{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:22:39Z","timestamp":1781184159861,"version":"3.54.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":1597,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["14150781"],"award-info":[{"award-number":["14150781"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["14150781"],"award-info":[{"award-number":["14150781"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Adipocyte fatty acid-binding protein (AFABP) is associated with cardiovascular diseases in type 2 diabetes. Whether circulating AFABP levels are associated with the risk of heart failure (HF) in type 2 diabetes remains undefined. We investigated the prospective association of circulating AFABP levels with incident HF hospitalization in type 2 diabetes, and its relationship to the use of sodium glucose co-transporter 2 inhibitors (SGLT2i) which reduce HF risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Baseline serum AFABP level was measured in 3322 Chinese participants without known history of cardiovascular diseases or hospitalization for HF, recruited from the Hong Kong West Diabetes Registry. Its association with incident HF hospitalization was evaluated using multivariable Cox regression analysis. Use of SGLT2i was included as a time-dependent covariate. Among these 3322 participants (52.9% men; mean age 60.0 \u00b1 12.6), 176 (5.3%) developed HF hospitalization over a median follow-up of 8 years. Seven hundred and thirty-one (22%) were started on SGLT2i during the study period (empagliflozin 55.1%, dapagliflozin 44.2%, canagliflozin 0.4%, and ertugliflozin 0.3%). Serum AFABP levels were significantly higher in participants who developed HF hospitalization than those who did not (men: 14.8 vs. 8.3 ng\/mL; women: 21.5 vs. 14.6 ng\/mL; all: 18.6 vs. 10.9 ng\/mL, P &amp;lt; 0.001). In multivariable Cox regression analysis, baseline serum AFABP level was significantly associated with incident HF hospitalization [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.06\u20131.80, P = 0.019] independent of the use of SGLT2i, in a model also consisting of age; sex; body mass index; smoking status; duration of diabetes; hypertension, dyslipidaemia; atrial fibrillation; presence of chronic kidney disease and albuminuria; glycated haemoglobin and high-sensitivity C-reactive protein levels; and use of metformin, insulin, aspirin, furosemide, and beta-blockers at baseline. High cumulative defined daily dose (cDDD) of SGLT2i was protective of incident HF hospitalization (HR 0.10, 95% CI 0.01\u20130.68, P = 0.019). The addition of circulating AFABP level to a clinical model of conventional HF risk factors provided significant improvement in the category-free net reclassification index (11.5%, 95% CI 1.6\u201322.1, P = 0.02) and integrated discrimination improvement (0.3%, 95% CI 0.1\u20131.7, P = 0.04). A dose-dependent reduction in cumulative incidence of HF hospitalization in response to SGLT2i, based on cDDD, was more clearly observed in participants with a higher baseline AFABP level above the sex-specific median (P for trend &amp;lt;0.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Circulating AFABP level is independently associated with incident HF hospitalization in type 2 diabetes and is potentially helpful in risk stratification for the prevention of HF hospitalization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13472","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T04:35:32Z","timestamp":1628224532000},"page":"3964-3974","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prospective Association of Serum Adipocyte Fatty Acid-Binding Protein with Heart Failure Hospitalization in Diabetes"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7569-409X","authenticated-orcid":false,"given":"Chi Ho","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Hong Kong, Queen Mary Hospital , 102 Pokfulam Road, Pokfulam, Pokfulam ,","place":["Hong Kong"]},{"name":"State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy Ka Chun","family":"Kan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Hong Kong, Queen Mary Hospital , 102 Pokfulam Road, Pokfulam, Pokfulam ,","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Tak Wai","family":"Lui","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Hong Kong, Queen Mary Hospital , 102 Pokfulam Road, Pokfulam, Pokfulam ,","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol Ho Yi","family":"Fong","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Hong Kong, Queen Mary Hospital , 102 Pokfulam Road, Pokfulam, Pokfulam ,","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren Shing Hei","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Hong Kong, Queen Mary Hospital , 102 Pokfulam Road, Pokfulam, Pokfulam ,","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele Mae Ann","family":"Yuen","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Hong Kong, Queen Mary Hospital , 102 Pokfulam Road, Pokfulam, Pokfulam ,","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing Sun","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Hong Kong, Queen Mary Hospital , 102 Pokfulam Road, Pokfulam, Pokfulam ,","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Cho","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Hong Kong, Queen Mary Hospital , 102 Pokfulam Road, Pokfulam, Pokfulam ,","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0668-033X","authenticated-orcid":false,"given":"Aimin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Hong Kong, Queen Mary Hospital , 102 Pokfulam Road, Pokfulam, Pokfulam ,","place":["Hong Kong"]},{"name":"State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-541X","authenticated-orcid":false,"given":"Karen