Novel adiposity indices, particularly waist-to-hip and waist-to-height ratios, were associated with incident heart failure via distinct proteomic pathways.
Cohort
Do novel adiposity indices associate with incident heart failure through distinct proteomic pathways?
Different adiposity indices reflect distinct proteomic and pathological stages in the progression to heart failure, offering mechanistic insights for individualized risk assessment.
OBJECTIVE: Obesity is a well-known heart failure (HF) risk factor, yet the biological pathways linking adiposity indices to HF remain unclear. This study aimed to identify proteomic mediators for five novel indices-waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHTR), body roundness index (BRI), weight-adjusted waist index (WWI), and translate mechanistic differences into clinical practice. METHODS: Using UK Biobank data, we applied Cox regression and linear regression to identify proteins associated with both HF and each index, followed by mediation and GO enrichment analyses. RESULTS: All five indices were associated with HF, with WHR and WHTR showing the strongest links. Shared pathways included angiogenesis and cardiac development. Each index occupied a distinct position along a pathological continuum: BRI (cell surface-related) as the upstream driver of early adipose dysfunction; WHR (inflammatory-fibrotic cascade) and WHTR (developmental-metabolic-inflammatory-hormonal) as intermediate downstream markers; WWI (vascular development) and WC (extracellular matrix remodeling) as terminal downstream markers of established organ damage. CONCLUSIONS: Each indicator occupies a distinct position in HF progression, offering unique mechanistic insights into its onset, and thus enabling individualized risk assessment and mechanism-based interventions for obese patients.
Yang et al. (Tue,) conducted a cohort in Heart failure. Novel adiposity indices (WC, WHR, WHTR, BRI, WWI) was evaluated on Incident heart failure. Novel adiposity indices, particularly waist-to-hip and waist-to-height ratios, were associated with incident heart failure via distinct proteomic pathways.