Analytical and diagnostic performance of troponin assays in patients suspicious for acute coronary syndromes

doi:10.1016/S0009-9120(00)00144-2

Clinical Biochemistry

Volume 33, Issue 5, July 2000, Pages 359-368

https://doi.org/10.1016/S0009-9120(00)00144-2 Get rights and content

Abstract

Background: The controversy whether there is a clinically significant difference between troponin T (cTnT) and troponin I (cTnI) in regard to predictive value and cardiac specificity is still ongoing.

Methods: We evaluated enzyme-linked immunosorbent assay systems for cTnI and cTnT in patients with acute coronary syndromes and multiple control groups to define threshold values for risk stratification and compare their predictive value.

Results: In 312 patients with noncardiac chest pain, cTnI levels were below the detection limit of 0.2 μg/L and cTnT levels were 0.011 [0.010–0.013] μg/L. In patients with end-stage renal failure (n = 26) and acute (n = 38) or chronic (n = 16) skeletal muscle damage, median concentrations were 0.20 [0.20–0.35], below the detection limit, and 0.20 [0.20–0.25] for cTnI, and 0.04 [0.01–0.10], 0.011 [0.005–0.025], and 0.032 [0.009–0.054] μg/L for cTnT. In patients with acute coronary syndromes (n = 1130), maximized prognostic value for 30-day outcome (death, infarction) was observed at a threshold level of 1.0 μg/L for cTnI (29.0% positive) and at 0.06 μg/L for cTnT (35.0% positive). Significant differences in the area-under-the-curve values were observed between cTnI and cTnT (0.685 vs. 0.802; p = 0.005). For both markers, the area-under-the-curve values did not increase with the second (within 24 h after enrollment) or third (48 h) blood draw. CTnI showed a less strong association with 30-day outcome than cTnT. When cTnI was put in a logistic multiple-regression model first, cTnT did add significant information.

Conclusion: By using the defined threshold values and the employed test systems, single testing for cTnI and cTnT within 12 h after symptom onset was appropriate for risk stratification. Despite the lower cardiac specificity for cTnT, it appears to have a stronger association with the patients’ outcome, whereas, as previously shown, the ability to identify patients who benefit from treatment with a GP IIb/IIIa receptor antagonist is similar.

Introduction

For patients with unstable coronary artery disease (i.e., unstable angina or non-Q-wave myocardial infarction), the main pathophysiological mechanism in the form of plaque rupture or erosion is followed by exposure of thrombogenic contents, such as collagen to the circulation 1, 2. The resulting platelet activation and platelet adhesion promotes thrombus friable formation. Pathohistological studies have disclosed focal cell necroses distal in the myocardium supplied by the culprit artery, which have been attributed to repetitive embolization from such liable thrombi 3, 4. In about one third of such patients, the resulting minor myocardial damage leads to increased values of troponin I (cTnI) and troponin T (cTnT; 5, 6, 7, 8, 9, 10). Although creatine kinase enzyme activity remains within the normal range, for such troponin-positive patients, a 5–10-fold higher incidence for mortality and nonfatal infarction during 30-day follow-up period has been observed 5, 6, 7, 8, 9, 10, 11.

The controversy whether there is a clinically significant difference between cTnI and cTnT in regard to predictive value and cardiac specificity is still ongoing. The main purpose of the present study was the definition of threshold values for each of the employed test systems—the AxSYM for cTnI and the Elecsys 2010 for cTnT—to maximize and compare their prognostic value in patients with acute coronary syndromes.

Section snippets

Patients with noncardiac chest pain

Patients had chest pain for less than 12 h before arrival in the emergency but did not provide evidence for coronary artery disease. These patients had to have no ST-segment changes during serial electrocardiographic recordings in the emergency room and negative treadmill testing, stress echocardiography, or angiogram (53%). Further, during 30-day follow-up, no major cardiac events (death, nonfatal infarction, or urgent revascularization) were recorded. A total of 312 patients were

Total imprecision

Using manufacturer-provided controls, total imprecision (CV) over a 6-month period was evaluated by performing 291 runs. For the AxSYM, CVs were 7.4% at 3.1 μg/L, 6.3% at 10.2 μg/L, and 5.1% at 31.2 μg/L. For the Elecsys 2010, CVs were 4.8% at 0.35 μg/L, 4.3% at 1.25 μg/L, and 4.1% at 31.2 μg/L. Total imprecision for samples close to the calculated threshold values (cTnI 1.0 μg/L; cTnT 0.08 μg/L) was investigated by using internal plasma controls from patients with “minor myocardial damage”

Analytical performance

In this study, the AxSYM cTnI assay provided acceptable analytical characteristics based on imprecision, detection limit, and limit of quantification. Stepwise dilution tests revealed a minimal detectable cTnI concentration of 0.2 μg/L. By using the Stratus CS, the same sample produced a test signal equal to 0.02 μg/L. This figure is close to the determined detection limit of the Stratus CS with 0.01 μg/L, a cTnI system that recently has been shown to provide outstanding analytical and

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Cited by (30)

