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The Prognostic Value of Troponin Levels Adjusted for Renal Function in Heart Failure – A Systematic Review Cover

The Prognostic Value of Troponin Levels Adjusted for Renal Function in Heart Failure – A Systematic Review

Romanian Journal of Internal Medicine
Volume 63 (2025): Issue 2 (June 2025)
By: Anca Breha,  Caterina Delcea,  Andreea Cristina Ivanescu and  Gheorghe Andrei Dan  
Open Access
|Apr 2025

Figures & Tables

Fig. 1

Flowchart for the process of article selection
Flowchart for the process of article selection

Fig. 2

Studies divided according to their results
Studies divided according to their results

General characteristics of the included studies

Author, yearStudy TypePopulation (N)Baseline PathologyDuration of Follow-upType of troponinMain Outcome(s)
Yilmaz Oztekin, 2023 [48]Retrospective cohort study249

  • Nonischemic CHF

  • LVEF 30 [25 – 35] %

30 monthshs-cTnTAll-cause mortality
Bosselmann, 2013 [49]Prospective cohort study424

  • CHF

  • LVEF < 45%

4.5 years (IQR: 2–7.7)hs-cTnTAll-cause mortality
Aulin, 2022 [26]Substudy of a RCT (ARISTOTLE)4568

  • CHF

  • All LVEF

1.9 years (median)hs-cTnT

  • HF hospitalization

  • All-cause mortality

Berge, 2022 [27]Retrospective analysis of a prospective cohort study (ACE 2 study)143

  • AHF

  • All LVEF

823 days (median)hs-cTnTAll-cause mortality
Berge, 2021 [31]Retrospective analysis of a prospective cohort study (ACE 2 study)143

  • AHF

  • All LVEF

464(median)Hs-TnTAll-cause mortality
Aimo, 2019 [28]Retrospective analysis of data from 3 cohorts1449

  • AHF

  • All LVEF

11 months (median)hs-cTnT

  • In-hospital mortality

  • All-cause mortality

  • Cardiovascular mortality

Ledwoch, 2021 [30]Retrospective cohort study971

  • AHF

  • All LVEF

30 dayshs-cTnTAll-cause mortality
Ledwoch, 2022 [29]Retrospective registry847

  • AHF

  • All LVEF

30 dayshs-cTnTAll-cause mortality
Jungbauer, 2014 [32]Prospective cohort study149

  • CHF

  • All LVEF

757 days (mean) (IQR 711-809)hs-cTnT

  • All-cause mortality

  • Composite endpoint of all-cause mortality or CHF-related rehospitalization

Guisado-Espartero, 2014 [33]Prospective cohort study RICA registry406

  • AHF

  • All LVEF

1 yearcTnT

  • All-cause mortality

  • Readmission for worsening HF

  • Composite of mortality or readmission

Zymliński, 2017 [22]Prospective cohort study130

  • AHF

  • LVEF 30 [24 – 38] %

1 yearhs-cTnICardiovascular mortality
O'Connor, 2011 [51]Substudy of an RCT (PROTECT study)288AHF with renal insufficiency60 days (primary) and 7 days (secondary)cTnT

  • Composite endpoint including worsening

  • HF despite treatment or worsening renal function

Barlera, 2013 [34]Prospective RCT (GISSI-HF)6975

  • CHF

  • All LVEF

3.9 yearshs-cTnTAll-cause mortality
Masson, 2012 [35]Substudy of two RCTs (Val-HeFT & GISSI-HF)5284

  • CHF

  • Reduced LVEF

Val-HeFT: 24 months (median); GISSI-HF: 47 months (median)hs-cTnT

  • All-cause mortality

  • HF mortality

  • Cardiovascular hospitalization

Lupon, 2013 [36]Prospective cohort study876

  • CHF

  • All LVEF

41.4 monthshs-cTnTAll-cause mortality
Ather, 2013 [37]Retrospective cohort study196

