Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T

Alberto Aimo; James L. Januzzi; Giuseppe Vergaro; A. Mark Richards; Carolyn S.P. Lam; Roberto Latini; Inder S. Anand; Jay N. Cohn; Thor Ueland; Lars Gullestad; Pål Aukrust; Hans Peter Brunner-La Rocca; Antoni Bayes-Genis; Josep Lupón; Rudolf A. de Boer; Yasuchika Takeishi; Michael Egstrup; Ida Gustafsson; Hanna K. Gaggin; Kai M. Eggers; Kurt Huber; Greg D. Gamble; Lieng H. Ling; Kui Tong Gerard Leong; Poh Shuah Daniel Yeo; Hean Yee Ong; Fazlur Jaufeerally; Tze P. Ng; Richard Troughton; Robert N. Doughty; Claudio Passino; Michele Emdin

doi:10.1002/ejhf.1701

Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T

Alberto Aimo^*, James L. Januzzi, Giuseppe Vergaro, A. Mark Richards, Carolyn S.P. Lam, Roberto Latini, Inder S. Anand, Jay N. Cohn, Thor Ueland, Lars Gullestad, Pål Aukrust, Hans Peter Brunner-La Rocca, Antoni Bayes-Genis, Josep Lupón, Rudolf A. de Boer, Yasuchika Takeishi, Michael Egstrup, Ida Gustafsson, Hanna K. Gaggin, Kai M. EggersKurt Huber, Greg D. Gamble, Lieng H. Ling, Kui Tong Gerard Leong, Poh Shuah Daniel Yeo, Hean Yee Ong, Fazlur Jaufeerally, Tze P. Ng, Richard Troughton, Robert N. Doughty, Claudio Passino, Michele Emdin

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

38 Citations (Scopus)

Abstract

Aims: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT) and soluble suppression of tumorigenesis-2 (sST2) predict outcome in chronic heart failure (HF). We assessed the influence of age on circulating levels and prognostic significance of these biomarkers. Methods and results: Individual data from 5301 patients with chronic HF and NT-proBNP, hs-TnT, and sST2 data were evaluated. Patients were stratified according to age: <60 years (n = 1332, 25%), 60–69 years (n = 1628, 31%), 70–79 years (n = 1662, 31%), and ≥ 80 years (n = 679, 13%). Patients (median age 66 years, 75% men, median left ventricular ejection fraction 28%, 64% with ischaemic HF) had median NT-proBNP 1564 ng/L, hs-TnT 21 ng/L, and sST2 29 ng/mL. Age independently predicted NT-proBNP and hs-TnT, but not sST2. The best NT-proBNP and hs-TnT cut-offs for 1-year and 5-year all-cause and cardiovascular mortality and 1- to 12-month HF hospitalization increased with age, while the best sST2 cut-offs did not. When stratifying patients according to age- and outcome-specific cut-offs, this stratification yielded independent prognostic significance over NT-proBNP levels only, or the composite of NT-proBNP and hs-TnT, and improved risk prediction for most endpoints. Finally, absolute NT-proBNP, hs-TnT, and sST2 levels predicted outcomes independent of age, sex, left ventricular ejection fraction category, ethnic group, and other variables. Conclusions: Soluble ST2 is less influenced by age than NT-proBNP or hs-TnT; all these biomarkers predict outcome regardless of age. The use of age- and outcome-specific cut-offs of NT-proBNP, hs-TnT and sST2 allows more accurate risk stratification than NT-proBNP alone or the combination of NT-proBNP and hs-TnT.

Original language	English
Pages (from-to)	2078-2088
Number of pages	11
Journal	European Journal of Heart Failure
Volume	22
Issue number	11
DOIs	https://doi.org/10.1002/ejhf.1701
Publication status	Published - Nov 2020
Externally published	Yes

Bibliographical note

Funding Information:
J.L.J. is supported in part by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; has received grant support from Novartis Pharmaceuticals, Roche Diagnostics, Abbott, Singulex and Prevencio, consulting income from Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Boehringer Ingelheim, Janssen, and Takeda. A.M.R. has sat on advisory boards and/or received speakers honoraria, travel support and/or grants from Novartis, Roche Diagnostics, Abbott Laboratories, Thermo Fisher and Critical Diagnostics. C.S.P.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research & Development LLC, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, WebMD Global LLC, Radcliffe Group Ltd and Corpus. R.L. has received grant support and travel reimbursements from Roche Diagnostics. H.P.B.L.R. reports unrestricted research grants and consulting fees from Roche Diagnostics, as well as unrestricted research grants from Novartis and GlaxoSmithKline outside this work. A.B.G. has received grant support from Roche Diagnosis, lecture honoraria from Roche Diagnostics and Critical Diagnostics, and consulting income from Roche Diagnostics, Critical Diagnostics, and Novartis. J.L. has received lecture honoraria from Roche Diagnostics and reports relationship with Critical Diagnostics. The UMCG, which employs R.A.d.B., has received research grants and/or fees from AstraZeneca, Abbott, Bristol‐Myers Squibb, Novartis, Novo Nordisk, and Roche. R.A.d.B. is a minority shareholder of scPharmaceuticals, Inc.; received personal fees from Abbott, AstraZeneca, MandalMed Inc, and Novartis, outside the submitted work. H.K.G. has received grant support from Roche and Portola; consulting income from Roche Diagnostics, Amgen and Ortho Clinical; research payments for clinical endpoint committees for EchoSense and Radiometer. All other authors have nothing to disclose. Conflict of interest:

