Zdenek Fejfar on the WHO Cardiovascular Diseases Unit in Geneva
[ed. The early history of the WHO CVD Unit (1959-1973) is recounted in this personal statement by Zdenek Fejfar , with our occasional paraphrasing and edit. It is a poignant and diplomatic account of the limitations of WHO, and only slightly exaggerates the WHO role in organizing the International Society of Cardiology and its scientific councils and epidemiological efforts. It shows a grasp by the Unit director of the fundamentals in CVD, of professional attitudes about prevention science, and of the organizational skills to unify a diverse community. It was remarkable to achieve any results at all with so little money and authority. Fejfar found genius in the idea of the UN itself: to facilitate discussion and compromise, to coordinate, to advance methods and ideas, and to forward projects under its auspicious aegis.]
Cardiovascular activity was proposed to the World Health Organization by the Indian Government in 1953. The programme was adopted by the World Health Assembly in Minneapolis, USA, in 1956 and financed to expand WHO activity in this field. The CVD unit was created and started to function on 15 March 1959, with one cardiologist, Fejfar, and one secretary.
The effort in CVD began with a series of conferences and reports on atherosclerosis and ischemic heart disease (1955), classification of atherosclerotic lesions (1957), prevention of rheumatic fever, and classification of hypertension and coronary heart disease for epidemiological studies (1958) (Wld.Hlth, Org.tech.Rep.Ser. 1955, No.97, 1957, No.117 and 126, 1958, No.143, 1959, No.168).
Epidemiology was considered important for international cooperation by members of the first scientific group, met in Geneva 16-18 March, 1959. Dr. J. Watt, director of the National Heart Institute in Bethesda, was chairman, and members included physiologist A. Keys and statistician Felix Moore, from the USA, epidemiologists A. Cochrane and J.N. Morris from the UK, physicians I. Page (USA), Sir George Pickering (UK), J.Speraksky (USSR) and H.J.Ustvedt (Norway) and a veterinary surgeon D.K.Detweiler (USA). Paul Wood (UK) suggested that WHO should eventually include experimental research on the relation between atherosclerosis and blood lipids; the role of thrombogenic factors in atherogenesis; and behaviour of the intima.”
We learnt rather quickly that having many good suggestion does not by itself ensure success. Reports published by WHO were more or less buried in ministries of health, and only a few cardiologists knew of them. To disseminate available knowledge about the problems of cardiovascular diseases and about new developments by WHO, required establishing a large circle of cooperating physicians and laboratories throughout the globe. The first task was to establish such cooperation with the leading cardiologists in the International Society of Cardiology (ISC) founded in 1950. Distinguished colleagues were nominated to a WHO panel of experts; later an official relation was established between WHO and ISC.
Research programme was the affair of Headquarters, but all regional directors, when properly briefed, provided help. During the first 10 years, some regional offices, first the European, became cooperating centres.
Prevention and Treatment
During the first years the main features as to how to treat and prevent major CVD were outlined in several meetings. Cor pulmonale was discussed in 1960, arterial hypertension and ischemic heart disease in 1961, rheumatic fever and rheumatic heart disease in 1966, and problems of rehabilitation in 1963. All reports were published in the TRS series and became the basis for regional meetings in Bucharest 1965, in Manila 1968, in Teheran 1972.
It became evident that publication of reports only, though written on advice of excellent experts, was insufficient. It was necessary to prove in pilot studies how to apply knowledge in a given country. Cooperation between outpatient and hospital services and the use of existing structures of health services were the two guiding principles. We never considered to establish special services for cardiac patients outside the local structure and organization of health care.
Programmes for rheumatic fever prevention were set in progress in 1970 in Egypt, Iran, Barbados, Cyprus and the Mongolian Peoples Republic, guided by Toma Strasser with analysis performed in Geneva Headquarters.
The hypertension control programme became possible with advances of hypertension treatment and by finding that in most populations only a small fraction of hypertensive patìents (less than 20%) was adequately treated. The control programme in the early 1970s was organized by Dr. Strasser and carried out in 18 model areas of 13 countries.
In a similar way, a programme for patients with cerebrovascular disease (community stroke registers) started following a meeting in Monaco in 1970; it was headed by Shuichi Hatano.
A pilot study on the management of acute myocardial infarction was undertaken in 20 areas of 18 countries in Europe, Israel and Australia (led by dr. Z Pisa, Mr. K. Uemura).
World Health Day “Your heart is your health” was held in 1972 and many countries actively participated with special stamps, broadcasts, and articles using WHO documentation. The broadcast series “Round the world with the WHO” also helped.”
