| CLINICAL IMPORTANCE |
CHARACTERIZATION |
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Association of mild transient elevation of troponin I levels with increased mortality and major cardiovascular events in the general patient population.
Gudmundsson GS, Kahn SE, Moran JF.
Division of Cardiology, Loyola University Medical Center, Maywood, Ill, USA.
|
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| Arch Pathol Lab Med. 2005 Apr;129(4):474-80. Abstract quote |
|
CONTEXT: The prognostic value of mild elevation of cardiac-specific troponin I (cTnI) levels is poorly defined, which can make interpretation of such an elevation difficult.
OBJECTIVE: To study the prognostic value of transient mild elevation of cTnI levels in the hospitalized patient population.
DESIGN: We performed a case-control study that compared the outcome of patients hospitalized for any cause with at least 2 subsequent transient cTnI measurements of 0.1 ng/mL or higher and less than 1.5 ng/mL with matched controls with cTnI levels less than 0.1 ng/mL. A cohort of 118 patients (mean +/- SD age, 67.4 +/- 14.0 years; 35.6% men) was followed up for an average +/- SD of 11.9 +/- 7.9 months. Seventy-one cases were matched with 37 controls in terms of demographics, coronary artery disease risk factors, and reason for admission. End points were all-cause mortality and major cardiovascular end points, including cardiovascular mortality, myocardial infarction, and revascularization.
RESULTS: The total event rate was significantly increased in the case group compared with the control group at 12, 6, and 3 months (62.0% vs 24.3%, 59.2% vs 16.2%, and 47.9% vs 5.4%, respectively; P < .001). At 12, 6, and 3 months, the cases had a significant increase in all-cause mortality (43.7% vs 16.2%, 40.8% vs 8.1%, and 33.8% vs 0.0%, respectively; P = .005) and major cardiovascular end points (26.8% vs 8.1%, 26.8% vs 8.1%, and 21.1% vs 5.4%, respectively; P = .02) compared with controls.
CONCLUSION: Transient mild elevation of cTnI levels in hospitalized patients is associated with an increase in all-cause mortality and major cardiovascular complications. Such elevations of cTnI levels can be considered a marker for both all-cause and cardiovascular morbidity and mortality.
|
Diagnostic and prognostic value of cardiac troponin I assays in patients admitted with symptoms suggestive of acute coronary syndrome.
Apple FS, Quist HE, Murakami MM.
Department of Laboratory Medicine and Pathology, Hennepin County Medical Center, University of Minnesota School of Medicine, Minneapolis 55415, USA. |
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| Arch Pathol Lab Med. 2004 Apr;128(4):430-4. Abstract quote |
|
CONTEXT: Increasing numbers of patients are presenting to emergency departments with symptoms suggestive of an acute myocardial infarction.
OBJECTIVE: To demonstrate the comparative performance of the Ortho Vitros Troponin I and Beckman Access AccuTnI assays used to detect myocardial infarction and to develop risk stratification schemes for all-cause death in patients who presented with myocardial ischemia symptoms that were suggestive of acute coronary syndrome (ACS).
DESIGN: The prospective enrollment of patients with ACS and the measurement of serial plasma samples by 2 commercial cardiac troponin I (cTnI) assays.
SETTING: A metropolitan medical center that admitted patients with ACS during a 2-month period.
PATIENTS: The study population consisted of 200 consecutively admitted patients who presented with symptoms that were suggestive of ACS.
RESULTS: Correlation scatterplots showed no significant bias between cTnI assays based on 659 specimens across the dynamic range of each assay. Only minor differences in slopes and intercepts were observed between assays when correlations were based across selected concentration ranges. The receiver operating characteristic curve areas for the detection of myocardial infarction were not significantly different (Ortho,.991; Beckman,.995). At the 99th percentile (Beckman, 0.04 microg/L; Ortho, 0.08 microg/L), each assay demonstrated 100% sensitivity with 78% and 80% specificity, respectively. Kaplan-Meier survival curves and the log-rank test were used to compare time-to-event data. Patients with increased baseline cTnI values had higher odds ratios of death than did those with normal concentrations. For Ortho, the 99th percentile cutoff was 5.9, and the 10% coefficient of variation cutoff was 10.3; for Beckman, the 99th percentile cutoff was 31.4, and the 10% coefficient of variation cutoff was 15.3.