Publisher Copyright:
© 2019 European Society of Cardiology

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10.1002/ejhf.1701

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Aimo, A., Januzzi, J. L., Vergaro, G., Richards, A. M., Lam, C. S. P., Latini, R., Anand, I. S., Cohn, J. N., Ueland, T., Gullestad, L., Aukrust, P., Brunner-La Rocca, H. P., Bayes-Genis, A., Lupón, J., de Boer, R. A., Takeishi, Y., Egstrup, M., Gustafsson, I., Gaggin, H. K., ... Emdin, M. (2020). Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T. European Journal of Heart Failure, 22(11), 2078-2088. https://doi.org/10.1002/ejhf.1701

@article{0634138f678c49d1a391e4eebfc16028,

title = "Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T",

abstract = "Aims: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT) and soluble suppression of tumorigenesis-2 (sST2) predict outcome in chronic heart failure (HF). We assessed the influence of age on circulating levels and prognostic significance of these biomarkers. Methods and results: Individual data from 5301 patients with chronic HF and NT-proBNP, hs-TnT, and sST2 data were evaluated. Patients were stratified according to age: <60 years (n = 1332, 25%), 60–69 years (n = 1628, 31%), 70–79 years (n = 1662, 31%), and ≥ 80 years (n = 679, 13%). Patients (median age 66 years, 75% men, median left ventricular ejection fraction 28%, 64% with ischaemic HF) had median NT-proBNP 1564 ng/L, hs-TnT 21 ng/L, and sST2 29 ng/mL. Age independently predicted NT-proBNP and hs-TnT, but not sST2. The best NT-proBNP and hs-TnT cut-offs for 1-year and 5-year all-cause and cardiovascular mortality and 1- to 12-month HF hospitalization increased with age, while the best sST2 cut-offs did not. When stratifying patients according to age- and outcome-specific cut-offs, this stratification yielded independent prognostic significance over NT-proBNP levels only, or the composite of NT-proBNP and hs-TnT, and improved risk prediction for most endpoints. Finally, absolute NT-proBNP, hs-TnT, and sST2 levels predicted outcomes independent of age, sex, left ventricular ejection fraction category, ethnic group, and other variables. Conclusions: Soluble ST2 is less influenced by age than NT-proBNP or hs-TnT; all these biomarkers predict outcome regardless of age. The use of age- and outcome-specific cut-offs of NT-proBNP, hs-TnT and sST2 allows more accurate risk stratification than NT-proBNP alone or the combination of NT-proBNP and hs-TnT.",

author = "Alberto Aimo and Januzzi, {James L.} and Giuseppe Vergaro and Richards, {A. Mark} and Lam, {Carolyn S.P.} and Roberto Latini and Anand, {Inder S.} and Cohn, {Jay N.} and Thor Ueland and Lars Gullestad and P{\aa}l Aukrust and {Brunner-La Rocca}, {Hans Peter} and Antoni Bayes-Genis and Josep Lup{\'o}n and {de Boer}, {Rudolf A.} and Yasuchika Takeishi and Michael Egstrup and Ida Gustafsson and Gaggin, {Hanna K.} and Eggers, {Kai M.} and Kurt Huber and Gamble, {Greg D.} and Ling, {Lieng H.} and Leong, {Kui Tong Gerard} and Yeo, {Poh Shuah Daniel} and Ong, {Hean Yee} and Fazlur Jaufeerally and Ng, {Tze P.} and Richard Troughton and Doughty, {Robert N.} and Claudio Passino and Michele Emdin",

