Biomarker-Informed Phenotyping of the Heart Failure Continuum: A Population-Based Evaluation of the Second Universal Definition of Heart Failure

A biomarker-informed heart failure continuum phenotype in 11,477 U.S. adults identifies Stage B (elevated NT-proBNP) with a 10-year adjusted mortality risk of 15.2%, comparable to Stage C at 14.2%.

• Why it matters: Clinically usable, computable HF staging aligned with the 2026 Universal Definition is needed to determine whether biomarker-defined pre-HF groups carry distinct mortality risk.
• What they did: Using NHANES 1999–2004 participants aged ≥20 years with linked National Death Index follow-up, four phenotypes were assigned and mortality associations estimated with survey-weighted Kaplan-Meier curves and multiply imputed Cox models.
• The result: In fully adjusted models, mortality hazard ratios vs no apparent risk were 1.58 for Stage A, 2.88 for Stage B, and 2.56 for Stage C; Stage B vs Stage A was higher (HR 1.83), while Stage C vs Stage B was not significant (HR 0.89).

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