University of Minnesota

Kalevi Pyörälä on the Course of Cardiovascular Epidemiology, 1992

My long-term friend, Henry Blackburn, has been wondering about changing my talk to reflections on the international development of cardiovascular epidemiology, and, against that background, that I should say something about the role of Finland. My first slide is a picture of Stadium Gate 27 because that is the gate behind which much of cardiovascular epidemiology in the world was developed. Finland, of course, has long-standing connections to this place.

So really, cardiovascular epidemiology started in this country and in this town. Ancel Keys was the first chief of what was called the Laboratory of Physiological Hygiene. He started those early studies to define the prevalence and incidence and risk factors of coronary heart disease, started in the late 1940s at the time when I went to medical school in Finland. And during the subsequent years Prof. Keys traveled around the world with his friend Paul Dudley White and visited many places, when finally his explorations led to the initiation of the Seven Countries Study, in which Finland participated.

Another important study that had a large effect on the research was also started in the late 1940s and in the 1950s was the International Atherosclerosis Project, a pathologic-anatomic study on atherosclerosis in different parts of the world. I’d like to mention that the initiators of that study also came to Finland and tried to attract Finnish scientists. But actually they didn’t meet with the scientists, they only met with bureaucrats who denounced anything at all about the importance of the study and thus unfortunately our country didn’t participate.

The word “prevention” in respect to CVD was probably mentioned for the first time in public by Keys in a paper he gave at Mt. Sinai Hospital in New York City that was published in 1953. And I learned from Henry that it was already in 1948 that he gave a lecture in Chicago in which he talked about hygienic measures and talked about research on the possible prevention of coronary heart disease.

In 1959 in this country an important document was published, a statement on atherosclerosis published by a group of distinguished cardiologist researchers led by Paul Dudley White. It is still interesting to look at what they said about factors that predispose to atherosclerosis. They are saying what we talk about today. And it is really very striking to see what they suggested, that you can’t change your heritage, but you can influence the other factors and, hence, lessen your risk of being a victim of cardiovascular disease. If there is a history of cardiovascular disease in your family it just means that you should be especially careful about factors you can control. Key factors are cholesterol, blood pressure, and cigarette smoking. And you should without fail consult your physician. These explicit recommendations are very pertinent even today.

The term “risk factor” was first mentioned in the medical literature in 1961 in a publication from the Framingham Study. Of course, Ancel Keys and the others had the idea about measurable physiological and lifestyle factors that predispose to coronary heart disease and other atherosclerotic diseases, but this paper probably used for the first time the term “risk factor.”

Then already in the 1950s, the first trials to test the effect of changing risk factors were launched. The first of them to be published was the Los Angeles Veterans Administration Diet Trials that you certainly know about. At the same time a study was launched to study the same issue in Finland, the so-called Finnish Mental Hospitals Study launched by Drs. Karvonen and Turpeinen and that was published about the same time as the Veteran’s Diet Study.

The U.S. National Diet-Heart Pilot Study was also planned and launched very early as part of a plan to do a major trial on dietary prevention of coronary heart disease. But finally the people determining whether to go on with this decided it wouldn’t be feasible. That led to the development of an alternative strategy to test a multi-factor prevention concept, a Multiple Risk Factor Intervention Trial, which got underway in the U.S. and independently in Europe and in Norway and Sweden.

Different trials on hypertension alone were undertaken in this country and at the same time also in England and in Australia and then, of course, the major Lipid Research Clinics Coronary Primary Prevention Trial using cholesterol-lowering drugs was launched and then published in 1984.

During the 1970s different strategies for prevention of coronary heart disease in the whole community were being developed. Fred Epstein in his favorite lecture in 1970-71 talked about the individual approach and community approach and later Geoffrey Rose in his paper on strategies of coronary prevention coined the term “high-risk strategy” and “mass strategy.” Mass strategy later became changed to “population strategy” and population strategy has since been a key word as we talk about prevention of coronary heart disease.

By the end of the 1960s and early 1970s the first community public health projects or demonstration projects were launched. The first of them was the Stanford Three City Project done by Jack Farquhar and his colleagues. And about the same time the North Karelia Project was started in Finland. These developments led to the beginning of the Five City Project in Stanford and the Minnesota Heart Health Program and the Pawtucket Health Program in Rhode Island; three sister projects. They were rather similar in their approach to the North Karelia Project we had in Finland.

Now I’m going to quickly go through a list of landmarks of coronary heart disease prevention and public health approach to that in your country. To emphasize one issue, that is, how quickly and efficiently you translate scientific information to public health policy. That is something unique which we non-Americans always have admired. And this started already in 1959 from the public statement on atherosclerosis. In the beginning, the American Heart Association played a key role in the exploration of public health recommendations and its reports were very important in those early days. And when we go on you will see the interplay between voluntary organizations and governmental organizations, while the National Heart, Lung, and Blood Institute research and control efforts have been very fruitful.

