Gut-inflammation-SPARC axis associates with mobility decline in congestive heart failure

Impaired gait speed (GS) is a powerful predictor of disability and mortality in congestive heart failure (CHF), yet molecular determinants of this functional decline remain poorly defined. Existing studies have focused largely on cardiac parameters, leaving a critical gap in identifying biomarkers that capture multisystem involvement. Here, we investigated plasma osteonectin (OSN), also known as secreted protein acidic and rich in cysteine (SPARC), as a novel biomarker for impaired GS in a cohort of 286 CHF patients. We evaluated cardiac function (LVEF), GS, and plasma levels of OSN, zonulin (gut permeability marker), and C-reactive protein (CRP). CHF patients exhibited significantly elevated OSN, zonulin, and CRP, all inversely correlated with GS (p < 0.0001). Multivariable adjusted analysis revealed a robust independent dose-response relationship, where every 0.1 m/s decrease in GS was associated with a significant increase in plasma OSN levels (t = 6.614, p < 0.0001). ROC curve analysis further confirmed this relationship, with OSN demonstrating high diagnostic accuracy (AUC = 0.822) for identifying poor functional performance. In the poor GS subgroup, OSN and zonulin were uniquely linked to CRP (p < 0.0001), suggesting a potential association between gut-barrier dysfunction, systemic inflammation, and OSN-related musculoskeletal remodeling. Collectively, these findings suggest that plasma OSN is an independent biomarker of functional impairment in CHF. While the cross-sectional design limits causal inference, OSN represents a promising tool for risk stratification and a potential therapeutic target to mitigate mobility loss in CHF.