The Utility of Sex-Specific Cut-offs for High-Sensitivity Troponin T for Long-Term All-cause Mortality Risk Assessment in Heart Failure

Introduction

High-sensitivity troponin T (hs-TnT) is commonly elevated in heart failure (HF) and may have different prognostic meaning in women and men. We assessed sex-related differences in hs-TnT and whether sex-aware interpretation improves long-term risk stratification after HF hospitalization.

Materials and Methods

We conducted a retrospective single-center cohort study derived from the HI-HF registry (2011–2014). The analysis included adults hospitalized for HF with admission hs-TnT, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and in-hospital echocardiography. We derived outcome-optimized sex-specific hs-TnT cut-offs by ROC analysis. The endpoint was long-term all-cause mortality (ascertained through August 2024). Kaplan-Meier and multivariable Cox models (including sex stratification, interaction testing, and landmark/time-dependent analyses) were performed.

Results

Our cohort included 404 patients. Over a median follow-up of 5.72 years (IQR 3.38–6.87), 149 deaths (36.9%) occurred.

Women had lower hs-TnT concentrations than men (median 14.18 vs 22.44 pg/mL). ROC-derived sex-specific mortality prognostic cut-offs were >15.83 pg/mL for women (AUC 0.773; sensitivity 70.7%; specificity 78.3%) and >19.02 pg/mL for men (AUC 0.725; sensitivity 75.0%; specificity 65.0%). Compared to the conventional cut-off of 14 pg/mL, the gender-adjusted values improved risk stratification by 22% for women and 23% for men.

For each gender-defined subgroup, increased hs-TnT levels were independently associated with all-cause long-term mortality in Cox analysis alongside NT-proBNP and hemoglobin levels in men (HR 1.91 (1.07 – 3.41), p=0.029), and NT-proBNP and age in women (HR 3.54 (2.07 – 6.07), p<0.001).

Prognostic effects were time-dependent, with stronger sex-related divergence beyond 1 year.

Conclusions

Sex-specific hs-TnT cut-off recalibration improved long-term mortality risk stratification in hospitalized heart failure patients. Increased levels of hs-TnT defined by the gender-specific analysis were independent predictors of the outcome in both men and women.