{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:07:46Z","timestamp":1792080466158,"version":"4.4.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Diabetes is prevalent worldwide and is associated with cardiovascular disease (CVD). Furthermore, due to the insulin resistance, diabetic populations are vulnerable to liver fibrosis, which increases the risk of CVD. Fibrosis-4 index (FIB-4)\u2014a non-invasive biomarker for liver fibrosis\u2014is crucial in predicting CVD among patients with liver diseases. However, the association between FIB-4, death, and CVD in the US diabetic population has not yet been investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We conducted a cross-sectional study using the data from the National Health and Nutrition Examination Survey (NHANES) 1999\u20132008. The mortality status was obtained from the National Death Index through December 31, 2015. Participants were divided into survivor and mortality group to compare the basic characteristics. The association between FIB-4, death, and CVD was analyzed using the restricted cubic spline method and Cox proportional hazards models. In stratified analysis, Participants were stratified based on age, sex, BMI, hypertension, or eGFR respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The participants (<jats:italic>N<\/jats:italic>\u2009=\u20093,471) were divided into survivor (<jats:italic>N<\/jats:italic>\u2009=\u20091,785) and mortality groups (<jats:italic>N<\/jats:italic>\u2009=\u20091,632), with the mortality group exhibiting significantly higher FIB-4 values. Moreover, the risk of all-cause mortality (HR 1.24; 95% CI, 1.17\u20131.32) and CVD mortality (HR 1.17; 95% CI, 1.04\u20131.31) increased with each FIB-4 SD increase after adjusting for all covariates. However, except for myocardial infarction, FIB-4 had no significant effect on the incidence of the other three CVD subtypes (congestive heart failure, coronary heart disease, and angina pectoris). In stratified analysis, we found that the effect of FIB-4 on CVD mortality was influenced by age, and FIB-4 is a risk factor for people older than 60 years (HR 1.14; 95% CI, 1.01\u20131.29).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Using data from NHANES 1999\u20132008, FIB-4 was found to be associated with all-cause and CVD mortality in the diabetic population, and this association was significantly affected by age. However, FIB-4 only affected the incidence of myocardial infarction. Future work should investigate the association between FIB-4 and CVD in the diabetic population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2023.1172178","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T05:25:59Z","timestamp":1695705959000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Association between FIB-4, all-cause mortality, cardiovascular mortality, and cardiovascular disease risk among diabetic individuals: NHANES 1999\u20132008"],"prefix":"10.3389","volume":"10","author":[{"given":"Lihua","family":"Guan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"B1","year":""},{"key":"B2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1097\/XCE.0000000000000116","article-title":"Epidemiology in diabetes mellitus and cardiovascular disease","volume":"6","author":"Fan","year":"2017","journal-title":"Cardiovasc Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1007\/PL00002934","article-title":"Mortality and causes of death in the WHO multinational study of vascular disease in diabetes","volume":"44","author":"Morrish","year":"2001","journal-title":"Diabetologia"},{"key":"B4","doi-asserted-by":"publisher","first-page":"519","DOI":"10.2337\/dc20-1778","article-title":"High prevalence of advanced liver fibrosis assessed by transient elastography among U.S. adults with type 2 diabetes","volume":"44","author":"Ciardullo","year":"2021","journal-title":"Diabetes Care"},{"key":"B5","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.addr.2021.04.008","article-title":"Cellular protein markers, therapeutics, and drug delivery strategies in the treatment of diabetes-associated liver fibrosis","volume":"174","author":"Lin","year":"2021","journal-title":"Adv Drug Deliv Rev"},{"key":"B6","doi-asserted-by":"publisher","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-analysis","volume":"71","author":"Younossi","year":"2019","journal-title":"J Hepatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2960","DOI":"10.1111\/jgh.15589","article-title":"Liver fibrosis and fatty liver as independent risk factors for cardiovascular disease","volume":"36","author":"Tamaki","year":"2021","journal-title":"J Gastroenterol Hepatol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1159\/000443344","article-title":"EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease","volume":"9","year":"2016","journal-title":"Obes Facts"},{"key":"B9","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American association for the study of liver diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"290","DOI":"10.5009\/gnl210084","article-title":"Cardiovascular risk is elevated in lean subjects with nonalcoholic fatty liver disease","volume":"16","author":"Kim","year":"2022","journal-title":"Gut Liver"},{"key":"B11","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1186\/s12876-021-02020-z","article-title":"PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD","volume":"21","author":"Akuta","year":"2021","journal-title":"BMC Gastroenterol"},{"key":"B12","year":""},{"key":"B13","year":""},{"key":"B14","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.2337\/dc22-S002","article-title":"Classification and diagnosis of diabetes: standards of medical care in diabetes-2022","volume":"45","year":"2022","journal-title":"Diabetes Care"},{"key":"B15","year":""},{"key":"B16","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/hep.21178","article-title":"Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection","volume":"43","author":"Sterling","year":"2006","journal-title":"Hepatology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1159\/000350377","article-title":"Association between water intake, chronic kidney disease, and cardiovascular disease: a cross-sectional analysis of NHANES data","volume":"37","author":"Sontrop","year":"2013","journal-title":"Am J Nephrol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"106545","DOI":"10.1016\/j.envint.2021.106545","article-title":"Association between pyrethroid exposure and cardiovascular disease: a national population-based cross-sectional study in the US","volume":"153","author":"Xue","year":"2021","journal-title":"Environ Int"},{"key":"B19","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1002\/JPER.17-0276","article-title":"Alcohol intake and periodontitis in adults aged >\/=30 years: NHANES 2009\u20132012","volume":"89","author":"Gay","year":"2018","journal-title":"J Periodontol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1161\/01.HYP.0000075790.33892.AE","article-title":"Seventh report of the joint national committee on the prevention, detection, evaluation, and treatment of high blood pressure (JNC 7): resetting the hypertension sails","volume":"41","author":"Lenfant","year":"2003","journal-title":"Hypertension"},{"key":"B21","doi-asserted-by":"publisher","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"B22","year":""},{"key":"B23","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1016\/j.cjca.2022.07.016","article-title":"FIB-4 predicts MACE and cardiovascular mortality in patients with nonalcoholic fatty liver disease","volume":"38","author":"Chew","year":"2022","journal-title":"Can J Cardiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0277729","DOI":"10.1371\/journal.pone.0277729","article-title":"Association of liver fibrosis biomarkers with overall and CVD mortality in the Korean population: the Dong-Gu study","volume":"17","author":"Choi","year":"2022","journal-title":"PLoS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.dld.2020.10.014","article-title":"Liver fibrosis marker is an independent predictor of cardiovascular morbidity and mortality in the general population","volume":"53","author":"Schonmann","year":"2021","journal-title":"Dig Liver Dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1002\/ehf2.13317","article-title":"Fibrosis-4 index reflects right ventricular function and prognosis in heart failure with preserved ejection fraction","volume":"8","author":"Nakashima","year":"2021","journal-title":"ESC Heart Fail"},{"key":"B27","doi-asserted-by":"publisher","first-page":"113888","DOI":"10.1016\/j.addr.2021.113888","article-title":"Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis","volume":"176","author":"Kumar","year":"2021","journal-title":"Adv Drug Deliv Rev"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1007\/s12072-021-10209-3","article-title":"Histological severity of nonalcoholic fatty liver disease is associated with 10-year risk for atherosclerotic cardiovascular disease","volume":"15","author":"Park","year":"2021","journal-title":"Hepatol Int"},{"key":"B29","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1111\/liv.13973","article-title":"Cardiovascular risk factors in non-alcoholic fatty liver disease","volume":"39","author":"Hagstrom","year":"2019","journal-title":"Liver Int"},{"key":"B30","doi-asserted-by":"publisher","first-page":"643","DOI":"10.3892\/etm.2022.11580","article-title":"A retrospective study on the relationship between fibrosis-4 index and all-cause mortality in patients with acute myocardial infarction","volume":"24","author":"Cao","year":"2022","journal-title":"Exp Ther Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"584","DOI":"10.3390\/jcm9020584","article-title":"Impact of the fibrosis-4 index on risk stratification of cardiovascular events and mortality in patients with atrial fibrillation: findings from a Japanese multicenter registry","volume":"9","author":"Saito","year":"2020","journal-title":"J Clin Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1536\/ihj.19-034","article-title":"The fibrosis-4 index is useful for predicting mortality in patients with pulmonary hypertension due to left heart disease","volume":"60","author":"Yokokawa","year":"2019","journal-title":"Int Heart J"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.1002\/ehf2.14087","article-title":"Liver fibrosis scores and atrial fibrillation incidence in heart failure with preserved ejection fraction","volume":"9","author":"Liu","year":"2022","journal-title":"ESC Heart Fail"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.2337\/dc22-0556","article-title":"Noninvasive fibrosis screening in fatty liver disease among vulnerable populations: impact of diabetes and obesity on FIB-4 score accuracy","volume":"45","author":"Kim","year":"2022","journal-title":"Diabetes Care"},{"key":"B35","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1007\/s11845-022-03019-5","article-title":"Reduced and more appropriate referrals of patients with type 2 diabetes using liver stiffness measurement compared to FIB-4","volume":"192","author":"Shanahan","year":"2022","journal-title":"Ir J Med Sci"},{"key":"B36","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1007\/s12072-015-9690-5","article-title":"High FIB-4 index as an independent risk factor of prevalent chronic kidney disease in patients with nonalcoholic fatty liver disease","volume":"10","author":"Xu","year":"2016","journal-title":"Hepatol Int"},{"key":"B37","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/hep.32163","article-title":"Population screening for liver fibrosis: toward early diagnosis and intervention for chronic liver diseases","volume":"75","author":"Gines","year":"2022","journal-title":"Hepatology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"100761","DOI":"10.1016\/j.aohep.2022.100761","article-title":"Liver steatosis and fibrosis markers\u2019 association with cardiovascular and renal damage in Japanese adults: the TMM BirThree cohort study","volume":"28","author":"Machida","year":"2023","journal-title":"Ann Hepatol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1007\/s13340-020-00453-7","article-title":"FIB-4 index-based surveillance for advanced liver fibrosis in diabetes patients","volume":"12","author":"Kawata","year":"2021","journal-title":"Diabetol Int"},{"key":"B40","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/ajg.2016.453","article-title":"Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis","volume":"112","author":"McPherson","year":"2017","journal-title":"Am J Gastroenterol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1053\/j.ajkd.2014.08.001","article-title":"Diabetic kidney disease: a report from an ADA consensus conference","volume":"64","author":"Tuttle","year":"2014","journal-title":"Am J Kidney Dis"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1172178\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T05:26:03Z","timestamp":1695705963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1172178\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,25]]},"references-count":41,"alternative-id":["10.3389\/fcvm.2023.1172178"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2023.1172178","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,25]]},"article-number":"1172178"}}