IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction: Findings From DAPA-HF

Carly Adamson; Paul Welsh; Kieran F Docherty; Rudolf A de Boer; Mirta Diez; Jarosław Drożdż; Andre Dukát; Silvio E Inzucchi; Lars Køber; Mikhail N Kosiborod; Charlotta E A Ljungman; Felipe A Martinez; Piotr Ponikowski; Marc S Sabatine; David A Morrow; Daniel Lindholm; Ann Hammarstedt; David W Boulton; Peter J Greasley; Anna Maria Langkilde; Scott D Solomon; Naveed Sattar; John J V McMurray; Pardeep S Jhund

doi:10.1016/j.jchf.2022.09.004

IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction: Findings From DAPA-HF

Carly Adamson, Paul Welsh, Kieran F Docherty, Rudolf A de Boer, Mirta Diez, Jarosław Drożdż, Andre Dukát, Silvio E Inzucchi, Lars Køber, Mikhail N Kosiborod, Charlotta E A Ljungman, Felipe A Martinez, Piotr Ponikowski, Marc S Sabatine, David A Morrow, Daniel Lindholm, Ann Hammarstedt, David W Boulton, Peter J Greasley, Anna Maria LangkildeScott D Solomon, Naveed Sattar, John J V McMurray^*, Pardeep S Jhund

^*Corresponding author af dette arbejde

Afdeling for Hjertesygdomme

14 Citationer (Scopus)

Abstract

BACKGROUND: Insulin-like growth factor-binding protein-7 (IGFBP-7) has been proposed as a potential prognostic biomarker in heart failure (HF), but the association between elevation in IGFBP-7 and HF outcomes in ambulant patients with heart failure with reduced ejection fraction (HFrEF) is unknown.

OBJECTIVES: The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial.

METHODS: The primary outcome was a composite of cardiovascular death or a worsening HF event. The risk of adverse outcome was compared across tertiles of IGFBP-7 concentration by means of Cox proportional hazard models adjusted for N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT). The efficacy of randomized treatment across IGFBP-7 tertiles was assessed. Change in IGFBP-7 at 12 months was compared with the use of geometric means.

RESULTS: A total of 3,158 patients had IGFBP-7 measured at baseline, and 2,493 had a repeated measure at 12 months. Patients in the highest tertile of IGFBP-7 had evidence of more advanced HFrEF. The adjusted HR for the primary endpoint in tertile 3, compared with tertile 1, was 1.48 (95% CI: 1.17-1.88). There was no modification of the benefit of dapagliflozin by baseline IGFBP-7 (P interaction = 0.34). Dapagliflozin did not change IGFBP-7 levels over 1 year (P = 0.34).

CONCLUSIONS: Higher IGFBP-7 in patients with HFrEF was associated with worse clinical profile and an increased risk of adverse clinical outcomes. IGFBP-7 provided prognostic information incremental to clinical variables, NT-proBNP, and hsTnT. The benefit of dapagliflozin was not modulated by IGFBP-7 level. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).

Originalsprog	Engelsk
Tidsskrift	JACC. Heart failure
Vol/bind	11
Udgave nummer	3
Sider (fra-til)	291-304
Antal sider	14
ISSN	2213-1779
DOI	https://doi.org/10.1016/j.jchf.2022.09.004
Status	Udgivet - mar. 2023

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10.1016/j.jchf.2022.09.004

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Adamson, C., Welsh, P., Docherty, K. F., de Boer, R. A., Diez, M., Drożdż, J., Dukát, A., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Ljungman, C. E. A., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Morrow, D. A., Lindholm, D., Hammarstedt, A., Boulton, D. W., Greasley, P. J., ... Jhund, P. S. (2023). IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction: Findings From DAPA-HF. JACC. Heart failure, 11(3), 291-304. https://doi.org/10.1016/j.jchf.2022.09.004