CONCLUSIONS: Comparable diagnostic and risk stratification abilities were demonstrated in patients with ACS by the Ortho Vitros and Beckman Access cTnI assays, with no significant analytic bias between cTnI assays.
|
Biochemical markers of myocardial injury test turnaround time: a College of American Pathologists Q-Probes study of 7020 troponin and 4368 creatine kinase-MB determinations in 159 institutions.
Novis DA, Jones BA, Dale JC, Walsh MK; College of American Pathologists.
Department of Pathology, Wentworth Douglass Hospital, Dover, NH 03820, USA. |
| Arch Pathol Lab Med. 2004 Feb;128(2):158-64. Abstract quote |
|
CONTEXT: Rapid diagnosis of acute myocardial infarction in patients presenting to emergency departments (EDs) with chest pain may determine the types, and predict the outcomes of, the therapy those patients receive. The amount of time consumed in establishing diagnoses of acute myocardial infarction may depend in part on that consumed in the generation of the blood test results measuring myocardial injury.
OBJECTIVE: To determine the normative rates of turnaround time (TAT) for biochemical markers of myocardial injury and to examine hospital and laboratory practices associated with faster TATs.
DESIGN: Laboratory personnel in institutions enrolled in the College of American Pathologists Q-Probes Program measured the order-to-report TATs for serum creatine kinase-MB and/or serum troponin (I or T) for patients presenting to their hospital EDs with symptoms of acute myocardial infarction. Laboratory personnel also completed detailed questionnaires characterizing their laboratories' and hospitals' practices related to testing for biochemical markers of myocardial injury. ED physicians completed questionnaires indicating their satisfaction with testing for biochemical markers of myocardial injury in their hospitals.
SETTING: A total of 159 hospitals, predominantly located in the United States, participating in the College of American Pathologists Q-Probes Program.
RESULTS: Most (82%) laboratory participants indicated that they believed a reasonable order-to-report TATs for biochemical markers of myocardial injury to be 60 minutes or less. Most (75%) of the 1352 ED physicians who completed satisfaction questionnaires believed that the results of tests measuring myocardial injury should be reported back to them in 45 minutes or less, measured from the time that they ordered those tests. Participants submitted TAT data for 7020 troponin and 4368 creatine kinase-MB determinations. On average, they reported 90% of myocardial injury marker results in slightly more than 90 minutes measured from the time that those tests were ordered. Among the fastest performing 25% of participants (75th percentile and above), median order-to-report troponin and creatine kinase-MB TATs were equal to 50 and 48.3 minutes or less, respectively. Shorter troponin TATs were associated with performing cardiac marker studies in EDs or other peripheral laboratories compared to (1) performing tests in central hospital laboratories, and (2) having cardiac marker specimens obtained by laboratory rather than by nonlaboratory personnel.
CONCLUSION: The TAT expectations of the ED physicians using the results of laboratory tests measuring myocardial injury exceed those of the laboratory personnel providing the results of those tests. The actual TATs of myocardial injury testing meet the expectations of neither the providers of those tests nor the users of those test results. Improving TAT performance will require that the providers and users of laboratory services work together to develop standards that meet the needs of the medical staff and that are reasonably achievable by laboratory personnel. |
|
Cardiac troponin T and C-reactive protein for predicting prognosis,
coronary atherosclerosis, and cardiomyopathy in patients undergoing
long-term hemodialysis.
deFilippi C, Wasserman S, Rosanio S, Tiblier E, Sperger H,
Tocchi M, Christenson R, Uretsky B, Smiley M, Gold J, Muniz H, Badalamenti
J, Herzog C, Henrich W.
Department of Medicine, University of Maryland School of Medicine,
Baltimore 21201, USA.
|
JAMA. 2003 Jul 16;290(3):353-9. Abstract quote
CONTEXT: Cardiac troponin T (cTnT) and C-reactive protein (CRP) are
prognostic markers in acute coronary syndromes. However, for patients
with end-stage renal disease (ESRD) the ability of combinations of these
markers to predict outcomes, and their association with cardiac pathology,
are unclear. O
OBJECTIVE: To investigate the association between levels of cTnT and
CRP and long-term risk of cardiac pathology and death in patients with
ESRD.
DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study initiated
February through June 1998 and enrolling 224 patients with ESRD from
5 hemodialysis centers in the Houston-Galveston region of Texas. Levels
of cTnT and CRP were analyzed at study entry in patients without ischemic
symptoms.
