Cardiovascular Research in Finland

Markku S. Nieminen: A review of the development of cardiovascular research and the importance of foundations in Finland.

In this review, I relate my personal experiences on the development of cardiovascular
research in Finland and the importance of foundations as supporters of research.

The known history of heart disease is long. Folk healers have a long history – they used extracts to treat various heart symptoms. Several plant extracts have effects similar to digitalis or a calming effect.

I remember a patient who came to see me in the 1980s. They suffered from ventricular arrhythmia. I ordered a series of basic tests and the results came back showing no issues. I prescribed beta blockers as medication. Some time later, they came back and said that
their condition had worsened and they experienced arrhythmia even more often.

The patient’s history, anamnesis, revealed that the patient had used natural therapies in St. Petersburg. The doctor had prescribed horse chestnut extract, which has a similar effect to digitalis. When taking the extract was interrupted the condition improved as the arrhythmias stopped.


Early cardiovascular research

Advancements in medicine were previously made through trial and error. In terms of heart disease, we were often powerless.

Early cardiovascular research was based on anatomical and pathological studies on the causes of diseases. Major topics included structural heart defects, the anatomical control systems of heart rhythm, valve diseases and atherosclerosis.

Atherosclerosis was described already in the beginning of the 19th century. Perhaps the best-known researcher is German pathologist Rudolf Virchow who described arterial plaques. It was found that they are partly caused by the accumulation of cholesterol on the arterial walls.

Cholesterol absorption was also one of the first research targets in Finland. Karl Kyrklund, a founding member of the Finnish Medical Society Duodecim, studied the absorption of fats in the small intestine. Since then this area of research – fats and cardiovascular disease – is one of the strongest lines of research throughout the history of medicine in Finland.

Duodecim medical journal was founded in 1885. Since its beginning, the journal has published articles on heart diseases and their treatment. In early days, digoxin, or digitalis, strophantin and quinine were already in use. Camphor drops were commonly used for their calming effect.

The technical development of the electrocardiogram, (ECG), in the 1920s revolutionised our understanding of heart disease. ECG helped identify characteristics of acute cardiac attacks in hospitals . The high prevalence of myocardial infarction noted in London was a surprise and attracted the attention of researchers.

A major patient group at hospital emergency clinics suffered from arrhythmia, hypertension and coronary diseases. Cardiovascular research quickly increased. For many decades from the 1940s onwards, research was typically done without separate funding in positions at university hospitals on top of regular duties and during free time.
Forms of support for research gradually began to develop also in Finland.


Finland took its cue from the Americans

American Paul Dudley White was one of the leading researchers in cardiology. He noted that cardiovascular morbidity was a major issue in the United States already back in the early 1900s. He and his colleagues founded the American Heart Association (AHA) in 1924. The aim was to develop research in heart disease and secondly to support heart patients with social issues that they faced, for example when returning to work.

The United States had become an economic power that other countries tried to learn from. AHA’s example showed how investments can be made in research and in the treatment and support of patients. The work of AHA was largely based on voluntary activities for prevention and supporting basic research. American colleagues recognised the high morbidity in the population. The need to develop education and research in cardiology specialty was obvious. The American College of Cardiology was founded in 1949.

Some of the leading clinicians in Finland became familiar with the approaches adopted by the Americans. Professor Pauli Soisalo visited England and the United States already back in the 1930s. Soisalo followed the example of AHA and was involved in establishing Finnish Heart Association (Sydäntautiliitto now called Sydänliitto) in Finland in 1954. The association worked according to the same principles as its American godparent.

Finland was actually one of the first countries to adopt the AHA model. Finnish Heart Association was also given permission to use the heart logo as its symbol.


Heart Foundation and the Finnish Foundation for Cardiovascular Research

Finnish Heart association founded Heart Foundation (Sydänsäätiö) in 1956 to support the research activities in Finnish Cardiology . The Finnish Patent and Registration Office did not approve of the foundation’s operating model and the donations of the foundation were not made exempt from tax. As a result, the same founding members founded Finnish Foundation for Cardiovascular Research (Sydäntutkimussäätiö) in 1970. The foundation gradually started its operations.

Over the years, the Finnish Foundation for Cardiovascular Research has evolved into a significant supporter of cardiovascular research. It allocates about two million euros per year in grants for projects and researchers.

The treatment of cardiovascular disease was centralised in the 1950s and 1960s to our biggest central hospitals and, for example early on to the Kivelä Hospital.


