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Seven Countries Study

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Ancel Keys

The Seven Countries Study is an epidemiological longitudinal study directed by Ancel Keys at what is today the University of Minnesota Laboratory of Physiological Hygiene & Exercise Science (LPHES). Begun in 1956 with a yearly grant of US$200,000 from the U.S. Public Health Service, the study was first published in 1978 and then followed up on its subjects every five years thereafter.

As the world's first multicountry epidemiological study, it systematically examined the relationships between lifestyle, diet, coronary heart disease and stroke in different populations from different regions of the world. It directed attention to the causes of coronary heart disease and stroke, but also showed that an individual’s risk can be changed.

Writing in 1975, project officer Henry Blackburn identified two "strikingly polar attitudes", characterising them as persisting "academic" and "pragmatic" views with "much talk from each and little listening between."[1]

History

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In the 1940s, a University of Minnesota researcher, Ancel Keys, postulated that the apparent epidemic of heart attacks in middle-aged American men was related to their mode of life and possibly modifiable physical characteristics. He first explored this idea in a group of Minnesota business and professional men (executives aged 45 to 55) that he recruited into a prospective study in 1947, the first of many cohort studies eventually mounted internationally. The U.S. Public Health Service agreed to fund the study (and then set up and proceeded to fund the Framingham Heart Study on a larger scale). The Minnesota men were followed through 1981 and the first major report appeared in 1963 after the fifteen-year follow-up study.[2][3]

The study contributed much to survey methods and confirmed larger studies that reported earlier on the predictive value for heart attack of several characteristics, the now-traditional risk factors of blood pressure and blood cholesterol level and cigarette smoking. Keys traveled widely with his wife Margaret who tested people's serum cholesterol. They sent their samples back to Minnesota for analysis. In 1952, Keys's hypothesis that coronary heart disease could be related to diet was first published in Voeding in The Netherlands.[4] His work in post-wartime Naples led him to seek organization and funding for studies of different populations, as did his subsequent work in Uganda; Cape Town, South Africa; Sardinia; Bologna; and Ilomantsi, Finland; and with Japanese men living in Hawaii and in Japan. He decided to concentrate on men living in villages, rather than those in cities where the population moved around frequently.[3]

In the mid-1950s, with improved methods and design, Keys recruited collaborating researchers in seven countries to mount the first cross-cultural comparison of heart attack risk in populations of men engaged in traditional occupations in cultures contrasting in diet, especially in the proportion of fat calories of different composition, the Seven Countries Study still under observation today.

The Seven Countries Study was formally started in fall 1958 in Yugoslavia. In total, 12,763 males, 40–59 years of age, were enrolled as 16 cohorts, in seven countries, in four regions of the world (United States, Northern Europe, Southern Europe, Japan). One cohort is in the United States, two cohorts in Finland, one in the Netherlands, three in Italy, five in Yugoslavia (two in Croatia, and three in Serbia), two in Greece, and two in Japan. The entry examinations were performed between 1958 and 1964 with an average participation rate of 90%, lowest in the US, with 75% and highest in one of the Japanese cohorts, with 100%.[5] The study has continued for more than 50 years.

Major findings

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The Seven Countries Study suggested that the risk and rates of heart attack and stroke (CVR), both at the population level and at the individual level, correlated directly and independently to the level of total serum cholesterol, in seven sampled out countries. It demonstrated that the correlation between blood cholesterol level and coronary heart disease (CHD) risk from 5 to 40 years follow-up is found consistently across different specially selected cultures in these seven countries. Cholesterol and obesity correlated with increased mortality from cancer.[6][7][8] The Seven Countries Study suggested that elevated blood pressure (hypertension) was correlated with risk of coronary heart disease and stroke. It showed that the mortality rate after a coronary heart disease event or stroke was associated with the level of hypertension. In several cohorts of the study, stroke deaths exceeded deaths from coronary heart disease.[9][10] It hinted that differences in overall mortality between the different regions of the seven countries are largely associated with variation in cardiovascular mortality.[11] Coronary deaths in the United States and Northern Europe greatly exceeded those in Southern Europe, even when controlled for age, cholesterol, blood pressure, smoking, physical activity, and weight.