  • AHF

  • LVEF 26 ± 13 %

5 yearscTnIAll-cause mortality
Lok, 2013 [38]Substudy of an RCT DEAL-HF209CHFMedian 8.7 years (8.7 ± 1 year)hs-cTnTAll-cause mortality
Egstrup, 2012 [39]Prospective cohort study416

  • CHF

  • LVEF ≤45%

Median 4.4 years (IQR: 1.9-7.5)hs-cTnTAll-cause mortality Composite outcome of all-cause mortality and cardiovascular hospitalization
Zhang, 2015 [40]Retrospective analysis of a prospective cohort study1189

  • CHF

  • Reduced LVEF

1 yearcTnT, cTnIAll-cause mortality
Kawahara, 2011 [20]Prospective cohort study95

  • Nonischemic CHF

  • LVEF <45%

4.25 yearshs-cTnICardiovascular mortality
Fabbri, 2015 [41]Retrospective analysis of SAFE-SIMEU database1234

  • AHF Median

  • LVEF 45%

1 year All-cause mortality
Lee, 2022 [42]Retrospective analysis of a prospective registry (KorAHF)4396

  • AHF

  • All LVEF

784 days (IQR 446–1116)hs-cTnIAll-cause mortality
Bayes-Genis, 2013 [43]Prospective cohort study879

  • CHF

  • LVEF 34 [26–43] %

3.46 years (mean)hs-cTnTAll-cause mortality
Felker, 2012 [44]Biomarker substudy within an RCT ASCEND-HF808

  • AHF

  • Median LVEF 25%

180 dayscTnI

  • All-cause mortality

  • Composite of 30-day mortality and rehospitalization

  • Dyspnea improvement at 6 and 24 h

  • Worsening HF or death to day 7

  • Length of stay

Mcdowell, 2023 [45]Biomarker substudy within an RCT (PARADIGM-HF trial)1559

  • CHF

  • LVEF ≤40%

30.7 months (mean)hs-cTnT

  • Composite endpoint (cardiovascular death or HF hospitalization)

  • Cardiovascular death

  • All-cause mortality

Demissei, 2021 [23]Post-hoc analysis of an RCT (RELAX-AHF)1161

  • AHF

  • All LVEF

180 dayshs-cTnTCardiovascular mortality
Tentzeris, 2011 [46]Prospective cohort study172

  • CHF

  • LVEF < 45%

1301 dayshs-cTNTAll-cause mortality or HF hospitalization
Bjurman, 2012 [47]Prospective cohort study131

  • AHF

  • LVEF 43.1 ± 13.8 %

3 yearscTnTAll-cause mortality
Horiuchi, 2021 [50]Retrospective analysis of a prospective cohort (AKINESIS study)787AHF1 yearhs-cTnI

  • All-cause mortality

  • HF hospitalization

  • WRF (defined as ≥0.3 mg/dL or 50% increase in creatinine within 5 days)

j_rjim-2025-0006_tab_005

Search strategyRetrieved Articles
((“heart failure”[Title/Abstract] OR “heart failure”[MeSH Terms]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“troponin”[Title/Abstract] OR “troponin”[MeSH Terms])) AND (2011:2024[pdat])1325
((“heart failure”[Title/Abstract] OR “heart failure”[MeSH Terms]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“troponin”[Title/Abstract] OR “troponin”[MeSH Terms])) AND ((english[Filter]) AND (2011:2024[pdat]))1280
(((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) NOT ((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) AND “case reports”[Publication Type])) NOT (((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) NOT ((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) AND “case reports”[Publication Type])) AND “animals”[MeSH Terms:noexp])) AND (english[Filter])1032
((((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) NOT ((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) AND “case reports”[Publication Type])) NOT (((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) NOT ((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) AND “case reports”[Publication Type])) AND “animals”[MeSH Terms:noexp])) AND “english”[Language] AND 2011/01/01:2024/12/31[Date - Publication]) NOT ((((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) NOT ((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) AND “case reports”[Publication Type])) NOT (((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) NOT ((((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms])) NOT ((“heart failure”[MeSH Terms] OR “heart failure”[Title/Abstract]) AND (“troponin”[MeSH Terms] OR “troponin”[Title/Abstract]) AND (“prognosis”[Title/Abstract] OR “prognosis”[MeSH Terms]) AND (“meta analysis”[Publication Type] OR “review”[Publication Type] OR “systematic review”[Filter]))) AND “case reports”[Publication Type])) AND “animals”[MeSH Terms:noexp])) AND “english”[Language] AND ((“infant”[MeSH Terms] OR “child”[MeSH Terms] OR “adolescent”[MeSH Terms]) AND 2011/01/01:2024/12/31[Date - Publication]))992