In 1959 we considered the globe a laboratory where one could find contrasting areas of cardiovascular disease prevalence. The opportunity was to relate the frequency of a disease with different ways of living and in different ethnic groups. We learnt, for example, that immigrant Indians had higher morbidity and mortality from ischemic heart diseases than local populations (Kampala, Singapore or Fiji). Searching for such contrasting places was the first task, together with preparations of standardized methodology.
Here, unfortunately, the situation was bleak. I learnt with dismay at the famous meeting in Princeton (April 1959) that population studies under way in the USA (Framingham, Albany, Seven Countries Study) or in the UK (bus drivers and conductors)) and a few others had been undertaken with various methods, making the eventual comparison and pooling of data very difficult. There was no agreement on such a simple method as the measurement of diastolic blood pressure (the 4th or 5th sound of Korotkov).
We had, first of all therefore, to work out and test comparable methods for epidemiological studies. They involved “Minnesota” coding of the ECG, testing the assessment of ocular fundi, direct and indirect measurement of the blood pressure, and working out comparable methods for blood cholesterol estimation. The laboratory of Dr. Gerald Cooper in the Center for Diseases Control in Atlanta, USA, became the international centre for standardization, and the Institute for Cardiovascular Research, since 1971 part of the Institute for Clinical and Experimental medicine (IKEM) in Prague, became that for the European Region. The smallest intraobserver and interobserver variability in ECG reading was [found] in those persons who were neither cardiologists nor epidemiologists, pointing to machine analysis as the best way for ECG coding, unless done in one central laboratory.
The 1960’s were indeed the golden age for research. We had funds for supporting cardiovascular projects and started modestly, promoting, on the advice of Archie Cochrane (UK) the establishment of the MRC Epidemiology Research Unit in Kingston, Jamaica, with Bill Miall in charge. Apart from other well known studies, a number of outstanding epidemiologists started their careers there (e.g. Ken Stewart and G. Fodor).
WHO activities were gradually growing in scope and depth. In 1961 a large scale autopsy study of atherosclerosis in the aorta and coronary arteries in subjects of both sexes, aged 10-79 years, who died between 1963-1965, was initiated in Malmö, Prague, Yalta, Riga and Tallin. All samples were collected in a standard way and were processed in the department of pathology in Malmö; data were analyzed periodically in Geneva. Specimens from 17,455 persons were collected covering about 77% of all deaths in the areas. The second study centred on young individuals started twenty-five years later. It will be of interest to learn about changes in populations where coronary mortality has been rising.
Since 1966, the CVD Unit coordinated studies on primary prevention of ischemic heart disease, attempting to find out to what extent mortality and morbidity from ischemic heart disease would change by lowering serum cholesterol. Clofibrate, known at that time as a drug with neglibible side effects, was chosen for lowering blood cholesterol level. This double blind study was at that time the largest, with 15,000 subjects observed for at least five years in Budapest, Edinburgh and Prague. Statistical analyses were done at the London School of Hygiene and Tropical Medicine. All information on mortality, morbidity, and side effects was evaluated by a committee in WHO Geneva.
The study proved, as the first of its kind, that indeed lowering serum cholesterol decreased the incidence of myocardial infarction (both fatal and nonfatal). At the same time, however, there was a slightly higher death rate from other causes in subjects taking clofibrate compared to those on placebo. This stirred up emotional discussions (see e.g. Editorial in the Lancet 1978, No.25, p.1131) which unfortunately overshadowed the beneficial effect of the drugs and the valuable experience of how to conduct, coordinate and evaluate a large scale preventive trial.
The programme was expanding gradually in developing areas, mostly on the continent of Africa, cardiomyopathies of unclear etiology were described under different names. With the help of consultant pathologists and clinicians, practical classification of cardiomyopathy was made into three main groups (hypertrophic, restrictive and congestive (now called dilated)). WHO groups from four continents became the scientific council on cardiomyopathies of the International Society of Cardiology.
Together with Jack Davis, pathologist from the UK, working for a number od years in Kampala (Uganda), whose name became connected with endomyocardial fibrosis, Chagas’ heart disease was studied in Latin America. This report stimulated interest for further work by PAHO (Pan American Health Organization, the WHO Regional Office for the Continent). A meeting in Israel explored immunological and electronmicroscopic methods for furthering research into the pathogenesis of congestive cardiomyopathies.