The Seven Countries Study was investigated further in regard to an eating pattern loosely characterized as the Mediterranean Diet.[12][13][14][11][15] What exactly is meant by "Mediterranean Diet" today, was detailed by Antonia Trichopoulou (wife of Dimitrios Trichopoulos),[16] and Anna Ferro-Luzzi.[17] The diet was publicized and popularized by Greg Drescher of the Oldways Preservation and Exchange Trust and by Walter Willett of the Harvard School of Public Health.[18][19][20][21][22]

The Seven Countries Study also showed that the slowly changing habits of a population in the Mediterranean region, from a healthy, active lifestyle and diet, to a less active lifestyle and a diet influenced by the Western pattern diet, significantly correlated with increased risk of heart disease.[23][24] Meanwhile, it has been confirmed by other researchers that there is an inverse association between adherence to the Mediterranean Diet and the incidence of fatal and non- fatal heart disease in initially healthy middle-aged adults in the Mediterranean region.[25]

The Seven Countries Study, along with other studies, e.g., the Framingham Heart Study and the Nurses' Health Study, showed the importance of overweight, obesity and regular exercise as health issues.[26][27][28][29] It showed a correlation between good cardiovascular health and dementia in the general population. It also showed that cardiovascular risk factors in mid life are significantly associated with increased risk of dementia death later in life.[30] It indicated that cigarette smoking is a highly significant predictor of the development of coronary heart disease, leading to excess rates of angina pectoris, myocardial infarction (MI) and coronary death, along with other studies about smoking, e.g., the Framingham Heart Study and the British Doctors Study.[31][32][33][34]

Influence on public health policy

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Initial results from the Seven Countries Study in North Karelia (Finland) prompted public pressure for the authorities to act to reduce historically high levels of chronic disease in the region. The results influenced a subsequent public health program, the North Karelia Project, which ran from 1972 until 1997, and which had among its aims a reduction in levels of peoples' saturated fat intake.[35]