Serum levels of cardiac troponin I in patients with status epilepticus and healthy cardiovascular system
2013, Archives of Medical Research
Citation Excerpt :
With respect to the biochemical and analytical differences of cTnT and cTnI, the comparability, measurement and clinical performance of these two subtypes are not the same (23). cTnT has been previously shown to be less specific for cardiac injuries (24) and recently demonstrated that the newer cTnI high-sensitivity assay could detect cardiac injury at even earlier intervals prior to histological findings (25). So far, most of the previous studies on assessment of troponin level in epileptic patients were used to assess cTnI, including the current study.
Status epilepticus (SE) is accompanied by acute and intense activation of the sympathetic nervous system, which might result in myocyte damage. However, there is insufficient evidence to assess cardiac biomarkers in SE patients. As a highly specific and sensitive biomarker of acute myocardial infarction, serum concentration of cardiac troponin I (cTnI) has been assessed in this study in a sample of SE patients without evidence of previous cardiovascular diseases.
In this analytical cross-sectional study, a total number of 30 patients with SE and no history of baseline cardiovascular disorders, aged between 12 and 60 years have been evaluated. Baseline, demographic characteristics and laboratory measurements including cTnI, creatine kinase (CPK) and CPK-MB were recorded for all of patients. cTnI was quantified using ELISA method with the precision of 0.01 ng/mL.
All cases had a cardiac troponin level <0.01 ng/mL except for one 60- year-old female with a history of seizure 3 years prior. The last seizure was 60 days prior and the patient had a reported cTnI level as 0.04 ng/mL, within normal limits. The mean serum levels of CPK and CK-MB were 202.20 (SD = 14.46) μg/l and 14.54 (SD = 1.49) ng/mL, respectively.
This investigation is one of the few to evaluate serum concentration of cTnI in generalized convulsive SE patients where no detectable elevation was observed in serum concentration of cTnI following SE episode. However, it is very important to take into account that all recruited SE patients included in this study had a healthy cardiovascular system.
So the reference values for cTroponin I must be modified in end stage renal disease?
2004, Immuno-Analyse et Biologie Specialisee
La troponine Ic (Tnlc) est actuellement reconnue comme un marqueur de souffrance myocardique. Cependant, sa signification chez l'insuffisant rénal chronique reste débattue. La Tnlc a été déterminée sur 191 patients hémodialysés, sans signe de cardiopathie évolutive et comparée avec des volontaires sains. Les valeurs de troponine observées ont été analysées en fonction des données cliniques selon deux seuils : soit un seuil épidémiologique au 99^e percentile, soit un seuil analytique donné par la sensibilité fonctionnelle définie par un CV de 20 %. Trente-trois pour cent des hémodialysés ont des valeurs supérieures à la sensibilité fonctionnelle et 1 % au 99^e percentile. Des valeurs de Tnlc supérieures à la sensibilité fonctionnelle sont significativement associées à des antécédents de maladie coronarienne (χ2 = 3,98, p < 0,05). En conclusion, les valeurs des Tnlc sont élevées chez les insuffisants rénaux chroniques et la sensibilité fonctionnelle peut être considérée comme un seuil d'alerte dans cette population.
CTnl values were determined with Access Accu Tnl (Beckman) in 191 hemodialysis patients without clinical signs of acute coronary artery disease and in 39 healthy volunteers in order to evaluate functional sensitivity (FS) as an optional threshold value predictive to prevalence of coronary artery disease. Prevalences of cTnl higher than FS, defined as a concentration with a total imprecision <20%, and the 99th value, given by the manufacturer, were respectively 33 and 13% in hemodialysis patients and 5 and 25% in healthy volunteers. Moreover, cTnl levels higher than FS are significantly associated with a history of coronary artery disease (χ2 =3.98, P <0.05). In addition, cTnl levels were not modified by hemodialysis sessions. In conclusion, cTnl levels are elevated in hemodialysis patients and FS appears as a threshold value associated with the prevalence of coronary heart disease in this population.
A rapid troponin I assay is not optimal for determination of troponin status and prediction of subsequent cardiac events at suspicion of unstable coronary syndromes
2004, International Journal of Cardiology
Background: Troponin is a specific marker of myocardial damage. For early prediction of coronary events in patients with suspicion of acute coronary syndromes the assay also needs to be highly sensitive. Methods and results: A rapid troponin I assay was performed prior to inclusion in 4447 acute coronary syndrome patients in the GUSTO-IV trial. A quantitative troponin T analysis was later performed on blood samples obtained at randomization by a central laboratory. There was an agreement between the rapid troponin I assay and troponin T (≤/>0.1 μg/l) in 3596 (80.9%) patients. A positive rapid troponin I was identifying any elevation of troponin T (>0.01 μg/l) in 1990 patients (90.4%) whereas a negative rapid troponin I was corresponding to negative troponin T (≤0.01 μg/l) in only 1217 patients (54.2%). Patients with a positive versus negative rapid troponin I had an increased risk of death or myocardial infarction at 30 days (9.3 vs. 5.9%; odds ratio, O.R. 1.64; 95% confidence interval, 1.31–2.06). Troponin T elevation (>0.1 μg/l) provided a better (10.5 v. 4.9%, O.R. 2.26; C.I. 1.79–2.85) risk stratification. Regardless of a positive or a negative rapid troponin I, the troponin T result (>0.1 vs. ≤0.1 μg/l) stratified the patients into high and low risk of events at 30 days, (10.3 vs. 5.7%, P=0.002) and (11.5 vs. 4.8%, P<0.001), respectively. Conclusion: In a population with non-ST elevation acute coronary syndrome a positive rapid troponin I assay is a specific indicator of troponin elevation and a predictor of early outcome. However, a negative rapid troponin I is not a reliable indicator of the absence of myocardial damage and does not indicate a low risk of subsequent cardiac events.