note = "Funding Information: J.L.J. is supported in part by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; has received grant support from Novartis Pharmaceuticals, Roche Diagnostics, Abbott, Singulex and Prevencio, consulting income from Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Boehringer Ingelheim, Janssen, and Takeda. A.M.R. has sat on advisory boards and/or received speakers honoraria, travel support and/or grants from Novartis, Roche Diagnostics, Abbott Laboratories, Thermo Fisher and Critical Diagnostics. C.S.P.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research & Development LLC, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, WebMD Global LLC, Radcliffe Group Ltd and Corpus. R.L. has received grant support and travel reimbursements from Roche Diagnostics. H.P.B.L.R. reports unrestricted research grants and consulting fees from Roche Diagnostics, as well as unrestricted research grants from Novartis and GlaxoSmithKline outside this work. A.B.G. has received grant support from Roche Diagnosis, lecture honoraria from Roche Diagnostics and Critical Diagnostics, and consulting income from Roche Diagnostics, Critical Diagnostics, and Novartis. J.L. has received lecture honoraria from Roche Diagnostics and reports relationship with Critical Diagnostics. The UMCG, which employs R.A.d.B., has received research grants and/or fees from AstraZeneca, Abbott, Bristol‐Myers Squibb, Novartis, Novo Nordisk, and Roche. R.A.d.B. is a minority shareholder of scPharmaceuticals, Inc.; received personal fees from Abbott, AstraZeneca, MandalMed Inc, and Novartis, outside the submitted work. H.K.G. has received grant support from Roche and Portola; consulting income from Roche Diagnostics, Amgen and Ortho Clinical; research payments for clinical endpoint committees for EchoSense and Radiometer. All other authors have nothing to disclose. Conflict of interest: Publisher Copyright: {\textcopyright} 2019 European Society of Cardiology",

year = "2020",

month = nov,

doi = "10.1002/ejhf.1701",

language = "English",

volume = "22",

pages = "2078--2088",

journal = "European Journal of Heart Failure",

issn = "1388-9842",

publisher = "John Wiley & Sons Ltd.",

number = "11",

}

Aimo, A, Januzzi, JL, Vergaro, G, Richards, AM, Lam, CSP, Latini, R, Anand, IS, Cohn, JN, Ueland, T, Gullestad, L, Aukrust, P, Brunner-La Rocca, HP, Bayes-Genis, A, Lupón, J, de Boer, RA, Takeishi, Y, Egstrup, M, Gustafsson, I, Gaggin, HK, Eggers, KM, Huber, K, Gamble, GD, Ling, LH, Leong, KTG, Yeo, PSD, Ong, HY, Jaufeerally, F, Ng, TP, Troughton, R, Doughty, RN, Passino, C & Emdin, M 2020, 'Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T', European Journal of Heart Failure, vol. 22, no. 11, pp. 2078-2088. https://doi.org/10.1002/ejhf.1701

Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T. / Aimo, Alberto; Januzzi, James L.; Vergaro, Giuseppe et al.
In: European Journal of Heart Failure, Vol. 22, No. 11, 11.2020, p. 2078-2088.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T

AU - Aimo, Alberto

AU - Januzzi, James L.

AU - Vergaro, Giuseppe

AU - Richards, A. Mark

AU - Lam, Carolyn S.P.

AU - Latini, Roberto

AU - Anand, Inder S.

AU - Cohn, Jay N.

AU - Ueland, Thor

AU - Gullestad, Lars

AU - Aukrust, Pål

AU - Brunner-La Rocca, Hans Peter

AU - Bayes-Genis, Antoni

AU - Lupón, Josep

AU - de Boer, Rudolf A.

AU - Takeishi, Yasuchika

AU - Egstrup, Michael

AU - Gustafsson, Ida

AU - Gaggin, Hanna K.

AU - Eggers, Kai M.

AU - Huber, Kurt

AU - Gamble, Greg D.

AU - Ling, Lieng H.

AU - Leong, Kui Tong Gerard

AU - Yeo, Poh Shuah Daniel

AU - Ong, Hean Yee

AU - Jaufeerally, Fazlur

AU - Ng, Tze P.

AU - Troughton, Richard

AU - Doughty, Robert N.

AU - Passino, Claudio

AU - Emdin, Michele

N1 - Funding Information: J.L.J. is supported in part by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; has received grant support from Novartis Pharmaceuticals, Roche Diagnostics, Abbott, Singulex and Prevencio, consulting income from Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Boehringer Ingelheim, Janssen, and Takeda. A.M.R. has sat on advisory boards and/or received speakers honoraria, travel support and/or grants from Novartis, Roche Diagnostics, Abbott Laboratories, Thermo Fisher and Critical Diagnostics. C.S.P.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research & Development LLC, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, WebMD Global LLC, Radcliffe Group Ltd and Corpus. R.L. has received grant support and travel reimbursements from Roche Diagnostics. H.P.B.L.R. reports unrestricted research grants and consulting fees from Roche Diagnostics, as well as unrestricted research grants from Novartis and GlaxoSmithKline outside this work. A.B.G. has received grant support from Roche Diagnosis, lecture honoraria from Roche Diagnostics and Critical Diagnostics, and consulting income from Roche Diagnostics, Critical Diagnostics, and Novartis. J.L. has received lecture honoraria from Roche Diagnostics and reports relationship with Critical Diagnostics. The UMCG, which employs R.A.d.B., has received research grants and/or fees from AstraZeneca, Abbott, Bristol‐Myers Squibb, Novartis, Novo Nordisk, and Roche. R.A.d.B. is a minority shareholder of scPharmaceuticals, Inc.; received personal fees from Abbott, AstraZeneca, MandalMed Inc, and Novartis, outside the submitted work. H.K.G. has received grant support from Roche and Portola; consulting income from Roche Diagnostics, Amgen and Ortho Clinical; research payments for clinical endpoint committees for EchoSense and Radiometer. All other authors have nothing to disclose. Conflict of interest: Publisher Copyright: © 2019 European Society of Cardiology