Details of studies evaluating heart failure hospitalizations

Author, yearType of biomarkerTroponin cut-offHR/OR (95%CI)HR/OR (95%CI)Parameters included in the adjusted/multivariable analysis
Unadjusted (univariable) analysisAdjusted (multivariable) analysis
O'Connor, 2011 [51]cTnT0.01 ng/mL1.64; p=0.08
0.03 ng/mL1.61; p =0.07
Espartero, 2014 [33]cTnT0.02 ng/mL1.25 (0.83-1.89); p=0.291.13 (0.72-1.77); p=0.59Age, Sex, BMI, Ischemic heart disease, Previous HF, Anemia, LVEF, NYHA III-IV, eGFR b 60 mL/min/1.73 m2, Troponin T, NT-proBNP
Aulin, 2022 [26]hs-cTnTContinuous variable (Log-transformed using natural logarithm)χ2 =5.54; p=0.062χ2=6.29; p=0.0454

  • Step 1: randomized treatment, age, sex, hypertension, diabetes mellitus, coronary artery disease, history of stroke/(TIA), (BMI), heart rate, sinus rhythm and renal function ([CrCl])

  • Step 2: Step 1 + NT-proBNP

Aimo, 2019 [28]hs-cTnTlimit of detection 5 ng/L, upper reference value 14 ng/L HR 0.97; 95%CI 0.87-1.09; p=0.59

  • NT-proBNP, hs-TnT, hs-CRP were log2-transformed.

  • The prognostic model includes the three biomarkers.

hs-cTnT 1.41 (1.35-1.47); p <0.001
eGFR ≥90 1.37 (1.06-1.76) p=0.014
mL/min/1.73 m2
eGFR 60-89
mL/min/1.73 m2 1.40 (1.31-1.50); <0.001
eGFR 30-59
mL/min/1.73 m2 1.45 (1.36-1.54); p<0.001
eGFR <30 mL/min/1.73 m2 1.17 (0.96-1.42); p =0.121

Details of studies evaluating all-cause mortality

3A. ALL-CAUSE MORTALITY IN CHRONIC HEART FAILURE
Author, yearType of biomarkerTroponin cut-offOutcomeHR/OR (95%CI)HR/OR (95%CI);Parameters included in the adjusted/multivariable analysis
Unadjusted (univariable) analysisAdjusted (multivariable) analysis
Barlera 2012 [34]hs-cTnT

