Keywords
myocardial infarction - prognosis - troponin T - kidney failure - renal insufficiency
Introduction
Acute coronary syndrome (ACS) is a condition characterized by thrombotic involvement of coronary arteries, presenting a potentially life-threatening situation. It involves a sudden reduction in coronary blood flow due to coronary occlusion.[1] ACS comprises two main categories: ST-segment elevation myocardial infarction (STEMI), characterized by occlusive and persistent thrombus, and non-STEMI (NSTEMI), typically nonocclusive or with transient thrombus. NSTEMI is the most frequently reported form of ACS and stands as a leading cause of mortality in both the United States and Europe. The annual incidence of NSTEMI-ACS exceeds 550,000 patients in the United States, with an approximate rate of 3 cases per 1,000 people in Europe.[2]
Diagnosing and treating cardiovascular system events involve a spectrum of care provided by emergency health services, defibrillation, coronary intensive care units, and pharmacotherapies. These pharmacotherapies include antiplatelet agents, antithrombotic, β-receptor blocking agents, angiotensin-converting enzyme inhibitors, and intravenous thrombolytic agents.[3]
[4] While primary angioplasty is a well-established treatment for STEMI, its applicability and efficacy in patients diagnosed with chronic kidney disease (CKD) or end-stage renal disease (ESRD) have not been thoroughly investigated. Typically, individuals with CKD and ESRD are often excluded from randomized controlled studies. However, retrospective studies in patients admitted to coronary intensive care units have consistently identified renal dysfunction as a crucial prognostic marker for long-term mortality, even after adjusting for factors such as age, gender, and comorbidities.[5]
Furthermore, retrospective studies involving patients with a history of acute myocardial infarction consistently demonstrate that renal dysfunction is independently associated with increased mortality. Its impact on mortality surpasses basic demographic data or administered treatments.[6] Despite the well-established efficacy of certain treatments for ACS, including those for individuals with renal dysfunction, in clinical studies, it is crucial for a comprehensive understanding of the effectiveness of these interventions in diverse patient populations. In this study, we aimed to evaluate the effect of delta troponin T (initial and first hour) value on short-term mortality in patients diagnosed with renal dysfunction and NSTEMI.
Materials and Methods
Design and Setting
The study was conducted prospectively, involving patients who presented to the Umraniye Training and Research Hospital suspected of NSTEMI between February 1, 2021, and August 1, 2022. This single-center, prospective, observational, and diagnostic accuracy study received approval from the local clinical research ethics committee (decision number: 2021/KK/25, Date: February 11, 2021).
Study Population
The study focused on patients diagnosed with NSTEMI and renal dysfunction who sought care at the study center. All eligible patients meeting the inclusion criteria over 18 months constituted the research population. We included patients who were over 18 years old, newly diagnosed with NSTEMI, had CKD (serum creatinine > 1.2 mg/dL and glomerular filtration rate [GFR] value < 90 mL/min), and provided informed consent were included. We excluded patients under 18 years old, those who did not provide informed consent, and individuals whose elevated delta troponin T was explained by pathologies other than NSTEMI.
Outcome Measures
The primary focus of the study was on the diagnostic value of the delta troponin T (it was calculated using initial and first-hour troponin T values) value in predicting 30-day mortality in patients with CKD and NSTEMI. Secondary outcomes aimed to assess the diagnostic values of initial and first-hour troponin in predicting 30-day mortality.
Statistical Analysis
Data analysis was performed using IBM SPSS Statistics (version 29.0). Normal distribution was assessed using the Shapiro–Wilk test. Nonnormally distributed continuous data were expressed as median (25–75% median) and analyzed using the Mann–Whitney U-test. Categorical data were expressed as frequency (%), and the chi-square or Fisher's exact test was employed for between-group comparisons. Receiver operating characteristics (ROC) analysis was performed for diagnostic performance, and the area under the curve was calculated. Optimal threshold values were determined using the Youden index, and diagnostic performance criteria were computed for dichotomized variables. The significance level was set at p < 0.05.