Adamson, C, Welsh, P, Docherty, KF, de Boer, RA, Diez, M, Drożdż, J, Dukát, A, Inzucchi, SE, Køber, L, Kosiborod, MN, Ljungman, CEA, Martinez, FA, Ponikowski, P, Sabatine, MS, Morrow, DA, Lindholm, D, Hammarstedt, A, Boulton, DW, Greasley, PJ, Langkilde, AM, Solomon, SD, Sattar, N, McMurray, JJV & Jhund, PS 2023, 'IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction: Findings From DAPA-HF', JACC. Heart failure, bind 11, nr. 3, s. 291-304. https://doi.org/10.1016/j.jchf.2022.09.004

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title = "IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction: Findings From DAPA-HF",

abstract = "BACKGROUND: Insulin-like growth factor-binding protein-7 (IGFBP-7) has been proposed as a potential prognostic biomarker in heart failure (HF), but the association between elevation in IGFBP-7 and HF outcomes in ambulant patients with heart failure with reduced ejection fraction (HFrEF) is unknown.OBJECTIVES: The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial.METHODS: The primary outcome was a composite of cardiovascular death or a worsening HF event. The risk of adverse outcome was compared across tertiles of IGFBP-7 concentration by means of Cox proportional hazard models adjusted for N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT). The efficacy of randomized treatment across IGFBP-7 tertiles was assessed. Change in IGFBP-7 at 12 months was compared with the use of geometric means.RESULTS: A total of 3,158 patients had IGFBP-7 measured at baseline, and 2,493 had a repeated measure at 12 months. Patients in the highest tertile of IGFBP-7 had evidence of more advanced HFrEF. The adjusted HR for the primary endpoint in tertile 3, compared with tertile 1, was 1.48 (95% CI: 1.17-1.88). There was no modification of the benefit of dapagliflozin by baseline IGFBP-7 (P interaction = 0.34). Dapagliflozin did not change IGFBP-7 levels over 1 year (P = 0.34).CONCLUSIONS: Higher IGFBP-7 in patients with HFrEF was associated with worse clinical profile and an increased risk of adverse clinical outcomes. IGFBP-7 provided prognostic information incremental to clinical variables, NT-proBNP, and hsTnT. The benefit of dapagliflozin was not modulated by IGFBP-7 level. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).",

keywords = "Heart Failure/drug therapy, Humans, Insulin-Like Growth Factor Binding Proteins, Proportional Hazards Models, Stroke Volume, Ventricular Dysfunction, Left",

author = "Carly Adamson and Paul Welsh and Docherty, {Kieran F} and {de Boer}, {Rudolf A} and Mirta Diez and Jaros{\l}aw Dro{\.z}d{\.z} and Andre Duk{\'a}t and Inzucchi, {Silvio E} and Lars K{\o}ber and Kosiborod, {Mikhail N} and Ljungman, {Charlotta E A} and Martinez, {Felipe A} and Piotr Ponikowski and Sabatine, {Marc S} and Morrow, {David A} and Daniel Lindholm and Ann Hammarstedt and Boulton, {David W} and Greasley, {Peter J} and Langkilde, {Anna Maria} and Solomon, {Scott D} and Naveed Sattar and McMurray, {John J V} and Jhund, {Pardeep S}",

