after rehabilitation in chronic heart failure. This research
will advance understanding of the mechanisms of action of
rehabilitation and investigate possible surrogate markers to
assess the effects of training. It will help promote this inexpensive nondrug strategy in chronic heart failure.”
Validating New Sequences for Cardiac Magnetic
Resonance Imaging
Professor Donal with his colleagues. He says, “As shown in this
photograph, research fellows, radiologists, methodologists, research
nurses, and scientists, work closely together in the same location
at the CHU Rennes (Pontchaillou Hospital). Photo courtesy of
Professor Donal.
Erwan Donal, MD, PhD, professor and cardiologist, Service
de Cardiologie, CHU Rennes, CIC-IT 804, LTSI INSERM
U1099, Université Rennes 1, Rennes, France, received a
grant from the FFC to validate new sequences for cardiac
magnetic resonance. He says, “At our institution, cardiologists, researchers and radiologists work closely together in
clinical practice and for research projects. The present grant
provided the opportunity to install a dedicated pack for cardiology on a research 3T magnetic resonance imaging machine.
In line with the goals of the grant, the group started a
prospective study to quantify the iron overload in the hearts
of patients with haemochromatosis. Professor Donal says,
“We hope to be able to validate the value of T2* for iron
overload quantification in the heart with a 3T magnetic resonance imaging machine and also to demonstrate the sensitivity of deformation imaging to appreciate the mechanical consequences on heart function of the iron overload.
The project involves a close collaboration between a radiology fellow, Anita Kiani, MD, and a cardiology fellow,
Maxime Fournet, MD.”
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Investigating the Use of Allogeneic Mesenchymal Stem
Cells for Ischaemic Heart Disease Patients
Dr Lamirault with his research colleagues. From left to right, front:
PhD student, Mariam Jouni; team leader, Professor Patricia
Lemarchand, MD, PhD; Dr Lamirault; and research engineer,
Virginie Forest, PhD; back row, MSc students, Stéphanie Dirou,
Pierre Teruin, and Julia Paulin; Nathalie Gaborit, PhD; and Karim
Si-Tayeb, PhD. Photo courtesy of Dr Lamirault.
Guillaume Lamirault, MD, PhD, cardiologist and staff
physician, l’institut du Thorax–Cardiology Department,
Nantes University Hospital, Nantes, France, and associate
professor of cell biology, l’institut du Thorax–UMR
INSERM 1087/CNRS 6291, Nantes (headed by Professor
Hervé Le Marec, MD, PhD), received an FFC grant to study
myocardial delivery of cytokine-primed mesenchymal stem
cells for ischaemic heart disease. He says, “Our research
investigates healthy-donor mesenchymal stem cells as an
allogeneic source of stem cells for cardiac repair. We hypothesised that priming these cells from healthy donors with
cytokines before administration to patients could boost their
efficiency for cardiac repair after acute myocardial infarction
and lessen long-term risk of alloimmunisation.” The group
is collaborating with the immunology team of Bernard
Vanhove, PhD (INSERM 1064, Nantes), on this project.
Grants for Reflection Group on
Cardiovascular Research
Studying the Functional Consequences of BAG3
Molecular Variants Associated With Human Dilated
Cardiomyopathy
Department is headed by Professor Michel Komajda, MD]
allows us access to biological materials from patients, most
significantly, DNA samples to identify the genetic causes
of hereditary cardiomyopathy.”
The team recently identified mutations responsible for
dilated cardiomyopathy in the BAG3 gene. BAG3 is a cytoprotective co-chaperone involved in proteostasis. Ms
Korniat’s aim is to decipher the molecular and cellular
mechanism leading from these mutations to the disease.
She is working on the hypothesis that mutation-dependent
impaired BAG3 function leads to proteotoxic cardiomyocyte death. Ms Korniat has carried out in vitro studies on
rat neonatal cardiomyocytes overexpressing BAG3. She is
also working on induced pluripotent stem cells-derived cardiomyocytes from patients carrying the mutant as a complementary, humanised, model. She says, “Identifying the
disease pathway should pinpoint new possible therapeutic
targets to cure this pathology.”
Designing and Validating New Stents
Cécilia Delattre with colleagues. Photo courtesy of Cécilia Delattre.
Cécilia Delattre, PhD student, INSERM U698, Bioengineering for Cardiovascular Imaging and Therapy,
Paris, France, received funding to design and validate new
stents for cardiovascular use. The European programme
“Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort” gathers together 14
labs and companies. Ms Delattre says, “In this context, our
purpose is to design a new stent coating to limit both
restenosis and late thrombosis. Our lab is focused on polysaccharides and particularly their uses for therapeutic and
imaging cardiovascular applications.” The group has prepared a copolymer of dextran and polybutylmethacrylate and
is evaluating its interactions with blood, in particular its
impact on thrombus formation. Ms Delattre is conducting
the work with Caroline Roques, PharmD, PhD, and Didier
Letourneur, PhD, from INSERM U698, and Professor Anne
Meddahi-Pelle, MD, PhD, from Université Paris 13.
Jennifer Taylor is a freelance medical journalist.
Agathe Korniat (5th left) with her research colleagues. Photo
courtesy of Agathe Korniat.
Agathe Korniat, PhD student, INSERM/UPMC UMRS956,
Pitié-Salpêtrière, Paris, France, received a 3-year scholarship
of €60000 to study the functional consequences of BAG3
molecular variants associated with dilated cardiomyopathy.
The project is directed by Eric Villard, PhD. Ms Korniat
says, “Our strong link with clinicians [the Cardiology
Editor: Christoph Bode, MD, FESC, FACC, FAHA
Managing Editor: Lindy van den Berghe, BMedSci, BM, BS
We welcome comments. E-mail: [email protected]
The opinions expressed in Circulation: European Perspectives
in Cardiology are not necessarily those of the editors or of
the American Heart Association.
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