“It Isn’t Always Fun.” – The Engines of Epidemiology
A History in Brief
Being a brief and undocumented history of the beginnings of cardiovascular disease epidemiology and prevention research and the present challenge to its application. This is a Minnesota colloquial perspective that will be broadened in a joint effort on-going with Darwin Labarthe and Kalevi Pyörälä: Prevention of Heart Attack and Stroke. A History of Research. Oxford University Press, in preparation.
A unique thing about the field of cardiovascular disease (CVD) epidemiology is that it was developed by cardiovascular experts who were not epidemiologists. Of course, the experts had to become epidemiologists to explore effectively the frequency, risk, and nature of these diseases in populations. They did this in the best traditions of science, developing the methods appropriate to the question and pursuing the research strategy appropriate to the stage of knowledge. The pioneers were physiologists, pathologists, chemists, internists, and cardiologists, clinical investigators with an occasional bench scientist and statistician thrown in. But at the outset of CVD Epidemiology epidemiologists were not much involved.
These pioneers had from the beginning a need to know. They quickly acquired the skills, along with the collaboration of statisticians, and proceeded haphazardly rather than in an orderly hierarchy of study as today, to develop case-control studies, surveys, cohort studies, and small and large trials, as they found appropriate to the knowledge gap and the burning question.
The prehistory of CVD epidemiology might include such pioneers as physiologist-pathologist Rudolph Virchow, who early in the 20th century concluded that mass diseases and epidemics were always the result of major departures in human behavior with the resultant breakdown of social institutions. The Russian pathologists, Ignatowski and Anitchkov, who first postulated diet effects and fed animals fatty diets, were moved by their observations of different arterial pathology in the Czarist elite versus the peasant classes at the turn of the century. Sir James MacKenzie first made observations, spoke, and wrote about cardiovascular disease outside the clinic and hailed prevention as an integral function of the practicing physician.
The notable early history would also include missionary types and travelers, Marco Polos such as Cornelis de Langen, young Dutch physician who compared the frequency of vascular diseases in his Dutch versus his Javanese patients, and actually studied their diets and cholesterol levels in the early 1900s, and his colleague, Isadore Snapper, who in the 1930s noted the absence of Western diseases among the Chinese and even speculated on the protective roles of vegetable fats in their diet. In the early 1950s, Ancel Keys and Paul Dudley White made peripatetic ward rounds in Italy and Spain and South Africa, Finland and Japan, and noted large differences in the burden of CVD among hospital populations as well as inj the peoples’ traditional lifestyles.
Formal studies in CVD epidemiology began with a handful of U.S. investigators in the late ’40s and burgeoned in the ’50s into wide efforts largely independent of each other. Those in the field soon came together, however, from a shared need for sound, common methods, along with a drive to communicate their new ideas and findings.
Ancel Keys, early in his long research career, chose investigative questions he intuited were important to wider health. He used applied physiology when it was needed and fresh, used nutrition and anthropometry when starvation was thrust upon the scene by World War II, and used epidemiology and population science when epidemic cardiovascular diseases emerged in the West following the second world war. Keys had an astute grasp of what was important to the larger public health. His skills in basic biological disciplines and mathematics, moreover, could impinge on the problem directly.
Keys describes in his memoirs how the CVD issues came to his attention from news reports of an apparent epidemic of heart attacks among American executives locally and nationally following World War II.1 He set up the first systematic cohort study in cardiovascular disease epidemiology, the Minnesota Longitudinal Study, also known as the CVD Study and the Minnesota Business and Professional Men Study, which was launched in the Fall of 1947. It was an enlightened undertaking but only on the scale of a sizable laboratory observation. Proper estimates of age specific event rates among upper economic level men of the Twin Cities area were not made. They were needed, of course, to accomplish the intended mission, to relate measures of physical traits and the mode of life, as Keys called it, to subsequent disease experience, over a reasonable period of 5 to 10 years.
Joseph Mountin, the Public Health Service Assistant Surgeon General, who conceived of a multi-part community project in Framingham, Massachusetts, had the counsel of a statistician, Felix Moore, to make proper estimates of sample size. These estimates indicated that a reasonable return in 10 to 20 years would require 5,000 or so men and women; of course, he underestimated the number of women needed. Framingham was able to start reporting preliminary findings, nevertheless, after eight years of operation, whereas the CVD program in Minnesota required 23 years for its first major report on risk prediction.