  • Continuous variable

  • Log-transformed, natural logarithm

Median 3.9 years HR 1.50 (1.24 – 1.81)NT-proBNP, NYHA class, age, COPD, SBP, DM, eGFR, sex, uricemia, LVEF, Hb, BMI, aortic stenosis
Bayes-Genis 2013 [43]hs-cTnTContinuous variable, logarithmic formMedian follow-up 3.46 (1.85 – 5.05) yearsTotal cohort HR 2.71 (2.25 – 3.26), p<0.001Total cohort HR 1.58 (1.27 – 1.97), p<0.001age, sex, ischemic etiology of HF, LVEF, NYHA class, DM, Hb (g/dL), serum Na (mmol/L), BB treatment, ACEI/ARB treatment, eGFR (in mL/min/1.73 m2), NT-proBNP, cystatin C, sST2
Renal insufficiency HR 2.62 (2.04 – 3.37), p<0.001Renal insufficiency subgroup HR 1.65 (1.24 – 2.2), p<0.001
McDowell 2023 [45]hs-cTnTContinuous variable, log transformedmedian 37 months HR 1.63 (1.31 – 2.03), p<0.001PREDICT-HF score: Age, sex, race, BMI, region, time since HF diagnosis, NYHA class, prior HF hospitalization, treatment with sacubitril-valsartan/beta-blocker, DM, PAD, prior MI, valvular heart disease, bundle branch block, prior PCI, LVEF, SBP, serum K, Cl, BUN, uric acid, albumin, bilirubin, total cholesterol, LDL, triglycerides, AST, Hb, absolute lymphocyte count, absolute neutrophil count, absolute monocyte count, NT-proBNP or BNP
Lupon 2013 [36]hs-cTnTContinuous variable quadratic term, logarithmic function of hs-cTnTMedian 41.4 (IQR 22.1 – 60.5) mHR 11.68 (5.51 – 24.75)HR 3.9 (1.81 – 8.41)age, sex, LVEF, eGFR, BMI, NYHA functional class, DM, COPD, AF, ischemic etiology, Hb, serum Na, BB treatment, and ACEI or ARB
Masson 2012 [5]hs-cTnT

  • 3 categories:

    • ↓ hs-cTnT over time (changes < −15%)

    • Stable levels (changes between −15% and +15%), or

    • ↑ levels (relative changes > +15%).

  • Median FU

  • ValHEFT 24 (1-3; 18-24) months

  • GISSI 47 (38 – 55) months

  • Val-HEFT 1.69 (1.49 – 1.92)

  • GISSI-HF 2.23 (1.86 – 2.69)

  • Val-HEFT 1.60 (1.41 – 1.82)

  • GISSI-HF 1.97 (1.58 – 2.46)

  • Val-HeFT: age, sex, BMI, LVEF (%), NYHA class (III or IV), ischemic etiology of HF, SBP, DBP, Hr, DM, AF, COPD, prescription of diuretics, beta-blockers or spironolactone, serum bilirubin, serum creatinine, log baseline hs-cTnT.

  • GISSI-HF: age, BMI, LVEF, NYHA class, ischemic etiology of HF, SBP, DBP, HR, DM, AF, COPD, prescription of diuretics or beta-blockers, serum bilirubin, serum creatinine, log baseline hs-cTnT.

  • Val-HEFT 1.59 (1.39 – 1.82)

  • GISSI-HF 1.88 (1.50 – 2.35)

  • Val-HeFT: previous parameters + baseline NT-proBNP and hs-CRP

  • GISSI-HF: previous parameters + baseline NT-proBNP and hs-CRP

Lok 2013 [38]hs-cTnThs-cTnT > 26.5 ng/mlMedian 8.4 yearsHR 1.53 (1.32 – 1.78)

  • Model 1: HR 1.45 (1.24 – 1.71)

  • Model 2: HR 1.36 (1.14 – 1.62)

  • Model 3: HR 1.27 (1.06 – 1.53)