Results
Patients meeting the inclusion criteria were included in the study, with an average age of 69 (54–74), and 44 (60.3%) were male. The median GFR of the patients was 64.4 mL/min (45.7–74.3). Baseline characteristics of the patients are presented in [Table 1]. Three (4.1%) patients experienced cardiac-related deaths within the first 24 hours. The 30-day mortality rate was 9.5%. Significant differences were observed in systolic and diastolic blood pressure, GFR, neutrophils, C-reactive protein, and creatinine between survivors and nonsurvivors within 30 days (p = 0.045, p = 0.020, p = 0.028, p = 0.049, p = 0.002, p = 0.005, respectively). A comparison of survivors and mortality groups is presented in [Table 2].
Table 1
Basic descriptive characteristics of patients
|
Variables
|
Median (25–75% quarterly)
Frequency (%)
|
|
Age (y)
|
69 (54–74)
|
|
Gender (male)
|
44 (60.3)
|
|
Vital parameters
|
|
Systolic blood pressure (mm Hg)
|
155 (132–162)
|
|
Diastolic blood pressure (mm Hg)
|
80 (65–96)
|
|
Pulse (beats/min)
|
86 (77–100)
|
|
SpO2 (%)
|
95 (93–98)
|
|
Laboratory parameters
|
|
White blood cell count (103/uL)
|
10 (7.4–12.6)
|
|
Neutrophil count (103/uL)
|
6.8 (4.7–8.6)
|
|
Lymphocyte count (103/uL)
|
2.1 (1.4–3.4)
|
|
Platelet count (103/uL)
|
276 (254–286)
|
|
C-reactive protein (mg/dL)
|
7.7 (1.6–14.8)
|
|
Brain natriuretic peptide[a] (pg/mL)
|
1387 (319–3295)
|
|
Blood urea nitrogen (mg/dL)
|
42.5 (35.4–51.3)
|
|
Creatinine (mg/dL)
|
1.07 (0.93–1.29)
|
|
Glomerular filtration rate (mL/min)
|
63.4 (45.7–74.3)
|
|
Aspartate aminotransferase (IU/L)
|
25 (19–36)
|
|
Alanine aminotransferase (IU/L)
|
18 (14–25)
|
|
RIFLE classification
|
|
Risk
|
52 (71.2)
|
|
Injury
|
15 (20.5)
|
|
Failure
|
1 (1.4)
|
|
Loss
|
2 (2.7)
|
|
End stage
|
3 (4.1)
|
|
Comorbidities
|
|
Diabetes mellitus
|
27 (37)
|
|
Hypertension
|
62 (84)
|
|
Coronary artery disease
|
41 (56.2)
|
|
Chronic obstructive lung disease
|
2 (2.7)
|
|
Chronic kidney disease
|
5 (6.8)
|
|
History of ischemic stroke
|
3 (4.1)
|
|
Peripheral vascular disease
|
2 (2.7)
|
|
Arrhythmia
|
6 (8.2)
|
|
Rheumatological disease
|
2 (2.7)
|
|
Chest pain with application
|
56 (76.7)
|
|
Mortality, 24 h
|
3 (4.1)
|
|
Mortality, 30 d
|
7 (9.6)
|
|
Mortality, 6 mo
|
8 (11)
|
Abbreviation: RIFLE, Risk of renal dysfunction, Injury to kidney, Failure or Loss of kidney function, and End-stage kidney disease.
a Brain natriuretic peptide variant was present in only 24 (32.9%) patients.