MAIN OUTCOME MEASURES: All-cause mortality during a mean follow-up of
827 (range, 29-1327) days. Secondary outcomes in predefined substudies
were coronary artery disease (CAD), decreased (< or =40%) left ventricular
ejection fraction (LVEF), and presence of left ventricular hypertrophy
(LVH).
RESULTS: One hundred seventeen (52%) patients died during follow-up.
For levels of cTnT and CRP, progressively higher levels predicted increased
risk of death compared with the lowest quartile (for cTnT quartile 2:
unadjusted hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.2-4.1;
quartile 3: HR, 2.7; 95% CI, 1.5-4.9; quartile 4: HR, 3.0; 95% CI, 1.6-5.3.
For CRP quartile 2: HR, 0.9; 95% CI, 0.5-1.6; quartile 3: HR, 1.8; 95%
CI, 1.1-3.1; quartile 4: HR, 1.8; 95% CI, 1.1-3.2). Both cTnT and CRP
remained independent predictors of death after adjusting for a number
of potential confounders. The combination of cTnT and CRP results provided
prognostic information when patients were divided into groups at or
above and below the biomarker medians (high cTnT/high CRP levels vs
low cTnT/low CRP levels for risk of death: HR, 2.5; 95% CI, 1.5-4.0).
Elevated levels of cTnT, but not CRP, were strongly associated with
diffuse CAD (n = 67; 0%, 25%, 50%, and 62% prevalence of multivessel
CAD across progressive cTnT quartiles, P<.001). An LVEF of 40% or
less was identified in 4 (9%), 3 (8%), 10 (27%), and 7 (19%) of patients
across cTnT quartiles (P =.07). No trend for cTnT levels was found among
patients with LVH (P =.45); similarly, no trend for CRP was found among
patients with LVH (P =.65) or an LVEF of 40% or less (P =.75).
CONCLUSIONS: Among stable patients with ESRD, increasing levels of
cTnT and CRP are associated with increased risk of death. Furthermore,
higher levels of cTnT may identify patients with severe angiographic
coronary disease. |
Prognostic Value of the Ortho Vitros Cardiac Troponin I Assay
in Patients With Symptoms of Myocardial Ischemia
Risk Stratification Using European Society of Cardiology/American College
of Cardiology Recommended Cutoff Values
Fred S. Apple, PhD,1 MaryAnn M. Murakami,1 Heidi H. Quist,1 Lesly A.
Pearce, MS,2 Stacey Wieczorek, PhD,3 and Alan H.B. Wu, PhD
|
Am J Clin Pathol 2003;120:114-120 Abstract quote
We evaluated the risk assessment value of a commercial cardiac troponin
(cTn; Ortho Vitros ECi, Ortho-Clinical Diagnostics, Raritan, NJ) I assay
in patients with symptoms of myocardial ischemia suggestive of acute coronary
syndrome and compared findings with those for a commercial cTnT assay
in the same population.
The cTn levels were measured by both assays in plasma samples from 273
patients during 24 hours after admission. Baseline and maximum concentrations
were used for risk stratification; cutoffs were the 99th percentile and
10% coefficient of variation. End points were all-cause death and cardiac
events within 60 days. Relative risks (RRs) were estimated using Cox proportional
hazards regression models and Kaplan-Meier curves. RRs of cardiac events
and death were significantly higher with increased baseline and maximum
concentrations using either cTnI cutoff.
The respective mortality rates for baseline cTnI of more than 0.08 µg/L
vs 0.08 µg/L or less were 17.4% vs 2.9% (P = .001); cardiac event
rates were 11.5% vs 3.6% (P = .03). Exclusion of patients with ST-segment
elevation had no significant effect on rates for either assay.
Mortality was higher in the intermediate (0.09-0.2 µg/L) than in
the low (£0.08 µg/L) group for cTnI, with directionally similar
results for cTnT. |
| Cardiac troponin T and cardiac troponin I: relative
values in short-term risk stratification of patients with acute coronary
syndromes. GUSTO-IIa Investigators.
Christenson RH, Duh SH, Newby LK, Ohman EM, Califf RM, Granger
CB, Peck S, Pieper KS, Armstrong PW, Katus HA, Topol EJ.
