{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:35:48Z","timestamp":1760142948994,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T00:00:00Z","timestamp":1705017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Based mainly on their personal experience, the authors try to describe the origin of cardiovascular disease (CVD) epidemiology and the problems and difficulties practitioners attempted to tackle and solve during the first few decades of this discipline, which started around the middle of the last century. Beyond identifying the characteristics of those who became CVD epidemiologists, a description is given of the initial structures of the involved studies, participation rates, risk factors measurements and standardization, clinical measurements and diagnostic criteria, mortality data collection and coding, data loading and analysis, plus a number of problems still unsolved at the beginning of the 2000s. Despite many obstacles, and the initial hostility of the medical\u2013scientific establishment, CVD epidemiology represented a revolution in researching in the bio-medical field. In the end, it also affected clinical research introducing the use of the quantitative approach bound to mathematical\u2013statistical procedures. After decades of hard work and the development of a number of innovative tools, CVD epidemiology received its deserved recognition, eventually being accepted as a reputable and independent scientific discipline. Yet, in several countries, especially those from Southern Europe, an academic recognition of CVD epidemiology is still lacking.<\/jats:p>","DOI":"10.3390\/jcdd11010020","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T03:54:34Z","timestamp":1705031674000},"page":"20","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Search of Risk Factors: The Origin and Early Stages of Cardiovascular Epidemiology"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6209-8416","authenticated-orcid":false,"given":"Alessandro","family":"Menotti","sequence":"first","affiliation":[{"name":"Association for Cardiac Research, 00182 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-7838","authenticated-orcid":false,"given":"Paolo Emilio","family":"Puddu","sequence":"additional","affiliation":[{"name":"Association for Cardiac Research, 00182 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,12]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Cholesterol metabolism and racial pathology","volume":"56","year":"1916","journal-title":"Geneeskd. Tijdschr. Voor Ned.-Indie"},{"unstructured":"Snapper, I. (1965). Chinese Lessons to Western Medicine, Grune & Stratton.","key":"ref_2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.0954-6820.1950.tb12300.x","article-title":"The relation of nutrition to health: A statistical study of the effect of the war-time on arteriosclerosis, cardiosclerosis, tuberculosis and diabetes","volume":"246","author":"Malmros","year":"1950","journal-title":"Acta Med. Scand."},{"key":"ref_4","first-page":"665","article-title":"Heart diseases in Tripolitania. A clinical and statistical study","volume":"4","author":"Menotti","year":"1963","journal-title":"Malat. Cardiovasc."},{"unstructured":"(1958). Report to the Government of Libya on Nutrition, Food and Agriculture Organization of the United Nations. FAO Report No. 920.","key":"ref_5"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1161\/01.CIR.28.3.381","article-title":"Coronary heart disease among Minnesota business and professional men followed fifteen years","volume":"28","author":"Keys","year":"1963","journal-title":"Circulation"},{"unstructured":"Dawber, T.R. (1980). The Epidemiology of Atherosclerotic Disease, Harvard University Press.","key":"ref_7"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.7326\/0003-4819-55-1-33","article-title":"Factors of risk in the development of coronary heart disease\u2013six-year follow-up experience. The Framingham Study","volume":"55","author":"Kannel","year":"1961","journal-title":"Ann. Intern. Med."},{"key":"ref_9","first-page":"1","article-title":"Epidemiological studies related to coronary heart disease. Characteristics of men aged 40-59 in Seven Countries","volume":"460","author":"Keys","year":"1967","journal-title":"Acta Med. Scand."