Table 2
Comparison of survivors and 30-day mortality group
|
Survivors
|
Nonsurvivors
|
p-Value
|
|
Age
|
69 (54–72)
|
72 (68–76)
|
0.390
|
|
Gender (male)
|
39 (59.1%)
|
5 (71.4%)
|
0.420
|
|
Vital parameters
|
|
Systolic blood pressure (mm Hg)
|
153 (126–181)
|
126 (60–153)
|
0.045
|
|
Diastolic blood pressure (mm Hg)
|
80 (71–99)
|
64 (35–80)
|
0.020
|
|
Pulse (beats/min)
|
86 (77–100)
|
79 (64–139)
|
0.587
|
|
SpO2 (%)
|
96 (93–98)
|
86 (85–95)
|
0.105
|
|
Laboratory parameters
|
|
White blood cell count (103/uL)
|
9.7 (7.2–12.4)
|
11.8 (11.8–13.3)
|
0.058
|
|
Neutrophil count (103/uL)
|
6.5 (4.5–8.6)
|
8.2 (7.3–9.2)
|
0.049
|
|
Lymphocyte count (103/uL)
|
2 (1.4–3.3)
|
3.2 (1.7–4)
|
0.379
|
|
Platelet count (103/uL)
|
274 (257–287)
|
277 (522–291)
|
0.161
|
|
C-reactive protein (mg/dL)
|
7.1 (1.5–12.9)
|
54.2 (12–113.3)
|
0.002
|
|
Blood urea nitrogen (mg/dL)
|
42 (34.9–51.7)
|
50.2 (39.7–51.2)
|
0.431
|
|
Creatinine (mg/dL)
|
1.05 (0.91–1.22)
|
1.32 (1.15–3.28)
|
0.005
|
|
Glomerular filtration rate (mL/min)
|
66.2 (46.1–76.5)
|
51.9 (13.5–57.1)
|
0.028
|
|
Aspartate aminotransferase (IU/L)
|
25.6 (19.3–35.5)
|
18 (17–147)
|
0.465
|
|
Alanine aminotransferase (IU/L)
|
18 (14–25)
|
23 (5–33)
|
0.859
|
|
Comorbidities
|
|
Diabetes mellitus
|
24 (36.4%)
|
3 (42.9%)
|
0.517
|
|
Hypertension
|
56 (84.8%)
|
6 (85.7%)
|
0.717
|
|
Coronary artery disease
|
37 (56.1%)
|
4 (57.1%)
|
0.639
|
|
Chronic obstructive lung disease
|
2 (3%)
|
0 (0%)
|
0.999
|
|
Chronic kidney disease
|
3 (4.5%)
|
2 (28.6%)
|
0.069
|
|
History of ischemic stroke
|
3 (4.5%)
|
0 (0%)
|
0.736
|
|
Peripheral vascular disease
|
1 (1.5%)
|
1 (14.3%)
|
0.184
|
|
Arrhythmia
|
4 (6.1%)
|
2 (28.6%)
|
0.099
|
|
Rheumatological disease
|
2 (3%)
|
0 (0%)
|
0.816
|
|
Chest pain with application
|
53 (80.3%)
|
3 (42.9%)
|
0.047
|
Primary Outcome Measures
The delta troponin T median for nonsurvivors was 56 ng/L (24.2–286.4), while the median for survivors was 29.4 ng/L (10.7–79.6). Although not statistically significant (Mann–Whitney U-test, p = 0.072), the difference was analyzed ([Table 3]).
Table 3
Primary and secondary outcome measures
|
Survivors
|
Nonsurvivors
|
p-Value
|
|
Delta troponin (ng/L)
|
29.4 (10.7–79.6)
|
56 (24.2–286.4)
|
0.072
|
|
Initial troponin (ng/L)
|
32.4 (16.8–128.6)
|
115.7 (17.2–590.6)
|
0.003
|
|
First hour troponin (ng/L)
|
90.1 (43–226.2)
|
392.8 (67.3–574.5)
|
0.022
|
Secondary Outcome Measures
The initial troponin median for nonsurvivors was 115.7 ng/L (17.2–590.6), significantly higher than the median for survivors, 32.4 ng/L (16.8–128.6; p = 0.003). Additionally, the first-hour troponin median for nonsurvivors was 392.8 ng/L (67.3–574.5), while the median for survivors was 90.1 ng/L (43–226.2), demonstrating a statistically significant difference (p = 0.022; [Table 3]).
ROC analysis for delta troponin T, initial troponin, and first-hour troponin values in predicting 30-day mortality yielded an area under the curve values of 0.626, 0.708, and 0.712, respectively. Sensitivity, specificity, and accuracy of initial and first-hour troponin values in predicting 30-day mortality were calculated. For initial troponin, sensitivity was 85.7%, specificity was 68.2%, and accuracy was 69.9%. Similarly, initial troponin exhibited a sensitivity of 85.7% ([Table 4]).
