Investigating Novel Inflammatory Biomarkers and Pathways in Cardiac Cachexia

Cardiac cachexia (CC) is an indicator of advanced heart failure (AHF), with significant unintentional weight loss (UWL) and poor prognosis. Its diagnostic criteria incorporate upregulation of established inflammatory cytokines. Identification of novel biomarkers, for example, via proteomic analyses, could unearth unstudied mechanisms behind CC formation with future applications in disease therapeutics. This study, therefore, aimed to explore the presence of contemporary, novel biomarkers, and mechanistic pathways in CC using targeted proteomics.

Patients with AHF or stable heart failure were recruited and the presence of CC/UWL was identified. AHF was identified using the American Heart Association "I NEED HELP" criteria, and CC was identified using the contemporary 2008 consensus definition. All patients underwent phlebotomy, with plasma proteomic analyses using Olink Target 96 Cardiovascular II panel. Median proteins concentrations were compared between the CC/UWL group and the rest of cohort, with enrichment analyses conducted to identify potential novel pathways behind disease formation. Area under the receiver operator curve analysis was conducted to determine whether significant biomarkers had potential in identifying CC/UWL.

Six proteins were differentially expressed in the CC/UWL group, of which four were novel: interleukin-27 and -4, vascular endothelial growth factor D, and bone morphogenetic protein-6. All were suitable biomarkers (area under the receiver operator curve range 0.741-0.826). Protein enrichment analyses yielded significant pathways in disease formation relating to immune regulation and cytokine signalling.

We identified four novel biomarkers in CC, all of which are feasible biomarkers of disease identification, with proposed pathways of potential pathogenesis. Further research should be undertaken to validate our findings to better understand the mechanistic pathways in functional studies, with onward consideration regarding whether our findings have therapeutic applications.