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. 2024 Sep;32(9):1658-1669.
doi: 10.1002/oby.24094. Epub 2024 Jul 22.

Proteomic biomarkers related to obesity in heart failure with reduced ejection fraction and their associations with outcome

Teun B Petersen  1   2 , Navin Suthahar  1 , Folkert W Asselbergs  3 , Marie de Bakker  1 , K Martijn Akkerhuis  1 , Alina A Constantinescu  1 , Jan van Ramshorst  4 , Peter D Katsikis  5 , Peter J van der Spek  6 , Victor A Umans  4 , Rudolf A de Boer  1 , Eric Boersma  1 , Dimitris Rizopoulos  2 , Isabella Kardys  1
Affiliations

Proteomic biomarkers related to obesity in heart failure with reduced ejection fraction and their associations with outcome

Teun B Petersen et al. Obesity (Silver Spring). 2024 Sep.

Abstract

Objective: Heart failure (HF) pathophysiology in patients with obesity may be distinct. To study these features, we identified obesity-related biomarkers from 4210 circulating proteins in patients with HF with reduced ejection fraction (HFrEF) and examined associations of these proteins with HF prognosis and biological mechanisms.

Methods: In 373 patients with trimonthly blood sampling during a median follow-up of 2.1 (25th-75th percentile: 1.1-2.6) years, we applied an aptamer-based multiplex approach measuring 4210 proteins in baseline samples and the last two samples before study end. Associations between obesity (BMI > 30 kg/m2) and baseline protein levels were analyzed. Subsequently, associations of serially measured obesity-related proteins with biological mechanisms and the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, left ventricular assist device implantation, and heart transplantation) were examined.

Results: Obesity was identified in 26% (96/373) of patients. A total of 30% (112/373) experienced a PEP (with obesity: 26% [25/96] vs. without obesity: 31% [87/277]). A total of 141/4210 proteins were linked to obesity, reflecting mechanisms of neuron projection development, cell adhesion, and muscle cell migration. A total of 50/141 proteins were associated with the PEP, of which 12 proteins related to atherosclerosis or hypertrophy provided prognostic information beyond clinical characteristics, N-terminal pro-B-type natriuretic peptide, and high-sensitivity troponin T.

Conclusions: Patients with HFrEF and obesity show distinct proteomic profiles compared to patients with HFrEF without obesity. Obesity-related proteins are independently associated with HF outcome. These proteins carry potential to improve management of obesity-related HF and could be leads for future research.

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