Table 4
Diagnostic performance of initial and first-hour troponin values in terms of 30-day mortality
|
Initial troponin
|
First-hour troponin
|
|
Area under the curve
|
0.708 (0.519–0.896)
|
0.712 (0.504–0.920)
|
|
Sensitivity
|
85.7% (42.1–99.6)
|
85.7% (42.1–99.6)
|
|
Specificity
|
68.2% (55.6–79.1)
|
75.8% (63.6–85.5)
|
|
Positive likelihood rate
|
2.69 (1.69–4.28)
|
3.54 (2.1–5.97)
|
|
Negative likelihood rate
|
0.21 (0.003–1.3)
|
0.19 (0.003–1.17)
|
|
Positive predictive value
|
22.2% (15.2–31.3)
|
27.3% (18.2–38.8)
|
|
Negative predictive value
|
97.8% (87.9–99.6)
|
98% (89–99.7)
|
|
Accuracy
|
69.9% (58–80.1)
|
76.7% (65.4–85.8)
|
Discussion
The current study evaluated the effect of delta troponin T value on short-term mortality in patients with CKD and NSTEMI. The delta troponin T median for patients who died within 30 days was 56, while the median for surviving patients was 29.4. Although not statistically significant (p = 0.072), the difference was analyzed. To our knowledge, the current study is the first to evaluate the relationship between delta troponin T and short-term mortality in patients with CKD and NSTEMI.
The diagnosis of ACS typically relies on a combination of clinical history, electrocardiography, and cardiac marker analysis.[7] However, it is important to note that the absence of abnormalities in these assessments does not definitively rule out the possibility of ACS.[8] The elucidation of mechanisms governing the release and clearance of cardiac troponins under normal conditions has been the subject of extensive research. Contrary to earlier emphasis solely on release mechanisms, recent insights underscore the significance of clearance mechanisms influencing serum troponin concentrations.[9] Clearance of troponins primarily involves reticuloendothelial system cells, troponin-specific proteases for degradation, and glomerular secretion through filtration.[10]
[11]
[12] Although the role of kidneys in troponin elimination has been debated due to the absence of troponins in urine for most patients, studies suggest a connection between high troponin concentrations and CKD.[9]
The Chronic Renal Insufficiency Cohort (CRIC) study demonstrated elevated troponin T in 81% of CKD patients without apparent cardiovascular symptoms, with lower GFR correlating with higher troponin T concentrations. Patients with GFR < 30 mL/min exhibited a threefold increase in troponin levels compared to those with GFR > 60 mL/min. While renal dysfunction contributes to increased troponin levels in CKD patients, normal troponin levels in some with low GFR suggest alternative factors at play.[13] Studies by Wilhelm et al and Røsjø et al confirmed a dependence between serum troponin levels and GFR rates.[14]
[15] In our study focusing on mortality in NSTEMI patients with renal failure, those who succumbed within 30 days exhibited significantly lower GFR and higher creatinine levels compared to survivors.
In cases of renal failure, skeletal muscle fibers undergo changes leading to uremic skeletal muscle disease, potentially involving reparative regeneration and cardiac troponin isoform expression. Studies even suggest the normal expression of cardiac-specific troponins during embryonic development.[16] Considering the relationship between cardiac troponin levels and nitrogen metabolism products, such as creatinine, it is plausible that these compounds directly affect cardiomyocytes. Additionally, long-term effects of CKD, such as increased myocardial workload and hypertrophy, may contribute to elevated troponin levels.[17]
[18]
CKD increases the risk of various cardiovascular complications, including atrial and ventricular arrhythmias, atrioventricular block, pulmonary congestion, acute mitral regurgitation, and cardiogenic shock.[19] Meta-analyses emphasize the prognostic value of cardiac troponins in chronic renal failure, aiding in identifying patients at high risk of overall and cardiovascular mortality.[20]
[21] Therefore, chronic renal failure is a common cause of elevated cardiac troponin levels, with mechanisms including decreased serum excretion, direct harmful effects of metabolic products, and increased myocardial hypertrophy. A meta-analysis by Khan et al involving 3,931 ESRD patients revealed a positive relationship between serum troponin T levels and mortality.[20] Another study in heart failure patients identified troponin T as a univariate predictor of all-cause death, cardiovascular death, and cardiovascular hospitalization, outperforming other parameters.[21] In our study, the evaluation of delta troponin T values showed low predictive performance for 30-day mortality.
Conversely, initial and first-hour troponin values demonstrated significant predictive potential for mortality risk within 30 days, exhibiting high sensitivity and low negative likelihood ratios. These results align with studies highlighting elevated serum troponin T values in cardiovascular disease patients with CKD. However, the study's limited sample size may impact the statistical power of the findings.
Conclusion
The present study's results demonstrated that delta troponin T is not associated with short-term mortality in patients with chronic renal dysfunction and NSTEMI. Larger studies are essential to validate these associations and strengthen the predictive potential of serum troponin values in this patient population.
