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Enzymes and Protein Markers |
Departments of
1
Pathology and
2
Medical and Research Technology, University of Maryland School of Medicine, Baltimore, MD 21201.
3
Department of Laboratory Medicine and Pathology, Hennepin
County Medical Center, Minneapolis, MN 55415.
4
Clinical Pathology, University of Texas Southwestern
Medical Center, Dallas, TX 75235-9072.
5
Beckman Instruments, Inc., Chaska, MN 55318-1084.
a Address correspondence to this author at: Clinical Pathology, University of Maryland Medical Center, 22 South Greene St., Baltimore, MD 21201. Fax 410-328-5880; e-mail rchriste{at}umabnet.ab.umd.edu.
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Biochemical markers of myocardial injury are considered the "gold standard" for the diagnosis of MI (2) and are particularly important in nondiagnostic electrocardiogram patients, a group accounting for 40–76% of MI patients at presentation (3). The MB isoenzyme of creatine kinase (CK-MB) represents the benchmark for comparison with other biochemical markers because the characteristic rise and fall of CK-MB in serial measurements is nearly pathognomonic for MI (4). By using CK-MB mass assays and a strategy that included sampling at presentation and after 3 h, 6 h, and 9 h, Gibler et al. (5) documented a diagnostic sensitivity of 100% and diagnostic specificity of 98.3% for MI diagnosis. CK-MB, however, is not a perfect marker because in populations with low disease prevalence, such as chest pain evaluation centers, the predictive value of a positive result is low (5). Also, depending on the methodology used for measurement, as long as 8–12 h may be required after myocardial injury before the diagnosis of MI can be made with high sensitivity and specificity (4). In addition, CK-MB is not cardiac specific (6); this lack of tissue specificity is particularly problematic for interpretation in patients with concomitant myocardial and skeletal muscle injury (6)(7)(8). The inadequacies of biochemical markers currently in use have generated considerable interest toward development of more cardiac-specific markers such as cardiac troponin I (cTnI).
cTnI is part of a new generation of biochemical markers that provides an additional clinical tool for assessment of the "acute coronary syndromes," a term that describes the continuum of myocardial injury ranging from angina, or so-called "reversible" ischemia, to Q-wave MI and definite tissue necrosis. Functionally, troponin I is a 24-kDa structural protein that interacts with troponin T, 37 kDa, and troponin C, 18 kDa, as part of the three-member troponin complex that is essential for contraction of striated muscle in both cardiac and skeletal tissue (9). Troponin I molecules from cardiac and skeletal muscle have different amino acid sequences; antibodies directed at these different sequences are the basis for development of cardiac-specific immunoassays (10). Studies have indicated that cTnI is a more specific marker in cases involving skeletal muscle injury and renal failure (11). Also, different cTnI immunoassays have demonstrated excellent potential for clinical use in the diagnosis of MI (12)(13)(14). Therefore, cTnI may have an important role in real-time strategies for evaluating acute coronary syndrome patients, an area that has been of intense interest, discussion, and study over recent years (15)(16)(17).
In this study, we evaluated the analytical and clinical performance for MI diagnosis of the ACCESS cTnI assay, intended for real-time measurement in clinical laboratories.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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patient samples
Patients without cardiac symptoms.
To estimate the reference
range for the ACCESS cTnI assay, we studied 61 ambulatory patients
scheduled for same-day surgery. None of these patients had evidence of
cardiac, renal, or skeletal muscle disease.
Suspected MI patients.
Serum samples from a total of 289
patients presenting within 12 h of acute chest pain suggestive of
cardiac ischemia were included in the study, 45 (16%) of whom were
diagnosed as having MI according to WHO criteria (18).
Table 1
lists the number of patients enrolled and the methods and
markers measured at each site. Although multiple methods and markers
were measured at the participating centers, only Stratus cTnI values
were used clinically at HCMC; CK-MB mass and total CK activity were
used clinically at UTSMC and UMAB.
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The mean age of the patient population was 54 years, with a range of 24–90 years; 55% of the patients were men; 39% were Caucasian, 49% were African American, 4% were Hispanic, and the remaining 8% were of other ethnicity. All patients had two or more serial serum samples collected within 24 h of presentation. Although the timing of blood collection was dependent on the individual hospital's protocol, all patients had specimens collected at presentation and at least 6–10 h later. Specimens were either analyzed within 8 h of collection or stored frozen, at -70 °C, then thawed once just before analysis.
