IGFBP7 (Insulin-Like Growth Factor-Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure

James L. Januzzi; Milton Packer; Brian Claggett; Jiankang Liu; Amil M. Shah; Michael R. Zile; Burkert Pieske; Adriaan Voors; Parul U. Gandhi; Margaret F. Prescott; Victor Shi; Martin P. Lefkowitz; John J. V. McMurray; Scott D. Solomon

doi:10.1161/CIRCHEARTFAILURE.118.005133

IGFBP7 (Insulin-Like Growth Factor-Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure

James L. Januzzi^*, Milton Packer, Brian Claggett, Jiankang Liu, Amil M. Shah, Michael R. Zile, Burkert Pieske, Adriaan Voors, Parul U. Gandhi, Margaret F. Prescott, Victor Shi, Martin P. Lefkowitz, John J. V. McMurray, Scott D. Solomon

^*Corresponding author for this work

Cardiovascular Centre (CVC)

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

50 Citations (Scopus)

Abstract

BACKGROUND: Increased activity of IGFBP7 (insulin-like growth factor-binding protein-7) is associated with cellular senescence, tissue aging, and obesity. IGFBP7 may be related to heart failure with preserved ejection fraction, a disease of elderly obese people.

METHODS AND RESULTS: In a subset of patients with heart failure with preserved ejection fraction (N=228) randomized to receive sacubitril/valsartan versus valsartan, IGFBP7 concentrations were measured at baseline, 12 weeks, and 36 weeks. Patient characteristics and echocardiographic measures including left atrial (LA) size and volume, ratio of early mitral inflow velocity/annular diastolic velocity, and ratio of early diastole/peak late diastolic velocity were assessed as a function of IGFBP7 concentration. Effect of sacubitril/valsartan on IGFBP7 concentrations was analyzed. With increasing baseline IGFBP7 quartiles, LA size and LA volume index (LAVi) were higher (both P= 34 mL/m(2) compared with lower LAVi at all time points (all P

CONCLUSIONS: Among patients with heart failure with preserved ejection fraction, concentrations of the cellular senescence biomarker IGFBP7 were associated with abnormalities in diastolic filling and LA dilation. Treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations compared with valsartan.

Original language	English
Article number	005133
Number of pages	9
Journal	Circulation-Heart failure
Volume	11
Issue number	10
DOIs	https://doi.org/10.1161/CIRCHEARTFAILURE.118.005133
Publication status	Published - Oct-2018

Keywords

atrial fibrillation
biomarkers
echocardiography
heart failure
valsartan
PRESERVED EJECTION FRACTION
TRIAL
BIOMARKERS
LCZ696
SKIN

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IGFBP7 (Insulin-Like Growth Factor–Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure
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Januzzi, J. L., Packer, M., Claggett, B., Liu, J., Shah, A. M., Zile, M. R., Pieske, B., Voors, A., Gandhi, P. U., Prescott, M. F., Shi, V., Lefkowitz, M. P., McMurray, J. J. V., & Solomon, S. D. (2018). IGFBP7 (Insulin-Like Growth Factor-Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure. Circulation-Heart failure, 11(10), Article 005133. https://doi.org/10.1161/CIRCHEARTFAILURE.118.005133

@article{bab287c2981e4b42adfaa60e9e8a5761,

title = "IGFBP7 (Insulin-Like Growth Factor-Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure",

abstract = "BACKGROUND: Increased activity of IGFBP7 (insulin-like growth factor-binding protein-7) is associated with cellular senescence, tissue aging, and obesity. IGFBP7 may be related to heart failure with preserved ejection fraction, a disease of elderly obese people.METHODS AND RESULTS: In a subset of patients with heart failure with preserved ejection fraction (N=228) randomized to receive sacubitril/valsartan versus valsartan, IGFBP7 concentrations were measured at baseline, 12 weeks, and 36 weeks. Patient characteristics and echocardiographic measures including left atrial (LA) size and volume, ratio of early mitral inflow velocity/annular diastolic velocity, and ratio of early diastole/peak late diastolic velocity were assessed as a function of IGFBP7 concentration. Effect of sacubitril/valsartan on IGFBP7 concentrations was analyzed. With increasing baseline IGFBP7 quartiles, LA size and LA volume index (LAVi) were higher (both P= 34 mL/m(2) compared with lower LAVi at all time points (all PCONCLUSIONS: Among patients with heart failure with preserved ejection fraction, concentrations of the cellular senescence biomarker IGFBP7 were associated with abnormalities in diastolic filling and LA dilation. Treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations compared with valsartan.",

keywords = "atrial fibrillation, biomarkers, echocardiography, heart failure, valsartan, PRESERVED EJECTION FRACTION, TRIAL, BIOMARKERS, LCZ696, SKIN",