I would like to point out that the 1970 Inter-Society Report, a joint effort of the American College of Cardiology, American Heart Heart Association, other non-government groups, and the National Heart, Lung, and Blood Institute was an important document and obviously had a large impact on the population strategy, worldwide.

An important landmark was the Consensus Development Conference in 1984 on lowering blood cholesterol to prevent heart disease and the subsequent National Cholesterol Education Program (NCEP) of NIH that stimulated similar activities in Europe. The European Atherosclerosis Society made strong recommendations in virtually all European countries, as a consequence of the National Cholesterol Education Program to really set guidelines for practicing physicians for cholesterol levels.

Let me turn to another aspect, which has been very important for us in Finland and that is what has happened within the framework of The International Society of Cardiology that was founded in 1950, but for a long time it was an organization of clinical cardiologists and had no interest in preventive cardiology. All changed in 1966 in connection with the World Congress of Cardiology in New Delhi, India because then scientific councils of the International Society were established and among them a Council on Epidemiology and Prevention of Cardiovascular Disease. Keys and White and Jerry Stamler, among others, were involved in those early steps. Ancel Keys was the first and then Henry Blackburn became chairman of the Council and Section on Epidemiology and Prevention of this international organization.

One of the important functions of this Council and Section has been to train and educate young researchers and clinical cardiologists in cardiovascular epidemiology and prevention in so-called 10-day international teaching seminars. The first of them was held in Makarska, Yugoslavia in 1968 where I had the opportunity to be a fellow, and I can tell you that that changed the direction of my professional life completely. The faculty members and fellows included Henry Blackburn, descriptionFred Epstein, descriptionMartti Karvonen, many others. Henry is absent here because he was busy playing the saxophone at the time the picture was taken. (No, in fact, he took the picture!) Henry Taylor is one you’d recognize and that’s Tom Chalmers of Boston, descriptionRichard Remington, Jerry Stamler, Geoffrey Rose, Fred Epstein, Martti Karvonen. Those seminars have since been continued annually and been located at many places around the world. More than 800 people from more than 70 countries around the world have been trained in this seminar series. And in 1982 some of the seminars became “advanced seminars” and went more deeply into details of cardiovascular epidemiology. The first one we organized in Finland.

Epidemiology and prevention of cardiovascular diseases has also stimulated international research between groups working in different countries. Also people from different countries have met and found common research interests and here are listed some of them. The WHO European Cooperative Trial in Multifactorial Trial in Industry was planned at the seminar held in 1970. Then Jerry Stamler stimulated a Collaborative Study, INTERSALT; an exercise for the fellows at the seminar to design a study of the relationship between salt and blood pressure. That later took off as a real study.

Another international aspect that is important not only for us, but for many other countries, has been within the framework of the World Health Organization and its Cardiovascular Disease Unit established formally as late as 1959 with Dr. Zdenek Fejfar from Czechoslovakia as the first chief of the unit. As you see, WHO was at first most concerned with rheumatic heart disease. The most important role of that organization was to call expert committees on prevention of coronary heart disease over several decades. Geoffrey Rose was the chairman of a 1981 Expert Committee and Henry Blackburn was Rapporteur, in other words, he wrote a document really that guidelines for community prevention of coronary heart disease, which should fit the comprehensive plans in many countries of the world. Population strategies would include primary prevention in the general population and high-risk strategy or secondary prevention to be done medically in concert, the programs supporting each other.

Let me now go back to the time when I was graduating from medical school to the early 1950s. At that time Ancel Keys was traveling around the world to try and locate countries where population comparisons of diet could be carried out and he had learned that Finland was one of those countries with very high saturated fat diet, from Karvonen who had been trained in the same place where Keys did his PhD work in physiology at Krogh’s laboratory in Denmark. They actually had never met before and then Karvonen came here and Ancel Keys came to Finland and in 1953-54 they started to plan pilot studies for what later became the Seven Countries Study and did some pilot studies in the northeastern communities of Finland in 1956. There they carefully examined and weighed the diets of the North Karelian people and this article is from the local newspaper describing how diligently and accurately measurements were made even including the diet of the local cats!

There is a story about that time of which you may have heard some version. At that time there was one single physician in the tiny Ilomantsi community hospital with two rooms – one for women and one for men – and Ancel Keys, Martti Karvonen, and Flamnio Fidanza, a biochemist from the University of Naples in Italy went to visit. There were eight beds in that room for men and the distribution of disease was five having myocardial infarcts and three men who were bitten by a bear. Fidanza became so scared that he packed up his things and went back and established his laboratory in a nearby town and never came back. [ed. Another version was that one-third of the patients had heart attacks, one-third pneumonia, and one-third had encountered Russian Bears!]