  • Model 1 = Age, gender

  • Model 2 = Model 1 + renal function (eGFR), HF etiology, NT-proBNP

  • Model 3 = Model 2 + GDF-15, hs-CRP, galectin 3

Yilmaz Oztekin 2023 [48]hs-cTnTHs-cTnT ≥ 21.5 ng/Lmedian follow-up of 30 monthsHR 1.012 (1.007–1.017), p<0.001HR:1.012, 95% CI:1.003–1.020, p= 0.005eGFR, hemoglobin, NT-proBNP, BMI, and left atrial diameter
Tentzeris 2011 [46]hs-cTnThs-cTnT > 14 pg/mLmedian follow-up 1301 [707 – 1636] days)HR 4.54; 95% CI, 1.92–10.73, p<0.001HR 1.92 (1.11 – 3.33) p=0.02age, sex, NYHA class, eGFR <60 mL/min/1.73m2, median NT-proBNP > 1809 pg/mL
Jungbauer 2014 [32]hs-cTnThs-cTnT > 14 ng/L3-year follow-upOR 4.80 (1.58 – 14.59) p = 0.0057HR 1.2 (1.03 – 1.50) p = 0.025Age, eGFR, LVEF, NYHA class > 2
Bosselmann 2013 [49]hs-cTnTQuartile groupsmedian follow-up of 4.5 (interquartile range: 2–7.7) years HR 3.07 (1.90 – 4.96) P<0.001age, sex, LVEF, NYHA class, DM, IHD, eGFR
Egstrup 2012 [39]hs-cTnTQuartile groupsMedian 4.4 (IQR 1.9 – 7.5) years

  • Q2, HR 1.8 (1.1 – 2.9), p = 0.014;

  • Q3, HR 2.7 (1.7 – 4.2), p = 0.001;

  • Q4, HR 4.6 (3.0 – 7.0), p = 0.001;

  • Q1 reference

  • Q2, HR 1.4, 95% CI 0.9 to 2.4, p _ 0.15;

  • Q3, HR 1.9, 95% CI 1.3 to 3.1, p _ 0.008;

  • Q4, HR 3.1, 95% CI 1.9 to 5.1, p _0.001)

age, gender, LVEF, NYHA class, DM, CAD, Hb, eGFR, interval of inclusion
The gender-specific 99th percentile concentration limit as established in a healthy population: men > 18 ng/L women > 8 ng/L

  • HR 1.4 (95% confidence interval 0.9 to 2.4, p 0.16) for quartile 2, 1.7 (0.9 to 2.5, p 0.12) for quartile 3, and 2.6 (1.6 to 4.4, p <0.001) for quartile 4

  • Troponin T 99th percentile 1.7 (1.2–2.5) 0.003

age, gender, LVEF, NYHA class, DM, CAD, Hb, eGFR, interval of inclusion, NT-proBNP
Aulin 2022 [26]cTnTContinuous variable Log-transformed, natural logarithm

  • Long-term all-cause mortality

  • Median follow-up 1.9 years

χ2 = 220χ2 = 127Step 1: randomized treatment, age, sex, HTN, DM, CAD, history of stroke/TIA, BMI, HR, SR, renal function (CrCl)
χ2 = 56Step 2: Step 1 + N-terminal B-type natriuretic peptide (NT-proBNP)
Zhang 2015 [40]Separate analysis for cTnT and cTnI90th percentile cTnT > 0.105 ng/ml1-year all-cause mortality OR 3.9 (1.96 – 7.76)age ≥75 years, NYHA class III/IV, AF, eGFR < 30 mL/min/1.73 m2, DM, use of diuretics
90th percentile cTnI1-year all-cause mortality OR 1.59 (0.65 – 3.88)age ≥75 years, NNYHA class III/IV, AF, eGFR < 30 mL/min/1.73 m2, diabetes, use of diuretics
3B. ALL-CAUSE MORTALITY IN ACUTE HEART FAILURE
Berge 2021 [31]hs-TnT

  • Continuous variable

  • Log-transformed, natural logarithm)

Long-term all-cause mortalityHR 1.37 (95%CI 1.10 – 1.71)HR 1.20 (95%CI 0.93 – 1.55)Age, male sex, BMI, NYHA class IV, COPD, DM, NT-proBNP, CRP, eGFR
Berge 2022 [27]hs-TnT

  • Continuous variable

  • Log-transformed, natural logarithm

 HR 1.37, 95% CI 1.10 – 1.61Not statistically significantNEWS2 score, age, male sex, BMI, smoking, NYHA class IV, HF, AF, COPD, CAD, hypertension, diabetes, NT-proBNP, CRP, eGFR
Ledwoch 2022 [30]hs-TcnT