In the 1950s, investigators of various bent but clinically and public-health oriented, recruited populations willy-nilly for descriptive and analytical studies, including California longshoremen, civil servants in Albany, New York and Los Angeles, civil servants and industrial populations in Chicago, rural populations, both black and white, in Georgia and South Carolina, industrial populations of American Telephone and Telegraph and DuPont companies, and U.S. railways, men born in 1914 in Sweden, civil servants of Whitehall in Great Britain, and some 14 cohorts of the Seven Countries Study, among others.
Several activities were underway by the time of the 1954 World Congress of Cardiology in Washington, DC, when Ancel Keys and Paul White held forth and brought the new field to the attention of mainstream cardiology. We young assistants in the audience at that symposium were proud to see our adventure thus highlighted and made relevant. And at the Beaconsfield Conference in 1956 we were in the front row, because those of us in the trenches had full responsibility for the diagnosis, classification, and coding of disease for the day when reports would be made and attempts begun to compare and perhaps even combine study results.
In 1957, the early CVD epidemiological results appeared formally in a supplement to the American Journal of Public Health.2 They showed for the first time the long-anticipated relationships among blood cholesterol and blood pressure and coronary disease risk, along with a lack of strong associations at first for other risk factors of interest.
Epidemiology again had a prominent role in symposia of the World Congress of Cardiology in Brussels in 1958. By this time, committees and subcommittees of the American Heart Association were actively involved in standardizing methodology and holding annual scientific meetings to discuss work in progress. The long, sometimes tortuous, trail of development of our scientific council of the American Heart Association was underway, a journey detailed elsewhere in all its pain and complexity.3 At the Brussels Congress of Cardiology, the International Society of Cardiology formalized a Research Committee which, at the 1966 New Delhi Congress, became the Scientific Council of Epidemiology and Prevention. That committee, headed by co-chairs Paul White and Ancel Keys, took great leaps forward in other meetings throughout the ’60s and ’70s, leading up to the seminal Makarska Conference. At Makarska, international and North American representatives laid out the strategy for surveys, surveillance, and preventive trials among those at high risk. The first sound was also heard there from the pioneers of community-wide health promotion programs that soon began in Finland and in California.
During this period, CVD epidemiology hit its stride and came to include preventive and community trials of risk factor lowering. The pace, and NIH support, were maintained well into the 1990s. The age-specific death rates from cardiovascular diseases and many cancers fell in parallel. Now, in the new millennium, some CVD death rates appear to be backsliding in company with a fall-back in improved risk factor levels and a diversion of research energies formerly devoted to prevention. Recently, sunshine clauses and retrenchments of classic and of newer prevention studies sponsored by NHLBI have had a negative impact on the function, staffing, and infrastructure of epidemiology. The support and the morale of its leaders and the careers of its young troops tumbled as molecular biology, genetics, and high-tech medicine and its scientist elite fully occupied the saddle. The richly productive and balanced research program maintained for so many years by the National Heart, Lung, and Blood Institute, in which bench, clinical and epidemiological research formed a powerful triumvirate, passed into obscurity at the very moment of greatest promise for a vast reduction in premature cardiovascular diseases.
Today, in the new millennium, a unique and historic opportunity to prevent the major modern diseases of industrial society may be lost by the absence of research efforts and public health programs among groups having greatest need, that is youth, women, the elderly, the poor, and other underserved populations.4 A national upturn in some cardiovascular disease rates (stroke) is already in progress. This red flag may bring hope for catching the eye of the people. “The people” will then have to influence their Congress to affect, in turn, the scientific elite now in charge at NIH and in academia. It is understandable but regrettable that this elite is wholly enamored these days by mechanisms and procedures in individuals, as well as by patents and profits in “technology transfer.” At this time of greatest opportunity to reduce the burden and prevent new epidemics of the common chronic diseases, for which the evidence and the potential are real and present, the scientific leadership can ill afford to ignore its responsibility for the public health or its civic duty to the common weal.
1. Ancel Keys. Adventures of a Medical Scientist. Sixty Years of Research in Thirteen Countries. University of Minnesota
2. Amer. J. Public Health 47 (Part II): 4, 1957
3. Blackburn H, Epstein FH. History of the Council on Epidemiology and Prevention, American Heart Association: The Pursuit of Epidemiology Within The American Heart Association: Prehistory and Early Organization. Circulation 1995; 4:1253-1262.
4. Blackburn, H, Keynote Address, NHLBI 50th Anniversary Symposium, San Francisco, February, 1998.