Anyhow, as the outcome of the Seven Countries Study, which started in Finland in 1959 a report was then produced on risk factors levels and you have seen this figure many times of the non-overlapping distributions of serum cholesterol in Finnish farmers and lumberjacks compared with Japanese fishermen. They barely overlap, but there’s a huge difference between those two populations.

The Finnish Heart Association was established in 1955. Actually, one of the main aims of this heart association was to support research on the coronary problem, which had been recognized in Finland. This heart association report really got to be the start of the Seven Countries Study in Finland and that was in 1959. And the first results of the Seven Countries Study were published in the international literature in 1965. But the Finnish Heart Association through the help of mass media in Finland made the results of the Finnish part of the study widely known and citizens learned that a diet high in saturated fat and cholesterol, high blood pressure, too much smoking, of course leads to the heavy heart disease problem in Finland.

New Finnish population studies were then launched around 1966, and I got involved in these through Martti Karvonen. I was doing clinical cardiology with a cardiology and cardiac surgery team and Martti Karvonen asked me to help him in one small study first. I got interested in a small part which led to my participation in the teaching seminar.

Developments in Finland finally led to the start of the North Karelia Project in 1972 and that was started in the same high coronary area that participated in the Seven Countries Study. It is the most eastern province of Finland, North Karelia, and the neighboring province Kuopio, was to serve as a reference area. The North Karelia Project was started in 1972 at the same time a new university with a medical school was established there and I came there in 1976.

Anyhow, the North Karelia Project was a very important demonstration project. It set up a community laboratory to study and develop methods for coronary heart disease prevention. The experience from North Karelia really then much influenced action in public health at the national level. The Tobacco Act, influencing the advertising of tobacco and any aspects of tobacco use in our country was launched and the North Karelia experience was used in the guidelines for hypertension, etcetera. And then in the 1980s there was more and more interest at the national level on various aspects of coronary heart prevention. A report in 1981 involved nutrition and health. Then the MONICA Study; a monitoring project started in 1982.

This report of the Joint National Experts on the Prevention of Coronary Heart Disease in Finland was very important because that combined voluntary and governmental health organization action. And then, following the American and European atherosclerosis recommendations we then formulated recommendations for the dietary treatment of other hyperlipidemias in adults.

In 1988 the Finnish Heart Association started its Heart and Nutrition Program that has become a very popular and effective program and, as I will tell you later, it seems to be having a good effect. We used the Seven Countries Study to tell to the public that cholesterol levels of Finns are too high and should go in the Japanese direction. And that led to some clashes with the dairy industry. This is a cartoon from one of the leading Finnish newspapers where I and a colleague attempted to throw out the chairman of the dairy industry who is making butter.

And these are the last national risk level milestones in coronary heart disease prevention. It culminated in the report to the government from its Committee on the Prevention of Coronary Heart Disease. This combined the previous experience and very strongly emphasizes prevention.

I’ll end up with some comments on the situation now in Finland. We still have rather high figures, although figures have come down, we are still on the third place on international statistics for coronary heart disease mortality in comparisons among men. For women it is somewhat better, we are around the middle of the list. The oldest women having somewhat better rates than men, so that the male-female ratio has been more favorable in Finland than in some other countries. And our country for the last 50 years has really belonged to the group of countries that is going downwards in coronary death rates, and the same for women.

[ed. Professor Pyörälä went on to present details of Finnish risk factor and disease trends that have suggested the influence of health promotion and policy changes there.]

RL: You’ve gone through an elegant history of the field. But now 30-40 years later, what do you see as the future of cardiovascular epidemiology and prevention? What are some of the issues from your perspective? It is a question we are asking ourselves now.

KP: There’s still much work to be done. As to research we still have something to add to explain differences between populations as shown from Finland. Maybe we have to know more about risk factor differences over time. At the same time, there’s still much information that has never been put into practice. You are doing well with this part in the United States. The United States in general has done well. We still have much work to do in practice in our country as our figures are still about 4 to 5 times higher than rates in southern Europeans. Probably within 25 or 30 years we could reach that level.

It is the credibility for prevention obtained by demonstrating that if you do those environmental things then something will improve, as you have done here, which we are trying to achieve in Finland. But perhaps we should learn more about why people change their habits and why some people don’t.

There is an increasing problem which we have to face in our country and that is social inequality in the understanding and accepting the need for a change in lifestyles. We need to reach the lower education level in Finland. That’s a very tough question. We need more research.

RL: Do you see trace elements as becoming significant issues? I’m thinking selenium, copper, iron,……

KP: That’s an interesting question scientifically, but at the same time we shouldn’t forget these major things we do know about. The scientists become excited about new things, and I think they can ignore the important old findings.

Unknown questioner: What is the trend in incidence of bear bites?

KP: The number of bears has increased, but the incidence of bear bites has been decreasing!