  • Continuous variable

  • Log-transformed, natural logarithm

30-day all-cause mortality

  • HFrEF OR 2.58 (95%CI 1.57 – 4.23)

  • HFmrEF OR 4.53 (95%CI 1.85 – 11.1)

  • HFpEF OR 1.48 (95%CI 0.89 – 2.46)

age, sex, NYHA class, DM, HTN, MI, AF, eGFR
Aimo 2019 [28]hs-cTnThs-cTnT ≥ 43 ng/L In-hospital mortality RR 2.7 (95%CI 1.7 – 4.5)

  • In-hospital mortality

  • Not statistically significant

  • 6-month ACM HR 1.73 (95%CI 1.17 – 2.54)

  • 12-month ACM HR 1.60 (95%CI 1.11 – 2.33)

  • 24-month ACM HR 1.89 (95%CI 1.27 – 2.82)

Patient cohort, age, sex, new-onset vs.worsening HF, history of CAD, admission LVEF, NYHA class, SBP, Hr, eGFR, Hb, Na, white blood cell count, history of AF, HTN, DM, COPD

  • Continuous variable

  • Log2-transformed

  • In-hospital mortality

  • HR 1.45 (95%CI 1.31 – 1.59)

  • In-hospital mortality

  • HR 1.30 (95%CI 1.07 – 1.60)
Ledwoch, 2021-2022 [30]hs-cTnT

  • eGFR ≥ 45 ml/min: hs-cTnT > 40 ng/L

  • eGFR < 45 ml/min: hs-cTnT > 55 ng/L

30-day all-cause mortality

  • eGFR ≥ 90ml/min AUC 0.75 (0.64 – 0.86)

  • eGFR 60 – 89 ml/min AUC 0.74 (0.62 – 0.85)

  • eGFR 45 – 59 ml/min AUC 0.77 (0.64 – 0.91)

  • eGFR 30 – 44 ml/min AUC 0.63 (0.50 – 0.75)

  • eGFR < 30 ml/min AUC 0.62 (0.49 – 0.74)

N/AN/A
Horiuchi 2021 [50]hs-cTnIContinuos variable log-2 transformed1-year all-cause mortality

  • Tertile 1 HR 0.88 (0.37 – 2.11)

  • Tertile 2 HR 1.10 (0.55 – 2.18)

  • Tertile 3 HR 1.20 (0.69 – 2.07)

HR 1.12 (1.03 – 1.22), p=0.012age, Black race, history COPD, oedema, SBP, Hr, Na, Hb, and BUN, BNP, sNGAL, uNGAL, and Gal3.
Guisado Espartero 2014 [33]cTnTcTnT > 0.02 ng/mL1-year all-cause mortality2.52 (1.58 – 4.01)1.91 (1.09 – 3.32)age, female sex, BMI > 25 kg/m2, IHD, previous HF, anemia, LVEF < 45%, NYHA III–IV, eGFR < 60 mL/min/1.73m2, NT-proBNP > 3264 pg/mL
Separate analysis of patients with eGFR<60: patients with eGFR < 60 mL/min/1.73 and intermediate-high TnT had more deaths than those with eGFR > 60 mL/min/1.73
Bjurman 2013 [47]cTnTcTnT>10ng/LAll-cause long-term mortality at 3 yearsHR 2.94 (1.06 – 8.15), p=0.038HR 147 (11.2 – 1929.8), p<0.001Age, ALP, urea, creatinine, orosomucoid, NT-proBNP, TnT, CK-MB, CysC
Ather 2013 [37]cTnI with 3 measurements during 3 different admissions

  • The median value of minimum cTnI was 0.03 ng/ml (IQR: 0.03 to 0.06 ng/ml

  • The median overall cTnI was 0.06 ng/ml (IQR: 0.04 to 0.1 ng/ml)