year = "2023",

month = mar,

doi = "10.1016/j.jchf.2022.09.004",

language = "English",

volume = "11",

pages = "291--304",

journal = "JACC. Heart failure",

issn = "2213-1779",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction

T2 - Findings From DAPA-HF

AU - Adamson, Carly

AU - Welsh, Paul

AU - Docherty, Kieran F

AU - de Boer, Rudolf A

AU - Diez, Mirta

AU - Drożdż, Jarosław

AU - Dukát, Andre

AU - Inzucchi, Silvio E

AU - Køber, Lars

AU - Kosiborod, Mikhail N

AU - Ljungman, Charlotta E A

AU - Martinez, Felipe A

AU - Ponikowski, Piotr

AU - Sabatine, Marc S

AU - Morrow, David A

AU - Lindholm, Daniel

AU - Hammarstedt, Ann

AU - Boulton, David W

AU - Greasley, Peter J

AU - Langkilde, Anna Maria

AU - Solomon, Scott D

AU - Sattar, Naveed

AU - McMurray, John J V

AU - Jhund, Pardeep S

PY - 2023/3

Y1 - 2023/3

N2 - BACKGROUND: Insulin-like growth factor-binding protein-7 (IGFBP-7) has been proposed as a potential prognostic biomarker in heart failure (HF), but the association between elevation in IGFBP-7 and HF outcomes in ambulant patients with heart failure with reduced ejection fraction (HFrEF) is unknown.OBJECTIVES: The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial.METHODS: The primary outcome was a composite of cardiovascular death or a worsening HF event. The risk of adverse outcome was compared across tertiles of IGFBP-7 concentration by means of Cox proportional hazard models adjusted for N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT). The efficacy of randomized treatment across IGFBP-7 tertiles was assessed. Change in IGFBP-7 at 12 months was compared with the use of geometric means.RESULTS: A total of 3,158 patients had IGFBP-7 measured at baseline, and 2,493 had a repeated measure at 12 months. Patients in the highest tertile of IGFBP-7 had evidence of more advanced HFrEF. The adjusted HR for the primary endpoint in tertile 3, compared with tertile 1, was 1.48 (95% CI: 1.17-1.88). There was no modification of the benefit of dapagliflozin by baseline IGFBP-7 (P interaction = 0.34). Dapagliflozin did not change IGFBP-7 levels over 1 year (P = 0.34).CONCLUSIONS: Higher IGFBP-7 in patients with HFrEF was associated with worse clinical profile and an increased risk of adverse clinical outcomes. IGFBP-7 provided prognostic information incremental to clinical variables, NT-proBNP, and hsTnT. The benefit of dapagliflozin was not modulated by IGFBP-7 level. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).

AB - BACKGROUND: Insulin-like growth factor-binding protein-7 (IGFBP-7) has been proposed as a potential prognostic biomarker in heart failure (HF), but the association between elevation in IGFBP-7 and HF outcomes in ambulant patients with heart failure with reduced ejection fraction (HFrEF) is unknown.OBJECTIVES: The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial.METHODS: The primary outcome was a composite of cardiovascular death or a worsening HF event. The risk of adverse outcome was compared across tertiles of IGFBP-7 concentration by means of Cox proportional hazard models adjusted for N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT). The efficacy of randomized treatment across IGFBP-7 tertiles was assessed. Change in IGFBP-7 at 12 months was compared with the use of geometric means.RESULTS: A total of 3,158 patients had IGFBP-7 measured at baseline, and 2,493 had a repeated measure at 12 months. Patients in the highest tertile of IGFBP-7 had evidence of more advanced HFrEF. The adjusted HR for the primary endpoint in tertile 3, compared with tertile 1, was 1.48 (95% CI: 1.17-1.88). There was no modification of the benefit of dapagliflozin by baseline IGFBP-7 (P interaction = 0.34). Dapagliflozin did not change IGFBP-7 levels over 1 year (P = 0.34).CONCLUSIONS: Higher IGFBP-7 in patients with HFrEF was associated with worse clinical profile and an increased risk of adverse clinical outcomes. IGFBP-7 provided prognostic information incremental to clinical variables, NT-proBNP, and hsTnT. The benefit of dapagliflozin was not modulated by IGFBP-7 level. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).

KW - Heart Failure/drug therapy

KW - Humans

KW - Insulin-Like Growth Factor Binding Proteins

KW - Proportional Hazards Models

KW - Stroke Volume

KW - Ventricular Dysfunction, Left

UR - http://www.scopus.com/inward/record.url?scp=85149733045&partnerID=8YFLogxK

U2 - 10.1016/j.jchf.2022.09.004

DO - 10.1016/j.jchf.2022.09.004

M3 - Journal article

C2 - 36592046

SN - 2213-1779

VL - 11

SP - 291

EP - 304

JO - JACC. Heart failure

JF - JACC. Heart failure

IS - 3

ER -

IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction: Findings From DAPA-HF

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