Department of Pathology, University of Maryland School of Medicine,
Baltimore, USA. |
Clin Chem 1998 Mar;44(3):494-501 Abstract quote
We compared cardiac troponins T (cTnT) and I (cTnI) collected within
3.5 h of ischemic symptoms for predicting clinical outcomes in 770 patients.
cTnT (cutoff > 0.1 microgram/L) and cTnI (cutoff > 1.5 micrograms/L)
were concordant (both positive or negative) in 90.4% of patients. Among
discordant results, 66 were cTnT positive and cTnI negative vs 8 who
showed the reverse (P < 0.001). Five cTnT-positive and cTnI-negative
patients died within 30 days; none who were cTnT negative and cTnI positive
died. cTnT showed a slightly greater association (chi 2 = 18.0, P <
0.001) with 30-day mortality than cTnI (chi 2 = 12.5, P = 0.002). The
area of the ROC curve for predicting 30-day mortality was significantly
larger (Z = 2.08; P = 0.0375) for cTnT, at 0.68 [95% confidence interval
(CI) 0.60-0.75], compared with cTnI, at 0.64 (95% CI 0.56-0.72).
When cTnI and the electrocardiogram (ECG) were put in a logistic multiple
regression model, cTnT added significant information (chi 2 = 8.03,
P = 0.045); however, cTnI did not add to a model containing cTnT and
the ECG (chi 2 = 0.84, P = 0.657). cTnT provided more information than
cTnI for predicting 30-day mortality early after presentation with acute
coronary syndromes. |
| Gold Standard for the diagnosis of acute myocardial infarction |
Eur Heart J 2000;21:1502
J Am Coll Cardiol 2000;36:959
Consensus document authored by a joint committee of the European Society
of Cardiology (ESC) and the American College of Cardiology (ACC) |
| Acute Coronary Syndrome consisting of unstable angine
(UA) or
non-Q-wave MI
Also known as UA/non-ST-elevation MI |
20 to 30 percent of patients with unstable angina have
elevated troponin
Increased risk of MI or mortality in the 30 to 45 days after discharge
Several trials (CAPTURE, TIMI, PRISM, PURSUIT, FRISC) using glycoprotein
IIb/IIIa inhibitors or low-molecular-weight (LMW) heparins, either as
primary therapy or in conjunction with angioplasty, have validified
the utility of using troponin to identify at risk patients |
| C-Reactive protein and cardiac troponin T in risk
stratification: differences in optimal timing of tests early after the
onset of chest pain.
de Winter RJ, Fischer J, Bholasingh R, van Straalen JP, de Jong
T, Tijssen JG, Sanders GT.
Departments of Cardiology, Clinical Chemistry, and Clinical Epidemiology
and Biostatistics, Academic Medical Center, University of Amsterdam,
1100 DD Amsterdam, The Netherlands. |
Clin Chem 2000 Oct;46(10):1597-603 Abstract quote
BACKGROUND: Increased C-reactive protein (CRP) is an important prognostic
indicator for early risk stratification in patients with an acute coronary
syndrome (ACS), independent of, and in combination with, increased cardiac
troponin T (cTnT). However, increases in both cTnT and CRP also occur
secondary to myocardial damage.
METHODS AND RESULTS: In 156 consecutive patients, early release kinetics
of CRP and cTnT were analyzed. The cutoff values were 3.0 mg/L for CRP
and 0.1 microgram/L for cTnT. In the 75 patients with a CRP below the
cutoff on admission, there was little change in CRP until 8 h after
the onset of symptoms. At 12 h after the onset of symptoms, the cumulative
proportions of abnormal CRP and cTnT in non-ST elevation ACS patients
were 27% and 89%, respectively (P <0.01). During the first 24 h after
the onset of symptoms, the median time above the cutoff was 20 h for
CRP and 5 h for cTnT (P <0.0001). CRP was below the cutoff on admission
significantly more often among patients receiving thrombolytic therapy
than in patients without an indication for reperfusion therapy (51%
vs 28%; P = 0.004).
CONCLUSIONS: Increased CRP as an early independent risk indicator should
be measured as soon as possible after the onset of symptoms, whereas
increased cTnT is most reliable at 12 or more hours after the onset
of symptoms. |
| Cardiac troponin T and C-reactive protein as markers
of acute cardiac allograft rejection.
Chance JJ, Segal JB, Wallerson G, Kasper E, Hruban RH, Kickler TS,
Chan DW.
Department of Pathology, Johns Hopkins Hospital, 600 N. Wolfe Street/Meyer
B-125, 21287-7065, Baltimore, MD, USA |
Clin Chim Acta 2001 Oct;312(1-2):31-9 Abstract quote
Due to myocyte damage and an associated inflammatory response, it is
possible that cardiac troponin T and C-reactive protein (CRP) concentrations
may correlate with the histologic grade of rejection in endomyocardial
biopsy samples obtained from patients who have received a heart transplant.
