Renal Dysfunction Influences the Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin I
Ian Gunsolus1, Yader Sandoval2,3,4, Stephen W Smith5
1Department of Laboratory Medicine and Pathology and.
Insights
Cardiac troponin (cTn) tests are less specific for myocardial infarction in chronic kidney disease (CKD) patients. Higher hs-cTnI levels indicate increased mortality risk, especially with renal dysfunction.
Area of Science:
- Cardiology
- Nephrology
- Clinical Diagnostics
Background:
- Cardiac troponin (cTn) assays, particularly high-sensitivity assays (hs-cTnI), are crucial for diagnosing myocardial infarction (MI).
- Chronic kidney disease (CKD) can affect cTn levels, potentially lowering assay specificity and impacting diagnostic accuracy.
- Understanding the influence of renal function on hs-cTnI performance is vital for accurate MI diagnosis and patient risk stratification.
Purpose of the Study:
- To evaluate the diagnostic accuracy of baseline and serial hs-cTnI measurements for MI in patients with varying degrees of renal function.
- To assess the association between hs-cTnI levels, renal function, and short-term (30-day) and medium-term (180-day) mortality.
- To determine if renal dysfunction impacts the 'rule-in' and 'rule-out' performance of hs-cTnI for MI.
Main Methods:
- A prospective study (NCT02060760) involving 1555 adults presenting with ischemic symptoms.
- hs-cTnI was measured using the Abbott assay with sex-specific 99th percentiles.
- Myocardial infarction was adjudicated using the universal definition; renal function was assessed by estimated glomerular filtration rate (eGFR).
Main Results:
- Specificity of hs-cTnI for MI decreased significantly with impaired renal function, from 93%-95% (eGFR≥90) to 40%-41% (dialysis).
- Positive predictive values also decreased with declining renal function.
- Mortality significantly increased across increasing hs-cTnI tertiles and was higher in patients with renal dysfunction.
- hs-cTnI rule-in performance for MI was reduced by renal dysfunction and dialysis, but rule-out performance was not significantly affected.
Conclusions:
- Renal dysfunction and dialysis reduce the specificity and positive predictive value of hs-cTnI for diagnosing myocardial infarction.
- Despite reduced rule-in performance, hs-cTnI maintains its rule-out capability across different renal function levels.
- Higher hs-cTnI concentrations are associated with increased mortality, underscoring the importance of considering renal function in hs-cTnI interpretation.
Abstract:
Measures of cardiac troponin (cTn) may have lower specificity for myocardial infarction in patients with CKD. We examined the diagnostic accuracy of baseline and serial high-sensitivity cTnI (hs-cTnI) measurements for myocardial infarction and 30- and 180-day mortality according to renal function. hs-cTnI was measured (Abbott assay) using sex-specific 99th percentiles (women, 16 ng/L; men, 34 ng/L) in 1555 adults presenting to the emergency department with symptoms suggesting ischemia (NCT02060760). Myocardial infarction was adjudicated along universal definition classification. Renal function did not significantly affect sensitivity or negative predictive values. Specificity decreased with impaired renal function from 93%-95% with normal function (eGFR≥90 ml/min per 1.73 m2; n=722) to 57%-61% with severely impaired renal function (eGFR<30 ml/min per 1.73 m2; n=81) and 40%-41% on dialysis (n=78). Positive predictive values decreased with decreasing renal function from 51%-57% with normal function to 27%-42% with severely impaired function and 15%-32% on dialysis. Receiver operating characteristic curve areas trended lower at baseline and 3 hours with renal impairment. Mortality increased significantly with increasing hs-cTnI tertile (1.3%, 6.0%, and 10.4%, respectively). Patients with hs-cTnI concentration exceeding concentrations in the 99th percentiles had a mortality rate (11.7%) significantly higher than that of patients with concentrations between 99th percentile concentrations and limit of detection (6.2%) or below limit of detection (1.1%). Renal dysfunction and dialysis reduced the rule-in performance but not the rule-out performance of hs-cTnI for myocardial infarction, and mortality increased in patients with higher hs-cTnI concentrations and any level of renal dysfunction.
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