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

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. Distinct proteomic profiles of obesity in HFrEF are associated with HF prognosis.