{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:55:02Z","timestamp":1760144102847,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"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>Purpose. To study a male Italian cohort (initially aged 40\u201359, n = 1712) during 61 years and the natural history of major CVD mortality categories including coronary heart disease (CHD), stroke and other heart diseases of uncertain etiology (HDUE), including congestive heart failure) along with their risk factor relationships. Methods and Results. Cox models were run with 12 covariates as possible predictors measured at entry to the study. About 93% of all CVD deaths were covered by the three major groups selected here (N = 751): 37.4% of them were diagnosed as CHD, 30.6% as stroke and 28.5% as HDUE. CHD declined in the last 20 years of follow-up, while a sharp increase in HDUE mortality was seen. Baseline mean levels of serum cholesterol were 209.6, 204.2 and 198.0 mg\/dL, respectively, for CHD, stroke and HDUE deaths: the multivariable coefficients of serum cholesterol were positive and significant for CHD (p &lt; 0.0001), and stroke (p = 0.0203) and not significant for HDUE (p = 0.3467). In Fine\u2013Gray models, the algebraic signs of cholesterol coefficients were opposite for CHD versus the other mortality categories (t = 3.13). The predictive performances of remaining risk factors were varied whereas that of Cox models was not very good, probably due to the attrition phenomenon and possible competing risks. Conclusion. Large differences in natural history and risk factors were found comparing the three CVD conditions, potentially indicating different etiologies and pointing to the need of not mixing them up in a grouped CVD category.<\/jats:p>","DOI":"10.3390\/jcdd11030094","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T06:35:30Z","timestamp":1711002930000},"page":"94","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mortality Time-Trends of Different Cardiovascular Diseases in a Practically Extinct Cohort of Italian Middle-Aged Men Followed-Up for 61 Years: A Possible Etiological Explanation?"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-7838","authenticated-orcid":false,"given":"Paolo Emilio","family":"Puddu","sequence":"first","affiliation":[{"name":"Association for Cardiac Research, 00182 Rome, Italy"},{"name":"EA 4650, Signalisation, \u00c9lectrophysiologie et Imagerie des L\u00e9sions d\u2019Isch\u00e9mie Reperfusion Myocardique, Universit\u00e9 de Normandie, 14000 Caen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9832-2742","authenticated-orcid":false,"given":"Paolo","family":"Piras","sequence":"additional","affiliation":[{"name":"Department of Structural Engineering, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6209-8416","authenticated-orcid":false,"given":"Alessandro","family":"Menotti","sequence":"additional","affiliation":[{"name":"Association for Cardiac Research, 00182 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ijcard.2015.05.151","article-title":"Lifetime prediction of coronary heart disease and heart disease of uncertain etiology in a 50-year follow-up population study","volume":"196","author":"Menotti","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.ijcard.2015.06.046","article-title":"Natural history of coronary heart disease and heart disease of uncertain etiology: Findings from a 50-year population study","volume":"197","author":"Puddu","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ijcard.2015.08.050","article-title":"Lifestyle behaviour and lifetime incidence of heart diseases","volume":"201","author":"Menotti","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1159\/000006744","article-title":"Relationship of some risk factors with typical and atypical manifestations of coronary heart disease","volume":"89","author":"Menotti","year":"1998","journal-title":"Cardiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ijcard.2004.12.092","article-title":"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","volume":"106","author":"Menotti","year":"2005","journal-title":"Int. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1016\/j.ijcard.2013.06.143","article-title":"Epidemiology of typical coronary heart disease versus heart disease of uncertain etiology (atypical) fatalities and their relationships with classic coronary risk factors","volume":"168","author":"Menotti","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.numecd.2019.11.010","article-title":"How the Seven Countries Study contributed to the launch and development of cardiovascular epidemiology in Italy. A historical perspective","volume":"30","author":"Menotti","year":"2020","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_8","unstructured":"WHO (1965). International Classification of Diseases, World Health Organization. Eight Revision."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kromhout, D., Menotti, A., and Blackburn, H. (2002). Prevention of Coronary Heart Disease. Diet, Lifestyle and Risk Factors in the Seven Countries Study, Springer Science & Business Media.","DOI":"10.1007\/978-1-4615-1117-5"},{"key":"ref_10","unstructured":"Rose, G., and Blackburn, H. (1968). Cardiovascular Survey Methods, World Health Organization."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1093\/ajcn\/36.4.680","article-title":"Anthropometric measurement of muscle mass: Revised equations for calculating bone-free arm muscle area","volume":"36","author":"Hemsfield","year":"1982","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/clinchem\/2.3.145","article-title":"Cholesterol in serum and lipoprotein fractions: Its measurement and stability","volume":"2","author":"Anderson","year":"1956","journal-title":"Clin. Chem."},{"key":"ref_13","first-page":"186","article-title":"Coronary heart disease in seven countries","volume":"41","author":"Keys","year":"1970","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/00031305.2019.1583913","article-title":"Moving to a world beyond \u201cp < 0.05\u201d","volume":"73","author":"Wasserstein","year":"2019","journal-title":"Am. Stat."