{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:23:15Z","timestamp":1790810595689,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mathematical models are able to reflect biological processes and to capture epidemiologic data. Thus, they may help elucidate roles of risk factors in disease progression. We propose to account for smoking, hypertension, and dyslipidemia in a previously published process-oriented model that describes the development of atherosclerotic lesions resulting in myocardial infarction (MI). The model is sex-specific and incorporates individual heterogeneity. It was applied to population-based individual risk factors and MI rates (Cooperative Health Research in the Region of Augsburg (KORA) study) together with subclinical atherosclerotic lesion data (Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study). Different model variants were evaluated, testing the association of risk factors with different disease processes. Best fits were obtained for smoking affecting a late-stage disease process, suggesting a thrombogenic role. Hypertension was mainly related to complicated, vulnerable lesions. Dyslipidemia was consistent with increasing the number of initial lesions. By accounting for heterogeneity, individual hazard ratios differ from the population average. The mean individual hazard ratio for smoking was twice the population-based hazard ratio for men and even more for women. Atherosclerotic lesion progression and MI incidence data can be related in a mathematical model to illuminate how risk factors affect different phases of this pathological process.<\/jats:p>","DOI":"10.1093\/aje\/kwac038","type":"journal-article","created":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T12:08:14Z","timestamp":1645877294000},"page":"1766-1775","source":"Crossref","is-referenced-by-count":17,"title":["From Atherosclerosis to Myocardial Infarction: A Process-Oriented Model Investigating the Role of Risk Factors"],"prefix":"10.1093","volume":"191","author":[{"given":"Cristoforo","family":"Simonetto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margit","family":"Heier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Christian","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Rospleszcz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,1]]},"reference":[{"issue":"6","key":"2022100608182790900_ref1","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/jnci\/66.6.1037","article-title":"Mutation and cancer: a model for human carcinogenesis","volume":"66","author":"Moolgavkar","year":"1981","journal-title":"J Natl Cancer Inst."},{"issue":"23","key":"2022100608182790900_ref2","doi-asserted-by":"crossref","first-page":"15095","DOI":"10.1073\/pnas.222118199","article-title":"Multistage carcinogenesis and the incidence of colorectal cancer","volume":"99","author":"Luebeck","year":"2002","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"3","key":"2022100608182790900_ref3","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s10552-007-9094-5","article-title":"Analysis of lung cancer incidence in the Nurses\u2019 Health and the Health Professionals\u2019 Follow-up Studies using a multistage carcinogenesis model","volume":"19","author":"Meza","year":"2008","journal-title":"Cancer Causes Control."},{"issue":"3","key":"2022100608182790900_ref4","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/ije\/dyv199","article-title":"Epidemiology, multistage models, and short-term mutagenicity tests","volume":"45","author":"Peto","year":"2016","journal-title":"Int J Epidemiol."},{"issue":"4","key":"2022100608182790900_ref5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0175386","article-title":"A mechanistic model for atherosclerosis and its application to the cohort of Mayak workers","volume":"12","author":"Simonetto","year":"2017","journal-title":"PLoS One."},{"issue":"10","key":"2022100608182790900_ref6","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1080\/09553002.2017.1310405","article-title":"Biologically-based mechanistic models of radiation-related carcinogenesis applied to epidemiological data","volume":"93","author":"R\u00fchm","year":"2017","journal-title":"Int J Radiat Biol."},{"issue":"1","key":"2022100608182790900_ref7","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1093\/aje\/kwn284","article-title":"Multistage modeling of leukemia in benzene workers: a simple approach to fitting the 2-stage clonal expansion model","volume":"169","author":"Richardson","year":"2009","journal-title":"Am J Epidemiol."},{"issue":"14","key":"2022100608182790900_ref8","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1002\/sim.8951","article-title":"Simulating the dynamics of atherosclerosis to the incidence of myocardial infarction, applied to the KORA population","volume":"40","author":"Simonetto","year":"2021","journal-title":"Stat Med."},{"issue":"suppl 1","key":"2022100608182790900_ref9","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1055\/s-2005-858234","article-title":"The MONICA Augsburg surveys\u2014basis for prospective cohort studies","volume":"67","author":"L\u00f6wel","year":"2005","journal-title":"Gesundheitswesen"},{"issue":"9","key":"2022100608182790900_ref10","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1161\/01.ATV.13.9.1291","article-title":"Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. 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