Salus Hospital opened in the 1920s

The private Salus Hospital was founded in Helsinki in the late 1920s. The hospital was later donated to the Jenny and Antti Wihuri Foundation, which incorporated it in the beginning of 1945 to the Wihuri Research Institute, founded around the same time. A central person and medical director of the Salus Hospital was Professor Pentti Halonen (1914–1983). He was Chief Physician of the Salus Hospital at the Wihuri Research Institute from 1947 onwards, Docent of Internal Medicine at the University of Helsinki 1946–1953 and Professor 1953–1981.

Halonen’s research focused on heart disease. His research focussed to research topics such as congenital heart defects, angina pectoris and strophanthin. He was a pioneer in modern Finnish cardiology and education in the field. Professor Halonen led a key research group in heart disease that worked at the Salus Hospital.

Another important centre or research group was the group of Professor Esko Nikkilä at the University of Helsinki 3rdDivision of Internal Medicine. Nikkilä and his research group gained recognition as the “cholesterol researchers”.

At the initiative of Sydäntautiliitto and WHO, Finland started conducting population studies to examine the morbidity and risk factors for cardiovascular disease. In the 1960s, Finland took part in the Seven Countries Study under Professor Martti J. Karvonen. Other similar studies included the risk factor Study in Policemen at the research unit at the Finnish Heart Association and likewise the Helsinki Businessmen Study of the 2nd Division of Internal Medicine. In addition, the Social Insurance Institution carried out population studies starting 1970:ies and ongoing at 5 year intervals.

Young researchers were required for these research setups. Many of them wrote a doctoral thesis and later became distinguished researchers in cardiovascular disease.

Funding and support for studies

The Wihuri Foundation was one of the first supporters of research in Finland. The Finnish Medical Society Duodecim decided to establish the Finnish Medical Foundation in 1960. It has awarded grants to medical research in all fields and also to cardiovascular research from its special funds.

The funds of the Finnish Cultural Foundation have also awarded grants to research in heart disease.

Heart morbidity increased and was a major cause of mortality at a young age. Several dedicated funds and foundations were set up to support the medical research of
cardiovascular disease. I have personally served as a specialist in cardiovascular research in the Aarne Koskelo Foundation, the Ida Montin Foundation and the Instrumentarium Science Foundation, and nearly 30 years in the Finnish Foundation for Cardiovascular Research.

Paavo Nurmi Foundation as a supporter

Another major supporter of the cardiovascular field is the Paavo Nurmi Foundation. It is actually the oldest foundation dedicated to cardiovascular research and earns special recognition.

Paavo Nurmi suffered an embolism in the late 1950s and was hospitalised. Back then, the only treatment was rest. While in bed rest, the idea of developing and supporting medical science began to take shape in Nurmi’s head. In winter 1968, he suffered an embolism in the right hemisphere of his brain, which left his left hand paralysed. Nurmi decided to go through with the idea he had been planning for years and establish a foundation to promote research in cardiovascular disease and
general public health.

The Paavo Nurmi Foundation was established on 15 February 1968. The first grants were awarded already in the following summer, based on the proposals of Professor Pentti I. Halonen and Professor Lauri Kalaja. A total of 190 000 marks (304 250 euros when converted to 2021 prices) were awarded.

The foundation quickly established its position in Finland. Grants have been awarded to researchers in cardiovascular disease almost every year. The foundation has also made headlines, for example when it donated acute care medical ambulances with medical officers in charge to the cities of Helsinki and Kuopio.


Strong international dimension

Professor Halonen had strong international networks and wanted to build relations with international researchers and especially with the British Cardiac Society.

Organising international symposia in Finland became a key task of the Paavo Nurmi Foundation. At first, symposia were organised every two years and slightly less often in the 2000s. The goal was to develop collaboration between Finnish and major international centres. Through these relations, Halonen’s successor, Professor Heikki Frick, spent a year in England as a researcher.

With support from various foundations, Finnish researchers in cardiology visited European centres and later the United States to get international contacts and experiences and be merited in cardiovascular research. This helped our cardiologists become successful researchers and take on leading roles in scientific communities in Finland and particularly in the European Society of Cardiology, today the world’s biggest community in the field.

In addition to this, Finnish cardiologists have held specialist positions in the specialist groups of both international societies and authorities. They have served on the management teams of several major multicentre studies and as specialists in the pharmaceutical industry.


Research topics

Professor Lauri Autio has written about early research in the field in his work entitled “Salus: Wihurin tutkimuslaitos ja suomalaisen sydäntutkimuksen alkuvaiheet”. The publication highlights several distinguished names in cardiology: Halonen, Pyörälä, Manninen, Heikkilä, Frick, Luomanmäki, Hakkila, Härtel, Louhija and Eisalo.