},{"unstructured":"Keys, A., and Keys, M. (1975). The Mediterranean Way, Doubleday & Co.","key":"ref_10"},{"unstructured":"(2023, July 10). Heart Attack Prevention. A History of Cardiovascular Epidemiology, by H. Blackburn., University of Minnesota. Available online: http:\/\/www.epi.umn.edu\/cvdepi\/.","key":"ref_11"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6853","DOI":"10.1038\/s41598-018-25128-x","article-title":"Weighted multi-marker genetic risk scores for incident coronary heart disease among individuals of African, Latino and East-Asian ancestry","volume":"8","author":"Iribarren","year":"2018","journal-title":"Sci. Rep."},{"unstructured":"Kromhout, D., Menotti, A., and Blackburn, H. (1994). A Scientific Adventure in Cardiovascular Disease Epidemiology, Marjan Nijssen-Kramer Studio and RIVM.","key":"ref_13"},{"doi-asserted-by":"crossref","unstructured":"Kundu, S., Rahman, A., Kabir, H., Al Banna, H., Hagan, J.E., Srem Sai, M., and Wang, L. (2023). Diabetes, hypertension, and comorbidity among Bangladeshi adults: Associated factors and socio-economic inequalities. J. Cardiovasc. Dev. Dis., 10.","key":"ref_14","DOI":"10.3390\/jcdd10010007"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"i721","DOI":"10.1136\/bmj.i721","article-title":"Primary prevention and risk factor reduction in coronary heart disease mortality among working aged men and women in eastern Finland over 40 years: Population based observational study","volume":"352","author":"Jousilahti","year":"2016","journal-title":"BMJ"},{"unstructured":"Rose, G., and Blackburn, H. (1968). Cardiovascular Survey Methods, World Health Organization.","key":"ref_16"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1097\/MBP.0000000000000437","article-title":"Validation of the Omron HBP-1320 for professional use according to the ANSI\/AAMI\/ISO 81060-2: 2013 protocol and the 2010 revision of the European Society of Hypertension International Protocol","volume":"25","author":"Saito","year":"2020","journal-title":"Blood Press. Monit."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1161\/01.CIR.21.6.1160","article-title":"The electrocardiogram in population studies. A classification system","volume":"21","author":"Blackburn","year":"1960","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0022-0736(96)80025-2","article-title":"Validation of a new computer program for Minnesota coding","volume":"29","author":"Kors","year":"1996","journal-title":"J. Electrocardiol."},{"key":"ref_20","first-page":"1","article-title":"Coronary heart disease in seven countries","volume":"41","author":"Keys","year":"1970","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/ije\/dyab116","article-title":"Are competing-risk models superior to standard Cox models for predicting cardiovascular risk in older adults? Analysis of a whole-of-country primary prevention cohort aged \u2265 65 years","volume":"51","author":"Cooper","year":"2022","journal-title":"Int. J. Epidemiol."},{"unstructured":"World Health Organization (1965). International Classification of Diseases and Causes of Death, WHO. [8th ed.].","key":"ref_22"},{"unstructured":"(2023, July 10). Verbal Autopsy Standards. The 2012 WHO Verbal Autopsy Instruments. Release Candidate 1, WHO, Geneva, July 2023. Available online: https:\/\/cdn.who.int\/media\/docs\/default-source\/mca-documents\/rmncah\/verbal-autopsy-standards-the-2012-who-verbal-autopsy-instrument---release-candidate-1.pdf?sfvrsn=68f9b5a4_1.","key":"ref_23"},{"doi-asserted-by":"crossref","unstructured":"Kromhout, D., Menotti, A., and Blackburn, H. (2002). Diet, Lifestyle and Risk Factors in the Seven Countries Study, Kluwer Academic Publisher.","key":"ref_24","DOI":"10.1007\/978-1-4615-1117-5"},{"unstructured":"Bradford-Hill, A. (2005). Encyclopedia of Biostatistics Online, John Wiley & Sons. Ltd.","key":"ref_25"},{"unstructured":"Puska, P., Tuomilehto, J., Nissinen, A., and Vartiainen, E. (1995). The North Karelia Project. 