All sites in this study performed ACCESS cTnI testing. Clinicians
determining the diagnosis of patients in this study were blinded to the
ACCESS cTnI results. Chart reviews were performed by members of the
investigation team at each site. As indicated in Table 1
, two of the
three sites performed CK-MB mass analysis, and two sites performed
Stratus cTnI testing on suspected MI patients. Thus, the numbers of
patients in each of the clinical performance evaluations are slightly
different.
Skeletal muscle injury/disease.
cTnI concentration was
measured in specimens from 58 patients with skeletal muscle diseases
(e.g., polymyositis) or skeletal muscle damage (e.g., trauma) having a
total CK activity >1000 U/L. Trauma patients with evidence or
suspicion of myocardial injury were excluded.
Chronic renal failure (CRF).
Fifty-five CRF patients, all of
whom had serum or plasma creatinine values >80.0 mg/L, were enrolled
for testing. CRF patients with concomitant cardiac disease were
excluded from this study.
cardiac marker measurements
ACCESS cTnI.
The ACCESS cTnI Immunoassay (Beckman Instruments)
is a two-site immunoassay using monoclonal antibodies described
previously (19). The ACCESS immunoassay system is a
bench-top random-access and continuous immunoassay analyzer that uses
chemiluminescent detection (20). cTnI can be measured with
on-analyzer time to first result of 15 min. All specimens in this study
were analyzed in duplicate with the ACCESS cTnI assay.
Stratus cTnI.
As indicated in Table 1
, cTnI was also assayed
with the Stratus II system (Dade International) according to the
manufacturer's instructions at the HCMC and UTSMC sites. The
characteristics of this two-site immunoassay have been described
previously (21). The assay time for the Stratus II system
is 10 min. The minimum detection limit is 0.35 µg/L; the cutoff for
MI detection used for comparison in this study was 1.5 µg/L, as
determined from clinical studies described in the manufacturer's
package insert. Typical interassay CVs were 7% at cTnI concentrations
of 2.0 µg/L, 8% at 1.5 µg/L, and 15% at 0.7 µg/L
(22).
Stratus CK-MB.
CK-MB mass was assayed with the Stratus II
system at the UMAB site in accordance with the manufacturer's
instructions (Table 1
). The detection limit is 0.4 µg/L, and the
upper limit of the reference range determined from evaluation studies
done at UMAB is 6.6 µg/L (Stratus CK-MB reference range study on 138
noncardiac ICU patients at the University of Maryland Medical Center,
unpublished data); however, 7.0 µg/L was used clinically at the UMAB
site and in this study.
ACCESS CK-MB.
The ACCESS CK-MB mass assay was performed by the
HCMC site in this study (Table 1
). This assay is based on two-site
immunoassay technology with monoclonal antibodies described previously
(23). The upper limit of the reference range was
determined from clinical studies of noncardiac hospitalized patients as
8.5 µg/L (data on file); the minimum detectable concentration is 0.3
µg/L.
analytical performance
Effect of dilution.
Three different sample pools were diluted
with equal volumes of assay diluent provided by the manufacturer as
recommended. The undiluted and the diluted specimens were analyzed in
triplicate, and the recoveries were calculated. An average recovery
within 10% of expected values was considered acceptable.
Precision study.
ACCESS cTnI imprecision was examined
following National Committee for Clinical Laboratory Standards protocol
EP5-T (24). Three concentrations of quality-control
materials from Beckman Instruments were analyzed in triplicate, in two
separate assays per day for 10 days, over a 20-day period, with use of
a single calibration curve. The data were analyzed by using one-stage
nested ANOVA to derive within-assay, between-assay, and total
imprecision.
Detection limit.
The detection limit was defined as the lowest
cTnI concentration corresponding to a signal 2 SD above the mean of 10
replicates of the zero calibrator. This was evaluated in four assays,
each using different calibration curves and reagent packs. The
analytical signal equivalent to 2 SD above the mean signal of the zero
calibrator was translated into cTnI concentration by interpolation
between the zero and 0.1 µg/L calibrators.
Limit of quantification.
