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

Research output: Contribution to journalArticleAcademicpeer-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 languageEnglish
Pages (from-to)778-786
Number of pages9
JournalJournal of Cardiac Failure
Volume28
Issue number5
Early online date18 Dec 2021
DOIs
Publication statusPublished - May 2022

Keywords

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

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