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

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

Open Access
|Apr 2026

Figures & Tables

Figure 1.

PRISMA consort flow diagram of the study.

Table 1

General characteristics for male and female patients

Demographics and risk factorsEntire group (n=404)Female (n=221)Male (n=183)p value*
General characteristics
Age (years)71.87 (±10.06)74.24 (±8.93)69.00 (±10.61)<0.001
Systolic BP (mmHg)144.77 (±29.14)147.29 (±30.53)141.80 (±27.21)0.077
Diastolic BP (mmHg)81.39 (±13.62)82.44 (±13.59)80.15 (±13.60)0.115
Heart rate (bpm)85.01 (±25.63)85.60 (±26.32)84.28 (±24.79)0.624
Heart failure characteristics
HFrEF129 (31.9%)50 (22.6%)79 (43.2%)<0.001
HFmrEF121 (30.0%)69 (31.2%)52 (28.4%)
HFpEF152 (37.6%)102 (46.2%)50 (27.3%)
NYHA class III243 (60.1%)134 (60.6%)109 (59.6%)0.827
NYHA class IV58 (14.5%)32 (14.5%)26 (14.5%)0.995
Hospitalization outcome
Length of stay (days)6.00 [5.00–8.00]6.00 [4.00–8.00]6.00 [5.00–9.75]0.498
Extended stay97 (24.1%)45 (20.5%)52 (28.4%)0.066
All causes mortality149 (36.9%)78 (35.3%)71 (38.8%)0.467
Comorbidities and risk factors
Arterial Hypertension325 (80.4%)184 (83.3%)141 (77.0%)0.117
COPD19 (4.7%)3 (1.4%)16 (8.7%)<0.001
History of stroke49 (12.1%)29 (13.1%)20 (10.9%)0.501
Atrial fibrillation191 (47.3%)104 (47.1%)87 (47.5%)0.923
Ischemic heart disease176 (43.6%)85 (38.5%)91 (49.7%)0.023
Prior myocardial infarction106 (26.2%)38 (17.2%)68 (37.2%)<0.001
Chronic kidney disease229 (56.7%)130 (58.8%)99 (54.1%)0.340
Type 2 Diabetes Mellitus131(32.4%)71 (32.1%)60 (32.8%)0.888
Obesity177 (43.8%)103 (46.6%)74 (40.4%)0.213
Thyroid dysfunction36 (8.9%)30 (13.6%)6 (3.3%)0.003
Echocardiographic characteristics
LVEF (%)42.06 (±12.48)44.59 (±11.54)39.12 (±12.91)<0.001
Severe aortic stenosis6 (1.5%)4 (1.8%)2 (1.1%)0.553
Severe aortic regurgitation5 (1.2%)3 (1.4%)2 (1.1%)0.811
Severe mitral regurgitation57 (14.1%)32 (14.5%)25 (13.7%)0.814
Pulmonary hypertension195 (48.3%)110 (49.8%)85 (46.4%)0.505
Pericardial effusion27 (6.7%)18 (8.1%)9 (4.9%)0.196
Aortic atheromatosis151 (37.4%)95 (43.0%)56 (30.6%)0.036
Biological characteristics
Hemoglobin (g/dL)13.13 (±1.91)12.61 (±1.70)13.77 (±1.98)<0.001
ESR (mm/h)19.00 [8.75–34.00]20.50 [10.00–33.25]17.50 [7.00–34.00]0.020
Serum Na (mmol/L)139.65 (±7.94)140.05 (±4.56)139.15 (±10.75)0.262
Serum K (mmol/L)4.36 (±0.50)4.34 (±0.55)4.38 (±0.43)0.469
eGFR (ml/min/1.73m2)71.92 [55.06–88.75]66.16 [49.09–84.39]78.29 [57.35–89.37]0.026
Glycemia (mg/dL)107.50 [94.00–134.50]111.50 [98.00–139.25]105.00 [88.75–126.75]0.401
Total cholesterol (mg/dL)163.80 [137.00–207.25]172.75 [140.75–223.15]155.00 [127.35–190.75]0.010
AST (UI/L)21.50 [17.47–28.57]21.00 [17.07–28.22]21.60 [17.62–28.72]0.264
ALT (UI/L)18.10 [14.00–26.15]17.50 [13.45–24.85]19.90 [14.12–31.55]0.030
NT-proBNP (ng/L)1687.50 [622.20–4319.75]1607.50 [504.62–3860.75]1777.50 [766.77–4859.00]0.595
hs-TnT (pg/mL)17.06 [10.43–29.42]14.18 [9.21–25.25]22.44 [12.77–33.53]<0.001

[i] Note: *for comparison of female with male patients

[ii] Abbreviations: BP – blood pressure; HFrEF – heart failure with reduced ejection fraction; HFmrEF – heart failure with mid-range ejection fraction; HFpEF – heart failure with preserved ejection fraction; COPD – Chronic obstructive pulmonary disease; LVEF – left ventricular ejection fraction; ESR – erythrocyte sedimentation rate; eGFR – estimated glomerular filtration rate; AST – aspartate aminotransferase; ALT – alanine aminotransferase; hsTnT – high-sensitivity troponin T.

