{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T18:30:37Z","timestamp":1784140237739,"version":"3.55.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T00:00:00Z","timestamp":1650672000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Conflicting evidence exists on cardiovascular disease (CVD) risk in patients with NAFLD, and data are lacking on whether NAFLD increases mortality after a CVD event. Moreover, life expectancy in NAFLD has not been studied. We therefore examined CVD risk and life expectancy in patients with NAFLD compared with the general population.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>In this nationwide population\u2010based cohort, all patients with NAFLD diagnosis and without baseline CVD (ascertaining from the Swedish National Patient Register from 1987 to 2016, <jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a010,023) were matched 10:1 on age, sex, and municipality to individuals from the general population (controls, <jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a096,313). CVD diagnosis and mortality were derived from national registers. Multistate models and flexible parametric survival models were used to estimate adjusted hazard ratios (aHRs) for CVD risk and loss in life expectancy due to NAFLD. We identified 1037 (10.3%) CVD events in patients with NAFLD and 4041 (4.2%) in controls. CVD risk was 2.6\u2010fold higher in NAFLD compared with controls (aHR = 2.61, 95% CI = 2.36\u20132.88) and was strongest for nonfatal CVD (aHR = 3.71, 95% CI = 3.29\u20134.17). After a nonfatal CVD event, the risk for all\u2010cause mortality was similar between patients with NAFLD and controls (aHR = 0.89, 95% CI = 0.64\u20131.25). Life expectancy in patients with NAFLD was, on average, 2.8 years lower than controls, with the highest loss of life\u2010years when NAFLD was diagnosed in middle age (40\u201360 years).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>NAFLD was associated with a higher risk of nonfatal CVD but did not affect post\u2010CVD mortality risk. Patients diagnosed with NAFLD have a lower life expectancy than the general population.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32519","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T04:11:02Z","timestamp":1649650262000},"page":"1495-1505","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":67,"title":["Risk of cardiovascular disease and loss in life expectancy in NAFLD"],"prefix":"10.1097","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1496-1799","authenticated-orcid":false,"given":"Ying","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Medicine,Huddinge,Karolinska Institutet,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Nasr","sequence":"additional","affiliation":[{"name":"Department of Medicine,Huddinge,Karolinska Institutet,Stockholm,Sweden"},{"name":"Department of Gastroenterology and Hepatology,Department of Health, Medicine and Caring Sciences,Link\u00f6ping University,Link\u00f6ping,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linnea","family":"Widman","sequence":"additional","affiliation":[{"name":"Division of Biostatistics,Institute of Environmental Medicine,Karolinska Institutet,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8474-1759","authenticated-orcid":false,"given":"Hannes","family":"Hagstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medicine,Huddinge,Karolinska Institutet,Stockholm,Sweden"},{"name":"Division of Hepatology,Department of Upper GI,Karolinska University Hospital,Stockholm,Sweden"},{"name":"Clinical Epidemiology Unit,Department of Medicine,Karolinska Institutet,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,4,23]]},"reference":[{"key":"hep32519-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1002\/hep.30251","article-title":"Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"69","year":"2019","journal-title":"Hepatology"},{"key":"hep32519-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.jhep.2019.06.021","article-title":"The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta\u2010analysis","volume":"71","year":"2019","journal-title":"J Hepatol"},{"key":"hep32519-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1001\/jama.288.21.2709","article-title":"The metabolic syndrome and total and cardiovascular disease mortality in middle\u2010aged men","volume":"288","year":"2002","journal-title":"JAMA"},{"key":"hep32519-bib-0004-20241017","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.1210\/jc.2007-0482","article-title":"Liver fat in the metabolic syndrome","volume":"92","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"hep32519-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/MEG.0000000000001075","article-title":"Synergistic increase in cardiovascular risk in diabetes mellitus with nonalcoholic fatty liver disease: a meta\u2010analysis","volume":"30","year":"2018","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"hep32519-bib-0006-20241017","article-title":"Risk for hepatic and extra\u2010hepatic outcomes in nonalcoholic fatty liver disease","year":"2021","journal-title":"J Intern Med"},{"key":"hep32519-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.jhep.2016.05.013","article-title":"Non\u2010alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta\u2010analysis","volume":"65","year":"2016","journal-title":"J Hepatol"},{"key":"hep32519-bib-0008-20241017","article-title":"Non\u2010alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults","volume":"367","year":"2019","journal-title":"BMJ"},{"key":"hep32519-bib-0009-20241017","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/hep.23314","article-title":"Decreased survival of subjects with elevated liver function tests during a 28\u2010year follow\u2010up","volume":"51","year":"2010","journal-title":"Hepatology"},{"key":"hep32519-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/liv.13973","article-title":"Cardiovascular risk factors in non\u2010alcoholic fatty liver disease","volume":"39","year":"2019","journal-title":"Liver Int"},{"key":"hep32519-bib-0011-20241017","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1002\/hep.27368","article-title":"Fibrosis stage is the strongest predictor for disease\u2010specific mortality in NAFLD after up