High altitude areas became another point of interest in view of the high frequency of patent ductus arteriosus and AV septal defect with high pulmonary artery pressure. There were also reports about a rather low prevaence of systemic hypertension, ischemic heart disease and vascular thrombosis. Research teams from Geneva University, headed by Pierre Moret, investigated cardiac metabolism in Bolivia and at a meeting organized jointly with George Lambert in la Paz in 1972, the broad spectrum of high altitude cardiological problems was presented.
We also attempted to open the more or less closed classification of lipoproteins (Fredrickson and Levy) by proposing to separate group II into IIa and IIb. The suggestion came from L.Carlsson (see Beaumot and Cooper, Bull. WHO, 1970, 43.891-915). The classification, meant originally as ‘working’ for a few years, is still in use.
An attempt to expand activity into the problem of arterial thrombosis in relation to atherogenesis and coronary heart disease was not realised because of the lack of time in the early seventies. By 1972, there were 131 institutes throughout the world cooperating with the CVD Unit of the World Health Organization:10 in the African regions, 22 in the regions of Americas, 11 in the Eastern Mediterranean region, 72 in the European region, 3 in South-East Asia and 13 in the Western Pacific regìon.
We did not finish, as we wished, the investigation into the role of trace elements (methodological problems).
In cooperation with the International Society of Cardiology, we sponsored and organized symposia on outstanding problems such as the metabolism of hypoxic and ischemic myocarìdium; myocardial blood flow, and neural and psychological mechanisms in cardiovascular diseases (see bibliography in WHO Chronicle 1974, 28, 55-64).
At a WHO meeting on worldwide cooperative efforts to control cardiovascular diseases held in Geneva (30 April – 4 May1973), 14 years of work was evaluated by 22 experts
(theoreticians, epidemiologists, clinicians) from 19 countries, and an intensified programme for 1973-1980 was outlined. In included the establishment of nationwide community programmes for comprehensive control of cardiovascular diseases as distinct from single disease control; continuation in creating the global network of cooperating national and regional laboratories, institutes and institutions to cooperate in research investigations and to apply rapidly new knowledge in general practice; to concentrate more effort on early phases of cardiovascular diseases, some of which begin in childhood; to work out programmes for improvement of cardiovascular health starting in the first years of life, continuing throughout the life span until old age. Details can be found in WHO Chronicle 1974, 28, pp. 55-64, 116-125 and
Achievements and failures
WHO’s activity on the available measures for CVD prevention and methodology for population studies soon became known to the cardiological world. Cooperation with the international Society of Cardiology (ISC) became fruitful for both organizations. During the IV. World Congress of Cardiology in 1962 in Mexico City, Lars Werkö, Kempton Maddox and myself suggested enlargement of the Scientific Committee of ISC by other specialists, apart from epidemiologists. This then became the nucleus of the Scientific Councils. They were created later in Delhi, (1966), when the danger of splitting the ISC into several specialized separate societies arose. The president of the Society, Pierre W. Duchosal, prepared, with my help, during 1964-1966, a proposal for the creation of the Scientific Board, composed of the chairmen of [proposed] Scientific Councils (Hypertension, Epidemiology, Clinical cardiology, Thrombosis, Cardiomyopathies, etc.) enabling the ISC and the later International Society and Federation of Cardiology (ISFC) to put under its umbrella any new specialized society.
The proposal was accepted by representatives of the national societies of cardiology during the 5th World Congress of Cardiology in New Delhi 1966. Later on, the permanent Secretariat of the Society was established in Geneva, mainly to be close to WHO. It became a tradition to invite the chief of the CVD Unit to all sessions of the Committeee of the Society and its Scientific Board.
The CVD Unit enjoyed excellent cooperation with cardiologists and other scientists all over the world. No one ever refused WHO invitations to come to give advice, write a paper or do a study. Our financial support, though small (usually one dollar from WHO for 20 of the other partners), enabled a number of good laboratories to expand or start new work. In countries with soft currency the need was for purchase of equipment, in others to pay the salaries. WHO reputation gradually grew and it became customery to say and write ‘according to the WHO classification, or standardization, or methodology.
We were, of course, lucky to have in this time a broadminded great personage as Director General, M.G.Candau from Brazil who had an enormous international reputation, who favoured our work. The Advisory Committee for Medical Research (several members were Nobel Prize winners), after sharp discussion, viewed our programme with friendly eyes. There was a good spirit of cooperation within the Organization. We could, for example, use to full extent in the early seventies the new computing facilities for the autopsy study of atherosclerosis.