Figure 2.

Central illustration. Derivation of sex-specific hs-TnT cut-off values and their implementation in survival analysis.

Table 2

Baseline characteristics for outcome sex-specific hs-TnT cut-off groups in men and women

A. Categorical variables
MenWomen
Variablehs-TnT <19.02 pg/mL n (%)hs-TnT ≥19.02 pg/mL n (%)OR (95% CI)phs-TnT <15.83 pg/mL n (%)hs-TnT ≥15.83 pg/mL n (%)OR (95% CI)p
Heart failure characteristics
NYHA III and IV38 (39.20%)55 (64.00%)2.75 (1.51–5.03)0.00166 (48.18%)60 (71.43%)2.69 (1.51–4.80)0.001
Clinical congestion25 (25.80%)48 (55.80%)3.64 (1.95–6.78)<0.0 0139 (28.47%)45 (53.57%)2.90 (1.64–5.11)<0.0 01
Hospitalization outcome
Extended stay (>7 days)16 (16.50%)36 (41.90%)3.65 (1.84–7.24)<0.0 0112 (8.76%)33 (40.24%)7.02 (3.35–14.68)<0.0 01
Comorbidities and risk factors
Hypertension76 (78.40%)65 (75.60%)0.86 (0.43–1.70)0.657117 (85.40%)67 (79.76%)0.67 (0.33–1.37)0.276
COPD9 (9.30%)7 (8.10%)0.87 (0.31–2.44)0.7850 (0.00%)3 (3.57%)Not estimable0.054*
Prior stroke7 (7.20%)13 (15.10%)2.29 (0.87–6.04)0.08715 (10.95%)14 (16.67%)1.63 (0.74–3.57)0.222
Atrial fibrillation45 (46.40%)42 (48.80%)1.10 (0.62–1.97)0.74159 (43.07%)45 (53.57%)1.53 (0.88–2.63)0.129
Ischemic heart disease51 (52.60%)40 (46.50%)0.78 (0.44–1.40)0.41353 (38.69%)32 (38.10%)0.98 (0.56–1.71)0.930
Prior myocardial infarction36 (37.10%)32 (37.20%)1.00 (0.55–1.83)0.98922 (16.06%)16 (19.05%)1.23 (0.60–2.50)0.568
Type 2 diabetes30 (30.90%)30 (34.90%)1.20 (0.65–2.22)0.56939 (28.47%)32 (38.10%)1.55 (0.87–2.75)0.137
Obesity42 (43.30%)32 (37.20%)0.78 (0.43–1.40)0.40269 (50.36%)34 (40.48%)0.67 (0.39–1.16)0.15 3
Peripheral artery disease11 (11.30%)10 (11.60%)1.03 (0.41–2.56)0.9517 (5.11%)5 (5.95%)1.18 (0.36–3.83)0.769*
Chronic kidney disease41 (42.30%)58 (67.40%)2.83 (1.55–5.18)0.00164 (46.72%)66 (78.57%)4.18 (2.25–7.77)<0.0 01
Echocardiographic characteristics
Severe aortic stenosis1 (1.00%)1 (1.20%)1.13 (0.07–18.34)1.000*0 (0.00%)4 (4.76%)Not estimable0.020*
Severe aortic regurgitation0 (0.00%)2 (2.30%)Not estimable0.219*0 (0.00%)3 (3.57%)Not estimable0.054*
Severe mitral regurgitation (grade 3–4)8 (8.20%)17 (19.80%)2.74 (1.12–6.72)0.02410 (7.30%)22 (26.19%)4.51 (2.01–10.10)<0.001
Severe tricuspid regurgitation9 (9.30%)13 (15.10%)1.74 (0.70–4.30)0.22613 (9.49%)22 (26.19%)3.38 (1.60–7.17)0.001
Pulmonary hypertension36 (37.10%)49 (57.00%)2.24 (1.24–4.06)0.00758 (42.34%)52 (61.90%)2.21 (1.27–3.86)0.005
Pericardial effusion5 (5.20%)4 (4.70%)0.90 (0.23–3.46)1.000*8 (5.84%)10 (11.90%)2.18 (0.82–5.76)0.110
Biological characteristics
eGFR <60 mL/min/1.73 m215 (15.50%)37 (43.00%)4.13 (2.06–8.28)<0.00134 (24.82%)47 (55.95%)3.85 (2.16–6.87)<0.001
B. Continuous variables
MenWomen
Variablehs-TnT <19.02 pg/mLhs-TnT ≥19.02 pg/mLphs-TnT <15.83 pg/mL median [Q1–Q3]hs-TnT ≥15.83 pg/mL median [Q1–Q3]p
General characteristics
Age (years)66.00 [60.00–74.50]73.00 [62.00–79.00]0.00673.00 [65.00–78.00]79.00 [74.25–83.00]<0.001
Hospitalization outcome
Length of stay (days)5.00 [4.00–7.00]7.00 [4.75–10.00]<0.0015.00 [4.00–6.00]7.00 [5.00–10.00]<0.001
Echocardiographic characteristics
LVEF / EF (%)46.00 [36.00–52.00]35.00 [25.00–45.00]<0.00150.00 [43.50–54.00]43.50 [33.75–50.00]<0.001
PAPS (mmHg)35.00 [28.00–43.00]42.00 [34.00–57.25]0.00335.00 [27.00–40.00]45.00 [32.50–55.00]<0.001
Biological characteristics
Hemoglobin (g/dL)14.30 [13.08–15.12]13.60 [11.98–14.90]0.02513.00 [12.10–13.90]11.92 [10.82–13.40]<0.001
ESR (mm/h)16.00 [6.00–27.00]18.00 [6.00–35.00]0.43519.00 [10.00–30.50]23.00 [12.50–48.00]0.061
Sodium (mmol/L)141.00 [138.00–142.00]140.00 [137.00–142.00]0.527141.00 [139.00–143.00]140.00 [137.00–143.00]0.017
Potassium (mmol/L)4.39 [4.05–4.74]4.32 [4.05–4.60]0.4444.39 [3.98–4.66]4.36 [3.93–4.74]0.990
Creatinine (mg/dL)0.94 [0.85–1.10]1.10 [0.90–1.43]<0.0010.80 [0.70–0.93]0.97 [0.80–1.27]<0.001
eGFR (ml/min/1.73m2)83.19 [66.95–92.72]64.86 [47.74–84.76]<0.00174.86 [59.86–92.14]55.83 [40.20–73.13]<0.001
Glycemia (mg/dL)104.00 [91.00–119.50]106.50 [94.00–126.75]0.496101.00 [90.00–124.50]117.00 [101.50–150.50]0.001
logBNP2.89 [2.54–3.13]3.40 [2.97–3.79]<0.0012.89 [2.56–3.26]3.46 [3.01–3.83]<0.001