In this study, 704 blood samples were obtained from 145 different heart
transplant recipients just prior to endomyocardial biopsy. Plasma specimens
were assayed for troponin T and CRP concentration and the results compared
with the assigned International Society of Heart and Lung Transplantation
(ISHLT) histologic grade. Rejection was defined as an ISHLT grade of
3A or higher. The negative predictive values were near 80% in all cases,
and a statistically significant increase in median troponin T concentration
was observed across ISHLT grades. After the first month posttransplantation,
the specificity of the troponin T test (cutoff 0.1 ng/ml) was 95% and
increased to 98% when false positives seen in renal disease patients
were excluded. Both tests demonstrated poor sensitivity and positive
predictive value for rejection. Neither CRP nor troponin T had sufficient
sensitivity to serve as an alternative to endomyocardial biopsy in the
diagnosis of acute cardiac allograft rejection. However, the troponin
T test had a high specificity, especially when patients with renal insufficiency
were excluded, and could serve as an adjunct test in this setting. When
combined with a normal serum creatinine, a troponin T>/=0.1 ng/ml prior
to endomyocardial biopsy correlated with graft rejection in almost all
cases, making biopsy unnecessary. |
| Clinical Significance of Low-Positive Troponin I
by AxSYM and ACS:180
James S. Lewis, Jr, MD
James F. Taylor
Andrew Z. Miklos, MD
Katherine S. Virgo, PhD
Michael H. Creer, MD
Detlef G. Ritter, MD |
Am J Clin Pathol 2001;116:396-402 Abstract quote
We compared troponin I (TnI) assays (AxSYM [Abbott]; ACS:180 [Bayer])
in blood samples with concentrations less than 10 ng/mL (<10 µg/L).
Discordant results were evaluated by linearity studies and by testing
for rheumatoid factor. Patients with discordant TnI results were compared
with patients with concordant results and patients with negative TnI
who had a new myocardial infarction or died within 2 months of initial
testing. Positive TnI cutoffs by AxSYM and ACS:180 were 0.7 ng/mL (0.7
µg/L) and 0.13 ng/mL (0.13 µg/L), respectively.
We identified 173 specimens that were repeatedly positive by at least
1 assay; 143 specimens were positive by both assays. Twenty samples
positive for TnI by AxSYM were negative by ACS:180, while 10 samples
positive by ACS:180 were negative by AxSYM. The discordant samples showed
no evidence of interfering substances, including rheumatoid factor.
Clinical follow-up showed that 26% of patients with elevated TnI by
both assays, 33% with TnI positive only by AxSYM, 22% with TnI positive
only by ACS:180, and 8% with negative TnI by AxSYM encountered at least
1 clinical end point.
Variable detection rates by these assays for low-positive TnI represent
a clinically significant problem. |
| Coronary Angiographic Findings in Patients With Clinical
Unstable Angina According to Cardiac Troponin I and T Concentrations
in Serum
A Comparative Analysis
Mauro Panteghini, MD, Claudio Cuccia, MD, Franca Pagani, MD, Claudia
Turla, MD, Graziella Bonetti, MD, and Elena Bonini, MD
From the Laboratorio Analisi Chimico Cliniche 1 (Drs Panteghini,
Pagani, and Bonetti) and the Cattedra and Divisione di Cardiologia (Drs
Cuccia, Turla, and Bonini), Azienda Ospedaliera Spedali Civili and Universitá,
Brescia, Italy
|
Arch Pathol Lab Med 2002;Vol. 126, No. 4, pp. 448–451.
Abstract quote
Context.—Elevated cardiac troponin levels have been reported
to identify unstable angina patients at high risk.
Objective.—To examine the relation of cardiac troponin I (cTnI)
and cardiac troponin T (cTnT) levels to findings of coronary angiography
in these patients.
Methods.—Samples for troponin estimation were taken every 4 hours
throughout the first 48 hours after admission before angiography in
34 patients with primary unstable angina. Patients were considered to
be troponin positive if the marker was increased (>0.04 g/L for cTnT
and >0.03 g/L for cTnI) in at least one sample collected.
