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 (≥102cm men and ≥88cm women). Biomarkers at baseline reflected adipogenesis, increased vascularization, reduced 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 (-14.8mmHg 95%CI: -18.45-11.12) compared to non-obese patients (-3.6mmHg 95%CI -7.82-0.66).
Conclusions: Among patients at risk for HF, 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.
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