See also

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References

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  1. ^ Blackburn Henry (1975). "Contrasting Professional Views on Atherosclerosis and Coronary Disease". N Engl J Med. 292 (2): 105–107. doi:10.1056/NEJM197501092920214. PMID 1109429.
  2. ^ Keys A, Taylor HL, Blackburn H, Brozek J, Anderson JT, Simonson E (1963). "Coronary Heart Disease among Minnesota Business and Professional Men Followed Fifteen Years". Circulation. 28 (3): 381–95. doi:10.1161/01.cir.28.3.381. PMID 14059458.
  3. ^ a b Keys, Ancel (1993). "The Inception and Pilot Surveys". In Kromhout, Daan; Menotti, Alessandro; Blackburn, Henry (eds.). The Seven Countries Study: A Scientific Adventure in Cardiovascular Disease Epidemiology. Utrecht, The Netherlands: printed by Brouwer Offset bv. pp. 16–25. ISBN 906960048X.
  4. ^ Keys, A. (1952). "The Cholesterol Problem". Voeding (13): 539–555.
  5. ^ Ancel Keys (ed), Seven Countries: A multivariate analysis of death and coronary heart disease, 1980. Cambridge, Mass.: Harvard University Press. ISBN 0-674-80237-3.
  6. ^ Kromhout, D (June 1999). "Serum cholesterol in cross-cultural perspective. The Seven Countries Study". Acta Cardiologica. 54 (3): 155–8. PMID 10478272.
  7. ^ Menotti, A; Lanti, M; Kromhout, D; Blackburn, H; Jacobs, D; Nissinen, A; Dontas, A; Kafatos, A; Nedeljkovic, S; Adachi, H (December 2008). "Homogeneity in the relationship of serum cholesterol to coronary deaths across different cultures: 40-year follow-up of the Seven Countries Study". European Journal of Cardiovascular Prevention and Rehabilitation. 15 (6): 719–25. doi:10.1097/HJR.0b013e328315789c. PMC 2642008. PMID 19050437.
  8. ^ Panagiotakos, DB; Pitsavos, C; Polychronopoulos, E; Chrysohoou, C; Menotti, A; Dontas, A; Stefanadis, C (July 2005). "Total cholesterol and body mass index in relation to 40-year cancer mortality (the Corfu cohort of the seven countries study)". Cancer Epidemiology, Biomarkers & Prevention. 14 (7): 1797–801. doi:10.1158/1055-9965.EPI-04-0907. PMID 16030119.
  9. ^ van den Hoogen PC, Feskens EJ, Nagelkerke NJ, Menotti A, Nissinen A, Kromhout D (Jan 2000). "The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world". N Engl J Med. 342 (1): 1–8. doi:10.1056/nejm200001063420101. PMID 10620642.
  10. ^ Menotti A, Jacobs DR Jr, Blackburn H, Kromhout D, Nissinen A, Nedeljkovic S, Buzina R, Mohacek I, Seccareccia F, Giampaoli S, Dontas A, Aravanis C, Toshima H (Mar 1996). "Twenty-five-year prediction of stroke deaths in the seven countries study: the role of blood pressure and its changes". Stroke. 27 (3): 381–7. doi:10.1161/01.str.27.3.381. PMID 8610299.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ a b Menotti A, Keys A, Aravanis C, Blackburn H, Dontas A, Fidanza F, Karvonen MJ, Kromhout D, Nedeljkovic S, Nissinen A, et al. (Jun 1989). "Seven Countries Study. First 20-year mortality data in 12 cohorts of six countries". Ann. Med. 21 (3): 175–9. doi:10.3109/07853898909149929. PMID 2765258.
  12. ^ Keys A, Aravanis C, Blackburn HW, Van Buchem FS, Buzina R, Djordjević BD, Dontas AS, Fidanza F, Karvonen MJ, Kimura N, Lekos D, Monti M, Puddu V, Taylor HL (1966). "Epidemiological studies related to coronary heart disease: characteristics of men aged 40-59 in seven countries". Acta Med Scand Suppl. 460: 1–392. PMID 5226858.
  13. ^ Keys A (1970). "Coronary heart disease in seven countries". Circulation. 41 (4): 1–200. doi:10.1161/01.CIR.41.4S1.I-1. PMID 5442783. S2CID 80146863.
  14. ^ Keys A, Menotti A, Aravanis C, Blackburn H, Djordevic BS, Buzina R, Dontas AS, Fidanza F, Karvonen MJ, Kimura N; et al. (Mar 1984). "The seven countries study: 2,289 deaths in 15 years". Preventive Medicine. 13 (2): 141–54. doi:10.1016/0091-7435(84)90047-1. PMID 6739443.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, van Staveren WA (Sep 2004). "Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project". JAMA. 292 (12): 1433–9. doi:10.1001/jama.292.12.1433. PMID 15383513.
  16. ^ Trichopoulou, Antonia; Costacou, Tina; Bamia, Christina; Trichopoulos, Dimitrios (26 June 2003). "Adherence to a Mediterranean Diet and Survival in a Greek Population". N Engl J Med. 348 (26): 2599–2608. doi:10.1056/NEJMoa025039. PMID 12826634.
  17. ^ Willett, W.C.; Sacks, F.; Trichopoulou, A.; Drescher., G.; Ferro-Luzzi, A.; Helsing, E.; Trichopoulos, D. (June 1995). "Mediterranean diet pyramid: a cultural model for healthy eating". American Journal of Clinical Nutrition. 61 (6): 1402S–6S. doi:10.1093/ajcn/61.6.1402s. PMID 7754995. We present a food pyramid that reflects Mediterranean dietary traditions, which historically have been associated with good health. This Mediterranean diet pyramid is based on food patterns typical of Crete, much of the rest of Greece, and southern Italy in the early 1960s, where adult life expectancy was among the highest in the world and rates of coronary heart disease, certain cancers, and other diet-related chronic diseases were among the lowest.