Precision was assessed in serial
dilutions of a serum with known cTnI concentration both with diluent,
supplied by the manufacturer, and with a cTnI-negative serum from a
healthy individual. The limit of quantification was defined as the
lowest concentration having a within-run CV 
20%.
cTnI assay correlation.
The relation between cTnI measurements
with the ACCESS and Stratus systems was compared in 502 samples after
exclusion of specimens with cTnI amounts outside the linear reportable
range of the test methods. Of the 502 samples, 114 (22.7%) had results
both above each cTnI assay's detection limit and within each
respective assay's dynamic range; 122 (24.3%) had one of the two
results below the detection limit, and 266 (53.0%) had both results
below the respective detection limits. Regression analysis was
performed for results that were both above the detection limit and
within the dynamic range for each assay (n = 114).
Evaluation of ACCESS cTnI cutoff for MI.
ROC curves were
constructed for the peak ACCESS cTnI concentrations attained within
24 h of presentation in samples collected prospectively from all
289 patients (Table 1
). The first result of duplicate testing was used
for all analyses.
Comparison between ACCESS cTnI and other markers for MI
diagnosis.
Clinical performance of the ACCESS cTnI assay was
compared with CK-MB mass measurements by the Stratus or ACCESS systems.
As indicated in Table 1
, 208 patients were included in this analysis,
30 of whom were diagnosed as having MI. After categorization according
to each assay's cutoff, Stratus CK-MB mass and ACCESS CK-MB mass
results were pooled to represent the performance of CK-MB mass in data
analysis.
Performance of the ACCESS cTnI assay was also compared with results for
the Stratus cTnI system in 201 patients, 36 of whom were diagnosed as
having MI, as indicated in Table 1
.
Peak concentrations within 24 h of presentation were used for analysis of the ACCESS cTnI assay and other markers. Diagnostic sensitivity and specificity were calculated at each marker or assay's respective cutoff concentration. Agreement between two markers or assays in classifying patients based on dichotomized test results being positive (above CK-MB mass or cTnI cutoffs) or negative (below CK-MB mass or cTnI cutoffs) for MI was analyzed by using the McNemar test (25).
ACCESS cTnI and Stratus cTnI data in serial specimens were plotted for eight MI patients, all of whom had four or more specimens collected for >24 h after presentation.
statistical analysis
Correlation between ACCESS cTnI and Stratus cTnI assays was
analyzed by least-squares regression. The McNemar test was used for
comparison of correlated proportions such as diagnostic sensitivity and
diagnostic specificity data between markers or assays. The McNemar test
was also used to evaluate groups of paired dichotomous results
(25). Briefly, the McNemar test evaluates whether the
number of patients with paired results that are discrepant, i.e.,
positive/negative or negative/positive, are distributed evenly between
the two assays. When the McNemar test shows statistically significant
"uneven" distribution of the discrepant results, performances of
the two assays are considered different. For a two-sided test with a
significance of 0.05, the sample size used in this study would be
sufficient to detect a difference up to 15% in specificity and
sensitivity between two markers with a power of 0.8 (26).
All statistical tests were two-tailed, with significance set at
P <0.05.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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shows total imprecision ranging from 6.0% to 13.5% for the
three quality-control materials used in this study.
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After dilution with equal volumes of assay diluent, values for three serum pools with cTnI of 5.91, 10.30, and 14.77 µg/L were 90.3%, 94.4%, and 98.0% of expected.
The detection limit for the ACCESS cTnI assay was 0.0055–0.0092 µg/L
in four assays, with a mean of 0.007 µg/L. The lowest cTnI
concentration that could be measured with a within-assay CV 20% was
0.046 µg/L.
Regression analysis of paired ACCESS and Stratus cTnI measurements in
114 specimens collected within 24 h of presentation from the 201
suspected MI patients for whom both measurements were performed yielded
the relationship: ACCESS cTnI = 0.0996 (Stratus cTnI) 0.049
µg/L (r = 0.811). The SD of the residuals
(Sy
x) was 0.61 µg/L, approximately equal to the
mean ACCESS cTnI value of 0.686 µg/L. Fig. 1
shows data points with ACCESS cTnI <1.0 µg/L and Stratus
cTnI <10.0 µg/L.