  • The median value of maximum cTnI was 0.15 ng/ml (IQR: 0.08 to 0.42 ng/ml)

  • delta cTnI equal to 0.01 ng/ml (IQR: – 0.05 to 0.09 ng/ml)

  • All-cause long-term mortality

  • (632 person-years)

  • Minimum cTnI: HR=5.8, 95% CI 1.7 to 19.7

  • Median cTnI: HR=2.3, 95% CI: 1.3 to 4.1

  • Delta cTnI: HR=1.1, 95% CI 1.04 to 1.23

  • Maximum cTnI was not associated with mortality

  • minimum TnI was the only TnI pattern significantly

  • associated with mortality, with a .2 value of 13.7, pb0.001 and HR of 13.7 (95% CI: 3.7 to 50.8)

  • minimum TnI > 0.04 ng/ml HR=1.6, 95% CI: 1.1 to 2.3,

age, gender, race, ischemic etiology of HF, EF, NYHA class, number of vessels having more than 50% stenosis on angiography, baseline admission TnI, baseline peak TnI, CV admission, HF admission and total number of admissions during the run-in period; history of smoking, HTN, PAD, AF, DM, COPD, CKD, LVF, CAD
Felker 2012 [44]cTnIContinuous variable, log transformed in using log base 2Death at 30 days

  • Doubling of cTnI: OR 1.23 (1.01 – 1.50), p=0.035

  • 20% increase of cTnI OR 3.39 (1.26 – 9.15), p=0.0158

  • Absolute change in troponin

  • OR 0.76 (0.57 – 1.02), p=0.063

Doubling of cTnI: OR 1.11 (0.89 – 1.38), p=0.37Age, log(BUN), serum sodium, hypotension (baseline), dyspnoea at rest
Death at 180 daysDoubling of cTnI: HR 1.25 (1.13 – 1.38), p<0.001Doubling of cTnI: HR 1.11 (0.99 – 1.25), p=0.086Age, log(BUN), serum sodium, hypotension (baseline), dyspnoea at rest (baseline).
Lee 2022 [42]cTnIcTnI≥0.05 ng/mL (elevated); <0.05 ng/mL (normal)Overall all-cause mortality

  • Compared to patients with non-IHF and normal troponin, subgroup categories:

  • Non-IHF and ↑ troponin HR 1.77 (1.52 – 2.07), p<0.001

  • IHF and normal troponin HR 1.61 (1.26 – 2.06), p<0.001

  • IHF and ↑ troponin HR 2.29 (1.97 – 2.66), p<0.001

  • Compared to patients with non-IHF and normal troponin, subgroup categories:

  • Non-IHF and ↑ troponin HR 1.60 (1.36 – 1.88), p<0.001

  • IHF and normal troponin HR 1.44 (1.12 – 1.85), p=0.005

  • IHF and ↑ troponin HR 1.88 (1.60 – 1.55), p<0.001

Age, sex, previous history of admission due to HF, HTN, DM, CKD, COPD, CVA, prior history of CAD, MI, malignancy, initial SBP, initial LVEF, initial Na, initial Cr, AF at admission, medication at discharge, including ACEI/ARB, BB, or AA
cTnI≥0.05 ng/mL90-day all-cause mortality

