---
title: "Troponin-defined myocardial injury predicts worse long-term survival in chronic kidney disease"
id: "plos-one-21-association-of-troponin-defined-myocardial-injury-with-adverse-long-term"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-21-association-of-troponin-defined-myocardial-injury-with-adverse-long-term"
content_type: "clinical_feed_article"
specialty: "Cardiology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354873"
published_at: "2026-07-30T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Troponin-defined myocardial injury predicts worse long-term survival in chronic kidney disease
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-21-association-of-troponin-defined-myocardial-injury-with-adverse-long-term
- **Specialty:** [Cardiology](https://medichelpline.com/clinical-feed/cardiology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0354873)
- **Published At:** 2026-07-30T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This is a retrospective analysis of NHANES (1999–2004) data assessing the association between **high-sensitivity troponin (hs-cTn)** elevations and long-term mortality among adults with chronic kidney disease (CKD). - The analytical cohort comprised 2,137 participants meeting KDIGO-based CKD criteria (eGFR <60 mL/min/1.73 m2 or UACR ≥30 mg/g); weighted to represent 22,772,953 records from the US civilian noninstitutionalized population. - Myocardial injury was defined as at least one elevated hs-cTn assay (either hs-cTnT or hs-cTnI) and was present in 26.6% of the weighted cohort. - Patients with troponin-defined myocardial injury were older, had lower eGFR, and higher prevalence of cardiovascular disease, hypertension, and diabetes compared with those without elevated hs-cTn. - Over a median follow-up of 11.6 years, survival at 1, 5, 10, and 15 years was worse in the troponin-elevated group. - After adjustment for baseline characteristics and comorbidities, troponin-defined myocardial injury was independently associated with increased risk of all-cause mortality (adjusted hazard ratio [aHR] 1.81, 95% CI 1.51–2.17) and cardiovascular mortality (aHR 2.03, 95% CI 1.47–2.79). - Sensitivity analyses excluding participants with pre-existing cardiovascular disease produced similar associations (all-cause mortality aHR 1.86, 95% CI 1.56–2.21; cardiovascular mortality aHR 2.44, 95% CI 1.83–3.24), supporting robustness of the findings. - The study emphasizes that hs-cTn elevations identify a high-risk phenotype in CKD but notes limitations: observational design prevents causal inference and single time-point troponin measurements limit assessment of temporal dynamics. - Data provenance, assay platforms, and analytic choices are reported: four hs-cTn assays were used (Roche hs-cTnT and three hs-cTnI assays), and stored serum samples were analyzed in 2018–2020; full data files are available on figshare as cited by the authors.
## Clinical Analysis & Structured Key Points
Association of troponin-defined myocardial injury with adverse long-term survival among patients with chronic kidney disease | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Objective Chronic kidney disease (CKD) is associated with increased mortality, however, the impact of troponin-defined myocardial injury within this population remains poorly understood. This study aimed to investigate the associations between troponin-defined myocardial injury and long-term mortality in CKD patients. Methods This observational study analyzed 22,772,953 weighted records of adult CKD patients from National Health and Nutrition Examination Survey (1999–2004) databases. Myocardial injury was defined by at least one elevated high-sensitivity troponin (hs-cTn) assay, present in 26.6% of the cohort. Cox regression models adjusted for baseline characteristics and comorbidities were used to assess the associations between troponin-defined myocardial injury and all-cause and cardiovascular mortality. Sensitivity analyses excluding patients with known cardiovascular disease (CVD) were performed to evaluate the robustness of the findings. Results Patients with troponin-defined myocardial injury were older and had a higher prevalence of CVD, hypertension, diabetes, as well as a lower estimated glomerular filtration rate (eGFR), compared with those without troponin-defined myocardial injury. Over a median follow-up of 11.6 years, survival was significantly worse among patients with troponin-defined myocardial injury at 1, 5, 10, and 15 years. The adjusted hazard ratios (aHR) for all-cause mortality and cardiovascular mortality in patients with troponin-defined myocardial injury were 1.81 (95% CI 1.51–2.17) and 2.03 (95% CI 1.47–2.79), respectively. Sensitivity analysis excluding records with pre-existing CVD showed similar trends, with an aHR of 1.86 (95% CI 1.56–2.21) for all-cause mortality and 2.44 (95% CI 1.83–3.24) for cardiovascular mortality. Conclusion As a marker for troponin-defined myocardial injury, hs-cTns were independently associated with worse long-term survival among CKD patients. However, the observational design precludes causal inference, and single time-point troponin measurements limit the assessment of dynamic changes in myocardial injury. Citation: Ma F, Han E, Gao J (2026) Association of troponin-defined myocardial injury with adverse long-term survival among patients with chronic kidney disease. PLoS One 21(7): e0354873. https://doi.org/10.1371/journal.pone.0354873 Editor: Shukri AlSaif, Saud Al-Babtain Cardiac Centre, SAUDI ARABIA Received: April 2, 2025; Accepted: July 13, 2026; Published: July 30, 2026 Copyright: © 2026 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All data files are available from the figshare database ( https://doi.org/10.6084/m9.figshare.31320880 ). Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Introduction Chronic kidney disease (CKD) is a significant global public health concern, affecting millions of individuals worldwide and leading to high rates of morbidity and mortality, particularly from cardiovascular disease (CVD) [ 1 – 4 ]. Cardiac troponins have gained particular attention in clinical practice due to their high sensitivity and specificity in detecting myocardial injury. Elevated troponin levels, even in the absence of acute coronary syndrome, have been associated with increased cardiovascular morbidity and mortality in the general population [ 5 , 6 ]. In patients with CKD, troponin elevation is commonly observed and has been linked to adverse cardiovascular outcomes, with or without current acute coronary syndrome [ 7 , 8 ]. However, the exact mechanisms underlying troponin elevation in CKD are not fully understood and may involve both myocardial injury and reduced renal clearance of the biomarker. Previous studies have demonstrated that troponin levels can predict short-term cardiovascular events in CKD patients [ 9 – 11 ]. However, only two studies have explored the association between troponin levels and long-term outcomes in this population. One investigation, with a median follow-up of 12.5 years, reported that the risk ratio for cardiovascular death or events associated with elevated high-sensitivity troponin T (hs-cTn T) was greater in patients with CKD than in those without CKD [ 12 ]. Similarly, an 8.5-year observational study found that baseline hs-cTn T levels were independently associated with all-cause mortality in patients with CKD [ 13 ]. Despite these findings, the association of both hs-cTn T and high-sensitivity troponin I (hs-cTn I), the prognostic implications of biomarker-defined troponin elevations as a phenotype, with all-cause and cardiovascular mortality specifically in the CKD population remain inadequately characterized and warrant further investigation. The aim of this study was to investigate the association between myocardial injury, as indicated by high-sensitivity troponin (hs-cTn) assays, and long-term survival outcomes in a large cohort of patients with CKD. Methods Study design and population This study evaluates a biomarker phenotype rather than a clinical diagnosis of true pathophysiologic myocardial injury. The data for this retrospective study was derived from the National Health and Nutrition Examination Survey (NHANES) database, a program conducted by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC). NHANES is a nationally representative survey that collects comprehensive information on the health and nutritional status of non-institutionalized civilian residents in the United States. The NHANES study protocol was approved by the National Center for Health Statistics Research Ethics Review Board, and all participants provided written informed consent [ 14 ]. We obtained NHANES data from 1999 to 2004. CKD was defined as an estimated glomerular filtration rate (eGFR) 22 ng/L for men and >14 ng/L for women. hs-cTn I (Abbott): > 35 ng/L for men and >17 ng/L for women. hs-cTn I (Siemens): > 58 ng/L for men and >39.6 ng/L for women. hs-cTn I (Ortho): > 12 ng/L for men and >9 ng/L for women [ 25 ]. No cross-assay standardization was attempted; each assay was interpreted using its manufacturer-specific, sex-stratified 99th percentile upper reference limit. The binary outcome of troponin-defined myocardial injury was defined as any assay exceeding its corresponding threshold, thereby aligning the clinical classification standard across platforms rather than assuming numerical equivalence of raw troponin values. Mortality data, classified according to the International Classification of Diseases (ICD) codes, were derived from death certificates to ensure consistency in determining causes of death. Cardiovascular mortality included heart-related diseases (ICD codes I00–I09, I11, I13, and I20–I51) and cerebrovascular conditions (ICD codes I60–I69). Pearson’s χ 2 or Mann-Whitney U test was used to compare baseline characteristics as appropriate. The associations between myocardial injury and all-cause mortality were analyzed by Kaplan-Meier survival curves and Cox regression models. Kaplan-Meier curves were survey-weighted to incorporate the complex survey design (strata and primary sampling units). Survey-weighted Cox proportional hazards models were used for hazard ratio estimation, accounting for strata and primary sampling units as specified by NHANES analytic guidelines. Cumulative incidence at specific time points were estimated using unweighted data to provide observed estimates. Variables that were statistically significant in univariate analyses were incorporated into