The staffing of the Unit was at high technical and moral level. Andy Burgess jr. from the USA, worked 18 months on standardizatioon of methods, and on return to the USA became member of Rutstein’s department of preventive medicine at Harvard University. Aubrey Kagan, originally taking part in J.N.Morris’s bus drivers and conductors study, was responsible for testing epidemiological methods and for the autopsy study of atherosclerosis. He left WHO for Stockholm to work with L. Levy on psychosomatic medicine. Igor Shkvatshabayia started work on the hypertension programme and on return home became director of Myasnikov’s Institute of Cardiology in Moscow. Toma Strasse from Beograd did an enormous amount of work since 1969, when he became in charge of rheumatic fever prevention and the hypertension control programme. He continued as secretary general of the World Hypertension League and published several important books on this topic, including that on cardiovascular diseases in old age. Shuichi Hatano, who was in charge of the cerebrovascular diseases programme, became one of the leaders in the Institute of Public Health in Tokyo. Don Badger worked with us as scientist for a couple of years, and on return home to the USA , became professor of physiology at the University of Illinois. Robertto Masironi was the first to do research on trace elements and is now responsible for WHO’s programme on smoking control.
There was also a WHO CVD research team in Africa, in Kampala and later in Accra. Dr. Paret, followed by Dr. A. Ikeme (later the Dean of the university in Jos) and Dr. Pole coming from Perth, all did fine work under sometimes difficult circumstances.
Medical people joining WHO with different cultural backgrounds would be rather helpless without good secretaries. At the start in 1959 it was Isabelle Mundy who took care of everything and everybody in the Unit. Since 1963, Barbara Pumfrey, and later on an excellent team of Mary-Jane Watson, Bunty Müller and Margaret Eddison, helped very much in carrying out all tasks.
I am also happy to mention the close cooperation with the Department of Cardiology at Geneva University, headed at that time by Professor P.W.Duchosal. I had the opportunity of taking part in the life of his department and to lecture to students.
A long term training programme was also satisfactory. Apart from traditional fellowships at the request of governments, the cardiovascular programme received research training grants given to WHO by the Swedish Society against Chest and Heart Diseases since 1959. Several young persons, later leading cardiologists in their countries, spent each a profitable year in Sweden. An annual advanced course in cardiology for physicians from developing countries was organized for several years in Copenhagen by Prof. A. Tybjaerg Hansen and Prof. Olesen. Financial support was from the Danish International Agency. The World Health Day 1972 “Your heart is your health” and World Heart Month were successful in informing the general public.
We might of course have done better. The start was slow. I had no experience in international work or in epidemiology, and my knowledge about the distribution of major cardiovascular diseases was scanty. The first large meeting on cardiovascular epidemiology was held in Princeton three weeks after my arrival in Geneva. Apart from Ancel Keys’ Seven Countries Study there was no experience of cooperative investigations. There was no other information about the prevalence of major cardiovascular diseases. When cooperative studies were undertaken, it became necessary for the participants to meet regularly to get to know each other and to improve the quality of work. However, funds were lacking for such gatherings unless local support was provided. For these reasons, we were able to coordinate directly for several years only two big studies (atherosclerosis and clofibrate).
It has not been easy to orientate cardiologists towards prevention, rather than to the customery diagnostics and treatment of patients with established disease, and to change their attitudes from preferring rarities to common conditions. The public in the early sixties was not prepared for an optmistic view. Cardiovascular diseases were considered in the developed world as more or less diseases of old age and not preventable. Besides, preventive measures are in general accepted slowly if they require continuing efforts, compared to one single activity such as vaccination. In the USA, for example, the first big effort to combat smoking in 1964 resulted within a year in the forced departure of the cardiologist, Luther Terry, from the post of Surgeon General. The effect, however, is clear now, 25 years later.
The principal cause of delay in implementing several good projects was insufficient financial resources. In 1973, funds for CVD programme projects represented 0.60% of the total effective working budget (1 dollar at that time = 4,31 SF). We failed at that time to create an International Institute similar to the WHO Cancer Research Institute in Lyon.
My time in WHO ended with Dr. Candau’s departure. The long term programme I was prevented from building in later years remained only on paper. (Zdenek Fejfar)
[ed. Dr. Fejfar does not speak of the polical ramifications of his recall to Prague, or of the long years of forced exclusion from international activities that resulted. Even after freedom arrived to his country, he remained low-key, devoted to his cardiovascular community, writing books and editorials in Czech, and maintaining unembittered his international friendships. (Henry Blackburn)]
Fejfar, Z. 1974. WHO Cardiovascular Diseases Unit 1959-1973: International cooperation in the fight with cardiovascular diseases. Manuscript. CVD History Archive, School of Public Health, Univ. of Minnesota.