From the 1940s to the 1960s, one of the main research topics was the absorption, effects and interactions of digoxin. Research was predominantly clinical. Other major topics were angina pectoris, congenital heart defects, the sauna and the effects of exercise training on cardiac function. Myocardial infarction became a topic from the 1960s onwards.

Experimental cardiovascular research gained a stronger foothold at Salus in the 1970s. Over the following decade, Salus focused on lipid research and treatment and the effects of medicine on cholesterol levels. Professor Petri Kovanen became head of the research unit at Salus, and his research group concentrated on cholesterol transfers and the metabolism of the vascular wall. Another key area of research focused on the significance of platelets and the effects of various pharmaceutical substances. In addition, the effects of smoking on platelet activity were also studied.

During the period of collaboration between the research groups at the Salus Hospital and the Helsinki University Central Hospital (HUCH) 1st Division of Internal Medicine, more than 50 doctoral theses were completed.


Research at HUCH

Research at the Helsinki University Central Hospital I Division of Internal Medicine continued under Halonen and his successor Frick primarily in the form of clinical research. Key research topics were blood fats, basic research concerning them, and pharmacotherapy studies. One key research series conducted in collaboration with a pharmaceutical company was related to gemfibrozil, which slightly reduces LDL cholesterol, but increases HDL cholesterol.

HUCH coordinated a demanding national multicentre study to study the effects of the gemfibrozil on coronary artery disease using coronary angiography in a double-blind 3 year follow-up study. This collaboration has grown stronger with the help of Professor Marja-Riitta Taskinen, as she has also paved the way for important international collaboration.

From the 1990s all the way to the 2000s, research has focused on the causes and consequences of myocardial infarction. The treatment of acute myocardial infarction by coronary angioplasty has been examined in international collaboration. In addition, the prevention of recurrent events with antibiotics and antithrombotics and by affecting platelet function has been examined.

Launched in 2004, the Corogene study has produced a wealth of knowledge about the genetic factors of coronary artery disease on the background of acute cardiac events. The research group was led by Juha Sinisalo, who became Professor of Cardiology at HUCH after me.

Research in cardiac insufficiency grew stronger with the Heart Transplant programme and the development of levosimendan for insufficiency by the pharmaceutical company Orion.

HUCH has coordinated the EuroHeart Failure Survey II and recently the so-called CardShock study. We have welcomed a new generation of leading researchers, including names such as Veli-Pekka Harjola and Johan Lassus.

Since the 1980s, Cardiology at HUCH has conducted extensive research on myocardial infarction, coronary interventions and surgery, valve diseases and the treatment of arrhythmia.


Research in Turku and Oulu

Successful cardiovascular Research has also been carried out in our other university hospitals. The faculty of medicine was established in in Turku University on 1943. Research in cardiology began there in the 1960s. The strongest areas were ECG research and trials. Matti Arstila was a pioneer in Turku.

The Centre for Rehabilitation Studies of the Social Insurance Institution Kela started operating in the Turku region in 1972. Among other topics, the centre studied myocardial infarction patients’ rehabilitation, blood pressure control and adverse effects of medical therapies in heart diseases.

Important research at the University of Turku in the 1980s and 1990s included two follow-up studies of children, LASERI 1983 and STRIP 1990, which focused on the risk factors of children and families associated with later cardiovascular disease. These important series of studies are still held in high regard around the world.

Research in cardiology in Turku has had a significant impact on research in clinical physiology. The Cyclotron-PET Centre, founded in 1974, has played a key role in this. It is a national research institute managed jointly by the University of Turku, Åbo Akademi University and the Hospital District of Southwest Finland.

The PET Centre develops the production of cyclotron-produced isotopes, research in clinical positron emission tomography (PET), clinical services and industrial applications. The PET Centre serves the entire country in terms of clinical PET studies. The long-standing director of the institute, Professor Juhani Knuuti is an internationally renowned, innovative director of research. Under his command, PET and clinical physiology, together with the Centre of Excellence in Cardiology at TYKS, form an important hub of research and services in cardiovascular imaging. Clinical cardiology and research in the field, in imaging and in treatment have been developed at TYKS under Professor Juhani Airaksinen. Over the last decade, a significant research programme on atrial fibrillation has been established.

A faculty of medicine was established at the University of Oulu in 1958. Research in cardiology has been a major field for decades within the branch of internal medicine and, for the past few years, at a separate centre. A major influence was Professor Juha Takkunen, who moved to Oulu from Helsinki. A number of doctoral theses were completed under his supervision from 1973 onwards on topics such as rheumatic heart disease, aortic stenosis, the effects of diabetes on the heart and arrhythmia.

