The Seven Countries Study: Netherlands
Rural small town Netherlands provided for comparison the intermediate diet pattern of central Europe – reliance on meat, butter fat, and tuberous vegetables, with a minimum of fruits, vegetables, legumes, grains, complex carbohydrates, and fibers. Because only one area was under consideration for study by the Dutch, the rural town of Zutphen, interest was confined to individual correlations of risk and disease. Dutch collaborators have been among the more vigorous to characterize the individual diet, and have conducted frequent, long-term follow-up of their cohort.
I have few adventures-in-the-field to recount, however, from the Zutphen surveys, because Minnesota and other “external” colleagues were not invited by the original principal investigator to participate in the standard baseline, five, and ten-year examinations. The happenings there are nevertheless modestly represented by Daan Kromhout in a companion volume, “The Seven Countries Study: A Scientific Adventure in Cardiovascular Disease Epidemiology.”
Studies among the good burgers of Zutphen have been especially rewarding as a result of the insistence of the independent Netherlands investigators to carry out annual rather than quinquennial surveys of its cohort. This departure from Seven Countries protocol has greatly enriched the data available, particularly on population trends in risk factors, and has enhanced the power of individual prediction from multiple measures of risk characteristics, including diet. The early results of these trends and predictions led the new director, Daan Kromhout, to renovate Seven Countries dietary surveys by reestablishing chemical analyses of foods to simulate those of the first surveys in many areas. This greatly raised the power of the study for ecologic correlations of diet, risk, and disease.
The Zutphen Study was the first anywhere to find in a population-based sample an association between regular fish consumption and low coronary heart disease risk. It went further, to elaborate the roles of fish and fish oils in cardiovascular disease; the role of dietary fiber in cancer; the inverse relationship of energy intake to coronary heart disease deaths; the association of dietary cholesterol with coronary disease mortality; the inverse relationship of Vitamin C intake to long-term mortality from lung cancer; and the association of sugar and calcium intake with long-term incidence of gall stones.
Repeated measures over the numerous surveys in Zutphen have allowed refinement of the prediction equations from the traditional cardiovascular disease risk factors, as well as of the relationship among skin folds, cigarette smoking and diabetes; the relationship of glucose tolerance to coronary heart disease; the relationship of physical activity to high- density lipoprotein cholesterol; the relationship of energy balance to serum cholesterol; the relationship of alcohol, calcium, and potassium intake to blood pressure; and the intercorrelations of saturated fatty acids, dietary cholesterol, and glucose tolerance.
The Zutphen Study has made major contributions to the methodology of measuring physical activity. The Netherlands group has also extended knowledge of the predictive power of occupation, of subjective feelings of health, and of mental depression, for coronary heart disease and death.
Louise Dalderup and FSP van Buchem
From Ancel Keys’ early contacts with distinguished Dutch nutritionists, M.J.L. Dols, P. Muntendam, and C. den Hartog, they were keen to be a part of the Seven Countries Study and named young academic nutritionist Louise Dalderup as the point person. Competent and well organized, Dalderup joined the activity with enthusiasm, participating in the Nicotera pilot survey in 1957. But when the Medical Research Council was finally considering the cost and commitment of joining the Seven Countries Study, they decided that a prestigious senior medical person should be in charge. Professor Van Buchem, recently retired from his position as Chief of Medicine, under a cloud that is not relevant to this story, took over the Zutphen Project with a vengeance. He was resistant to ideas about standardization or to any true collaboration. He allowed no “interference” in the surveys by visitors from Minnesota or elsewhere. Though he frequently created diversions at meetings of the international investigators, we thought that he had eventually signed on to the common study protocol, minus direct quality control or supervision of the field team.
Imagine our surprise, months later in Minnesota, when we received at Stadium Gate 27, the data from the first round Zutphen survey consisting of poor carbon copies of the medical histories and physical forms, and no electrocardiograms. In response to our written and then telegraphic communications, we were informed that the electrocardiograms would not leave Dutch premises, being “too valuable to risk their loss in surface transportation.” Air transportation in those days was too costly to be considered. The proposed solution to this standoff: send Blackburn to Holland to read and code the Zutphen electrocardiograms.
Already scheduled for a trip to Venice for the Research Committee of the International Society of Cardiology, plus a follow-up visit to Geneva to complete the Rose-Blackburn WHO survey manual, I made it a family affair. Wife and kids went to Nelly’s parents in Geneva, and I jaunted about the continent on Seven Countries Study business.
Van Buchem’s solicitous care of the Zutphen electrocardiograms was so intense that he insisted they be read and coded only in his own study, which in summer was in his beach cottage at Noordwyk. He maintained, furthermore, that I should stay in that somber bourgeois home with him and his wife. I opted rather to stay in a local resort hotel, spending a pleasant eight days there. I read cardiograms for several hours every morning chez van Buchem, to the limit of my concentration, and every afternoon took tennis lessons at the resort’s clay courts, and then ran the beach.
The Nordic shore was eerie. My youth on the bright beaches of Florida did not prepare me for the monochrome North Sea beaches, gray sands, puny dunes, chill, steely surf, and scudding dark clouds. The natives bask under an occasional pallid sun behind brightly colored windbreaks, the only color to be seen. Dogs and horses cavort on the sand along with bathers, joggers, and kite flyers.
In the end, all standard requirements of the study, and all eccentricities on both sides, were satisfactorily accommodated and no lasting harm done to the Minnesota-Dutch collaboration. As documented in the companion volume to this, “The Seven Countries Study. An Adventure in Cardiovascular Disease Epidemiology,” Daan Kromhout and company – innovative and delightful colleagues – became a central force in the study following van Buchem’s retirement.
Kromhout single-handedly instigated a renaissance in the nutritional studies of the Seven Countries Study, bringing to bear his education in nutrition at Wageningen and in epidemiology at Minnesota. He was named principal investigator of the Zutphen Study by Netherlands authorities in 1978, and began participating in the rebirth of Seven Countries Study activities that dated from the Iraklion meeting of investigators in 1979.
Quietly and industriously, Kromhout has effectively exploited the rich data from Zutphen in pioneer investigations of the individual and population correlations of nutrients – particularly fishes, fish oils, and anti-oxidants – with chronic disease mortality.
Representing the second generation of investigators in the Seven Countries Study, he is most appreciated for his innovative concepts and for maintaining excellent collaboration with the original principal investigators. He has renewed, refined, and extended the dietary hypotheses of the study; set into motion effective new investigations and editorial processes; and shared with others a vigorous new leadership throughout the study. Just as the efforts of Hironori Toshima stimulated the study with the remarkable scientific and social conference of 1993 in Fukuoka, so did Kromhout’s efforts boost the study with his editorship of the publication, “The Seven Countries Study. A Scientific Adventure in Cardiovascular Disease Epidemiology.” Kromhout was the one who initiated the book, obtained funds for its support, and pushed it through to publication in the Netherlands in 1994. He and the Dutch also sponsored a delightful scientific meeting of Seven Countries investigators and others at the 30th anniversary of the Zutphen Study in 1990.
Kromhout remains an active investigator in the Seven Countries Study and of other issues in nutrition. His stature and work have been recognized by his being named Director of Public Health in the National Institute of Health and Environmental Protection in Bilthoven, and by his participation in other international collaborative studies, including MONICA and INTERSALT.
The energy, quiet efficiency, and collegiality of Daan Kromhout is centrally involved in this international study of human characteristics and disease risk.