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Title: Thymosin beta-4 is elevated in women with heart failure with preserved ejection fraction
Authors: Drum C.L. 
Tan W.K.Y.
Chan S.-P. 
Pakkiri L.S.
Chong J.P.C. 
Liew O.-W. 
Ng T.-P. 
Ling L.-H. 
Sim D.
Leong K.-T.G.
Yeo D.P.S.
Ong H.-Y. 
Jaufeerally F.
Wong R.C.C.
Chai P.
Low A.F. 
Davidsson P.
Liljeblad M.
Söderling A.-S.
Gan L.-M.
Bhat R.V.
Purnamawati K.
Lam C.S.P. 
Richards A.M. 
Keywords: amino terminal pro brain natriuretic peptide
biological marker
CD40 antigen
CD40 ligand
sex hormone
thymosin beta4
troponin T
actin binding protein
biological marker
thymosin beta(4)
all cause mortality
clinical trial
controlled study
heart failure with preserved ejection fraction
heart failure with reduced ejection fraction
heart infarction
heart left ventricle ejection fraction
liquid chromatography-mass spectrometry
major clinical study
middle aged
New York Heart Association class
priority journal
prognostic assessment
prospective study
protein blood level
protein expression
proximity extension assay
sex difference
X chromosome linkage
comparative study
disease exacerbation
follow up
heart failure
heart stroke volume
liquid chromatography
mass spectrometry
sex factor
Chromatography, Liquid
Disease Progression
Follow-Up Studies
Heart Failure
Mass Spectrometry
Microfilament Proteins
Middle Aged
Prospective Studies
Sex Factors
Stroke Volume
Issue Date: 2017
Citation: Drum C.L., Tan W.K.Y., Chan S.-P., Pakkiri L.S., Chong J.P.C., Liew O.-W., Ng T.-P., Ling L.-H., Sim D., Leong K.-T.G., Yeo D.P.S., Ong H.-Y., Jaufeerally F., Wong R.C.C., Chai P., Low A.F., Davidsson P., Liljeblad M., Söderling A.-S., Gan L.-M., Bhat R.V., Purnamawati K., Lam C.S.P., Richards A.M. (2017). Thymosin beta-4 is elevated in women with heart failure with preserved ejection fraction. Journal of the American Heart Association 6 (6). ScholarBank@NUS Repository.
Abstract: Background-Thymosin beta-4 (TB4) is an X-linked gene product with cardioprotective properties. Little is known about plasma concentration of TB4 in heart failure (HF), and its relationship with other cardiovascular biomarkers. We sought to evaluate circulating TB4 in HF patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction compared to non-HF controls. Methods and Results-TB4 was measured using a liquid chromatography and mass spectrometry assay in age- and sexmatched HFpEF (n=219), HFrEF (n=219) patients, and controls (n=219) from a prospective nationwide study. Additionally, a 92-marker multiplex proximity extension assay was measured to identify biomarker covariates. Compared with controls, plasma TB4 was elevated in HFpEF (985 [421-1723] ng/mL versus 1401 [720-2379] ng/mL, P<0.001), but not in HFrEF (1106 [556-1955] ng/mL, P=0.642). Stratifying by sex, only women (1623 [1040-2625] ng/mL versus 942 [386-1891] ng/mL, P<0.001), but not men (1238.5 [586-1967] ng/mL versus 1004 [451-1538] ng/mL, P=1.0), had significantly elevated TB4 in the setting of HFpEF. Adjusted for New York Heart Association class, N-terminal pro B-type natriuretic peptide, age, and myocardial infarction, hazard ratio to all-cause mortality is significantly higher in women with elevated TB4 (1.668, P=0.036), but not in men (0.791, P=0.456) with HF. TB4 is strongly correlated with a cluster of 7 markers from the proximity extension assay panel, which are either X-linked, regulated by sex hormones, or involved with NF-?B signaling. Conclusions-We show that plasma TB4 is elevated in women with HFpEF and has prognostic information. Because TB4 can preserve EF in animal studies of cardiac injury, the relation of endogenous, circulating TB4 to X chromosome biology and differential outcomes in female heart disease warrants further study. © 2017 The Authors and AstraZeneca.
Source Title: Journal of the American Heart Association
ISSN: 20479980
DOI: 10.1161/JAHA.117.005586
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