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The subset of data with ACCESS cTnI values <0.25 µg/L and Stratus cTnI values <2.5 µg/L were not significantly correlated (r = 0.156).
Figure 2
shows serial cTnI data from eight MI patients, all of whom had
sampling over >24 h after presentation. Note that panels A, B, C, and
D of Fig. 2
show parallel patterns for the ACCESS and Stratus cTnI
methods; panels A, B, and D also show similar cTnI increases, expressed
as multiples of the diagnostic cutoff. On the other hand, panels E, F,
G, and H show patterns of rise and fall that differ substantially in
their ACCESS and Stratus cTnI values.
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clinical performance evaluation
ACCESS cTnI for 61 ostensibly healthy ambulatory individuals were
undetectable in 59 (96.7%; 95% CI, 92.2–100%); cTnI values were
0.03 and 0.10 µg/L in the remaining two.
Figure 3
, top, shows ACCESS cTnI data for the overall population of 289
patients enrolled in the study (Table 1
); the corresponding ROC curve
for these data is displayed in Fig. 3
, bottom. Analysis of this ROC
curve yielded an optimum cutoff of 0.15 µg/L for the diagnosis of MI
with the ACCESS cTnI assay. At this 0.15 µg/L cutoff, the diagnostic
sensitivity was 88.9% (95% CI, 79.7–98.1%), and the diagnostic
specificity was 91.8% (95% CI, 88.4–95.2%) for the ACCESS cTnI
assay.
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Diagnostic sensitivity and specificity for the ACCESS cTnI and CK-MB
mass assays were compared by using each marker's respective cutoff in
the 208 patients indicated in Table 1
. Diagnostic sensitivity was 90%
(95% CI, 79.3–100%) for both markers; diagnostic specificity was
93.8% (95% CI, 90.3–100%) for ACCESS cTnI and 91.6% (95% CI,
87.5–100%) for CK-MB mass (P >0.05, power = 0.8).
The agreement in classifying patients as either MI or non-MI with the ACCESS cTnI and CK-MB mass markers was examined with the McNemar test (see Materials and Methods). The markers were in agreement for 186 (89.4%) of the 208 patients. Among the 22 patients having discordant results, 9 (1 MI and 8 non-MI) were ACCESS cTnI positive (>0.15 µg/L) but CK-MB mass negative (<7.0 µg/L); the remaining 13 (1 MI and 12 non-MI) were ACCESS cTnI negative but CK-MB mass positive. There was no statistically significant difference between the ACCESS cTnI and CK-MB mass makers by the McNemar test (power = 0.8).
Diagnostic sensitivity and specificity of the ACCESS cTnI and Stratus
cTnI assays were compared for 201 patients (Table 1
) by using
respective cutoff values of 0.15 and 1.5 µg/L. With these cutoffs,
diagnostic sensitivity was 86.1% (95% CI, 74.8–97.4%) for both cTnI
assays; diagnostic specificities were 92.1% (95% CI, 88.0–97.4%)
for the ACCESS cTnI assay and 94.5% (95% CI, 91.1–97.4%) for the
Stratus cTnI assay (no statistically significant difference; power
= 0.8).
Agreement between the ACCESS cTnI and Stratus cTnI assays with regard
to classifying individual patients as either MI or non-MI was examined
with the McNemar test (see Materials and Methods). Both cTnI
assays were in diagnostic agreement for 34 of the 36 MI patients and in
153 of 165 non-MI patients (93.0% agreement overall). Among the 14
patients having discordant results shown in Fig. 4
, 9 patients (1 MI and 8 non-MI) were ACCESS cTnI positive
(>0.15 µg/L) but Stratus cTnI negative (<1.5 µg/L); five patients
(1 MI and 4 non-MI) were ACCESS negative but Stratus positive. Note
that in Fig. 4
, the magnitude of difference between the ACCESS and
Stratus discordant cTnI results was substantial; all but two results
were beyond the 95% CI of each respective assay's cutoff. There was
no statistically significant difference between the cTnI assays in
diagnostic performance by the McNemar test (power = 0.8).