Siu Ling","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Hong Kong, Queen Mary Hospital , 102 Pokfulam Road, Pokfulam, Pokfulam ,","place":["Hong Kong"]},{"name":"State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"2026012114224382500_ehf213472-bib-0001","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1016\/S0140-6736(18)30314-3","article-title":"Trends in cause-specific mortality among adults with and without diagnosed diabetes in the USA: an epidemiological analysis of linked national survey and vital statistics data","volume":"391","author":"Gregg","year":"2018","journal-title":"Lancet"},{"key":"2026012114224382500_ehf213472-bib-0002","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.cardfail.2019.05.007","article-title":"Type 2 diabetes mellitus and heart failure, a scientific statement from the American Heart Association and Heart Failure Society of America","volume":"25","author":"Dunlay","year":"2019","journal-title":"J Card Fail"},{"key":"2026012114224382500_ehf213472-bib-0003","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.115.002560","article-title":"Risk related to pre-diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial","volume":"9","author":"Kristensen","year":"2016","journal-title":"Circ Heart Fail"},{"key":"2026012114224382500_ehf213472-bib-0004","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1093\/eurheartj\/ehz486","article-title":"2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD","volume":"41","author":"Cosentino","year":"2020","journal-title":"Eur Heart J"},{"key":"2026012114224382500_ehf213472-bib-0005","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N Engl J Med"},{"key":"2026012114224382500_ehf213472-bib-0006","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and cardiovascular and renal events in type 2 diabetes","volume":"377","author":"Neal","year":"2017","journal-title":"N Engl J Med"},{"key":"2026012114224382500_ehf213472-bib-0007","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1056\/NEJMoa1812389","article-title":"Dapagliflozin and cardiovascular outcomes in type 2 diabetes","volume":"380","author":"Wiviott","year":"2019","journal-title":"N Engl J Med"},{"key":"2026012114224382500_ehf213472-bib-0008","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N Engl J Med"},{"key":"2026012114224382500_ehf213472-bib-0009","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa1911303","article-title":"Dapagliflozin in patients with heart failure and reduced ejection fraction","volume":"381","author":"McMurray","year":"2019","journal-title":"N Engl J Med"},{"key":"2026012114224382500_ehf213472-bib-0010","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1056\/NEJMoa2022190","article-title":"Cardiovascular and renal outcomes with empagliflozin in heart failure","volume":"383","author":"Packer","year":"2020","journal-title":"N Engl J Med"},{"key":"2026012114224382500_ehf213472-bib-0011","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa2030183","article-title":"Sotagliflozin in patients with diabetes and recent worsening heart failure","volume":"384","author":"Bhatt","year":"2021","journal-title":"N Engl J Med"},{"key":"2026012114224382500_ehf213472-bib-0012","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1056\/NEJMoa2030186","article-title":"Sotagliflozin in patients with diabetes and chronic kidney disease","volume":"384","author":"Bhatt","year":"2021","journal-title":"N Engl J Med"},{"key":"2026012114224382500_ehf213472-bib-0013","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1373\/clinchem.2005.062463","article-title":"Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome","volume":"52","author":"Xu","year":"2006","journal-title":"Clin Chem"},{"key":"2026012114224382500_ehf213472-bib-0014","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/89076","article-title":"Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis","volume":"7","author":"Makowski","year":"2001","journal-title":"Nat Med"},{"key":"2026012114224382500_ehf213472-bib-0015","doi-asserted-by":"crossref","first-page":"10273","DOI":"10.1074\/jbc.M109.097907","article-title":"Adipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH2-terminal kinases and activator protein-1","volume":"285","author":"Hui","year":"2010","journal-title":"J Biol Chem"},{"key":"2026012114224382500_ehf213472-bib-0016","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1042\/CS20160465","article-title":"Adipose-specific inactivation of JNK alleviates atherosclerosis in apoE-deficient mice","volume":"130","author":"Kwok","year":"2016","journal-title":"Clin Sci (Lond)"},{"key":"2026012114224382500_ehf213472-bib-0017","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1042\/CS20150073","article-title":"Deficiency of adipocyte fatty-acid-binding protein alleviates myocardial ischaemia\/reperfusion injury and diabetes-induced cardiac dysfunction","volume":"129","author":"Zhou","year":"2015","journal-title":"Clin Sci (Lond)"},{"key":"2026012114224382500_ehf213472-bib-0018","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.112.004176","article-title":"Elevated circulating adipocyte-fatty acid binding protein levels predict incident cardiovascular events in a community-based cohort: a 12-year prospective study","volume":"2","author":"Chow","year":"2013","journal-title":"J Am Heart Assoc"},{"key":"2026012114224382500_ehf213472-bib-0019","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00125-018-4742-8","article-title":"Prospective associations of circulating adipocyte fatty acid-binding protein levels with risks of renal outcomes and mortality in type 2 