PY - 2020/11

Y1 - 2020/11

N2 - Aims: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT) and soluble suppression of tumorigenesis-2 (sST2) predict outcome in chronic heart failure (HF). We assessed the influence of age on circulating levels and prognostic significance of these biomarkers. Methods and results: Individual data from 5301 patients with chronic HF and NT-proBNP, hs-TnT, and sST2 data were evaluated. Patients were stratified according to age: <60 years (n = 1332, 25%), 60–69 years (n = 1628, 31%), 70–79 years (n = 1662, 31%), and ≥ 80 years (n = 679, 13%). Patients (median age 66 years, 75% men, median left ventricular ejection fraction 28%, 64% with ischaemic HF) had median NT-proBNP 1564 ng/L, hs-TnT 21 ng/L, and sST2 29 ng/mL. Age independently predicted NT-proBNP and hs-TnT, but not sST2. The best NT-proBNP and hs-TnT cut-offs for 1-year and 5-year all-cause and cardiovascular mortality and 1- to 12-month HF hospitalization increased with age, while the best sST2 cut-offs did not. When stratifying patients according to age- and outcome-specific cut-offs, this stratification yielded independent prognostic significance over NT-proBNP levels only, or the composite of NT-proBNP and hs-TnT, and improved risk prediction for most endpoints. Finally, absolute NT-proBNP, hs-TnT, and sST2 levels predicted outcomes independent of age, sex, left ventricular ejection fraction category, ethnic group, and other variables. Conclusions: Soluble ST2 is less influenced by age than NT-proBNP or hs-TnT; all these biomarkers predict outcome regardless of age. The use of age- and outcome-specific cut-offs of NT-proBNP, hs-TnT and sST2 allows more accurate risk stratification than NT-proBNP alone or the combination of NT-proBNP and hs-TnT.

AB - Aims: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT) and soluble suppression of tumorigenesis-2 (sST2) predict outcome in chronic heart failure (HF). We assessed the influence of age on circulating levels and prognostic significance of these biomarkers. Methods and results: Individual data from 5301 patients with chronic HF and NT-proBNP, hs-TnT, and sST2 data were evaluated. Patients were stratified according to age: <60 years (n = 1332, 25%), 60–69 years (n = 1628, 31%), 70–79 years (n = 1662, 31%), and ≥ 80 years (n = 679, 13%). Patients (median age 66 years, 75% men, median left ventricular ejection fraction 28%, 64% with ischaemic HF) had median NT-proBNP 1564 ng/L, hs-TnT 21 ng/L, and sST2 29 ng/mL. Age independently predicted NT-proBNP and hs-TnT, but not sST2. The best NT-proBNP and hs-TnT cut-offs for 1-year and 5-year all-cause and cardiovascular mortality and 1- to 12-month HF hospitalization increased with age, while the best sST2 cut-offs did not. When stratifying patients according to age- and outcome-specific cut-offs, this stratification yielded independent prognostic significance over NT-proBNP levels only, or the composite of NT-proBNP and hs-TnT, and improved risk prediction for most endpoints. Finally, absolute NT-proBNP, hs-TnT, and sST2 levels predicted outcomes independent of age, sex, left ventricular ejection fraction category, ethnic group, and other variables. Conclusions: Soluble ST2 is less influenced by age than NT-proBNP or hs-TnT; all these biomarkers predict outcome regardless of age. The use of age- and outcome-specific cut-offs of NT-proBNP, hs-TnT and sST2 allows more accurate risk stratification than NT-proBNP alone or the combination of NT-proBNP and hs-TnT.

UR - http://www.scopus.com/inward/record.url?scp=85077906204&partnerID=8YFLogxK

U2 - 10.1002/ejhf.1701

DO - 10.1002/ejhf.1701

M3 - Article

C2 - 31919929

AN - SCOPUS:85077906204

SN - 1388-9842

VL - 22

SP - 2078

EP - 2088

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 11

ER -

Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T

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