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Figure 5
shows cTnI concentrations in specimens from 113 patients with
either skeletal muscle disease/injury or CRF, each of which was
measured with both the ACCESS and Stratus assays. Four patients with
skeletal muscle disease having Stratus cTnI results >1.5 µg/L also
showed ACCESS cTnI results >0.15 µg/L. There was no statistically
significant difference between the two cTnI assays in these CRF or
skeletal muscle injury patients (power = 0.8).
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The ACCESS cTnI assay demonstrated acceptable analytic performance
based on our examination of detection limit and limit of
quantification, imprecision, and cTnI recovery. The detection limit,
the minimum concentration that can be distinguished from zero, was in
the range of 0.01 µg/L. Such a low limit is favorable, this
characteristic having been shown to be important in clinical
applications such as risk stratification (22). The limit
of quantification of the ACCESS assay, indicating the minimum cTnI
concentration having within-assay imprecision 20% CV, was 0.046
µg/L, well below the determined cutoff for MI diagnosis.
The ACCESS and Stratus cTnI assays were highly correlated
(r = 0.811); however, there was a 10-fold difference
between cTnI results, as indicated by both the slope of 0.0996 and the
comparable diagnostic sensitivity and specificity at a cutoff of 0.15
µg/L for the ACCESS system and 1.5 µg/L for the Stratus. This
apparent 10-fold difference in assays measuring the same analyte
clearly points out a need for standardization. In addition, however,
there was substantial residual scatter indicated by the large
Syx, suggesting that some
fundamental factor other than a straightforward difference in
standardization between the two assays might be involved. This issue
will be discussed further later.
Specificity of the ACCESS cTnI assay was examined in noncardiac populations, which included ambulatory surgery patients, patients with skeletal muscle disease or injury, and patients with CRF. For ambulatory surgery patients, cTnI was undetectable in 96.7% of the subjects with the ACCESS cTnI assay. The two ambulatory patients in whom cTnI was detectable had values of 0.03 and 0.10 µg/L, substantially lower than the cutoff value of 0.15 µg/L for MI diagnosis. Although cTnI is rarely increased in conditions other than cardiac injury (27)(28), high cTnI results have been observed among CRF and skeletal muscle damage patients (29)(30). Therefore, it was not surprising that some of these patients in this study had detectable ACCESS cTnI concentrations, as were also seen in concurrent Stratus cTnI measurements. There was no statistically significant difference, however, between these two cTnI assays in the occurrence of above-normal cTnI results. Because cTnI has been recognized as highly specific for cardiac tissue on grounds of biochemical understanding and clinical experience (27)(31), speculation exists that the increased cTnI results of patients with skeletal muscle injury or renal failure may indicate occult minor cardiac injury and that patients showing such cTnI increases are at higher risk for an adverse outcome (32). However, this issue cannot be substantiated without additional invasive testing or large outcome-based studies.
ROC curve analysis of all 289 suspected MI patients enrolled at the three independent study sites identified a cutoff value of 0.15 µg/L with the ACCESS cTnI assay for MI diagnosis. By using this cutoff value, the ACCESS cTnI assay demonstrated diagnostic sensitivity of 88.9% (95% CI, 79.7–98.1%) and diagnostic specificity of 91.8% (95% CI, 88.4–95.2%) for this patient population.
CK-MB mass and the ACCESS cTnI assay results appeared comparable in terms of diagnostic sensitivity, diagnostic specificity, and ability to classify individual patients as MI or non-MI in the population studied. Also, the ACCESS and the Stratus cTnI assays appeared comparable in the population studied, showing no statistically significant difference in either diagnostic sensitivity, diagnostic specificity, or ability to classify individual patients as MI or non-MI at respective cutoffs of 0.15 and 1.5 µg/L. Although the sensitivity and specificity of the ACCESS cTnI appear to be similar to the CK-MB mass or Stratus cTnI assays, it is important to note, based on type I error analysis, that the number of patients included in this study limited the power to state that the assays were equivalent. In fact, although the observed differences in sensitivity and specificity were small, the statistical power of 0.8 used here meant there was a one-in-five (20%) chance that the actual differences in sensitivity or specificity between the assays could be as large as 15%. The potential for a 15% difference in sensitivity or specificity dictated by both the power of 0.8 and the number of patients included in this study may be viewed as relatively large.