[i] Abbreviation: hs-TnT – high-sensitivity troponin T; OR – odds ratio; CI – confidence interval; Q1–Q3 – interquartile range; COPD – chronic obstructive pulmonary disease; eGFR – estimated glomerular filtration rate; LVEF – left ventricular ejection fraction; PAPS – pulmonary artery systolic pressure; ESR – erythrocyte sedimentation rate.

Table 3

Independent parameters associated with increased hs-TnT – Multivariable analysis

Men hs-TnT ≥ 19.02 pg/mLWomen hs-TnT ≥ 15.83 pg/mL
HR* (95%CI)p valueHR** (95%CI)p value
Clinical congestion2.24 (1.16–5.07)0.019Age1.08 (1.02–1.14)0.005
LnNT-proBNP3.30 (1.42–7.67)0.005LnNT-proBNP4.22 (2.02–8.81)< 0.001
eGFR0.97 (0.95–0.99)0.001eGFR0.98 (0.96–0.99)0.016
LVEF0.96 (0.93–0.99)0.027

[i] Note: *Adjusted for age, NYHA class, chronic obstructive pulmonary disease, chronic kidney disease, severe mitral regurgitation, estimated pulmonary artery systolic pressure, hemoglobin – variables without independent correlation with increased hs-TnT

[ii] Note: **Adjusted for NYHA class, clinical congestion, chronic obstructive pulmonary disease, chronic kidney disease, LVEF, severe aortic stenosis, severe mitral regurgitation, severe tricuspid regurgitation, estimated pulmonary artery systolic pressure, hemoglobin, serum sodium, glycemia – variables without independent correlation with increased hs-TnT

Figure 3.