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Menotti, A., Puddu, P.E., Kafatos, A.G., 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.","DOI":"10.3390\/jcdd10050201"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"521","DOI":"10.2143\/AC.60.5.2004974","article-title":"Forty-year mortality from cardiovascular diseases and their risk factors in men of the Italian rural areas of the Seven Countries Study","volume":"60","author":"Menotti","year":"2005","journal-title":"Acta Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ijcard.2016.05.043","article-title":"Competing risks and lifetime coronary heart disease incidence during 50 years of follow-up","volume":"219","author":"Puddu","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.ijcard.2016.11.157","article-title":"Lifetime competing risks between coronary heart disease mortality and other causes of death during 50 years of follow-up","volume":"228","author":"Puddu","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.ijcard.2016.07.210","article-title":"Risk factors measured in middle-aged men predicting coronary events in geriatric age","volume":"222","author":"Menotti","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1161\/CIRCULATIONAHA.105.548206","article-title":"Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age","volume":"113","author":"Leip","year":"2006","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0140-6736(98)10279-9","article-title":"Lifetime risk of developing coronary heart disease","volume":"353","author":"Larson","year":"1999","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1161\/01.CIR.0000039105.49749.6F","article-title":"Lifetime risk for developing congestive heart failure: The Framingham Heart Study","volume":"106","author":"Larson","year":"2002","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/S1474-4422(07)70291-0","article-title":"Lifetime risk of stroke and dementia: Current concepts, and estimates from the Framingham Study","volume":"12","author":"Seshadri","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.amjcard.2004.03.023","article-title":"Framingham risk score and prediction of lifetime risk for coronary heart disease","volume":"94","author":"Wilson","year":"2004","journal-title":"Am. J. Cardiol."},{"key":"ref_25","first-page":"619","article-title":"Short-term versus long-term risk for coronary artery disease: Implications for lipid guidelines","volume":"6","year":"2006","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1001\/jama.2012.14312","article-title":"Lifetime risk and years lived free of total cardiovascular disease","volume":"308","author":"Wilkins","year":"2012","journal-title":"JAMA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.atherosclerosis.2020.08.014","article-title":"Lifetime risk predictions for cardiovascular diseases: Competing risks analyses on a population-based cohort in Sweden","volume":"312","author":"Stenling","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1177\/2047487313516563","article-title":"Lifetime risk for cardiovascular disease in a Chinese population: The Chinese Multi-Provincial Cohort Study","volume":"22","author":"Wang","year":"2015","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Prospective Studies Collaboration (2002). Age-specific relevance of usual blood pressure to vascular mortality: A meta-analysis of individual data for one million adults in 61 prospective studies. Lancet, 360, 1903\u20131913.","DOI":"10.1016\/S0140-6736(02)11911-8"},{"key":"ref_30","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 55000 vascular deaths. Lancet, 370, 1829\u20131839.","DOI":"10.1016\/S0140-6736(07)61778-4"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Prospective Studies Collaboration (2009). Body-mass index and cause-specific mortality in 900,000 adults: Collaborative analyses of 57 prospective studies. Lancet, 373, 1083\u20131096.","DOI":"10.1016\/S0140-6736(09)60318-4"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1093\/eurheartj\/ehw450","article-title":"Genomic prediction of coronary heart disease","volume":"37","author":"Abraham","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_33","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.","DOI":"10.3390\/jcdd10120482"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1177\/2047487318821250","article-title":"Coronary heart disease mortality trends during 50 years as explained by risk factor changes. The European cohorts of the Seven Countries Study","volume":"27","author":"Menotti","year":"2020","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/0002-9149(94)90140-6","article-title":"Coronary angiographic findings in asymptomatic men with suspected silent myocardial ischemia (the ECCIS Project)","volume":"73","author":"Antoniucci","year":"1994","journal-title":"Am. J. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Puddu, P.E., and Menotti, A. (2023). Heart diseases of uncertain etiology: A new definition of heart failure for epidemiological studies. J. Cardiovasc. Dev. Dis., 10.","DOI":"10.3390\/jcdd10030132"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1056\/NEJMoa2109191","article-title":"Childhood cardiovascular risk factors and adult cardiovascular events","volume":"386","author":"Jacobs","year":"2022","journal-title":"N. Engl. J. Med."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/11\/3\/94\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:17:18Z","timestamp":1760105838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/11\/3\/94"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,21]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["jcdd11030094"],"URL":"https:\/\/doi.org\/10.3390\/jcdd11030094","relation":{},"ISSN":["2308-3425"],"issn-type":[{"type":"electronic","value":"2308-3425"}],"subject":[],"published":{"date-parts":[[2024,3,21]]}}}