ECG and arrhythmia became major areas of research at the centre in Oulu under Professor Heikki Huikuri. The centre has developed heart rate variability research and ECG prognostic studies, in addition to particularly valuable research on life threatening severe arrhythmia and its causes.


Education expanded to Kuopio and Tampere

Helsinki, Turku and Oulu were responsible for medical education in Finland all the way until 1972 when education also began at the universities of Kuopio and Tampere. Experts from Helsinki were appointed to the staff of the faculty of medicine in Kuopio. In Kuopio Professor of Internal medicine Kalevi Pyörälä, our most esteemed internationally recognized cardiologist further advanced the epidemiological research of heart disease. During his time, Kuopio coordinated Finland’s participation in the Euroaspire survey of the European Society of Cardiology and developed the European risk chart Score for estimating coronary heart disease and cardiovascular morbidity. Kuopio also led the Finnish FINAMI study, which compared differences in morbidity between eastern and western Finland.

Pyörälä established a line of research in Kuopio focusing on diabetes and the heart, which launched Professor Markku Laakso’s career in the genetic and molecular background of chronic diseases.

Professor Jussi Huttunen served as associate professor of internal medicine at the University of Kuopio 1975–1978. His research interests were also in essential risk factors on heart disease, diabetes and other metabolic diseases. He later continued his research as director of the National Public Health Institute of Finland.

Another interesting institute is the A.I. Virtanen Institute for Molecular Sciences (AIVI), which operates in Kuopio under the University of Eastern Finland. It responds to the global health challenges created by the aging of the population and changes in lifestyle. The institute focuses on the research of cardiovascular and brain diseases. One of its famous research groups is the one led by Professor Seppo Ylä-Herttuala, which studies how vasculature and affected tissue can be treated by gene transfer using various viral vectors.

The Tampere University (TAYS) and its faculty of medicine was established at the same time as the one in Kuopio. There too, cardiovascular research was initially based on collaboration with clinical physiology.

Tampere has participated in national studies on heart disease. Research began to flourish again in 2004 when the Heart Hospital was founded. Key areas have been arrhythmia studies and research where special signs are detected in cardiograms to identify the risk of
heart disease.

TAYS has also collected material on cardiovascular mortality by autopsy materials and taken part in the LASERI study.


Research and funding

A key facilitator of development has been the research conducted at the University of Helsinki, which has evolved out of research groups from the Salus Hospital. Experienced researchers moved to Oulu and especially to Kuopio. The Oulu school has educated researchers and brought research expertise to Tampere and Turku. One of the strengths of Oulu has been that it had more posts in education than Helsinki. Research has been and continues to be highly important to develop clinical skills and knowledge. Research provides a way to build networks.

Research funding was previously based on the University Hospital Act, which created excellent opportunities to do research along with hospital work. University hospitals were reimbursed 12 per cent of their education and research costs by the state.

An amendment was introduced in 1997 whereby statutory funding became special state funding, the value of which in terms of supporting research has become substantially devalued.

The significance of private foundations for cardiovascular research is high. Many foundations have supported the work of research groups and the career of young researchers.

The Paavo Nurmi Foundation donated a professorship in 2013 for research in coagulation disorders, a position held by Professor Riitta Lassila. She is also one of the students of the Wihuri Research group at the Salus Hospital.

Foundations have also supported research conducted at centres abroad by dedicated scholarships. This has enabled international networking and given Finnish researchers international recognition through several collaboration projects.


Closing words

When reviewing research applications, I have noticed that the same applicants apply for funding from several foundations in the same year. This makes the funding of young researchers, in particular, challenging. One researcher may receive substantial funding from several foundations and another may receive less, for his or her theses.

Funding should be developed. Could we consider the idea of bringing the foundations that support cardiovascular research together to form a body similar to the Finnish Cultural Foundation where funding would be applied for once a year? This would make possible that funding would be allocated based on performance. Funding would be distributed according to the research funding decision of a single foundation.

The visibility of foundations would remain the same or even improve. This arrangement would clarify and simplify the review process. Savings would also be incurred in administrative costs.

In my article, I have highlighted individuals who have played an important role in Finnish cardiovascular research. I have followed research in the field in Finland and abroad for half a century, so my article is based on my long career as a researcher and working in hospitals. I could mention dozens of researchers and educators, but that is not possible within the scope of this article.

With respect for Finnish cardiovascular research,

Markku S. Nieminen

Professor of Cardiology 1997–2015, University of Helsinki
Chief Physician at the Division of Cardiology, Director of the Department of Medicine and
Heart Lung Center, retired since 2016