Survival analysis stratified by hs-TnT values for A – Women, and B – Men.

Table 4

Univariate Cox regression for all-cause mortality – comparison across groups

PredictorMenWomen
HR95% CIpHR95% CIp
General characteristics
Age (per 1 year)1.031.01–1.050.0131.081.05–1.11<0.001
Heart failure characteristics
NYHA III and IV1.821.13–2.940.0142.141.32–3.490.002
Clinical congestion1.741.09–2.770.0201.871.20–2.920.006
Cardiovascular risk factors and comorbidities
HTN0.760.45–1.280.2980.630.37–1.090.097
Atrial fibrillation1.320.83–2.110.2401.961.24–3.080.004
Prior stroke1.470.75–2.880.2581.090.58–2.060.797
IHD1.140.72–1.820.5800.770.48–1.230.270
Prior MI1.360.85–2.180.2030.910.50–1.650.759
Type 2 diabetes0.820.49–1.370.4441.240.78–1.970.358
CKD1.781.09–2.890.0212.311.40–3.810.001
Obesity0.460.27–0.770.0030.540.34–0.860.009
Echocardiographic characteristics
LVEF (per 1%)0.970.95–0.99<0.0010.960.95–0.98<0.001
ePASP (per 1mmHg)1.031.01–1.050.0021.031.01–1.050.004
Severe MR2.081.16–3.730.0152.341.39–3.930.001
Severe TR1.710.89–3.260.102.611.58–4.32<0.001
Severe AS1.590.22–11.470.652.210.69–7.020.18
Biological characteristics
hs-TnT sex-specific cut-off2.661.62–4.34<0.0015.503.38–8.94<0.001
hs-TnT ≥14 pg/mL2.111.26–3.560.0055.663.36–9.53<0.001
lnNTproBNP (per 1 unit)1.571.31–1.88<0.0011.581.34–1.87<0.001
eGFR (per 1 mL/min/1.73m2)0.990.98–1.000.0330.980.97–0.990.001
Hemoglobin (per 1 g/dL)0.800.72–0.89<0.0010.890.78–1.000.056
Serum Na (per 1mmol/L)0.990.98–1.020.910.960.91–1.000.053
Serum K (per 1 mmol/mL)0.890.51–1.550.671.420.94–2.140.092

[i] Abbreviations: AS – aortic stenosis; CKD – chronic kidney disease; ePASP – estimated pulmonary artery systolic pressure; HTN – arterial hypertension; IHD – ischemic heart disease; LVEF – left ventricular ejection fraction; MI – myocardial infarction; MR – mitral regurgitation; TR – tricuspid regurgitation.

Figure 4.

Hierarchical Cox Regression Analysis showing the incremental clinical value of sex-specific increased hs-TnT.

Table 5

Stepwise multivariable Cox analysis for all-cause long-term mortality

Independent predictors for all-cause long-term mortality
MenWomen
HR* (95%CI)p valueHR** (95%CI)p value
Hemoglobin (per 1g/dL)0.88 (0.78–0.98)0.021Age (per 1 year)1.05 (1.02–1.09)0.003
LnNT-proBNP (per 1 unit)1.28 (1.03–1.59)0.025LnNT-proBNP (per 1 unit)1.22 (1.01–1.47)0.035
hs-TnT ≥ 19.02 pg/mL1.91 (1.07–3.41)0.029hs-TnT ≥ 15.83 pg/mL3.54 (2.07–6.07)< 0.001

[i] Note: *Adjusted for NYHA class, clinical congestion, atrial fibrillation, chronic kidney disease, obesity, age, LVEF, estimated pulmonary artery systolic pressure, severe mitral regurgitation, severe tricuspid regurgitation – variables without independent prognostic value in the final steps of the regression

[ii] Note: **Adjusted for NYHA class, clinical congestion, atrial fibrillation, chronic kidney disease, obesity, LVEF, estimated pulmonary artery systolic pressure, severe mitral regurgitation, severe tricuspid regurgitation, severe aortic stenosis, serum sodium, hemoglobin – variables without independent prognostic value in the final steps of the regression