multivariate analyses. The full candidate variable list, with inclusion and exclusion rationale, is provided in S1 Table . In addition to statistically significant variables, we also included variables deemed potentially clinically relevant based on prior literature or clinical expertise, even if they did not reach statistical significance in univariate testing. Multicollinearity was formally assessing using the variance inflation factor (VIF), with VIF > 5 indicating high correlation and potential exclusion to ensure model stability ( S2 Table ). Model 1 was unadjusted. Model 2 was adjusted for age, sex, and race. Model 3 was adjusted for age, sex, race, stain use, and ACEI/ARB, which were forced into the model due to their clinical relevance. Additional covariates were selected from the remaining candidate list ( S1 Table ) using a stepwise forward selection procedure with entry and stay p-values of P 0.05), indicating a good model fit. The events-per-variable (EPV) ratio was 87.0 for all-cause mortality and 32.7 for cardiovascular mortality, both exceeding the recommended minimum threshold of EPV ≥ 10 [ 26 ]. The primary outcome of this analysis was the association between myocardial injury and long-term all-cause mortality in patients with CKD. A second focus was the association with long-term cardiovascular mortality. A formal test for effect modification was conducted to assess whether the association between myocardial injury and mortality differed by the specific hs-cTn assay used. This was performed by introducing an interaction term (assay type × myocardial injury status) into the primary Cox proportional hazards model (model 3). The significance of the interaction was evaluated using a likelihood ratio test, comparing the model with the interaction term to the nested model without it. To evaluate the robustness of our modeling approach, we performed sensitivity analyses using (1) a forced-entry Cox model with all candidate variables entered simultaneously, and (2) inverse probability of treatment weighting (IPTW) using propensity scores. To assess the isolated impact of myocardial injury, patients with pre-exisiting CVD were excluded in additional sensitivity analyses. All statistical analysis were conducted using R software (R-4.3.2). A P -value < 0.05 was considered statistically significant. Results Baseline characteristics A total of 22,772,953 weighted records with CKD were included in the analysis, all of them were adults, with a minimum age of 20 year, and no missing vital status. The weighted records reflect the estimated population size; the actual participant count is 2,137 unweighted records. Those with troponin-defined myocardial injury, based on at least a single hs-cTn assay, accounted for 26.6% (6,067,451 records, 725 unweighted) of the cases. The distribution of the hs-cTn values in both arms of the study is available in Table 1 . Table 2 presents the baseline characteristics of the cohort study participants. Patients with troponin-defined myocardial injury were older (77.0 vs 58.1, P < 0.001), more likely to be Non-Hispanic White race (75.8 vs 71.2%, P < 0.001) and Non-Hispanic Black (14.1 vs 9.2%, P < 0.001). They had higher rates of former smokers (41.5 vs 30.3%, P < 0.001) and current smokers (13.1 vs 2.2%, P < 0.001), and a greater prevalence of CVD (44.5 vs 15.4%, P < 0.001), hypertension (69.8 vs 47.3%, P < 0.001), diabetes (32.9 vs 23.2%, P < 0.001). Additionally, they exhibited higher uric acid levels (6.4 vs 5.8, P < 0.001), lower eGFR (50.1 vs 84.0, P < 0.001), and lower UACR (34.4 vs 41.3, P = 0.035) compared with those without troponin-defined myocardial injury. Download: PNG larger image TIFF original image Table 1. Median and interquartile range of troponin values grouped by the type of hs-cTn assay used to define myocardial injury. https://doi.org/10.1371/journal.pone.0354873.t001 Download: PNG larger image TIFF original image Table 2. Baseline characteristics of CKD patients. https://doi.org/10.1371/journal.pone.0354873.t002 Outcomes The median follow-up duration was 11.6 years (IQR 5.8–16.8). Survival outcomes revealed that individuals with troponin-defined myocardial injury experienced significantly poorer survival probabilities compared with those without troponin-defined myocardial injury at various time points. At 1 year, survival probabilities were 94.0% for those with troponin-defined myocardial injury versus 98.4% for those without. This disparity widened over time, with survival probabilities declining to 62.0% versus 90.4% at 5 years, 30.1% versus 75.6% at 10 years, and 14.7% versus 61.2% at 15 years ( Fig 2 ). Download: PNG larger image TIFF original image Fig 2. Kaplan-Meier survival curve for all-cause mortality in CKD patients using any hs-cTn assay to define myocardial injury. https://doi.org/10.1371/journal.pone.0354873.g002 To address potential heterogeneity from pooling different hs-cTn assays, we formally tested for interaction between assay type and myocardial injury status on mortality. The likelihood ratio test for the interaction term was not statistically significant, indicating that the observed association between myocardial injury and mortality was consistent across the
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