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This study aimed to identify proteomic mediators for five novel indices\u2014waist circumference (WC), waist\u2010to\u2010hip ratio (WHR), waist\u2010to\u2010height ratio (WHTR), body roundness index (BRI), weight\u2010adjusted waist index (WWI), and translate mechanistic differences into clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2010related) as the upstream driver of early adipose dysfunction; WHR (inflammatory\u2010fibrotic cascade) and WHTR (developmental\u2010metabolic\u2010inflammatory\u2010hormonal) as intermediate downstream markers; WWI (vascular development) and WC (extracellular matrix remodeling) as terminal downstream markers of established organ damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Each indicator occupies a distinct position in HF progression, offering unique mechanistic insights into its onset, and thus enabling individualized risk assessment and mechanism\u2010based interventions for obese patients.<\/jats:p>\n                  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