to 33 years of follow\u2010up","volume":"61","year":"2015","journal-title":"Hepatology"},{"key":"hep32519-bib-0012-20241017","article-title":"Non\u2010alcoholic fatty liver disease and incident major adverse cardiovascular events: results from a nationwide histology cohort","year":"2021","journal-title":"Gut"},{"key":"hep32519-bib-0013-20241017","article-title":"Non\u2010alcoholic fatty liver disease and mortality among US adults: prospective cohort study","volume":"343","year":"2011","journal-title":"BMJ"},{"key":"hep32519-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/hep.26156","article-title":"Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States","volume":"57","year":"2013","journal-title":"Hepatology"},{"key":"hep32519-bib-0015-20241017","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1053\/j.gastro.2020.01.043","article-title":"Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: a systematic review and meta\u2010analysis","volume":"158","year":"2020","journal-title":"Gastroenterology"},{"key":"hep32519-bib-0016-20241017","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish national inpatient register","volume":"11","year":"2011","journal-title":"BMC Public Health"},{"key":"hep32519-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1080\/00365521.2020.1820566","article-title":"Validity of administrative codes associated with cirrhosis in Sweden","volume":"55","year":"2020","journal-title":"Scand J Gastroenterol"},{"key":"hep32519-bib-0018-20241017","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s10654-016-0117-y","article-title":"Registers of the Swedish total population and their use in medical research","volume":"31","year":"2016","journal-title":"Eur J Epidemiol"},{"key":"hep32519-bib-0019-20241017","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/hep.31726","article-title":"Administrative coding in electronic health care record\u2010based research of NAFLD: an expert panel consensus statement","volume":"74","year":"2021","journal-title":"Hepatology"},{"key":"hep32519-bib-0020-20241017","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s10654-017-0316-1","article-title":"The Swedish cause of death register","volume":"32","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"hep32519-bib-0021-20241017","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity analysis in observational research: introducing the E\u2010value","volume":"167","year":"2017","journal-title":"Ann Intern Med"},{"key":"hep32519-bib-0022-20241017","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1002\/sim.2712","article-title":"Tutorial in biostatistics: competing risks and multi\u2010state models","volume":"26","year":"2007","journal-title":"Stat Med"},{"key":"hep32519-bib-0023-20241017","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/hep.27598","article-title":"The clinical course of cirrhosis: The importance of multistate models and competing risks analysis","volume":"62","year":"2015","journal-title":"Hepatology"},{"key":"hep32519-bib-0024-20241017","doi-asserted-by":"crossref","first-page":"5286","DOI":"10.1002\/sim.5943","article-title":"Estimating the loss in expectation of life due to cancer using flexible parametric survival models","volume":"32","year":"2013","journal-title":"Stat Med"},{"key":"hep32519-bib-0025-20241017","doi-asserted-by":"crossref","first-page":"5486","DOI":"10.1002\/sim.3064","article-title":"Flexible parametric models for relative survival, with application in coronary heart disease","volume":"26","year":"2007","journal-title":"Stat Med"},{"key":"hep32519-bib-0026-20241017","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1177\/1536867X0900900206","article-title":"Further development of flexible parametric models for survival analysis","volume":"9","year":"2009","journal-title":"Stata J"},{"key":"hep32519-bib-0028-20241017","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1002\/hep.29546","article-title":"Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: a 20 year\u2010community study","volume":"67","year":"2018","journal-title":"Hepatology"},{"key":"hep32519-bib-0029-20241017","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S2468-1253(21)00308-3","article-title":"Non\u2010alcoholic fatty liver disease and risk of fatal and non\u2010fatal cardiovascular events: an updated systematic review and meta\u2010analysis","volume":"6","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"hep32519-bib-0030-20241017","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1136\/gutjnl-2020-320622","article-title":"NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications","volume":"69","year":"2020","journal-title":"Gut"},{"key":"hep32519-bib-0031-20241017","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.14309\/ajg.0000000000000401","article-title":"Women with nonalcoholic fatty liver disease lose protection against cardiovascular disease: a longitudinal cohort study","volume":"114","year":"2019","journal-title":"Am J Gastroenterol"},{"key":"hep32519-bib-0032-20241017","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1111\/j.1572-0241.2008.02034.x","article-title":"Suspected nonalcoholic fatty liver disease and mortality risk in a population\u2010based cohort study","volume":"103","year":"2008","journal-title":"Am J Gastroenterol"},{"key":"hep32519-bib-0033-20241017","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/j.1478-3231.2004.0969.x","article-title":"Non\u2010alcoholic fatty liver disease\u2013a common and benign finding in octogenarian patients","volume":"24","year":"2004","journal-title":"Liver Int"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.32519","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.32519","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.32519","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T23:53:44Z","timestamp":1729209224000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/hep.32519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,23]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.32519","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,23]]},"assertion":[{"value":"2021-11-19","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-07","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}