The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial

Job A J Verdonschot; JoÃo Pedro Ferreira; Anne Pizard; Pierpaolo Pellicori; Hans-Peter Brunner La Rocca; Andrew L Clark; Franco Cosmi; Joe Cuthbert; Nicolas Girerd; Olivia J Waring; Michiel H T M Henkens; Beatrice Mariottoni; Johannes Petutschnigg; Patrick Rossignol; Mark R Hazebroek; John G F Cleland; Faiez Zannad; Stephane R B Heymans; HOMAGE “Heart Omics in AGEing” consortium

doi:10.1016/j.cardfail.2021.12.005

The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial

Job A J Verdonschot, JoÃo Pedro Ferreira, Anne Pizard, Pierpaolo Pellicori, Hans-Peter Brunner La Rocca, Andrew L Clark, Franco Cosmi, Joe Cuthbert, Nicolas Girerd, Olivia J Waring, Michiel H T M Henkens, Beatrice Mariottoni, Johannes Petutschnigg, Patrick Rossignol, Mark R Hazebroek, John G F Cleland, Faiez Zannad, Stephane R B Heymans^*, HOMAGE “Heart Omics in AGEing” consortium

^*Corresponding author for this work

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

Abstract

BACKGROUND: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone.

METHODS AND RESULTS: Protein biomarkers (n = 276) from the Olink Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (Pinteraction = 0.001), showing a stronger decrease of blood pressure in obese patients (-14.8 mm Hg 95% confidence interval -18.45 to -11.12) compared with nonobese patients (-3.6 mm Hg 95% confidence interval -7.82 to 0.66).

CONCLUSIONS: Among patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure.

Original language	English
Pages (from-to)	778-786
Number of pages	9
Journal	Journal of Cardiac Failure
Volume	28
Issue number	5
Early online date	18 Dec 2021
DOIs	https://doi.org/10.1016/j.cardfail.2021.12.005
Publication status	Published - May 2022

Keywords

Obesity
biomarker
heart failure
spironolactone
INSULIN-RESISTANCE
ADRENOMEDULLIN
ADIPOKINE
PEOPLE
LEPTIN
FAT

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Verdonschot, J. A. J., Ferreira, J. P., Pizard, A., Pellicori, P., Brunner La Rocca, H.-P., Clark, A. L., Cosmi, F., Cuthbert, J., Girerd, N., Waring, O. J., Henkens, M. H. T. M., Mariottoni, B., Petutschnigg, J., Rossignol, P., Hazebroek, M. R., Cleland, J. G. F., Zannad, F., Heymans, S. R. B., & HOMAGE “Heart Omics in AGEing” consortium (2022). The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial. Journal of Cardiac Failure, 28(5), 778-786. https://doi.org/10.1016/j.cardfail.2021.12.005

@article{cea4fb647fb042af9235b344d529a99f,

title = "The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial",

abstract = "BACKGROUND: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone.METHODS AND RESULTS: Protein biomarkers (n = 276) from the Olink Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (Pinteraction = 0.001), showing a stronger decrease of blood pressure in obese patients (-14.8 mm Hg 95% confidence interval -18.45 to -11.12) compared with nonobese patients (-3.6 mm Hg 95% confidence interval -7.82 to 0.66).CONCLUSIONS: Among patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure.",

keywords = "Obesity, biomarker, heart failure, spironolactone, INSULIN-RESISTANCE, ADRENOMEDULLIN, ADIPOKINE, PEOPLE, LEPTIN, FAT",

author = "Verdonschot, {Job A J} and Ferreira, {Jo{\~A}o Pedro} and Anne Pizard and Pierpaolo Pellicori and {Brunner La Rocca}, Hans-Peter and Clark, {Andrew L} and Franco Cosmi and Joe Cuthbert and Nicolas Girerd and Waring, {Olivia J} and Henkens, {Michiel H T M} and Beatrice Mariottoni and Johannes Petutschnigg and Patrick Rossignol and Hazebroek, {Mark R} and Cleland, {John G F} and Faiez Zannad and Heymans, {Stephane R B} and {HOMAGE “Heart Omics in AGEing” consortium}",

year = "2022",

month = may,

doi = "10.1016/j.cardfail.2021.12.005",

language = "English",

volume = "28",

pages = "778--786",

journal = "Journal of Cardiac Failure",

issn = "1071-9164",

publisher = "Churchill Livingstone Inc Medical Publishers",

number = "5",

}

Verdonschot, JAJ, Ferreira, JP, Pizard, A, Pellicori, P, Brunner La Rocca, H-P, Clark, AL, Cosmi, F, Cuthbert, J, Girerd, N, Waring, OJ, Henkens, MHTM, Mariottoni, B, Petutschnigg, J, Rossignol, P, Hazebroek, MR, Cleland, JGF, Zannad, F, Heymans, SRB & HOMAGE “Heart Omics in AGEing” consortium 2022, 'The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial', Journal of Cardiac Failure, vol. 28, no. 5, pp. 778-786. https://doi.org/10.1016/j.cardfail.2021.12.005

TY - JOUR

T1 - The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure

T2 - Proteomic Insights from the HOMAGE Trial

AU - Verdonschot, Job A J

AU - Ferreira, JoÃo Pedro

AU - Pizard, Anne

AU - Pellicori, Pierpaolo

AU - Brunner La Rocca, Hans-Peter

AU - Clark, Andrew L

AU - Cosmi, Franco

AU - Cuthbert, Joe

AU - Girerd, Nicolas

AU - Waring, Olivia J

AU - Henkens, Michiel H T M

AU - Mariottoni, Beatrice

AU - Petutschnigg, Johannes

AU - Rossignol, Patrick

AU - Hazebroek, Mark R

AU - Cleland, John G F

AU - Zannad, Faiez

AU - Heymans, Stephane R B

AU - HOMAGE “Heart Omics in AGEing” consortium

PY - 2022/5

Y1 - 2022/5

N2 - BACKGROUND: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone.METHODS AND RESULTS: Protein biomarkers (n = 276) from the Olink Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (Pinteraction = 0.001), showing a stronger decrease of blood pressure in obese patients (-14.8 mm Hg 95% confidence interval -18.45 to -11.12) compared with nonobese patients (-3.6 mm Hg 95% confidence interval -7.82 to 0.66).CONCLUSIONS: Among patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure.

AB - BACKGROUND: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone.METHODS AND RESULTS: Protein biomarkers (n = 276) from the Olink Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (Pinteraction = 0.001), showing a stronger decrease of blood pressure in obese patients (-14.8 mm Hg 95% confidence interval -18.45 to -11.12) compared with nonobese patients (-3.6 mm Hg 95% confidence interval -7.82 to 0.66).CONCLUSIONS: Among patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure.

KW - Obesity

KW - biomarker

KW - heart failure

KW - spironolactone

KW - INSULIN-RESISTANCE

KW - ADRENOMEDULLIN

KW - ADIPOKINE

KW - PEOPLE

KW - LEPTIN

KW - FAT

U2 - 10.1016/j.cardfail.2021.12.005

DO - 10.1016/j.cardfail.2021.12.005

M3 - Article

C2 - 34933097

SN - 1071-9164

VL - 28

SP - 778

EP - 786

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

IS - 5

ER -

The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial

Abstract

Keywords

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