Results.—An increased troponin (I or T) concentration was documented
in 14 patients (41.2%). Twelve patients (35.3%) had elevations of both
markers, whereas the remaining 2 patients had elevations of cTnI or
cTnT alone. Patients with or without increased troponin levels did not
differ with respect to degree of coronary disease at angiography. However,
patients with elevated troponin concentrations had more complex lesion
characteristics. In 69% of patients with increased cTnI levels and in
77% of patients with increased cTnT levels, type B2 or C lesions were
documented with presence of ulcerated plaques and thrombus formation.
In contrast, only 23% of the patients with elevated cTnI or cTnT levels
had type A lesions compared with 71% of patients with negative troponin
concentrations.
Conclusions.—Patients with unstable angina who have significant
release of cTnI and/or cTnT have evidence of more complex lesions on
coronary angiography, supporting the hypothesis that both troponins
might be used without distinction as surrogate markers for microembolization
from thrombus formation on a disrupted plaque. |
|
Troponin T levels in patients with acute coronary syndromes, with or
without renal dysfunction.
Aviles RJ, Askari AT, Lindahl B, Wallentin L, Jia G, Ohman EM, Mahaffey
KW, Newby LK, Califf RM, Simoons ML, Topol EJ, Berger P, Lauer MS.
Department of Cardiology, the Cleveland Clinic Foundation, Cleveland,
OH 44951, USA. |
N Engl J Med 2002 Jun 27;346(26):2047-52 Abstract quote
BACKGROUND: Among patients with suspected acute coronary syndromes,
cardiac troponin T levels have prognostic value. However, there is concern
that renal dysfunction may impair the prognostic value, because cardiac
troponin T may be cleared by the kidney.
METHODS: We analyzed the outcomes in 7033 patients enrolled in the
Global Use of Strategies to Open Occluded Coronary Arteries IV trial
who had complete base-line data on troponin T levels and creatinine
clearance rates. The troponin T level was considered abnormal if it
was 0.1 ng per milliliter or higher, and creatinine clearance was assessed
in quartiles. The primary end point was a composite of death or myocardial
infarction within 30 days.
RESULTS: Death or myocardial infarction occurred in 581 patients. Among
patients with a creatinine clearance above the 25th percentile value
of 58.4 ml per minute, an abnormally elevated troponin T level was predictive
of an increased risk of myocardial infarction or death (7 percent vs.
5 percent; adjusted odds ratio, 1.7; 95 percent confidence interval,
1.3 to 2.2; P<0.001). Among patients with a creatinine clearance
in the lowest quartile, an elevated troponin T level was similarly predictive
of increased risk (20 percent vs. 9 percent; adjusted odds ratio, 2.5;
95 percent confidence interval, 1.8 to 3.3; P<0.001). When the creatinine
clearance rate was considered as a continuous variable and age, sex,
ST-segment depression, heart failure, previous revascularization, diabetes
mellitus, and other confounders had been accounted for, elevation of
the troponin T level was independently predictive of risk across the
entire spectrum of renal function.
CONCLUSIONS: Cardiac troponin T levels predict short-term prognosis
in patients with acute coronary syndromes regardless of their level
of creatinine clearance. |
| INTERFERING DISEASES OR SUBSTANCES
THAT ALTER LEVELS |
CHARACTERIZATION |
| DEGRADATION |
|
|
Degradation of cardiac troponin I in serum complicates comparisons
of cardiac troponin I assays.
Shi Q, Ling M, Zhang X, Zhang M, Kadijevic L, Liu S, Laurino JP.
Spectral Diagnostics Inc., 135-2 The West Mall, Toronto, Ontario,
Canada M9C 1C2.
|
Clin Chem 1999 Jul;45(7):1018-25 Abstract quote
BACKGROUND: Up to a 20-fold variation in serum cardiac troponin I (cTnI)
concentration may be observed for a given patient sample with different
analytical methods. Because more limited variation is seen for control
materials and for purified cTnI, we explored the possibility that cTnI
was present in altered forms in serum.
METHODS: We used four recombinantly engineered cTnI fragments to study
the regions of cTnI recognized by the Stratus(R), Opus(R), and ACCESS(R)
immunoassays. The stability of these regions in serum was analyzed with
Western blot.