  • Non-IHF

  • HR 3.08 (2.27 – 4.17), p<0.001

  • IHF HR 3.47 (2.02 – 5.93), p<0.001

  • Non-IHF

  • HR 2.47 (1.81 – 3.37), p<0.001

  • IHF

  • HR 2.91 (1.65-5.12), p<0.001
cTnI≥0.05 ng/mLPost-90-day all-cause mortality

  • Non-IHF

  • HR 1.41 (1.18 – 1.68), p<0.001

  • IHF

  • HR 1.03 (0.81 – 1.32), p=0.79

  • Non-IHF

  • HR 1.36 (1.13 – 1.63), P<0.001

  • IHF

  • N/A
Fabbri 2015 [41]cTnT or cTnI

  • cTnT ≥ 50 ug/L

  • cTnI ≥0.5 ng/L

1-year all-cause mortality HR 1.21 (1.05 – 1.39)age, sex, new-onset dysrhythmias, cardiac valvular diseases, CAD, presence PM or ICD, history of AHF, CKD, COPD, DM, CVD, cognitive defects, poor nutritional status, compliance with pharmacology prescriptions (ACEI, ARB, BB, loop diuretics, MRA, anticoagulants, antithrombotic agents), plasma Na<135 mEq/L, NT-proBNP > 5000ng/L, eGFR < 30 mL/min/1.73m2

Details of studies evaluating cardiovascular mortality

AUTHOR/YEARType of biomarkerTroponin cut offHR/OR (95%CI)HR/OR (95%CI)Parameters included in the adjusted/multivariable analysis
Unadjusted (univariable) analysisAdjusted (multivariable) analysis
Zymliński 2017 [22]hs-cTnI>= URL1.44-systolic blood pressure, natural logarithm of N-terminal pro-B type natriuretic peptide, diabetes mellitus and chronic kidney disease.
Increase vs stable/decrease2.221.90 (0.84–4.29)
1Ln/pgml1.97 (1.88–7.87)1.67 (1.01–2.76)
Increase vs decrease3.84 (1.88–7.87)3.22 (1.52–6.82)
Kawahara 2011 [21]hs-cTnIhs-cTnI at baseline (ng/mL) (≥0.03 = 1, b0.03 = 0)15.89510.679age, sex, NYHA class, body weight, creatinine
5.7 (1.2–7.9)
Demissei 2017 [23]hs-cTnT 1.63 (1.46–1.81)1.64 (1.44–1.88)Adjusted for a pre-defined baseline model encompassing clinical variables (geographic region, systolic blood pressure, orthopnoea, angina, hyperthyroidism, mitral regurgitation, and atrial fibrillation/flutter at screening), laboratory parameters (white blood cell count, lymphocyte %, blood urea nitrogen, sodium, potassium, calcium, and total protein), and study treatment. The covariate orthopnoea on the ordinal scale (0,1,2,3) was dichotomized into binary as: orthopnoea: 2/3 vs. 0/1. Rationale: there were 0 subjects who died due to cardiovascular causes for orthopnoea level ‘none
Masson 2012 [5]hs-cTnTupper limit of 13.5 ng/LMortality for worsening heart failure Val-HeFT 2.32 (1.90–2.82)2.26 (1.78–2.86)age, BMI, LVEF, NYHA class, ischemic etiology of HF, systolic and diastolic blood pressures, prescription of diuretics, beta-blockers or spironolactone, serum creatinine, log baseline hs-cTnT.
age, BMI, LVEF, NYHA class, ischemic etiology of HF, systolic and diastolic blood pressures, heart rate, diabetes mellitus, atrial fibrillation, COPD, prescription of diuretics or betablockers, serum bilirubin, serum creatinine, log baseline hs-cTnT.
Mortality for worsening heart failure GISSI-HF 2.99 (2.30–3.89)2.9 (2.08–4.03)
DOI: https://doi.org/10.2478/rjim-2025-0006 | Journal eISSN: 2501-062X | Journal ISSN: 1220-4749
Journal RSS Feed
Language: English
Page range: 107 - 126
Submitted on: Feb 15, 2025
|
Published on: Apr 6, 2025
Published by: N.G. Lupu Internal Medicine Foundation
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
troponin,
outcome,
CKD,
renal dysfunction,
heart failure,
hospitalizations,
kidney function,
kidney disease,
mortality
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Internal medicine, other,
Cardiology,
Gastroenterology,
Rheumatology

© 2025 Anca Breha, Caterina Delcea, Andreea Cristina Ivanescu, 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.

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