20 Years Results and Experiences, National Public Health Institute Finland.","key":"ref_26"},{"doi-asserted-by":"crossref","unstructured":"Veterans Administration Cooperative Study Group (1967). Effect of treatment on morbidity in hypertension: Results in patients with diastolic blood pressure averaging 115 through 129 mmHg. JAMA, 202, 1028\u20131034.","key":"ref_27","DOI":"10.1001\/jama.202.11.1028"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/S0140-6736(81)91338-6","article-title":"Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo Study Group of a randomised trial in healthy men","volume":"2","author":"Hjerman","year":"1981","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1056\/NEJM198711123172001","article-title":"Helsinki Heart Study: Primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease","volume":"317","author":"Frick","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/qjmed\/hcn158","article-title":"History of the cholesterol controversy in Britain","volume":"102","author":"Thompson","year":"2009","journal-title":"QJM"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/0021-9681(77)90055-8","article-title":"Identifying subsets of major risk factors in multivariate estimation of coronary risk","volume":"30","author":"Menotti","year":"1977","journal-title":"J. Chronic Dis."},{"doi-asserted-by":"crossref","unstructured":"Prospective Studies Collaboration (2007). Blood cholesterol and vascular mortality by age, sex and blood pressure: A meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet, 370, 1829\u20131839.","key":"ref_32","DOI":"10.1016\/S0140-6736(07)61778-4"},{"doi-asserted-by":"crossref","unstructured":"Puddu, P.E., and Menotti, A. (2023). Heart disease of uncertain etiology: A new definition of heart failure for epidemiological studies. J. Cardiovasc. Dev. Dis., 10.","key":"ref_33","DOI":"10.3390\/jcdd10030132"},{"doi-asserted-by":"crossref","unstructured":"Menotti, A., Puddu, P.E., Kafatos, A., Tolonen, H., Adachi, H., and Jacobs, D.R. (2023). Cardiovascular mortality in 10 Cohorts of middle-aged men followed-up 60 years until extinction: The Seven Countries Study. J. Cardiovasc. Dev. Dis., 10.","key":"ref_34","DOI":"10.3390\/jcdd10050201"},{"doi-asserted-by":"crossref","unstructured":"Puddu, P.E., Piras, P., Kafatos, A., Adachi, H., Tolonen, H., and Menotti, A. (2023). Competing risks of coronary heart disease mortality versus other causes of death in 10 cohorts of middle-aged men of the Seven Countries Study followed for 60 years to extinction. J. Cardiovasc. Dev. Dis., 10.","key":"ref_35","DOI":"10.3390\/jcdd10120482"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e003768","DOI":"10.1161\/JAHA.116.003768","article-title":"Folic acid supplementation and the risk of cardiovascular diseases: A meta-analysis of randomized controlled trials","volume":"5","author":"Li","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41591-020-0800-0","article-title":"Polygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers","volume":"26","author":"Mars","year":"2020","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"139","DOI":"10.7326\/0003-4819-150-2-200901200-00012","article-title":"Personalized genetic prediction: Too limited, too expensive, or too soon?","volume":"150","author":"Ioannidis","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1097\/HJR.0b013e32832d49e1","article-title":"Artificial neural network versus multiple logistic function to predict 25-year coronary heart disease mortality in the Seven Countries Study","volume":"16","author":"Puddu","year":"2009","journal-title":"Eur. J. Cardiovasc. Prev. Rehabil."},{"doi-asserted-by":"crossref","unstructured":"Alaa, A.M., Bolton, T., Di Angelantonio, W., Rudd, J.H.F., and van der Schaar, M. (2019). Cardiovascular disease risk prediction using automated machine learning: A prospective study of 423,604 UK Biobank participants. PLoS ONE, 14.","key":"ref_40","DOI":"10.1371\/journal.pone.0213653"}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/11\/1\/20\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:45:10Z","timestamp":1760103910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/11\/1\/20"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,12]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["jcdd11010020"],"URL":"https:\/\/doi.org\/10.3390\/jcdd11010020","relation":{},"ISSN":["2308-3425"],"issn-type":[{"type":"electronic","value":"2308-3425"}],"subject":[],"published":{"date-parts":[[2024,1,12]]}}}