RESULTS: The measurement of several control materials and different
forms of purified cTnI using selected commercial assays demonstrated
five- to ninefold variation. Both the Stratus and Opus assays recognized
the N-terminal portion (NTP) of cTnI, whereas the ACCESS assay recognized
the C-terminal portion (CTP) of cTnI. Incubation of recombinant cTnI
in normal human serum produced a marked decrease in cTnI concentration
as determined with the ACCESS, but not the Stratus, immunoassay. Western
blot analysis of the same samples using cTnI NTP- and CTP-specific antibodies
demonstrated preferential degradation of the CTP of cTnI.
CONCLUSIONS: The availability of serum cTnI epitopes is markedly affected
by the extent of ligand degradation. The N-terminal half of the cTnI
molecule was found to be the most stable region in human serum. Differential
degradation of cTnI is a key factor in assay-to-assay variation.
|
| FIBRIN CLOTS |
|
| HEPARIN |
|
|
Lower cardiac troponin T and I results in heparin-plasma than in
serum.
Stiegler H, Fischer Y, Vazquez-Jimenez JF, Graf J, Filzmaier K,
Fausten B, Janssens U, Gressner AM, Kunz D.
Institut fur Klinische Chemie und Pathobiochemie, Medizinische
Klinik I, and Klinik fur Thorax-, Herz- und Gefasschirurgie, Universitatsklinikum
der RWTH Aachen, 52074 Aachen, Germany.
|
Clin Chem 2000 Sep;46(9):1338-44 Abstract quote
BACKGROUND: The use of plasma rather than serum for determination of
cardiac troponins can improve turnaround time and potentially avoid
incomplete serum separation that may produce falsely increased results.
We investigated the influence of incomplete serum separation and the
effect of heparin-plasma on cardiac troponin concentrations.
METHODS: Serum and heparin-plasma samples were drawn simultaneously
from 100 patients (50 patients with acute coronary syndrome and 50 patients
after open heart surgery) and measured on three different analytical
systems, two for determination of cardiac troponin I (cTnI; Abbott AxSYM
and Bayer ACS:Centaur) and one for cardiac troponin T (cTnT; Roche Elecsys
cTnT STAT). Serum samples were reanalyzed after a second centrifugation
to assess the influence of incomplete serum separation.
RESULTS: Mean results (+/- 95% confidence interval) in heparin-plasma
compared with serum were 101% +/- 2% (AxSYM cTnI), 94% +/- 3% (ACS:Centaur
cTnI), and 99% +/- 3% (Elecsys cTnT). Differences >20% were seen in
11% of results on the ACS:Centaur, 9% of results on Elecsys cTnT, and
2% of results on the AxSYM. For the Elecsys cTnT assay, the magnitude
of the difference between serum and plasma was independent of the absolute
concentration and confined to individual samples, and was reversed by
treatment with heparinase. A second centrifugation had no effect on
serum results by any of the assays.
CONCLUSION: The concentrations of troponins measured in heparin-plasma
are markedly lower than in serum in some cases.
|
| HETEROPHILIC ANTIBODIES |
|
|
Performance of the enhanced Abbott AxSYM cardiac troponin
I reagent in patients with heterophilic antibodies.
Yeo KT, Storm CA, Li Y, Jayne JE, Brough T, Quinn-Hall
KS, Fitzmaurice TF.
Department of Pathology, Dartmouth Medical School
and Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon,
NH 03756, USA.
|
Clin Chim Acta 2000 Feb 25;292(1-2):13-23 Abstract quote
The presence of heterophilic antibodies in the serum of a small subpopulation
of individuals continues to cause false results for modern-day immunoassays.
In order to determine the frequency of heterophilic antibody (HA)-related
false positives within our population of positive cardiac troponin I
(cTnI) patients, we assayed 200 samples using the original in-house
cTnI assay (Abbott AxSYM) and the Bayer ACS:180 cTnI, which we had previously
observed to be more effective at blocking HA interference.
Four samples were identified as false positives based on discordant
results between the two assays, as well as the correction of the false
positives by treatment of the samples with heterophilic antibody blocking
reagent (HBR). An 'enhanced' version of the AxSYM cTnI reagent was designed
to greatly reduce or eliminate HA interference, and has now replaced
the original reagents. The present study shows that the enhanced reagent
significantly reduced or eliminated much of the HA interference.
Comparative studies between the enhanced cTnI reagent and the original
Abbott AxSYM cTnI reagent showed excellent correlation and equivalent
diagnostic concordance, when HA samples were excluded from the analysis.
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| CHRONIC RENAL FAILURE |
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Cardiac troponin elevations in chronic renal failure: prevalence
and clinical significance.
Musso P, Cox I, Vidano E, Zambon D, Panteghini M.
