{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:23:31Z","timestamp":1791483811082,"version":"4.3.4"},"reference-count":79,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,1,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Cardiovascular disease (CVD) is the leading cause of mortality among patients with NAFLD. The aim of our study was to develop a machine learning algorithm integrating clinical, lifestyle, and genetic risk factors to identify CVD in patients with NAFLD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We created a cohort of patients with NAFLD from the UK Biobank, diagnosed according to proton density fat fraction from magnetic resonance imaging data sets. A total of 400 patients with NAFLD with subclinical atherosclerosis or clinical CVD, defined by disease codes, constituted cases and 446 NAFLD cases with no CVD constituted controls. We evaluated 7 different supervised machine learning approaches on clinical, lifestyle, and genetic variables for identifying CVD in patients with NAFLD. The most significant clinical and lifestyle variables observed by the predictive modeling were age (59\u00a0years [54.00\u201363.00 years]), hypertension (145\u00a0mm\u00a0Hg [134.0\u2013156.0\u00a0mm\u00a0Hg] and 85\u00a0mm\u00a0Hg [79.00\u201393.00 mm\u00a0Hg]), waist circumference (98\u00a0cm [95.00\u2013105.00 cm]), and sedentary lifestyle, defined as time spent watching TV &gt;4\u00a0h\/d. In the genetic data, single\u2010nucleotide polymorphisms in IL16 and ANKLE1 gene were most significant. Our proposed ensemble\u2010based integrative machine learning model achieved an area under the curve of 0.849 using the random forest modeling for CVD prediction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">We propose a machine learning algorithm that identifies CVD in patients with NAFLD through integration of significant clinical, lifestyle, and genetic risk factors. These patients with NAFLD at higher risk of CVD should be flagged for screening and aggressive treatment of their cardiometabolic risk factors to prevent cardiovascular morbidity and mortality.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.022576","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T12:48:04Z","timestamp":1640004484000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Machine Learning Approach to Classify Cardiovascular Disease in Patients With Nonalcoholic Fatty Liver Disease in the UK Biobank Cohort"],"prefix":"10.1161","volume":"11","author":[{"given":"Divya","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Biostatistics Princess Margaret Cancer CentreUniversity Health Network Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3827-8262","authenticated-orcid":false,"given":"Neta","family":"Gotlieb","sequence":"additional","affiliation":[{"name":"Division of Adult Gastroenterology University Health NetworkToronto General Hospital Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Farkouh","sequence":"additional","affiliation":[{"name":"Peter Munk Cardiac Centre, Heart and Stroke Richard Lewar Centre University of Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyur","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University Health NetworkToronto General Hospital Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Princess Margaret Cancer CentreUniversity Health Network Toronto Ontario Canada"},{"name":"Biostatistics Division Dalla Lana School of Public Health University of Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1960-8449","authenticated-orcid":false,"given":"Mamatha","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Medicine Multi\u2010Organ Transplant ProgramToronto General Hospital Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04724.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002484"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29466"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i14.1491"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0088-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0010-0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.05.013"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.09090769"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2007.01531.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570161115666170621075619"},{"key":"e_1_3_2_14_2","first-page":"201","article-title":"Non\u2010alcoholic fatty liver disease (NAFLD)\u2014the hepatic component of metabolic syndrome","volume":"57","author":"Juneja A","year":"2009","unstructured":"Juneja A. Non\u2010alcoholic fatty liver disease (NAFLD)\u2014the hepatic component of metabolic syndrome. JAPI. 2009;57:201.","journal-title":"JAPI"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.09.021"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.07.052"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2019.08.008"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-020-01192-4"},{"key":"e_1_3_2_19_2","first-page":"101215","article-title":"NAFLD, and cardiovascular and cardiac diseases: factors influencing risk, prediction and treatment","author":"Targher G","unstructured":"Targher G, Corey KE, Byrne CD. NAFLD, and cardiovascular and cardiac diseases: factors influencing risk, prediction and treatment. Diabetes Metab. 2021;47:101215. doi: 10.1016\/j.diabet.2020.101215","journal-title":"Diabetes Metab"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.12.012"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.5114\/ceh.2018.73155"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174944"},{"key":"e_1_3_2_23_2","first-page":"1","article-title":"Learning from longitudinal data in electronic health record and genetic data to improve cardiovascular event prediction","volume":"9","author":"Zhao J","year":"2019","unstructured":"Zhao J, Feng Q, Wu P, Lupu RA, Wilke RA, Wells QS, Denny JC, Wei W\u2010Q. Learning from longitudinal data in electronic health record and genetic data to improve cardiovascular event prediction. Sci Rep. 2019;9:1\u201310.","journal-title":"Sci Rep"},{"key":"e_1_3_2_24_2","first-page":"1","article-title":"Study of cardiovascular disease prediction model based on random forest in eastern China","volume":"10","author":"Yang