Open AccessThymosin Beta‐4 Is Elevated in Women With Heart Failure With Preserved Ejection Fraction
Author(s) -
Drum Chester L.,
Tan Warren K. Y.,
Chan SiewPang,
Pakkiri Leroy S.,
Chong Jenny P. C.,
Liew OiWah,
Ng TzePin,
Ling LiengHsi,
Sim David,
Leong KuiToh G.,
Yeo Daniel P. S.,
Ong HeanYee,
Jaufeerally Fazlur,
Wong Raymond C. C.,
Chai Ping,
Low Adrian F.,
Davidsson Pia,
Liljeblad Mathias,
Söderling AnnSofi,
Gan LiMing,
Bhat Ratan V.,
Purnamawati Kristy,
Lam Carolyn S. P.,
Richards A. Mark
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.005586
Subject(s) - medicine , heart failure , ejection fraction , hazard ratio , natriuretic peptide , cardiology , myocardial infarction , biomarker , endocrinology , brain natriuretic peptide , prospective cohort study , confidence interval , biochemistry , chemistry
Background Thymosin beta‐4 ( TB 4) is an X‐linked gene product with cardioprotective properties. Little is known about plasma concentration of TB 4 in heart failure ( HF ), and its relationship with other cardiovascular biomarkers. We sought to evaluate circulating TB 4 in HF patients with preserved ( HF p EF ) or reduced ( HF r EF ) ejection fraction compared to non‐ HF controls. Methods and Results TB 4 was measured using a liquid chromatography and mass spectrometry assay in age‐ and sex‐matched HF p EF (n=219), HF r EF (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 TB 4 was elevated in HF p EF (985 [421–1723] ng/mL versus 1401 [720–2379] ng/mL, P <0.001), but not in HF r EF (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 TB 4 in the setting of HF p EF . 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 TB 4 (1.668, P =0.036), but not in men (0.791, P =0.456) with HF . TB 4 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 ‐κB signaling. Conclusions We show that plasma TB 4 is elevated in women with HF p EF and has prognostic information. Because TB 4 can preserve EF in animal studies of cardiac injury, the relation of endogenous, circulating TB 4 to X chromosome biology and differential outcomes in female heart disease warrants further study.