Thymosin Beta‐4 Is Elevated in Women With Heart Failure With Preserved Ejection Fraction
Journal of the American Heart Association, 2017
Drum C., Tan W., Chan S., Pakkiri L., Chong J., Liew O., Ng T., Ling L., Sim D., Leong K., Yeo D., Ong H., Jaufeerally F., Wong R., Chai P., Low A., Davidsson P., Liljeblad M., Söderling A., Gan L., Bhat R., Purnamawati K., Lam C., Richards A.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
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.