L","year":"2020","unstructured":"Yang L, Wu H, Jin X, Zheng P, Hu S, Xu X, Yu W, Yan J. Study of cardiovascular disease prediction model based on random forest in eastern China. Sci Rep. 2020;10:1\u20138. doi: 10.1038\/s41598\u2010020\u201062133\u20105","journal-title":"Sci Rep"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213653"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.114.000954"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60404-8"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0172921","article-title":"Characterisation of liver fat in the UK Biobank cohort","volume":"12","author":"Wilman HR","year":"2017","unstructured":"Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, Gyngell M, Neubauer S, Bell JD, Banerjee R, et al. Characterisation of liver fat in the UK Biobank cohort. PLoS One. 2017;12:e0172921. doi: 10.1371\/journal.pone.0172921","journal-title":"PLoS One"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.06.005"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-019-06072-4"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29639"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.12.036"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2010.05.005"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpy022"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.11.075"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat.31989"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.3109\/08037051.2014.868629"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003100"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.109"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018628609742"},{"key":"e_1_3_2_43_2","first-page":"18","article-title":"Classification and regression by randomForest","volume":"2","author":"Liaw A","year":"2002","unstructured":"Liaw A, Wiener M. Classification and regression by randomForest. R News. 2002;2:18\u201322.","journal-title":"R News"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1117\/3.633187.ch1"},{"key":"e_1_3_2_45_2","volume-title":"Logistic Regression","author":"Wright RE","year":"1995","unstructured":"Wright RE. Logistic Regression. American Psychological Association; 1995."},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1996.tb02080.x"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1080\/00401706.1970.10488634"},{"key":"e_1_3_2_48_2","first-page":"41","volume-title":"IJCAI 2001 Workshop on Empirical Methods in Artificial Intelligence","author":"Rish I","year":"2001","unstructured":"Rish I. An empirical study of the naive bayes classifier. In IJCAI 2001 Workshop on Empirical Methods in Artificial Intelligence. New York: IBM. 2001;3:41\u201346."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.2307\/2531595"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-45014-9_1"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-82098-3"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41746-019-0105-1"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e509"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.11.312"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP270538"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20081948"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.1731"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14240"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1177\/2047487317711048"},{"key":"e_1_3_2_61_2","first-page":"811","article-title":"Sedentary behaviour and risk of all\u2010cause, cardiovascular and cancer mortality, and incident type 2 diabetes: a systematic review and dose response meta\u2010analysis","volume":"9","author":"Patterson R","year":"2018","unstructured":"Patterson R, McNamara E, Tainio M, H\u00e9rick de S\u00e1 T, Smith AD, Sharp SJ, Edwards P, Woodcock J, Brage S, Wijndaele K. Sedentary behaviour and risk of all\u2010cause, cardiovascular and cancer mortality, and incident type 2 diabetes: a systematic review and dose response meta\u2010analysis. Springer. 2018;9:811\u2013829. doi: 10.1007\/s10654\u2010018\u20100380\u20101","journal-title":"Springer"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2015.1077989"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1562943"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0145-7"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-020-01207-9"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0206174"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28142"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1319"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8101510"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1177\/0300060513483405"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2011.06.010"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152278"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pop.2014.02.010"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(19)30023-4"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15192"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.07.030"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26156"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2019.02.005"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.10.008"},{"key":"e_1_3_2_80_2","first-page":"76","article-title":"Non\u2010alcoholic fatty liver disease: growing burden, adverse outcomes and associations","volume":"8","author":"Kumar R","year":"2020","unstructured":"Kumar R, Priyadarshi RN, Anand U. Non\u2010alcoholic fatty liver disease: growing burden, adverse outcomes and associations. J Clin Transl Hepatol. 2020;8:76.","journal-title":"J Clin Transl Hepatol"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.022576","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:10:34Z","timestamp":1715598634000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.022576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":79,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1,4]]}},"alternative-id":["10.1161\/JAHA.121.022576"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.022576","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,4]]},"assertion":[{"value":"2021-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e022576"}}