  18. ^ Kushi LH, Lenart EB, Willett WC (Jun 1995). "Health implications of Mediterranean diets in light of contemporary knowledge. 1. Plant foods and dairy products". Am J Clin Nutr. 61 (6): 1407S–1415S. doi:10.1093/ajcn/61.6.1407s. PMID 7754996.
  19. ^ Kushi LH, Lenart EB, Willett WC (Jun 1995). "Health implications of Mediterranean diets in light of contemporary knowledge. 2. Meat, wine, fats, and oils". Am J Clin Nutr. 61 (6): 1416S–1427S. doi:10.1093/ajcn/61.6.1416s. PMID 7754997.
  20. ^ Willett WC (Feb 2006). "The Mediterranean diet: science and practice". Public Health Nutr. 9 (1A): 105–10. doi:10.1079/phn2005931. PMID 16512956.
  21. ^ Fung TT, Rexrode KM, Mantzoros CS, Manson JE, Willett WC, Hu FB (Mar 2009). "Mediterranean diet and incidence of and mortality from coronary heart disease and stroke in women". Circulation. 119 (8): 1093–100. doi:10.1161/circulationaha.108.816736. PMC 2724471. PMID 19221219.
  22. ^ Eat, Drink, and Be Healthy: The Harvard Medical School Guide to Healthy Eating. By Walter C. Willett. Free Press. 2005. ISBN 0-7432-6642-0
  23. ^ Kafatos A, Diacatou A, Voukiklaris G, Nikolakakis N, Vlachonikolis J, Kounali D, Mamalakis G, Dontas AS (Jun 1997). "Heart disease risk-factor status and dietary changes in the Cretan population over the past 30 y: the Seven Countries Study". Am J Clin Nutr. 65 (6): 1882–6. doi:10.1093/ajcn/65.6.1882. PMID 9174487.
  24. ^ Menotti A, Keys A, Kromhout D, Blackburn H, Aravanis C, Bloemberg B, Buzina R, Dontas A, Fidanza F, Giampaoli S, et al. (Sep 1993). "Inter-cohort differences in coronary heart disease mortality in the 25-year follow-up of the seven countries study". Eur J Epidemiol. 9 (5): 527–36. doi:10.1007/bf00209531. PMID 8307138. S2CID 39022334.
  25. ^ Martínez-González MA, García-López M, Bes-Rastrollo M, Toledo E, Martínez-Lapiscina EH, Delgado-Rodriguez M, Vazquez Z, Benito S, Beunza JJ (2010). "Mediterranean diet and the incidence of cardiovascular disease: A Spanish cohort". Nutr Metab Cardiovasc Dis. 21 (4): 237–44. doi:10.1016/j.numecd.2009.10.005. PMID 20096543.
  26. ^ Visscher TL, Seidell JC, Menotti A, Blackburn H, Nissinen A, Feskens EJ, Kromhout D (Apr 2000). "Underweight and overweight in relation to mortality among men aged 40-59 and 50-69 years: the Seven Countries Study". Am J Epidemiol. 151 (7): 660–6. doi:10.1093/oxfordjournals.aje.a010260. PMID 10752793.
  27. ^ Kromhout D, Bloemberg B, Feskens E, Menotti A, Nissinen A (Apr 2000). "Saturated fat, vitamin C and smoking predict long-term population all-cause mortality rates in the Seven Countries Study". Int J Epidemiol. 29 (2): 260–5. doi:10.1093/ije/29.2.260. PMID 10817122.
  28. ^ Kromhout D, Bloemberg B, Seidell JC, Nissinen A, Menotti A (Mar 2001). "Physical activity and dietary fiber determine population body fat levels: the Seven Countries Study". Int J Obes Relat Metab Disord. 25 (3): 301–6. doi:10.1038/sj.ijo.0801568. PMID 11319625.
  29. ^ Keys A, Aravanis C, Blackburn H, Van Buchem FS, Buzina R, Djordjevic BS, Fidanza F, Karvonen MJ, Menotti A, Puddu V, Taylor HL (Apr 1972). "Probability of middle-aged men developing coronary heart disease in five years". Circulation. 45 (4): 815–28. doi:10.1161/01.cir.45.4.815. PMID 5016014.
  30. ^ Alonso A, Jacobs DR Jr, Menotti A, Nissinen A, Dontas A, Kafatos A, Kromhout D (May 2009). "Cardiovascular risk factors and dementia mortality: 40 years of follow-up in the Seven Countries Study". J Neurol Sci. 280 (1–2): 79–83. doi:10.1016/j.jns.2009.02.004. PMID 19251275. S2CID 709629.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  31. ^ Menotti A, Lanti M, Nedeljkovic S, Nissinen A, Kafatos A, Kromhout D (Jan 2006). "The relationship of age, blood pressure, serum cholesterol and smoking habits with the risk of typical and atypical coronary heart disease death in the European cohorts of the Seven Countries Study". Int J Cardiol. 106 (2): 157–63. doi:10.1016/j.ijcard.2004.12.092. PMID 16321686.
  32. ^ Jacobs DR Jr, Adachi H, Mulder I, Kromhout D, Menotti A, Nissinen A, Blackburn H (Apr 1999). "Cigarette smoking and mortality risk: twenty-five-year follow-up of the Seven Countries Study". Arch Intern Med. 159 (7): 733–40. doi:10.1001/archinte.159.7.733. PMID 10218754.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  33. ^ Doll R, Peto R, Boreham J, Sutherland I (Jun 2004). "Mortality in relation to smoking: 50 years' observations on male British doctors". BMJ. 328 (7455): 1519. doi:10.1136/bmj.38142.554479.ae. PMC 437139. PMID 15213107.
  34. ^ Freund KM, Belanger AJ, D'Agostino RB, Kannel WB (Jul 1993). "The health risks of smoking. The Framingham Study: 34 years of follow-up". Ann Epidemiol. 3 (4): 417–24. doi:10.1016/1047-2797(93)90070-k. PMID 8275219.
  35. ^ Jauho M (May 2021). "The North Karelia Project (1972-1997) and the Origins of the Community Approach to Cardiovascular Disease Prevention". Am J Public Health. 111 (5): 890–895. doi:10.2105/AJPH.2020.306016. PMC 8034030. PMID 33734841.
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