Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Nov 2017)

Thymosin Beta‐4 Is Elevated in Women With Heart Failure With Preserved Ejection Fraction

  • Chester L. Drum,
  • Warren K. Y. Tan,
  • Siew‐Pang Chan,
  • Leroy S. Pakkiri,
  • Jenny P. C. Chong,
  • Oi‐Wah Liew,
  • Tze‐Pin Ng,
  • Lieng‐Hsi Ling,
  • David Sim,
  • Kui‐Toh G. Leong,
  • Daniel P. S. Yeo,
  • Hean‐Yee Ong,
  • Fazlur Jaufeerally,
  • Raymond C. C. Wong,
  • Ping Chai,
  • Adrian F. Low,
  • Pia Davidsson,
  • Mathias Liljeblad,
  • Ann‐Sofi Söderling,
  • Li‐Ming Gan,
  • Ratan V. Bhat,
  • Kristy Purnamawati,
  • Carolyn S. P. Lam,
  • A. Mark Richards

DOI
https://doi.org/10.1161/JAHA.117.005586
Journal volume & issue
Vol. 6, no. 6

Abstract

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BackgroundThymosin 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 ResultsTB4 was measured using a liquid chromatography and mass spectrometry assay in age‐ and sex‐matched 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‐κB signaling. ConclusionsWe 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.

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