Department of Cardiology, Ospedale Civile, Ivrea, Italy.
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Clin Biochem 1999 Mar;32(2):125-30 Abstract quote
OBJECTIVES: The aim of the study was investigate the prevalence of
abnormal values of cardiac troponin T (cTnT) and cardiac troponin I
(cTnI) in patients with chronic renal failure (CRF) and their clinical
significance.
DESIGN AND METHODS: We investigated the concentrations of cTnT and
cTnI in 49 CRF patients without heart disease or diabetes. Cardiac TnT
values were measured with a second generation immunoassay and cTnI with
two immunoassays with different analytical sensitivity. All CRF patients
underwent regular clinical follow-up over a 18-month period.
RESULTS: No patients with CRF had elevated values of cTnI when measured
with one assay and only 2 patients displayed minimally elevated values
with the second assay. In contrast, 23 CRF patients (47%) displayed
cTnT concentrations elevated above the upper reference limit. The elevated
cTnT values observed were below the values detected in acute myocardial
infarction and were not associated with adverse cardiac events during
follow-up.
CONCLUSIONS: Mildly elevated cTnT concentrations are common in patients
with CRF and do not appear to be associated with adverse coronary events.
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| HETEROPHILE ANTIBODIES |
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False-positive AxSYM cardiac troponin I results in a 53-year-old woman.
Knoblock RJ, Lehman CM, Smith RA, Apple FS, Roberts WL.
Division of Clinical Pathology, Department of Pathology, University
of Utah Health Sciences Center, Salt Lake City, Utah 84108, USA.
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Arch Pathol Lab Med 2002 May;126(5):606-9 Abstract quote
A number of classes of endogenous antibodies, including heterophile,
rheumatoid factor, and autoantibodies, can interfere with immunoassay
measurements of many different analytes. Heterophile and rheumatoid
factor antibody interferences have been described previously for the
AxSYM cardiac troponin I assay. Several commercial products have been
developed to neutralize heterophile antibody interferences.
We describe a patient with multiple apparently falsely elevated cardiac
troponin I results that were unique to the AxSYM analyzer. These cardiac
troponin I results diluted linearly. When treated with 2 different heterophile-blocking
reagents, the magnitudes of the falsely elevated results increased 17-
and 26-fold, and these results also demonstrated dilution linearity.
This interfering substance could be removed by passage through an immobilized
protein A column and by polyethylene glycol precipitation. It does not
appear to be a classic heterophile antibody, nor is it a paraprotein.
Laboratorians must remain constantly vigilant for immunoassay interferences
that lead to clinically significant inaccurate results and must recognize
that accepted methods for detecting and neutralizing the interference
may be ineffective.
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| RHEUMATOID FACTOR |
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False-positive troponin I in the MEIA due to the presence of rheumatoid
factors in serum. Elimination of this interference by using a polyclonal
antisera against rheumatoid factors.
Dasgupta A, Banerjee SK, Datta P.
Department of Pathology and Laboratory Medicine, University of
Texas-Houston Medical School 77030, USA.
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Am J Clin Pathol 1999 Dec;112(6):753-6 Abstract quote
We report false-positive cardiac troponin (cTn) I results in the microparticle
enzyme immunoassay (MEIA) using the AxSYM analyzer.
We studied serum samples from 12 patients with positive rheumatoid
factor but with no indication of myocardial infarction (MI); 2 also
had positive antinuclear antibody (ANA) titers. Serum samples from 7
patients with positive ANA titers and negative rheumatoid factors also
were studied. Total creatine kinase (CK) was run using a Hitachi 747
analyzer, cTnT using an Elecsys 2010 analyzer, and cTnI and CK-MB using
an AxSYM analyzer.
We observed no measurable cTnI and cTnT concentrations in 12 control
samples or in specimens with positive ANA titers and negative rheumatoid
factors. In contrast, samples from 7 of 12 patients containing rheumatoid
factors had measurable cTnI concentrations. Four specimens showed cTnI
concentrations more than 2.0 micrograms/L, the suggested diagnostic
cutoff for MI. None of the specimens showed detectable cTnT. The concentrations
of total CK and CK-MB were within normal ranges in all specimens. False-positive
results were observed only with the MEIA for cTnI.
This interference can be eliminated by using a polyclonal antisera
against rheumatoid factor. The chemiluminescent assay for cTnI showed
no detectable cTnI concentration in any specimen.
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