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Thymosin beta-4 is elevated in women with heart failure with preserved ejection fraction
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نویسنده
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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.
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منبع
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journal of the american heart association - 2017 - دوره : 6 - شماره : 6
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چکیده
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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-κb 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.
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کلیدواژه
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Biomarker; Cardiac biomarkers; CD40/CD40L; Heart failure; Liquid chromatography-mass spectrometry; Proximity extension assay; Thymosin beta-4
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آدرس
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cardiovascular research institute,national university health system,singapore,department of medicine,yong loo lin school of medicine,national university of singapore,singapore,department of surgery,yong loo lin school of medicine,national university of singapore,singapore,translational laboratory in genetic medicine,agency for science,technology and research, Singapore, cardiovascular research institute,national university health system,singapore,nus graduate school for integrative sciences and engineering,national university of singapore, Singapore, cardiovascular research institute,national university health system,singapore,department of medicine,yong loo lin school of medicine,national university of singapore,singapore,department of mathematics and ostatistics,college of science,health and oengineering,la trobe university,melbourne, Australia, cardiac department,national university hospital, Singapore, cardiovascular research institute,national university health system,singapore,department of medicine,yong loo lin school of medicine,national university of singapore, Singapore, cardiovascular research institute,national university health system,singapore,department of medicine,yong loo lin school of medicine,national university of singapore, Singapore, cardiovascular research institute,national university health system,singapore,department of psychological medicine,national university of singapore, Singapore, department of medicine,yong loo lin school of medicine,national university of singapore,singapore,national university heart centre singapore, Singapore, national heart centre singapore,singapore,duke-nus medical school, Singapore, changi general hospital, Singapore, tan tock seng hospital, Singapore, department of medicine,yong loo lin school of medicine,national university of singapore,singapore,department of cardiology,khoo teck puat hospital, Singapore, singapore general hospital,singapore,duke-nus medical school, Singapore, national university heart centre singapore, Singapore, national university heart centre singapore, Singapore, department of medicine,yong loo lin school of medicine,national university of singapore,singapore,national university heart centre singapore, Singapore, innovative medicines and early development,cardiovascular and ometabolic diseases,astrazeneca r and d,gothenburg, Sweden, innovative medicines and early development,cardiovascular and ometabolic diseases,astrazeneca r and d,gothenburg, Sweden, innovative medicines and early development,cardiovascular and ometabolic diseases,astrazeneca r and d,gothenburg, Sweden, innovative medicines and early development,cardiovascular and ometabolic diseases,astrazeneca r and d,gothenburg, Sweden, innovative medicines and early development,cardiovascular and ometabolic diseases,astrazeneca r and d,gothenburg, Sweden, translational laboratory in genetic medicine,agency for science,technology and research, Singapore, national heart centre singapore,singapore,duke-nus medical school, Singapore, cardiovascular research institute,national university health system,singapore,department of medicine,yong loo lin school of medicine,national university of singapore,singapore,christchurch heart institute,university of otago, New Zealand
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Authors
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