diabetes","volume":"62","author":"Lee","year":"2019","journal-title":"Diabetologia"},{"key":"2026012114224382500_ehf213472-bib-0020","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1136\/heartjnl-2013-303735","article-title":"Fatty acid binding protein 4 predicts left ventricular mass and longitudinal function in overweight and obese women","volume":"99","author":"Engeli","year":"2013","journal-title":"Heart"},{"key":"2026012114224382500_ehf213472-bib-0021","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1042\/CS20120004","article-title":"Circulating adipocyte fatty acid-binding protein levels are independently associated with heart failure","volume":"124","author":"Liu","year":"2013","journal-title":"Clin Sci (Lond)"},{"key":"2026012114224382500_ehf213472-bib-0022","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/eurjhf\/hfs196","article-title":"Fatty acid-binding protein 4 and incident heart failure: the Cardiovascular Health Study","volume":"15","author":"Djousse","year":"2013","journal-title":"Eur J Heart Fail"},{"key":"2026012114224382500_ehf213472-bib-0023","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.1210\/jc.2014-1832","article-title":"Serum adipocyte fatty acid binding protein levels are positively associated with subclinical atherosclerosis in Chinese pre- and postmenopausal women with normal glucose tolerance","volume":"99","author":"Hao","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"2026012114224382500_ehf213472-bib-0024","volume-title":"Anatomical therapeutic chemical (ATC)\/defined daily dose (DDD) index on sodium-glucose Co-transporter 2 inhibitors","author":"WHO Collaborating Centre for Drug Statistics","year":"2019"},{"key":"2026012114224382500_ehf213472-bib-0025","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1186\/1475-2840-12-72","article-title":"Parallel evolution of circulating FABP4 and NT-proBNP in heart failure patients","volume":"12","author":"Cabre","year":"2013","journal-title":"Cardiovasc Diabetol"},{"key":"2026012114224382500_ehf213472-bib-0026","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12933-020-01080-x","article-title":"The adipokine fatty-acid binding protein 4 and cardiac remodeling","volume":"19","author":"von Jeinsen","year":"2020","journal-title":"Cardiovasc Diabetol"},{"key":"2026012114224382500_ehf213472-bib-0027","doi-asserted-by":"crossref","DOI":"10.1038\/nutd.2014.3","article-title":"Adipocyte fatty acid-binding protein levels are associated with left ventricular diastolic dysfunction in morbidly obese subjects","volume":"4","author":"Baessler","year":"2014","journal-title":"Nutr Diabetes"},{"key":"2026012114224382500_ehf213472-bib-0028","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s12933-014-0126-7","article-title":"Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population","volume":"13","author":"Fuseya","year":"2014","journal-title":"Cardiovasc Diabetol"},{"key":"2026012114224382500_ehf213472-bib-0029","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.118.008997","article-title":"Association of circulating adipokines with echocardiographic measures of cardiac structure and function in a community-based cohort","volume":"7","author":"von Jeinsen","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"2026012114224382500_ehf213472-bib-0030","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.2337\/dc07-0413","article-title":"Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort","volume":"30","author":"Tso","year":"2007","journal-title":"Diabetes Care"},{"key":"2026012114224382500_ehf213472-bib-0031","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s12933-020-01167-5","article-title":"Association between adipocyte fatty acid-binding protein with left ventricular remodelling and diastolic function in type 2 diabetes: a prospective echocardiography study","volume":"19","author":"Wu","year":"2020","journal-title":"Cardiovasc Diabetol"},{"key":"2026012114224382500_ehf213472-bib-0032","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1161\/CIRCRESAHA.109.200501","article-title":"Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease","volume":"105","author":"Lamounier-Zepter","year":"2009","journal-title":"Circ Res"},{"key":"2026012114224382500_ehf213472-bib-0033","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1161\/CIRCULATIONAHA.116.021887","article-title":"Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications","volume":"134","author":"Heerspink","year":"2016","journal-title":"Circulation"},{"key":"2026012114224382500_ehf213472-bib-0034","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1373\/clinchem.2018.289157","article-title":"Circulating adipocyte fatty acid-binding protein concentrations predict multiple mortality outcomes among men and women with diabetes","volume":"64","author":"Lee","year":"2018","journal-title":"Clin Chem"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ehf2.13472","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ehf2.13472","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/8\/5\/3964\/65567642\/eschf_8_5_3964.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/8\/5\/3964\/65567642\/eschf_8_5_3964.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T19:28:17Z","timestamp":1769023697000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/8\/5\/3964\/8345897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,6]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,8,6]]},"published-print":{"date-parts":[[2021,10,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.13472","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10]]},"published":{"date-parts":[[2021,8,6]]},"assertion":[{"value":"2020-12-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}