A rapid troponin I assay was performed prior to inclusion in 4447 acute coronary syndrome patients in the GUSTO-IV trial and related to a centrally analyzed quantitative troponin T test. A positive rapid troponin I was well corresponding to any elevation of troponin T (>0.01 μg/l) and predicted an unfavorable outcome at 30 days. However, a negative rapid troponin I was corresponding to troponin T ≤0.01 μg/l in only half of the patients. Troponin T >0.1 μg/l vs. ≤0.1 μg/l provided a better risk stratification than the rapid troponin I result. For patients with troponin T elevation (>0.1 μg/l) the 30 day event rate was high regardless of the rapid troponin I result.
Interaction between heparin and cardiac troponin T and troponin I from patients after coronary bypass surgery
2002, Clinical Biochemistry
Objectives: Heparin is thought to play a crucial role in the clinical monitoring of patients with acute coronary syndrome as well as after coronary bypass surgery in that it interferes with different commercial immunoassay test systems for cardiac troponin T (cTnT) and troponin I (cTnI). The mechanism, however, by which heparin apparently affects the cTnT and cTnI levels in plasma is not yet resolved.
Design and methods: We analyzed the effect of heparin by simultaneously collecting serum and heparin plasma samples from 32 patients after coronary bypass surgery. The cTnT and cTnI levels were determined using the Roche/Elecsys, the Dade-Behring/Opus and the Bayer/ACS:Centaur immunoassay systems in the absence or in the presence of either heparinase or protamine. Association between the cardiac troponins and the anticoagulant has been demonstrated by affinity chromatography using heparin as the ligand.
Results: The data obtained indicate that heparin produces an apparent decrease in cTnT as well as of cTnI levels, analyzed either by the Elecsys, the Opus or the ACS:Centaur immunoassay systems. Individual patients show a wide variation in the discrepancies between serum and heparin plasma troponin especially in the cTnT immunoassay. Pretreatment of the heparin plasma samples either with heparinase or protamine cannot completely reverse the heparin-induced decrease in cTnT and cTnI levels and therefore addition of these reagents to the commercial test systems could not significantly improve the performance of the assay. When serum is supplemented with increasing concentrations of heparin, and cardiac troponin levels were reanalysed, significantly lower recoveries for the cTnT than for the cTnI immunoassays were detectable. Affinity chromatography with heparin Sepharose demonstrates that cTnT and cTnI interact differentially with the negatively charged ligand. Whereas cTnI shows minor affinity to the immobilized heparin and is eluted at near physiological conditions, cTnT is bound and can be quantitatively recovered only by solutions of high ionic strength.
Conclusions: We conclude, therefore, that the apparent decrease in cTnT values by addition of heparin is a result of direct molecular interaction between the negatively charged glycosaminoglycan and clusters of basic residues within the sequence of the cardiac protein. In contrast, the effect of heparin on the cTnI immunoassay systems, is primarily indirect, most possibly induced by changes within the sample matrix itself.
Biochemical markers of sudden cardiac death
2019, Revista de Chimie
High-sensitive troponin is associated with subclinical imaging biosignature of inflammatory cardiovascular involvement in systemic lupus erythematosus
2018, Annals of the Rheumatic Diseases

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AnalyticalAnalytical and diagnostic performance of troponin assays in patients suspicious for acute coronary syndromes

Abstract

Introduction

Section snippets

Patients with noncardiac chest pain

Total imprecision

Analytical performance

Am Heart J

Clin Biochem

Lancet

Am Heart J

Plaque fissuring—the cause of acute myocardial infarction, sudden ischemia mortality, and crescendo angina

Br Heart J

Coronary plaque erosion without rupture into a lipid core

Circulation

Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac mortality

Circulation

Unstable angina with fatal outcomedynamic coronary thrombosis leading to infarction and/or sudden mortality: autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion

Circulation

Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes

N Engl J Med

Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I

N Engl J Med

Evaluation of a rapid whole blood ELISA for quantification of Troponin I in patients with acute chest pain

Clin Chem

Cardiac troponins I and T in patients with suspected acute coronary syndromea comparative study in a routine setting

Clin Chem

Applicability of cardiac troponin T and I for early risk stratification in unstable coronary disease

Circulation

Analytical
Analytical and diagnostic performance of troponin assays in patients suspicious for acute coronary syndromes