Supplementary Table 1

STROBE checklist

ItemSTROBE recommendation (cohort)Where addressed in this manuscript
1Indicate study design in the title or abstract; provide an informative, balanced summary.Abstract (Methods).
2Explain scientific background and rationale.Introduction (background and gap).
3State specific objectives, including prespecified hypotheses.Introduction-final paragraph.
4Present key elements of study design early in the paper.Materials and Methods-Study design, setting, and data source.
5Describe setting, locations, and relevant dates (recruitment, exposure, follow-up).Materials and Methods-Study design/setting; Outcome and follow-up.
6aGive eligibility criteria and methods of selection; describe follow-up methods.Materials and Methods-Study population; Outcome and follow-up; Flow diagram showing derivation from HI-HF parent cohort.
6bFor matched studies, give matching criteria and number of exposed/unexposed.Not applicable (no matching).
7Clearly define outcomes, exposures, predictors, confounders, effect modifiers; diagnostic criteria.Materials and Methods-Definitions; Biomarker classification; Statistical analysis (covariate set).
8For each variable, give data sources and details of assessment; comparability between groups.Materials and Methods-Clinical variables; Echocardiography; Biomarker assays.
9Describe efforts to address potential sources of bias.Materials and Methods-Bias and confounding paragraph.
10Explain how study size was arrived at.Materials and Methods-Study population (cohort = all eligible patients meeting criteria).
11Explain handling of quantitative variables; groupings and rationale.Materials and Methods-Troponin categories; ln(NT-proBNP); landmark/time re-zeroing.
12aDescribe all statistical methods, including confounding control.Materials and Methods-Statistical analysis (Cox models; covariate adjustment).
12bDescribe methods for subgroup analyses and interactions.Materials and Methods-Statistical analysis (sex and troponin interaction).
12cExplain how missing data were addressed.Materials and Methods-Statistical analysis (patients with missing data were excluded).
12dIf applicable, explain how loss to follow-up was addressed.Materials and Methods-Outcome and follow-up (registry-based ascertainment; censoring).
12eDescribe sensitivity analyses.Results (time-dependent covariates)
13aReport numbers at each stage (eligible, included, followed-up, analysed).Results-Study population; PRISMA diagram with counts
13bGive reasons for non-participation at each stage.PRISMA diagram provided; Materials and Methods-Study population.
13cConsider use of a flow diagram.PRISMA diagram provided
14aGive characteristics of study participants and information on exposures/confounders.Results-Baseline (Table 1; troponin category tables).
14bIndicate number of participants with missing data for each variable of interest.Patients with missing data were excluded
14cSummarize follow-up time (e.g., average/total follow-up).Results-Follow-up summary (median and IQR).
15Report numbers of outcome events or summary measures over time.Results-Deaths; Kaplan–Meier; Cox models.
16aGive unadjusted and adjusted estimates with precision; state confounders and why included.Results-Univariable and multivariable Cox tables; covariate list in Materials and Methods-Statistical analysis.
16bReport category boundaries when continuous variables categorized.Results-hs-TnT thresholds stated, outcome sex-specific cutoffs stated.
16cIf relevant, translate relative risk into absolute risk for a meaningful time period.Not required; optional.
17Report other analyses (subgroups, interactions, time-dependent, sensitivity).Results-LVEF subgroup analysis; sex-stratified models; interaction models; time-dependent and landmark analyses.
18Summarize key results with reference to objectives.Discussion-opening paragraph.
19Discuss limitations and potential bias/imprecision (direction/magnitude).Discussion-Limitations section.
20Give cautious overall interpretation considering objectives, limitations, and other evidence.Discussion-Interpretation and comparison with literature.
21Discuss generalisability (external validity).Discussion-final paragraph (Generalisability).
22Give funding source and role of funders.Funding: None
Supplementary Table 2

Troponin cut-off for all-cause mortality stratified by sex and LVEF

MenWomen
AUC 95%CICut-off Se, Spp valueAUC 95%CICut-off Se, Spp value
LVEF < 50%0.644, 0.557–0.726> 23.25 64.29%, 63.64%0.0040.742 0.654–0.818> 16.50 75.00%, 73.13%<0.001
LVEF ≥ 50%0.690 0.543–0.813>10.96 86.67%, 48.57%0.0150.772 0.678–0.849> 15.05 61.54%, 82.89%<0.001

[i] Abbreviations: AUC – area under the curve; CI – confidence interval; LVEF – left ventricular ejection fraction; Se – sensitivity; Sp – specificity.

DOI: https://doi.org/10.2478/rjim-2026-0008 | Journal eISSN: 2501-062X (formerly 1220-4749) | Journal ISSN: 1220-4749
Language: English, Romanian
Page range: 116 - 132
Submitted on: Apr 13, 2026
Published on: Apr 28, 2026
Published by: N.G. Lupu Internal Medicine Foundation
In partnership with: Paradigm Publishing Services

© 2026 Anamaria Draghici, Caterina Delcea, Gheorghe-Andrei Dan, published by N.G. Lupu Internal Medicine Foundation
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.