{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:05:35Z","timestamp":1789545935348,"version":"build-2803163510"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,11,6]]},"abstract":"\n Background<\/jats:title>\n \n Thymosin beta\u20104 (\n TB<\/jats:styled-content>\n 4) is an X\u2010linked gene product with cardioprotective properties. Little is known about plasma concentration of\n TB<\/jats:styled-content>\n 4 in heart failure (\n HF<\/jats:styled-content>\n ), and its relationship with other cardiovascular biomarkers. We sought to evaluate circulating\n TB<\/jats:styled-content>\n 4 in\n HF<\/jats:styled-content>\n patients with preserved (\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n ) or reduced (\n HF<\/jats:styled-content>\n r\n EF<\/jats:styled-content>\n ) ejection fraction compared to non\u2010\n HF<\/jats:styled-content>\n controls.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n TB<\/jats:styled-content>\n 4 was measured using a liquid chromatography and mass spectrometry assay in age\u2010 and sex\u2010matched\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n (n=219),\n HF<\/jats:styled-content>\n r\n EF<\/jats:styled-content>\n (n=219) patients, and controls (n=219) from a prospective nationwide study. Additionally, a 92\u2010marker multiplex proximity extension assay was measured to identify biomarker covariates. Compared with controls, plasma\n TB<\/jats:styled-content>\n 4 was elevated in\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n (985 [421\u20131723] ng\/mL versus 1401 [720\u20132379] ng\/mL,\n P<\/jats:italic>\n <0.001), but not in\n HF<\/jats:styled-content>\n r\n EF<\/jats:styled-content>\n (1106 [556\u20131955] ng\/mL,\n P<\/jats:italic>\n =0.642). Stratifying by sex, only women (1623 [1040\u20132625] ng\/mL versus 942 [386\u20131891] ng\/mL,\n P<\/jats:italic>\n <0.001), but not men (1238.5 [586\u20131967] ng\/mL versus 1004 [451\u20131538] ng\/mL,\n P<\/jats:italic>\n =1.0), had significantly elevated\n TB<\/jats:styled-content>\n 4 in the setting of\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n . Adjusted for New York Heart Association class, N\u2010terminal pro B\u2010type natriuretic peptide, age, and myocardial infarction, hazard ratio to all\u2010cause mortality is significantly higher in women with elevated\n TB<\/jats:styled-content>\n 4 (1.668,\n P<\/jats:italic>\n =0.036), but not in men (0.791,\n P<\/jats:italic>\n =0.456) with\n HF<\/jats:styled-content>\n .\n TB<\/jats:styled-content>\n 4 is strongly correlated with a cluster of 7 markers from the proximity extension assay panel, which are either X\u2010linked, regulated by sex hormones, or involved with\n NF<\/jats:styled-content>\n \u2010\u03baB signaling.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We show that plasma\n TB<\/jats:styled-content>\n 4 is elevated in women with\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n and has prognostic information. Because\n TB<\/jats:styled-content>\n 4 can preserve EF in animal studies of cardiac injury, the relation of endogenous, circulating\n TB<\/jats:styled-content>\n 4 to X chromosome biology and differential outcomes in female heart disease warrants further study.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.005586","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T00:25:26Z","timestamp":1497399926000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Thymosin Beta\u20104 Is Elevated in Women With Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"6","author":[{"given":"Chester L.","family":"Drum","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute, National University Health System, Singapore"},{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren K. Y.","family":"Tan","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, National University Health System, Singapore"},{"name":"NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew\u2010Pang","family":"Chan","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, National University Health System, Singapore"},{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Department of Mathematics & Statistics, College of Science, Health & Engineering, La Trobe University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leroy S.","family":"Pakkiri","sequence":"additional","affiliation":[{"name":"Cardiac Department, National University Hospital, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny P. C.","family":"Chong","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, National University Health System, Singapore"},{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oi\u2010Wah","family":"Liew","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, National University Health System, Singapore"},{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tze\u2010Pin","family":"Ng","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, National University Health System, Singapore"},{"name":"Department of Psychological Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieng\u2010Hsi","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"National University Heart Centre Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sim","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore, Singapore"},{"name":"Duke\u2010NUS Medical School, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui\u2010Toh G.","family":"Leong","sequence":"additional","affiliation":[{"name":"Changi General Hospital, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P. S.","family":"Yeo","sequence":"additional","affiliation":[{"name":"Tan Tock Seng Hospital, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hean\u2010Yee","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Department of Cardiology, Khoo Teck Puat Hospital, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazlur","family":"Jaufeerally","sequence":"additional","affiliation":[{"name":"Singapore General Hospital, Singapore"},{"name":"Duke\u2010NUS Medical School, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond C. 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