Insight Into the Biological Link Between Novel Adiposity Indices and Incident Heart Failure.

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.