author = "Januzzi, {James L.} and Milton Packer and Brian Claggett and Jiankang Liu and Shah, {Amil M.} and Zile, {Michael R.} and Burkert Pieske and Adriaan Voors and Gandhi, {Parul U.} and Prescott, {Margaret F.} and Victor Shi and Lefkowitz, {Martin P.} and McMurray, {John J. V.} and Solomon, {Scott D.}",

year = "2018",

month = oct,

doi = "10.1161/CIRCHEARTFAILURE.118.005133",

language = "English",

volume = "11",

journal = "Circulation-Heart failure",

issn = "1941-3289",

publisher = "Lippincott Williams and Wilkins",

number = "10",

}

Januzzi, JL, Packer, M, Claggett, B, Liu, J, Shah, AM, Zile, MR, Pieske, B, Voors, A, Gandhi, PU, Prescott, MF, Shi, V, Lefkowitz, MP, McMurray, JJV & Solomon, SD 2018, 'IGFBP7 (Insulin-Like Growth Factor-Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure', Circulation-Heart failure, vol. 11, no. 10, 005133. https://doi.org/10.1161/CIRCHEARTFAILURE.118.005133

TY - JOUR

T1 - IGFBP7 (Insulin-Like Growth Factor-Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure

AU - Januzzi, James L.

AU - Packer, Milton

AU - Claggett, Brian

AU - Liu, Jiankang

AU - Shah, Amil M.

AU - Zile, Michael R.

AU - Pieske, Burkert

AU - Voors, Adriaan

AU - Gandhi, Parul U.

AU - Prescott, Margaret F.

AU - Shi, Victor

AU - Lefkowitz, Martin P.

AU - McMurray, John J. V.

AU - Solomon, Scott D.

PY - 2018/10

Y1 - 2018/10

N2 - BACKGROUND: Increased activity of IGFBP7 (insulin-like growth factor-binding protein-7) is associated with cellular senescence, tissue aging, and obesity. IGFBP7 may be related to heart failure with preserved ejection fraction, a disease of elderly obese people.METHODS AND RESULTS: In a subset of patients with heart failure with preserved ejection fraction (N=228) randomized to receive sacubitril/valsartan versus valsartan, IGFBP7 concentrations were measured at baseline, 12 weeks, and 36 weeks. Patient characteristics and echocardiographic measures including left atrial (LA) size and volume, ratio of early mitral inflow velocity/annular diastolic velocity, and ratio of early diastole/peak late diastolic velocity were assessed as a function of IGFBP7 concentration. Effect of sacubitril/valsartan on IGFBP7 concentrations was analyzed. With increasing baseline IGFBP7 quartiles, LA size and LA volume index (LAVi) were higher (both P= 34 mL/m(2) compared with lower LAVi at all time points (all PCONCLUSIONS: Among patients with heart failure with preserved ejection fraction, concentrations of the cellular senescence biomarker IGFBP7 were associated with abnormalities in diastolic filling and LA dilation. Treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations compared with valsartan.

AB - BACKGROUND: Increased activity of IGFBP7 (insulin-like growth factor-binding protein-7) is associated with cellular senescence, tissue aging, and obesity. IGFBP7 may be related to heart failure with preserved ejection fraction, a disease of elderly obese people.METHODS AND RESULTS: In a subset of patients with heart failure with preserved ejection fraction (N=228) randomized to receive sacubitril/valsartan versus valsartan, IGFBP7 concentrations were measured at baseline, 12 weeks, and 36 weeks. Patient characteristics and echocardiographic measures including left atrial (LA) size and volume, ratio of early mitral inflow velocity/annular diastolic velocity, and ratio of early diastole/peak late diastolic velocity were assessed as a function of IGFBP7 concentration. Effect of sacubitril/valsartan on IGFBP7 concentrations was analyzed. With increasing baseline IGFBP7 quartiles, LA size and LA volume index (LAVi) were higher (both P= 34 mL/m(2) compared with lower LAVi at all time points (all PCONCLUSIONS: Among patients with heart failure with preserved ejection fraction, concentrations of the cellular senescence biomarker IGFBP7 were associated with abnormalities in diastolic filling and LA dilation. Treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations compared with valsartan.

KW - atrial fibrillation

KW - biomarkers

KW - echocardiography

KW - heart failure

KW - valsartan

KW - PRESERVED EJECTION FRACTION

KW - TRIAL

KW - BIOMARKERS

KW - LCZ696

KW - SKIN

U2 - 10.1161/CIRCHEARTFAILURE.118.005133

DO - 10.1161/CIRCHEARTFAILURE.118.005133

M3 - Article

SN - 1941-3289

VL - 11

JO - Circulation-Heart failure

JF - Circulation-Heart failure

IS - 10

M1 - 005133

ER -

IGFBP7 (Insulin-Like Growth Factor-Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure

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