Chronic kidney disease (CKD) carries a high burden of morbidity and mortality, with cardiovascular disease (CVD) being a leading cause of death in this population. Cardiac troponins measured with high-sensitivity assays (hs-cTn) detect myocardial injury with greater precision than older tests, and elevated hs-cTn concentrations have been linked to worse cardiovascular outcomes in the general population. In people with CKD, persistent or elevated troponin levels are commonly observed and may reflect a combination of myocardial injury and impaired renal clearance of the biomarker. Prior work has linked hs-cTn to short-term events in CKD and, in a limited number of studies, to long-term mortality; however, the prognostic implications of a troponin-defined injury phenotype using both hs-cTnT and hs-cTnI across a representative CKD cohort remained incompletely characterized. The present analysis aimed to evaluate associations between troponin-defined myocardial injury and long-term all-cause and cardiovascular mortality in a large, nationally representative sample of adults with CKD.
This retrospective observational study used data from the National Health and Nutrition Examination Survey (NHANES) cycles 1999–2004. CKD was defined according to KDIGO criteria as either an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. eGFR was calculated using the CKD-EPI equation. Exclusion criteria for the analytic sample included age under 20 years, missing follow-up data, or unavailable hs-cTn measurements.
Stored serum samples from NHANES participants were analyzed for hs-cTn between 2018 and 2020 at the University of Maryland School of Medicine. Four assays were used: hs-cTnT (Roche Cobas e601) and three hs-cTnI assays (Abbott ARCHITECT i2000SR, Siemens Centaur XP, and Ortho Vitros 3600). The study evaluated a biomarker phenotype—presence of at least one elevated hs-cTn result—rather than adjudicated clinical myocardial infarction.
Demographic and clinical covariates included age, sex, race/ethnicity, body mass index (BMI), education level, smoking status, anemia, history of CVD (self-reported physician diagnosis of heart failure, chronic coronary heart disease, angina, myocardial infarction, or stroke), diabetes, hypertension, hyperlipidemia, lipid values, eGFR, UACR, C-reactive protein, and use of statins or renin–angiotensin system blockers. Standard NHANES sampling weights were applied to produce estimates representative of the noninstitutionalized US population. Cox proportional hazards models adjusted for baseline covariates and comorbidities were used to estimate associations between troponin-defined myocardial injury and both all-cause and cardiovascular mortality. Sensitivity analyses excluded participants with pre-existing CVD to assess robustness.
The final analytic sample included 2,137 NHANES participants meeting CKD criteria; when weighted, these records represented 22,772,953 individuals. Troponin-defined myocardial injury, defined by the presence of at least one elevated hs-cTn assay, occurred in 26.6% of the weighted cohort. Participants with elevated hs-cTn were older and had a higher prevalence of established cardiovascular disease, hypertension, and diabetes, and had lower mean eGFR compared with those without elevated hs-cTn.
Over a median follow-up of 11.6 years, survival was consistently worse among participants with troponin-defined myocardial injury at 1, 5, 10, and 15 years. In multivariable Cox models adjusting for demographic factors and comorbid conditions, the presence of elevated hs-cTn was independently associated with higher risk of all-cause mortality (adjusted hazard ratio [aHR] 1.81; 95% confidence interval [CI] 1.51–2.17) and cardiovascular mortality (aHR 2.03; 95% CI 1.47–2.79).
Sensitivity analyses that excluded participants with self-reported pre-existing CVD produced similar results, 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, indicating that the association persisted even in those without known clinical CVD at baseline.
In this nationally representative CKD cohort, a troponin-defined myocardial injury phenotype identified by a single elevated hs-cTn measurement was associated with substantially worse long-term survival. The observed associations held after adjustment for multiple demographic and clinical covariates and were robust to exclusion of participants with prior CVD, supporting the concept that elevated hs-cTn marks a high-risk state in CKD.
The mechanisms linking elevated hs-cTn to adverse outcomes in CKD are likely multifactorial and may include subclinical myocardial ischemia or structural heart disease, chronic myocardial stress, and reduced renal clearance of troponin fragments. The authors emphasize that this analysis characterizes a biomarker phenotype rather than proving active myocardial necrosis or causation.
Limitations reported by the investigators include the observational design, which precludes causal inference, and reliance on single time-point troponin measurements, which limits assessment of dynamic changes or acute versus chronic elevations. Additionally, the hs-cTn assays were performed on stored samples years after collection, although assay platforms and procedures are described. Self-reported history was used to define pre-existing CVD, which may introduce misclassification.
Elevated high-sensitivity troponin, used to define a myocardial injury phenotype, was independently associated with increased long-term all-cause and cardiovascular mortality among adults with CKD in NHANES. These findings suggest that hs-cTn elevations identify a higher-risk subgroup within CKD, but further research is needed to clarify mechanisms and to determine whether serial measurements or targeted interventions can modify risk. The observational nature of the study and single time-point biomarker assessment are important caveats to interpretation.