Although this study was not designed to elucidate the issue of concomitant skeletal and cardiac muscle injury, considering the high specificity of cTnI for cardiac muscle (33)(34)(35), the ACCESS cTnI assay should have the advantage of providing a more accurate MI diagnosis in patients having conditions associated with skeletal muscle injury and increased CK-MB mass, such as may occur in perioperative MI (8).
Despite 93.0% concordance between the ACCESS and Stratus assays, there
were apparent differences in the cTnI measurements. Data presented in
Fig. 4
demonstrated that virtually all discordant results between
ACCESS cTnI and Stratus cTnI assays showed large pair-wise differences,
which was in accordance with the poor correlation (r =
0.156) at relatively low cTnI values and the large SD of the residuals
at higher cTnI concentrations. Evidently, fundamental differences in
epitope recognition or differences in interaction with antibodies
between the ACCESS and Stratus cTnI immunoassays exist. Reportedly, the
release of cTnI by damaged myocardium is similar to other myofibril
components such as tropomyosin and myosin light chain
(36). In this model, the cytosolic pool of the free
component is released first, shortly after myocyte damage, followed by
the release of the components as products of myofibrillar breakdown
(36). Evidently, the molecular structures of these two
released forms differ; hence, the cTnI composition in circulation
changes with time after MI. This hypothesis is also supported by the
obvious differences between patterns in ACCESS and Stratus cTnI values
in measurements of serial specimens from MI patients displayed in Fig. 2
. Differences in epitope presentation of the various forms of cTnI, as
well as how these forms are altered in circulation, may in part explain
the discordance between the ACCESS and Stratus cTnI immunoassays.
In conclusion, the data presented here show that the ACCESS cTnI assay provides a useful clinical tool for the diagnosis of MI. The ACCESS cTnI assay demonstrated acceptable analytical performance and, in the populations studied here, appeared to be diagnostically comparable with both CK-MB mass and the Stratus cTnI assays for the diagnosis of MI. The ACCESS cTnI also showed comparable specificity to the Stratus cTnI assay in non-MI patients with skeletal muscle injury and CRF. Although this study was not designed to compare real-time availability of cardiac markers, the ACCESS cTnI assay is available on a random-access platform designed for rapid turnaround of results.
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Acknowledgments |
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Footnotes |
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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S. Liu, M. Y. Zhang, Q. Song, X. Zhang, L. Kadijevic, and Q. Shi Extra Leader Sequence Affects Immunoactivity of Cardiac Troponin I Clin. Chem., August 1, 1999; 45(8): 1300 - 1302. [Full Text] [PDF]
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Q. Shi, M. Ling, X. Zhang, M. Zhang, L. Kadijevic, S. Liu, and J. P. Laurino Degradation of Cardiac Troponin I in Serum Complicates Comparisons of Cardiac Troponin I Assays Clin. Chem., July 1, 1999; 45(7): 1018 - 1025. [Abstract] [Full Text] [PDF]
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F. S. Apple, R. H. Christenson, R. Valdes Jr., A. J. Andriak, A. Berg, S.-H. Duh, Y.-J. Feng, S. A. Jortani, N. A. Johnson, B. Koplen, et al. Simultaneous Rapid Measurement of Whole Blood Myoglobin, Creatine Kinase MB, and Cardiac Troponin I by the Triage Cardiac Panel for Detection of Myocardial Infarction Clin. Chem., February 1, 1999; 45(2): 199 - 205. [Abstract] [Full Text] [PDF]
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F. S. Apple, A. J. Maturen, R. E. Mullins, P. C. Painter, M. S. Pessin-Minsley, R. A. Webster, J. Spray Flores, R. DeCresce, D. J. Fink, P. M. Buckley, et al. Multicenter Clinical and Analytical Evaluation of the AxSYM Troponin-I Immunoassay to Assist in the Diagnosis of Myocardial Infarction Clin. Chem., February 1, 1999; 45(2): 206 - 212. [Abstract] [Full Text] [PDF]
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O. Hetland and K. Dickstein Cardiac troponins I and T in patients with suspected acute coronary syndrome: a comparative study in a routine setting Clin. Chem., July 1, 1998; 44(7): 1430 - 1436. [Abstract] [Full Text] [PDF]
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), data used for calculating the
regression line; (
), data points below the detection limit of the
ACCESS and (or) Stratus cTnI methods, which were not included in the
regression analysis.
